1

36

I can recall, after the start up of the new
process.

So there was a gradual phase in of

product from the new process, but I couldn't give
you any data at all, exactly when material began
to actually be sold from the new process.
Q

That was going to be my next question, there was
an overlap then between the old process and the
new process?

A

Correct.

Q

And that was roughly 18 months, you said?

A

On the order of 18 months, yes.

Q

Was the old process eventually shut down in the

FORM LASER BOND A PENGAD/INDY 1-800-631-6909

489 building?
A

The old, yes, it was.

Q

When you began your new

responsibilities with

regard to research on the new process, did someone
else in the organic chemicals research department,
was someone else assigned to doing any work or
continuing with any work on the old process?
A

I just simply don't recall how that —

the mind

has gotten kind of vague as to specifically^what
was done, by whom, when, and all that.
Q

Where there certain people within your department

$131 0 - 151

37

in 1975 that were assigned to the 2,4-D process
beside yourself?

A

MR. WAGNER:

This is the new process?

MR. SCHULER:

The new or the old

Well, Harry Brust was certainly -- continued work
on the new process.

At this point I'll have to

admit I simply don't recall who else.
Q

Let me ask you this question, and if you don't
know, just tell me and I'll move on, prior to
1975, when you became involved with organic
chemicals research, do you know who was involved
in the department, if anyone, doing research on

FORM LASER BONO A PENGAD/ÍNDY t -000*631-6989

2,4-D?
A

Harry Brust.

Q

You said he's a chemist?

A

Yes.

And I know we had some engineers involved in

that project, but I simply, at this point, don't
remember who those individuals were.
Q

Let me show you the report that we've talked about
in this case, and I've highlighted some things.
I'm just going to ask you to identify it fc^r now,
and if you have a copy of it, it will save me some
time.

132

38

A

Yes,

that's

my

report.

(Discussion held off the record.)
(Plaintiff's Exhibit 1 was marked for
identification.)
MR. SCHULER:
Q

Back on the record.

Looking back at Plaintiff's Exhibit 1, here, this
is your report from October 27th, is that 1978?

A

Yes.

Q

And you did this report for what purpose, Dr.
Krumel?

A

The purpose was to document some, essentially the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

research that is described in the report.
Q

That's your answer, I take it?

A

Does that answer your question?

Q

I think so.

There's some writing, I don't know,

maybe this was from a prior lawsuit or something,
but I've got some writing on top of mine that I
see you don't have on top of yours.

Do you

recognize what that may be up there?
A

Well, the report was obviously sent to somebody by

j

somebody.

Q

But you don't recognize it?

A

No.

Steve, Steve, it means nothing to me.

133

p - iil

39

Q

In any event, this research was on the formation
and removal of impurities in the 2,4-D process,
correct?

A

In the new 2,4-D process, yes.

Q

And this was co-authored by Mr. R.F. Arnold?

A

Ray Arnold is a laboratory technician who works
with me.

I was -- his part of the project is he

ran the experiments or ran -- ran many of the
experiments that are described in the report, but
I'm the one that's responsible for the
interpretation of the data.

Ray was not qualified

to do that.
Q

And this was sent to, or it said receiver's

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

signature, Peter Owen?
A

Reviewer's signature, Peter Owen was my immediate
supervisor.

And the technique we use in report

writing at Dow is the authors submit the report to
the supervisor, and their supervisor has to sign
the report before it can be issued.
Q

What was Mr. Owen's position?

A

He was, as I said, he was my immediate supervisor
at that time.

Q

Is he still with the company?

134 . CH1“6

40

A

Yes.

Q

Is he still in organic chemicals research?

A

No.

He's off in another department.

At this

point, I can't tell you exactly what his job is.
Q

Up at the upper right-hand corner of Plaintiff's
Exhibit 1, it says laboratory report code, OC,
slash, 78, dash, 85.

Do you know what that code

stands for?
A

OC is merely the designation for organic
chemicals.

It was the designation used by our

library system to designate organic chemicals
research.

The number, it just means it's the 85th

report written in 1978, to come out of this

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

department.
Q

And then below that, it's hard to make this out
because of the copy I have, but it appears to be a
lab number, is that right?

A

Yes.

Q

Let me —

A

I beg your pardon?

Q

Is it 05 or?

A

050.

Q

And what is the significance

j

of the050 lab

135

CMU

41

number, if any?
That gets into some of the accounting and
recharging of research dollars within the company.
It has no meaning to the report, really, other
than just to designate.

The 050 is a laboratory

number for accounting.

The problem number is a

method for internal recharging.
Q

What do you mean by internal recharging?

A

Well, how I'm paid, how my salary is paid.

Q

And the problem number here is 9, six zeros?

A

Correct.

It has absolutely nothing to do with the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

report, itself.
Q

With the subject matter?

A

Yes.

Q

Looking down at the descriptive summary with
conclusions, let me just ask you a couple
questions about that.

One of the findings that

you outline here is a new and unexpected class of
non-acetic impurities, correct?
A

Mm-hmm.

Q

¥es?

A

Yes.

Q

And you mention two of the major components were

f

136

42

tetrachloroxanthone and octachlorospirobixanthene?
A

Yes.

Q

And what type of impurities are those, I mean -maybe that's a bad question, but can you
categorize those impurities in any way?
MR. WAGNER:

I object to the form of the

question, compound, vague.
A

Well, xanthone is an accepted organic

nomenclature

for a particular class of compounds.
Spirobixanthene, again, is the same thing.
accepted nomenclature.

It's

What they are is organic

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

chemicals that were detected in the product.
Q

In the final product of 2,4-D?

A

That's where we first observed them, yes.

Q

And when you mention that the impurities were
causing problems in the subsequent formulation of
2,4-D as amine salts, what were you referring to,
what did you mean by causing problems?

A

The issue occurred as we stated before, the plant
started up in May of '77.

By that fall, what we

started observing, we have a quality controj. test
for our amines, where we mix a small amount of the
amine salts with water, shake them up, centrifuge

137

£HW3

43

the samples and look at suspended solids, and we
have a certain amount of solids in that that's an
acceptable spec.
The problem that you run into, we
started to see more of these solids, but where the
problem really came up was when the formulated
product was applied in the field, we started
getting increasing customer complaints from
plugged spray nozzles.

At which point we went

back and started looking specifically at those
solids, and in these solids, that was where we
first observed some of the compounds, the
tetrachloroxanthene and the octachloro-

FORM LASER BOND A PENGAD/INDY 1-800*631-6989

spirobixanthene.
Q

And this whole paper, if I understand it
correctly, was devoted to exploring the
possibility for attempting to control, minimize or
eliminate these impurities in the 2,4-D?

A

Correct.

It was targeted at solving a customer

complaint issue.
Q

Do you recall whether there was a specific
customer that did complain?

A

I can't answer -- I just simply don't remember

138

44

where the specific complaints came from.
Q

Do you remember how you got notice of the
complaint, that there was a complaint, and
assigned this project?
MR. WAGNER:

I object to the form of the

question, compound.
A

I don't recall the exact sequence of events.

I

believe people are mentioned in this report, a
Joyce King, from formulations, in the 9001
building.

It's on page 8 at the bottom.

She is

in our -- or she was in our formulations and TS&D
area at the time.

She would be working with our

manufacturing supervision, who was working very

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

closely with our R&D supervision in my department.
So the whole sequence of events I don't
remember, but the bottom line came, I was assigned
the job of getting involved in attempting to
understand the formation and how we could get rid
of them to solve a quality issue.
Q

Do you know whether the old process that, from
your earlier testimony, I understand was st^Lll
ongoing at this time, was evaluated for these
impurities, as well?

139

45

A

We tested the samples, and none were found.

Q

When you say we, who are you referring to?

A

Again, our team, the we in this case would have
been someone from our analytical sciences
department, and that someone was most likely, as
best I can recall, Dale Humbert.

Q

Humbert?

A

Who is listed as a recipient on the back of this
report under 574 building, D. Humbert.

He was the

chief analytical scientist supporting this area.
Q

And from an overview standpoint, this report, you
mention that the number of treatments and
potential solutions that you examined, none

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

appeared to be totally successful, correct?
MR. WAGNER:

I object to the form of the

question.
A

That answer is -- yes, that's correct.

Q

In my copy here, there's a blank that appears to
be filled in on the one you have, the last
paragraph.

Can I see that for a second?
MR. WAGNER:

j

Sure.

(Discussion held off the record.)
(Plaintiff's Exhibit 2 was marked for

140

ÌHfcO.

46

identification.)
MR. SCHULER:
Q

Back on the record.

Let me just follow through this report briefly
with you.

My page 1 is a table of contents,

correct?
A

Yes.

Q

Page 2 appears to be an introductory section?

A

Yes.

Q

And that's where you mention at the top that the
process, I think the word new is even blanked out,
a new process for preparing high purity 2,4-D was

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

started in May 1977 at the 943 building?
A

948.

Q

Okay, it looks like 943 on mine, okay, 948
building.

You mention that the high purity molten

acid is transferred by pipeline to the 489
building where it is formulated into esters and
water soluble amine salts, which would be the
final product, correct?
A

Yes.

Q

You mention that the impurities that you fc^bnd
were never detected during laboratory or pilot
plant development work, correct?

141

47

A

Correct.

Q

Again, there's a word missing, I've got to ask, or
there appears that there's a word missing, anyway.
In any event, you mentioned, also, in this first
paragraph, that the impurities were not found in
the old process, correct?

A

Yes.

Q

And that was what you referred to earlier when you
said there was some testing done in the old
process, correct?

A

Yes.

Q

Who is R. McLachlan?

A

He's an analytical

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

department as

scientist in the same

Dale Humbert.

Q

Is he still there?

A

I don't believe he is.

I have

not -- I've lost

track of him.
Q

How about Mr. Humbert,

is hestill

A

He's still in the company.

there?

He's not in analytical

anymore, but I don't know specifically where he

j

is.
Q

Mr. McLachlan, in any event, was the one who
analyzed precipitates and found the TCX and the

142

48

ocsx?
A

He's the one that wrote the report.

Who actually

did the work, I assume Dick did, but I don't know
that for a fact.
Q

But that's what you put in here, correct?

A

Yes, that —

Q

And the chemicalformulas

yes.
for the TCX

and OCSX are

outlined there, correct?
A

Correct.

Q

You mention that

the TCXfrom

the screening

program at the plant showed levels of 200 to 500
parts per million in the crude reaction mass, and
again, I'm missing words here.

It says the

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

recycle —
A

Recycle sodium dichlorophenate.

Q

-- solution and in the final product.

Okay.

Levels of 1,000 to 2,000 parts per million were
found in the, and I'm missing —
A

Would you want to just work off that, and we'll --

Q

-- were found in the perc solvent, and as much as
10 percent in the still tars, perc still ta^s?

A

Correct.
MR. WAGNER:

I object.

143

49

Q

The toxicological significance of TCX and OCSX, is
that unknown to you?

A

Only what's reported in this report.

I think on

the next page, our page 6, is what I knew
toxicologically about this material.
Q

Where did you get the report on page 6?

A

It should be referenced.

Q

So you don't know where that information comes

It apparently is not --

from?
A

Not specifically, anymore.

There's a reference

to, in the reference section on page 57, the very
back of the report, reference two.
Q

What reference are you referring to?

A

Reference number two.

Q

P. Keller?

A

P. Keller, yes, that is from the --

Q

Health and environmental toxicology?

A

Yes, so —

Q

Looking at that for a minute, on page 357 of
Plaintiff's Exhibit 2, it says P. Keller et a l ,
H-E-T, and some numbers, K, dash, 2372, das|i,
parentheses,
for?

18.

Do you know what that stands

50

A

I have no idea.

Q

That would be the toxicology report?

A

It is possible that that's the toxicology report.

Q

And you're thinking --

A

I don't know that for a fact.

Q

Because it says HET?

A

Correct.

Q

Going back to page 3, it talks about 11 other
minor components structurally similar to the
above.

When you say structurally similar to the

above, what are you referring to there?
A

Without having seen reference one for many, many
years, I just simply don't recall.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

Q

Besides the TCX and the OCSX, though, there were
other components that were discovered, as well?

A

The compound shown as 8-5, and that is shown on
page 4, and then on page 8 are two other
impurities that were found, but specifically what
the 11 minor impurities refer to, I have simply
forgotten.

Q

Go to page 4 for a second, the 8-5, you cal^. this
another significant impurity.

What was the reason

for calling it that?

145

51

A

Because it was detected in quantities that
occasionally were comparable to what we were
seeing for the OCSX and the TCX.

Q

Do you know the toxicological significance of 8-5?

A

I'm not aware of any data on that compound
specifically.

Q

Had the page 6 initial screening for toxicity
report that you incorporated in this, that was
research that you did not do yourself, correct?

A

No, sir.

Q

However, the report that you incorporated in
Plaintiff's Exhibit 2 does appear to indicate
chloracne response for different concentrations

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

and different doses of the TCX and OCSX, correct?
A

I only see, in this one, one concentration applied
several times.

Q

Well, correct me if I'm wrong, here, it looks to
me like there are two.

One is four grams per

kilogram and the other is five grams per kilogram.
A

Well, one is a tar sample that contains some TCX,
some OCSX, and but you asked me, I thought ^ou
asked me specifically about TCX?

Q

Well, I mentioned TCX and OCSX, as well.

146

52

MR. WAGNER:
question.

Why don't we reask the

Now, I'm confused about what's on the

table.
Q

My question was initially that the report that you
incorporated in here by reference shows a
chloracnegeneric response in various
concentrations to both TCX and OCSX, correct?
MR. WAGNER:

I object to the form of the

question.
A

The answer to the question is yes, to the best of
my knowledge.

Q

The diagram on page 7 is just a diagram of the
process, would that be a fair statement?

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

A

It is a very simplified diagram of the process,
yes.

Q

Do you know, when referring to the top of page 8,
whether any data was obtained for long-term
effects of these impurities that you found?

A

I don't know.

Q

At the bottom of page 8

you referenced earlier

some other workers, and one is
A

Yes.

Q

Organic chemicals research?

S.Siegel,

•

Oj^R?

fl-rt5

53

A
Q

And was that someone who worked with you?

A

That was someone that was working alongside me,
yes.

As best I can recall, he was working more in

the quality area directly with Joyce King and
Susan Shell.
Q

Susan Shell was in the production end?

A

Yes, she was production supervisor.

Q

Located in building 489?

A

Yes, so she would have been production supervisor

FORM LASER BOND A PENGAD/INDY 1-000-631-6989

of the ester and amines portion of the process.
Q

And Judy, was it?

A

Joyce.

Q

Joyce King was in the formulation end and located
in Building 9001?

A

Yes.

Q

You mention in the last paragraph above the
chemical symbols on page 8 that there were two
other impurities called complex one and complex
two, and you diagrammed those that were found,

j

also, correct?
A

Yes.

Q

So we have, to keep track of all this, we have the

148

54

TCX, the OCSX, the 8-5, and the complex one and
complex two impurities, so far?
MR. WAGNER:

I object to the form of the

question.
Q

Referenced in your report, correct?

A

Yes.

Q

Do you know the toxicological significance of the
impurities, complex one and complex two?

A

No, I don't.

Incidentally, for correctness,

there's a slight misprint on number four.

The C

shown in the middle shows CL; that should be CH.
This should be -- may I?

FORM LASER BOND A PENGAD/INDY 1-000-631-6989

Q

That's CH there?
MR. WAGNER:

If you're going to correct

MR. SCHULER:

I'll correct it on this

it --

one because it's marked up already.

That should

be CH?
THE DEPONENT:
MR. WAGNER:

Yes.
How in the world you can

j

remember that, I'll never know.
THE DEPONENT:

Well, I just noticed it.

CH stands for?

149

55

The C stands for the chemical compound for carbon.
The H is the chemical symbol for hydrogen.

The CL

is the chemical symbol or chlorine, and that would
be an impossible structure.
Q

And the OH is the chemical symbol --

A

For the hydroxyl.

Q

Oxygen and hydrogen?

A

Yes.

Q

K.E. First, referring to page 9, what role did
that individual have in this report, if any?

A

Ken First, at that time, was in process
engineering, and I had actually even forgotten his
involvement, but he did some computer modeling of
rates of formulation based upon the data that I
generated, or that Ray Arnold and I generated.
And the contribution I think in his
report was to -- oh, goodness, I'm not sure what
page it's on, but he talked about, if we
maintained a certain level in the recirculating
perc, we would maintain another level in the
product.

It's in the report someplace.

I'|n not

sure exactly what page that's on.
We'll get to that.

I just wanted to know who that

56

was.

Let's refer to page 9, Dr. Krumel, for a

minute.

At the bottom of page

9,

after you

essentially have outlined the impurities that we
have already discussed, you decide to focus on
TCX, correct?
A

Yes.

Q

And you stated the reason for the focus on TCX,
one of the reasons was that it was a major
impurity.

A

What did you mean by that?

Of these -- of the small amount of things that we
found in the solids, it was a major component.

Q

By volume, you mean, or some other yardstick?

A

Typically what we're talking about would be by

FORM LASER BOND A PENGAD/INDY 1-000-631-6989

weight percent within these traces of solids that
were found.
Q

I want to ask you to skip over to page 21.

One of

the comments that you made on page 21 is that a
recurring problem for the past several months was
how to explain the fact that the plant observed
TCX formation rates that were five times greater
than the lab.

Did you ever find the reasonjfor

that?
MR. WAGNER:

I object to the form of the

151

57

question.
A

No, we never really did, nothing more than what's
explained in this report.

Q

In the first sentence of the last paragraph,

full

paragraph on page 21 of Plaintiff's Exhibit 2, you
mention that in addition to TCX, OCSX and 8-5 are
known to be formed measurable quantities during
the reaction to 2,4-D -- maybe I didn't read that
properly.

In addition to TCX, OCSX and 8-5 are

known to be formed in measurable quantities during
the reaction to 2,4-D.

When you say measurable

quantities, can you tell me the relationship
between the three, perhaps reflected in percentage

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

as far as the ratio of the weights found?
MR. WAGNER:
A

I object to the form.

Without specifically reviewing data and numbers,
just simply don't recall, but we mentioned in the
report 200 to 500 parts per million of TCX was
found.

Measurable quantities would, in that

context, would mean comparable numbers, but
specific data, I just simply don't recall,

j

On page 28, referring you to 28, and you can't
tell because mine is the expurgated copy, here,

I

58

but in the middle paragraphs you mention some TCX
is formed in the reactor and was found throughout
the 948 building process.

When you say that, are

you referring to the fact that the TCX was found
at various points in the process or actually in
the building, itself?
MR. WAGNER:

I object to the form of the

question.
A

It was found in various process streams.

As we

indicated before, it was found in the reactor
crude.

It was found in the recycle

dichlorophenate solution, and it was found in the
recirculating perc, so it's found inside the

FORM LASER BOND A PENGAD/INDY 1-800-631*6989

chemical process, itself.
Q

Was it found in the final product, 2,4-D?

A

I think, back on page whatever, it was indicated
that yes, we did find it in the product, itself.

Q

Referring to the bottom of page 29, you make note
of the fact that the 8-5 impurity is not
efficiently removed with perc extraction, hence
most of what is made goes out with the product.
Why was that a concern?
MR. WAGNER:

I object to the form of the

9'

59

question.
Again, because it is, the trace levels that were
in the product are insoluble in the amines
formulating mixture and would again result in
small amounts of solids that I think we discussed
earlier.
Q

In the table five above that statement you have
some numbers for initial and final as far as TCX
and 8-5 in parts per million, correct?

A

Yes.

Q

What does that refer to, initial and final, in
that chart?

A

I have to read the chart.

What we did was

FORM LASER BOND A PENGAD/INDY 1-800*631-6989

simulate the process in the laboratory, and to
take a sample of the crude sodium salt of 2,4-D,
extract with perchloroethylene, in the laboratory,
and analyze the sodium 2,4-D before and after
extraction with perchloroethylene, and these are
merely the results of those experiments.
Q

Is the final referred to in the final product, or
is that at some other juncture that you extracted
the TCX and 8-5?
MR. WAGNER:

You mean the columns,

60

final, is that what you're referring to?
MR. SCHULER:
A

Yes.

This would refer to the sodium.

This would not

refer to the final product, but rather to the
intermediate sodium 2,4-D.
Q

At the bottom of page 30 you refer to the 2,4-D
reaction as developed by H. Brust.

Is that

referring to this new process?
A

Correct.

Q

At the bottom of page 31, you mention that
formation of the TCX cannot be limited to much
less than 60 percent per million.

Is that with

reference to the final product of this new

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

process, or sodium or the amine version of 2,4-D?
MR. WAGNER:

I object to the form of the

question.
A

This refers to laboratory experiments which, as
you can see, were run at 72 hours at 160 degrees
in glass equipment.

This is not refering to

plant.
Q

So this is the product that you were getting in
the laboratory?

A

Correct.

D'^1
4 5 5 -------------

61

Q

Did you ever test the final product from the plant
to determine a TCX concentration?
MR. WAGNER:

I object to the form of the

question.
A

The product in the plant was analyzed routinely
for these compounds.

Q

And is there information here in this report with
regard to that, or would that be located in some
other report?
MR. WAGNER:

I object to the form of the

question.
A

There may be a reference within the report here or
there.

I don't specifically recall talking about

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

specific plant data.

All of the numbers reported

in various tables, to the best of my recollection,
are all laboratory generated numbers.
Q

So you were using, you simulated the process or
reconstructed the process in the laboratory, and
the numbers in this report are with regard to the
product you produced in the laboratory?

A

Correct, other than the numbers that we discussed
at the very beginning, where we said we found 200
to 500 parts in the reactor crude and in the

------------------------------------------------- r s e ------------

62

recycle, those were plant data.
Q

With the plant data that you mentioned, it would
be generally higher than the laboratory data for
as far as the content of the impurities was
concerned?

A

We observed that, I think I mentioned it a little
bit ago, where you were asking me, it's on page
21, where the plant observed TCX formation rates
that were five times or so higher than laboratory.

Q

Referring to page 35, you make reference to an
earlier report, and it's got a number, footnote
16.

Is that the report that's listed as 16 in the

FORM LASER BOND A PENGAD/iNDY 1-800-631-6989

reference section on page 57?
A

I recall the work.

Q

What's listed as 16 on page 57 has some numbers
behind it.

I do not recall the report.

Organic chemistry, I assume is the OC?

A

Yes.

Q

And then 78, dash, 17 stands for what, if you
know?

A

I guess I don't remember specifically.

The thing

that confuses me a little bit is the LR, because
that is a code that we used to use for letter
reports, which were a way of documenting results

63

back at that time.

I think I mentioned earlier

the numbering code that we used.

Well, we

mentioned it on this report, but the 78-17 LR, I
don't specifically remember how we used to number
those.
Q

What about the 39, dash, 78?

A

That, I'm not sure about that, either.

Q

There's a reference in the reference section,
number 12, also, to some work done by, is it Dr.
Brust?

A

Yes.

Q

And refers to organic chemicals, again, with
long number, dash, 2, and then a 2-26-73.

a

Do you

FORM LASER BOND A PENGAD/INDY 1-800-631*6989

know what that refers to, number 12?
A

That's one of Dr. Brust's research reports.

I

can't tell you from the number exactly which

one.

The date is the date that the report was issued.
The numbering code is, the 0730013 is a coding
system that was used for a period of years.
CHECK CHECK CHECK.

j

Q

Any significance to that?

A

Nothing as far as a -- I don't specificalloy
recall.

64

Q

Was there a specific number that was assigned to
subject matter, for example, like 2,4-D, was there
a specific file or series of files pertaining to a
particular chemical like that?

A

Different coding systems were used at different
times.

Now, whether there was a coding system

specifically designed to 2,4-D, I don't recall.
Q

You don't remember whether there were specific
codes that were assigned to certain chemicals,

for

example, to keep research, no matter what aspect
it dealt with, but in regard to a certain chemical
in that area that existed?
MR. WAGNER:

I object to the form of the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

question.
A

I don't specifically recall all that went into how
they specifically assigned codes, because it
changed at times.

And what was used specifically

at the time this report was issued, I don't really
remember.
Q

Was the research or the organization of the
product of the research computerized back i^i 1975?

A

Was the research computerized in 1975?

Q

I mean the organization of the reports?

159

65

A

Oh, no, these were not done by, on computer.

Q

But were they filed?

Was there a computer index

of the reports, if you know?

A

MR. WAGNER:

In 1975?

MR. SCHULER:

In 1975.

In 1975 was there a computer?

I don't know for

certain.
Q

At the bottom of page 36, or on page 36 I should
say, you make a comparison in the first paragraph
between the two processes, the 489 building and
the new process in the 948 building, correct?
MR. WAGNER:

I object to the form of the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

question.
A

Are you talking about under item four?

Q

Yes.

A

Well, the process in 489 building did use a step
involving the use of bleach that was not used in
the new process, that's correct.

Q

And were you making some type of an estimate as to
whether adding a bleaching step would improve or
reduce, help to reduce the impurities that jkere
found in the new process, is that what you were
doing there?

160

66

A

Yes.

Q

And it is apparently submitted to somebody by the

It was an option we wanted to consider.

name of K.E. First?
A

That's the same Ken First we discussed earlier.

Q

And he estimated a cost of doing that at 500,000,
is that what that is?

A

Yes.

Q

So that wasn't pursued because of the -- it wasn't
cost effective?
MR. WAGNER:

I object to the form of the

question.
A

Yeah, as stated in the report, it was dropped due
to the marginal benefits that we concluded.

FORM LASER BOND A PENGADMNDY 1-800-631-6969

Q

At the top of page 38 you mention the capacity of
the 948 building up to that point in time, and I
just want to know, need to know the numbers you're
referring to there, it's 100 to 120 what per day?

A

It's 100 to 120,000 pounds per day.

Q

What, the new process?

A

Yes.

Q

Do you know at this time or, let me go back^ do
you know as of May of 1977 whether the 948
building was running at that capacity?

161

V

67

A

In May of '77 when we started up?

Q

Yes.

A

No, it was not.

Q

What about when this report was done in October?

A

The date would basically refer to the date this
report was issued, so we're talking about,
essentially now, October 1978.

What the running

rate was in October of '77, which is, I assume,
the date you're asking about?
Q

Yes.

A

I don't know.

Q

That's right, this report was October of '78, so
you're referring to the full capacity as of

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

October of '78?
A

Correct.

Q

And in your statement in the next sentence with
regard to the impurities in the 2,4-D product is
what, 20 parts per million of TCX?

A

Yes.

Q

And 20 parts per million of 8-5?

A

Plus or minus some.

What the ranges are,

i j don't

recall.
Q

You mention in a couple of paragraphs down that

162

68

further work is justified only if the levels of
impurities presently found in the product prove
unacceptable in the future from a toxicity,
environmental or performance standpoint.

Do you

recall whether there was any further research done
in any of those areas to determine whether these
impurities were unacceptable?
MR. WAGNER:

I object to the form of the

question.
A

No, I don't recall.

Q

You did not do any research in those areas, I take
it?

A

The work that we would have done in those areas

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

would have been continuing to work in the plant,
monitoring and making sure that we were, in fact,
operating within these ranges.
Q

You mean the ranges of 20 parts per million?

A

Yes.

Q

Was there a quality control laboratory set up in
each building, for example, the 948 building for

j

2,4-D and the 489 building for 2,4-D?
A

Yes.

Q

And so the analyses that you referred to earlier

163

69

with regard to quality control were performed
right there in the plant, if you will?
A

Correct.

Q

As opposed to the organic chemicals research
laboratory?

A

We did very, very few analyses ourselves, in our
department.

We would rely on the quality control

laboratories, as well as the analytical sciences
laboratory.
Q

Was there a quality control officer assigned, for
example, to building 489?

A

I can't answer how that was -- I don't know how
that was managed those days.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

Q

Was that a separate department in 1975, quality
control?

A

The quality control work, during the time frame
we're talking here, was done within the plants.
How the data was managed in reference to a quality
control officer, or as you brought up, I just -- I
don't know.
MR. WAGNER:

Let's take a quick b^reak.

(Recess.)
BY MR. SCHULER:

164

70

The acknowledgment section on page 56 of
Plaintiff's Exhibit 2 mentions a number of people,
some of whom you've already referred to, Dr.
Krumel, but let me ask you about some of the
others.
A

Who is T. Evans?

Tom Evans was an analytical scientist, as was Gary
Jewett, as was Penn, P-E-N-N, Schloemann -- well,
as I indicated, for their analytic support.

Q

I just wanted to identify them.

Did they all work

on some aspect of preparing this report that we
have marked as Plaintiff's Exhibit 2?
A

They all would have provided input in the
analytical results that were described within the
report.

I couldn't identify for you specifically

what each one of those individuals did at this
time, but they were all part of providing the
analytical backup for this report.
Q

Did any of them do any research on 2,4-D prior to
the new process, the old process, we'll call it?

A

Not that I recall.

Q

I asked you about some of the documents listed on
page 57, the reference section.
Mr. Dhingra, D-H-I-N-G-R-A?

Who is

71

A

Yes, Yog Dhingra.

Q

Who is that?

A

He's a chemist who was involved in the phenoxy
area during the time I was in the cellulose ether
area.

So specifically what he was doing and what

he was referring to in this reference, I can't
tell you right now.
Q

Mr. Fern or Ms. Fern, whatever that is, do you
know who that is, it's the next one down, number
14?

A

That's a misprint.

That's what I was afraid of.

You can -- back to page 31, I refer to Dhingra and

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

Fear, reference 14.
Q

So that's Fear?

A

The name should be Fear, F-E-A-R, Dennis Fear.

He

was an engineer who was very much involved in
process modeling.

Now, we'd have to look at the

report if you want to get specifically as to what
he did.
Q

The work that you did in the organic chemical
research laboratory, was that originally committed
to what's referenced here in some places as a lab
book?

166

9' ^

72

MR. WAGNER:

I object to the form of the

question, over broad.
Our standard way of initially documenting our
work, as we're doing the experiments, is to write
them up in research data books.

The results of

our work described in these research data books is
then summarized in these research reports.
Q

So the summary, this research report would be the
summary of what's in the research data book for a
particular experiment?

A

Correct, or a particular project.

Q

There's a reference at the bottom where it talks
about laboratory notebook references, and it has

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

your name and Mr. Arnold?
A

OC 417 and OC 640, those are code numbers for the
data books.

The pages merely describe, so in

research data back OC 417 for Ray Arnold, you will
find the work that is summarized in this report
described in pages 109 to 150.

And in data book

640 from pages 1 to pages 73, and likewise in my
research data book, OC 559, you will find w^rk
described in this report on pages 95 to 131.

This

is the way we have of referencing our reports back

167

73

to the original data.
All right.

After this was completed, did you do

any further research with regard to these
impurities in the new 2,4-D process?
MR. WAGNER:

I object to the form of the

question.
A

Not that I can recall.

Q

Did you do any further research into the old 2,4-D
process after October of 1978?
MR. WAGNER:

I object to the form of the

question.
A

Not that I can specifically recall.

Q

At some point in this report, this 2,4-D was

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

referred to as Rhone-Progil acid.

Do you know

what that means?
A

Yes.

Rhone-progil was a company in Europe that

produced 2,4-D acid at that time.

Their material

happened to be particularly pure, so we had a
sample of it that we used for research purposes
only.
Q

And that's why you refer to it by that name I

A

Rhone-Progil, yes.

Q

Was the new process for 2,4-D developed to reach

1£ &

U

74

the level of purity that had been developed by
this Rhone-Progil company?
MR. WAGNER:

I object to the form of the

question.
A

To my knowledge, there's no connection.

Q

Did you, other than writing your report, and I
assume, let me go back and ask this question, I
assume this report, that we have marked as
Plaintiff's Exhibit 2 here, was written for
intercompany use?

A

Yes.

Q

Did you ever write any report for use outside the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

company, to anyone outside the company?
MR. WAGNER:

On any subject at any time?

MR. SCHULER:

No, on this subject.

A

On this subject, no, I've not.

Q

Did you ever communicate information to anyone
outside the company regarding the fact that there
were these impurities in this new 2,4-D process
that were found and outlined in your report that

I

we marked as Plaintiff's Exhibit 2?
A

Not that I recall.

Q

Do you know whether anyone else at Dow Chemical

169

1)

75

Company communicated information in this report
that we marked as Plaintiff's Exhibit 2 to anyone
else outside the company at any point in time?
A

Not to my knowledge.

Q

Do you know a Mr. Wisniewski, D.F Wisniewski?

A

Dave Wisniewski.

Q

What was his position back in '78 or '79, if you
know?

A

He was an analytical chemist that offered support
to the general phenoxy area.

Specifically what he

was doing at that time, I can't tell you.
(Plaintiff's Exhibit 3 was marked for
identification.)

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

Q

Let me show you this document here and ask if
you've seen this before, and you might show your
counsel there, too.

Let me see the date on that.

A

December 16th, 1979.

Q

Have you ever seen that document before?

A

Not that I recall.

Q

You weren't involved in any of the research that
went into the preparation of that document?^

A

No, sir.

Q

Mr. Wisniewski appears to at least have done some

170

76

!

toxicological oriented research.

Do you know if

he's a toxicologist or not?
MR. WAGNER:

I object to the form of the

question.
A

No.

Mr. Wisniewski was definitely, he was an

analytical chemist.
Q

Is Mr. Wisniewski still with the company?

A

Mr. Wisniewski passed away a number of years
ago.

Q

So the right answer is no.

He may be with some company -MR. WAGNER:

Q

—

Spiritually.

not with Dow Chemical Company.

Do you know

what his background was, Mr. Wisniewski's

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

background, I'm talking about scientific
specialty, obviously?
A

Well, Wisniewski worked in the analytical
department.

What his specific scientific

background training is, no, I don't know.
Q

Well, I don't see your name on this one, either,
but let me ask you if you've seen that before?

A

This would be a document having been prepared
within the analytical department, and no, I had no
involvement in its preparation, nor do I recognize

171

s

«'1

77

it specifically.
(Plaintiff's Exhibit 4 was marked for
identification.)
Q

There's a sheet attached here to this Plaintiff's
Exhibit 4.

It's very difficult for me to read,

and probably it will be for you, too, but can you
make out, it appears to say release rerouting
sheet.

Have you seen a form like that before?

A

I have no idea what this is.

Q

Have you ever testified in any form before the
Environmental Protection Agency, for example, or
the Department of Agriculture, regarding these

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

type of chemicals?
A

No, I haven't.

Q

Have you ever written any reports that were
furnished to the EPA that you're aware of?
MR. WAGNER:

Q

On any subject?

On the subject of these chemicals, 2,4-D, 2,4,5-T,
Silvex?

A

Not that I can recall at this time.

Q

Do you know who Marguerite Leng is?

A

Yes, I know Marguerite.

Q

What is her position -- well, let's start with is

j

172

9

78

she still with the company today?
A

No, she's retired.

Q

What was her position when she was last with the
company, if you know?

A

She was -- I can't give you her exact title.

She

was in the regulatory department in some capacity,
but I don't know exactly.
Q

Do you know if scientific reports were provided to
her on a regular, continuing basis, particularly
regarding these chemicals?
MR. WAGNER:

I object to the form of the

question.
A

The only reports that I would know would have been

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

distributed would have been, to whom I can say the
reports were distributed were the ones that were
listed on the back cover here, and if she isn't on
that list, then I can't answer, then I don't know
if she was or not.
Q

Have you ever been involved with her in terms of,
and I'm not just limiting it to these chemicals,
but have you ever been involved with her in|the
sense that you submitted a copy of a scientific
report to her and she reviewed it for some

173

79

purpose?
A

I don't specifically recall having done that.

Q

Have you ever been involved with her in any type
of work at Dow Chemical?

A

Only very much on the periphery.

Marguerite

happens to be a personal friend, and I know her
more from that standpoint than the work
standpoint.
Q

Outside of being a personal friend of hers, I'm
talking about whether you actually worked with her
on any type of reporting or scientific work?

A

Not that I can specifically recall at this time.

Q

And just so I'm clear on this, do you know whether

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

she ever edited any reports that you submitted?
A

Not to my knowledge.

Q

Do you know an Andrew Watson?

A

I know the name, but I don't know the individual.

Q

Would the function of determining the
effectiveness of end product 2,4-D, for example,
for its ultimate purpose, killing weeds, would
that be done by another department other th^n
yours?
Yes.

174

80

Q

What department would be involved in doing that?

A

Well, at that time the department was known as the
agricultural product department.

In the 9008,

9001 building area, the person we mentioned
before, Joyce King is one who is more likely to
get involved in that type of activity.
Q

Was she involved from the agricultural product
standpoint with 2,4-D back in 1975?

A

The only time I specifically know that she was
involved with this project was when we were
working on the product, on the issue of xanthones
and related compounds over the time frame
described in this report.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

Q

Have you been involved at all in the registration
process for 2,4-D, to your knowledge?
MR. WAGNER:

I object to the form of the

question.
A

The only involvement that I would have had is to
supply process descriptions to the individuals who
actually -- who prepare for reregistration
packages, and I have provided information o^i
occasion to those individuals.

Q

Let me see if I understand this, process

175

81

description for reregistration packages, what
would that entail?
Well, the reregistration -- a small piece of the
reregistration process or package is to describe
the chemical process for producing the product.
And I would -- I have in the past provided
information to that.

I can't give you specific

dates off the top of my head when I've done that,
but I know I've done that.
Q

Did you do that in connection with 2,4-D?

A

Yes.

Q

Can you give me an approximate time period when

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

you did that with respect to 2,4-D?
A

Early to mid eighties time frame.

Q

Can you tell me what individuals you dealt with,
in other words, who you furnished these process
descriptions to for the reregistration package?

A

I don't specifically recall at this time.

Q

Was there a particular department that dealt with
the registration process?

A

The ag chemicals product department did thaj£, so
it would be an individual in that department.

Q

Is that department presently located in any

176

82

specific building?
A

Well, since the formation of DowElanco, the
organization is now very much different than it
was during the time we're talking about here.

All

of the activities that were out of the 9001
building and 9008 building are now here in
Indianapolis with DowElanco.
Q

Have you ever had any input into the labeling
process for 2,4-D?

A

No.

Q

Do you know whether the 2,4-D label ever reflected
the impurities that you found in your report of

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

October of 1978?
A

Not to my knowledge.

Q

Do you know whether the 2,4-D label ever reflected
any impurities found in the product prior to
October of 1978?
MR. WAGNER:

I object to the form of the

question, over broad.
A

Not to my knowledge

Q

Would the agricultural products department ^lso
have responsibility for labeling, to your
knowledge?

177

83

A

I can't answer that specifically, but I would
assume yes.

Q

Do you know, for example, back in 1975, any
individuals' names who might have had that
responsibility?

A

No, I don't —

I don't know any names since that

was far removed from my involvement in the
project.
Q

Back in 1975, and I apologize if I asked this
question or a version of it earlier, but I want to
be clear about this, back in 1975, besides
yourself, who else, if anyone, in the agricultural
chemical process or products research section had
responsibility for any aspect of the 2,4-D

FORM LASER BOND A PENGAD/iNDY 1-800-631-6989

research?
MR. WAGNER:

It was asked and answered.

I don't think he remembered it.
MR. SCHULER:

I think he mentioned

Mr. Brust.
MR. WAGNER:
A

That's right.

I did happen to think of one more individual, a
gentleman by the name of Quentin Hutchcroft.

Q

Is he still with the company, Mr. Hutchcroft?

178

84

A

No.

He left the company many years ago.

He was a

colleague of mine, and he and I worked together on
an aspect of the process.
Q

Anyone else that you recall?

A

That's the only additional person that I can
recall that I didn't mention earlier.

Q

I think you testified that you, maybe I
misunderstood you, but I want to be clear about
this, you haven't done any further research on
2.4- D after this 1978 project, is that correct?

A

I was -- I was the process chemist responsible for
2.4- D process research until approximately 1983,
1984, time frame.

I think you asked the question

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

in the context of specifically this report that we
have been discussing, and -Q

A

-- and to the best of my knowledge, I've not done
any work since that report.

Q

When you say work since this report, you were
responsible, but there was no, once the process
got up and running, there was no further research
from your department on the 2,4-D process or
2,4-D, itself?
/

85

MR. WAGNER;

I object to the form of the

question.
A

Oh, yes, oh, yes.

Q

Can you give me an idea of what other research was
done on 2,4-D after October of '78 up until '83?

A

We were —

well, we did some further research on a

modified process over what was described for, I
think we discussed the plant in Aratu, Brazil,
there was process research done in that area.
There was process research done in the area of
other trace impurities in the process.

We were

doing a lot of work during those days in the area
of related -- related to waste brine treatment
clean up.

Those are three key areas that I can

recall.
Q

Waste brine being a by-product of the process?

A

Yes, one of the by-products of the process was an
18 to 20 percent sodium chloride stream.

Q

And what else, anything else comes to mind?

A

Those are the key areas of our research, and
continued support of the process.

When plaj^t

problems crop up now and then, and these can be
any one of a number of different things, that

180

86

we're constantly asked to provide technical
support to the plant, to the manufacturing staff.
Q

Have you done any research with regard to 2,4,5-T
or Silvex since 1975?

A

Yes.

Q

And can you give me some examples of research
you've done and the time period it may have
occurred?

A

In addition to the 2,4-D acid process that was run
in 489 building, we did have a process that
produced 2,4,5-T and 2,4,5 -- well, Silvex esters.
We called that the direct ester process.

And,

yes, I was involved in sampling and evaluating

FORM LASER BOND A PENGAD/INDY 1-800-631*6989

results in the areas of 2,3,7,8 TCDD and other
polychlorinated dibenzo-para-dioxins, and we did
some research in that time frame about further
reducing those impurities from our product.
Q

And when you say that time frame, you're referring
to 1975, 1976, somewhere around there?

A

The peak time frame of 1975 to 1979, when the

j

direct ester process was shut down.
Q

Did you generate reports?

A

Yes.

181

87

Q

On that?

A

Yes.

Q

Do you have any of the reports with you today?

A

No, sir.
MR. SCHULER:

Are you taking the

position that Dow has them, and he doesn't have
them, that's why you're not producing it?
MR. WAGNER:

Correct, they're not his

reports.
Q

From 1975through

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

of TCDD in

1979, did

you find the

presence

either Silvex or 2,4,5-T endproduct?

A

Yes.

Q

And do you recall at what levels you found it?

A

Typically the levels could range in the .03 to .07
parts per million of 2,3,7,8 TCDD.

Q

Was there a fluctuation from batch to batch?

A

Yes.

Q

Did you ever find the presence of TCDD at a higher
level than .07 parts per million in any batch that
you sampled?
MR. WAGNER:

I object to the form^of the

question.
A

I don't recall specific data.

When I tell you the

182

V '9**

88

.03 to .07, those are ranges that I recall that we
would see in the product in that mid-1970 time
frame.
Q

Can you give me a rough idea how many reports were
generated about that subject matter, the finding
of TCDD or other dioxins in 2,4,5-T or Silvex?

A

I couldn't give you an exact number or even a
close number at this point.

Q

Those reports, I assume, were written and used for
intercompany purposes?
MR. WAGNER:

A

I object to the form.

Certainly anything that I wrote that would have
summarized results would have been done for

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

intercompany purposes.

What happened to the data

beyond that point, I can't comment.
Q

Who else worked with you in this particular
analysis or research into the presence of these
dioxins in those end products?

A

Well, Mr. Arnold would have provided technical
support, laboratory support to me.

Mr. Siegel

that we mentioned earlier, has done work in^that,
during, again, this 1975-1979 time frame.
Q

Other than Mr. Arnold and Mr. Siegel, anybody else

183

9

89

that you can recall?
A

Not that I recall specifically

at this time.

Q

Was this, for lack of a better

term, kind of a

continuing monitoring process when you tested
these chemicals for the presence of TCDD or other
dioxins?
MR. WAGNER:

I object to the form of the

question.
A

Right.

Q

How frequently would you test these products

for

the presence of those contaminants?
MR. WAGNER:

I object to the form of the

question.

FORM LASER BOND A PENGAD/INDY 1-000-631-6989

A

In our direct ester process, I don't recall the
frequentcy that we did at that time.

This was a

quality control lab, analytical lab function that
I was only off on the periphery of with access to
the data.
Q

When you say the direct ester process, would you
also test the amine version of 2,4,5-T?

A

I don't recall that we produced an amine fo^m of
2,4,5-T at that time.

Q

What about Silvex, was that tested?

184

90

A

The Silvex esters would have been tested, as would
the 2,4,5-T esters.

Q

The amine formulation of 2,4,5-T was not
manufactured by Dow, you're saying from '75 to
'79?
MR. WAGNER:

I object to the form of the

question.
Q

Or did I misunderstand you?

A

I don't recall that we manufactured the amine form
of those compounds at that time.

Q

At some earlier time did the company do that, if

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

you know?
A

Not that I know of specifically.

Q

Where would these records be kept from your
testing of these end products for TCDD or other
dioxins?

A

Well, the records we're talking about are records
that were generated, as I said before, by the
quality control labs and by the analytical lab, so
it would be within whatever, wherever their

j

documentation is maintained.
Q

Would that be in the plant or some other place, if
you know?

I

1S5

91

Some would be in the plant, and some would be
within our central reporting index.
MR. WAGNER:

Was your question directed

to today or back then, Dick?
MR. SCHULER:

During the period of 1975

THE DEPONENT:

Yes, that's when I was

to '79.

answering.
MR. WAGNER:

I thought so.

During the period from 1975 to 1979, do you know
whether there was any listing on the labels for
2,4,5-T or Silvex that those products contained
either TCDD or any other dioxin contaminants?

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

MR. WAGNER:

I object to the form of the

question.
A

I don't know.

Q

Do you know whether any information from 1975 to
1979 was furnished to the government with regard
to the dioxin contents of those end products?
MR. WAGNER:

Same objection.

I am not aware specifically of information t^hat
was submitted to the government on that subject.
Were you involved in the decision to shut down

186

0, % & ■

92

production of Silvex and 2,4,5-T?
A

No, I wasn't.

Q

Do you know who was involved in that decision?

A

The managers of ag production and of the product
department whose names -- who the specific
individuals that would have met to make that
decision, I couldn't answer at this time.

Q

Do you know who the individuals were that may have
been involved in making the decision?

A

I can't give you a specific name.

Q

Did you have, once a decision was made, did you
have any role in shutting down of the process?

A

No.

Once the process was shut down, it was shut

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

down, and being an organic chemist working in
research, I had no involvement in the project.
Q

Were you aware, between 1975 and 1979, of any
hearings that were ongoing with regard to what's
known as a rebuttable presumption against
registration for either Silvex or 2,4,5-T?

A

I knew about them, but I had no involvement in
them, and I couldn't -- don't recall any ofjthe
specific details at this time.

Q

You don't recall furnishing any information that

187

93

was used in the course of those hearings?
A

No, sir, no specific information that I recall.
MR. WAGNER:

Let's take a quick break.

(Recess.)
BY MR. SCHULER:
Q

Back in 1975, was the 2,4-D that was manufactured
by Dow Chemical primarily sold in its amine form?
MR. WAGNER:

I object, no predicate as

to personal knowledge.
A

It was sold.

I can't comment as to whether it was

sold primarily as the amine formulation.

We

certainly sold a significant quantity of it as the
amine formulation, but I don't know the balance of

FORM LASER BOND A PENGAD/1NDY 1-800-631-6989

esters, amines and acids sold.
Q

Do you have any knowledge of the total amount of
2,4-D sold on an annualized basis, for example,
back in 1975 and 1976?

A

I couldn't give you a number from personal
knowledge.

Q

It would be speculation.

You mentioned that the, in your report that we
marked as Plaintiff's Exhibit 2, that this |)48
building at capacity could crank out 100 to
120,000 pounds a day, correct?

188

94

A

Yes.

Q

What did building 489, what was its capacity, if
you know?

A

I don't recall that number anymore.

Q

Do you know if it was similar to the 948 building
or not?

A

It would have been in that magnitude, but a
specific number, I just don't remember.

Q

Were there any other buildings that Dow Chemical
had, back in 1975 and '76, that produced 2,4-D
other than those?

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

MR. WAGNER:
Q

In Midland, yes.

A

No, sir.

In Midland?

Those were the only places it was

produced at that time.
Q

Were there other locations back at that time that
produced the chemical on behalf of Dow?

A

The subsidiary produced 2,4-D for Dow in New
Zealand, Ivan Watkins Dow, W-A-T-K-I-N-S.

Q

Any other locations around the world?
MR. WAGNER:

j

In 1975?

Q

Yes, the '75-'76 time period.

A

No.

Those were it, those were the facilities.

189

95

Q

Do you know, and again, if you don't know this
information just tell me and I'll move on, but do
you know in what units the chemical 2,4-D was sold
in '75 and '76?

In other words, was it sold by

the ton, by the pound, by the gallon?
A

It was sold in a variety of different containers;
gallons, five gallons, 55-gallons, tank cars,
different products were sold in different
containers, specifically, you know, the specific
balance.

Q

In 1975 and 1976, would you be aware of what the
five gallon container looked like?
MR. WAGNER:

For?

FORM LASER BOND A PENGAD/INDV 1-800-631-6989

MR. SCHULER:
A

Amines, esters?

Q

Amines.
MR. WAGNER:

2,4-D.

I object

tothe

form of the

question, not specific.
A

I have seen the cans, but after 17 years, to
recall exactly what was on the can and how it

j

looks, I don't.
Q

Were the

A

Metal.

cans metal or plasticback then?

190

96

Q

And do you recall the color of the cans?

A

Not anymore.

Q

Same question for Silvex, would you recall the
color of the cans?

Was it sold in cans?

MR. WAGNER:

I object, compound, no

predicate.
A

Silvex, I can't recall specifically the way Silvex
was supplied.

Q

Same question with regard to 2,4,5-T?
MR. WAGNER:

Same objection.

A

And the same answer as for Silvex.

Q

Do you know what the unit price was for a

FORM LASER BOND A PENGAD/INDY 1*800-631-6989

five-gallon can of 2,4-D back in '75 and '76?
A

No, I don't remember that.

Q

Who would know that information?

A

That would be information that would available
from the commercial function.

Q

Agricultural products division?

A

Yes —

well, DowElanco now, if those records still

exist.
Q

Do you have any opinions with regard to the^
toxicity of 2,4-D as it applies to human beings?
MR. WAGNER:

No predicate as to

97

expertise in that area.

You mean his opinion

today?
MR. SCHULER:

Yes.

MR. WAGNER:

Well, the question is

whether or not you have an opinion.
A

Go ahead.

Well, as an organic chemist, not trained in
toxicology, I don't feel I can render an opinion
on that.

Q

Have you participated in any other, had input in
any reviews that the EPA has instituted with
regard to the safety of 2,4-D?
MR. WAGNER:

I think it's been asked and

MR. SCHULER:

I asked about Silvex and

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

answered.

2,4,5-T before.
MR. WAGNER:
A

You're correct.

I'm sorry, with the dialogs -MR. SCHULER:

Could you read that back.

(The requested material was read by the
reporter.)
MR. WAGNER:

I object to the formjl

A

No.

Q

Back in 1975 and 1976, were you aware of any

1^0

98

published literature that, I know you're not a
toxicologist, but I'm asking you in your capacity
as a scientist, were you aware of any published
literature with regard to the potential for
carcinogenicity of 2,4-D or Silvex?
A

For the potential of carcinogenicity, no.

Q

Same question with regard to 2,4-D, same time
period?

A

No.

Q

Do you, yourself, subscribe to scientific journals
other than what may be available to you in the Dow
library?

A

As a member of the American Chemical Society, I

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

receive their weekly publication, Chemical and
Engineering News.

Otherwise, all of the

scientific journals that I read are provided to me
through Dow.
Q

Do you know a fellow by the name of Leonard or Len
Smith?

A

Yes.

Q

And what is his position or was his positio^ at
Dow?

A

I don't know what his position was at the time,

.193

99

over the time frame that we're talking about here.
Q

Is he still with the company?

A

He's with DowElanco.

Q

Here in Indianapolis now?

A
Q

Do you know what his position is?

A

He just moved, and I forget his new title.

Q

When you were doing your analysis as reflected in
your report of October of 1978, did you take
hygienic precautions in dealing with those
chemicals that are outlined in that report?

A

Yes, I did.

I used the standard, good laboratory

practices that we follow in our department.
Q

What kind of precautions did you take back in
1977-'78, when you were working on this report?

A

Lab coat, impervious rubber gloves, glasses,
goggles, all of our work was performed in a
properly ventilated hood, the standard precautions
that we take with toxic and hazardous chemicals.

Q

Do you wear any special type of pants, for
example, or does the coat come down pretty j--

A

It was a typical knee-length laboratory coat.

Q

And do you wear any type of special shoes or boots

100

or anything like that?
A

No.

Q

When you say you work in a ventilated laboratory
hood, what does that look like?

A

The typical laboratory hood is a bench top,
perhaps typically they're six feet wide, about 30
inches deep, with air movement sweeping across so
that we're adequately protected.

Q

The fumes are sucked up into the exhaust, if you
will?

A

Yes.

Q

Did you ever wear a respirator in dealing with any
of the materials outlined in your October '78

FORM LASER BOND A PENGAD/INDY 1-800-631-6909

report?
A

No.

Q

Otherthan the

research that we've discussed here

today involving 2,4-D and 2,4,5-T and Silvex, have
you done any other research with respect to those
chemicals that we haven't discussed here today or
touched on in your testimony?
MR. WAGNER:
A

Yes.

Q

What type ofresearch?

I object as to breadth.

195

101

Well, notably we did some research in the 2,4,5-T
area where we learned how to further reduce the
quantities of dioxins from the product.

I think I

gave you numbers to the best of my recollection of
.03 to .07.

We developed technology, again, I

can't give you a concrete date, but in the '77-'78
time frame, to further reduce those levels in the
ranges of, again, as best I can recall,
Q

.01, .02.

And what, do you recall the type of technology
that was developed or methods that were developed
to reduce the TCDD down to that level?

A

The post treatment, prior to formulation, with

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

activated carbon.
Q

I'm not sure I understand -- post final product --

A

The technical product, before it is formulated
into the final product, was passed through a bed
of activated carbon.

Q

And the carbon helped to filter out some of those
impurities, at least down to that level?

A

It removed the impurities down to this level of,
again, as best I recall,

.01,

j

.02, .03, in jthat

range.
Q

And to the best of your recollection, that would

196

102

have been in the '77 to '78 time period?
A

Plus or minus a little, yes.

Q

Who else would have worked on that project with
you?

A

Sanford Siegel, in the laboratory.

Q

Who else would have been involved with that
project outside the laboratory as far as
implementation of the carbon filters are
concerned?

A

That would have been, obviously, with the
engineers in the plant.

Specifically who the

engineer or engineers were at this time, I don't
recall.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

Q

Was anyone from agricultural products involved
with that decision to approve the use of the
carbon filters, for example?

A

I don't remember the decision process for specific
implementation of all that.

Q

But you were involved doing the lab work?

A

I was involved developing the technology, yes.

Q

Any other research that you did with respect to
2,4-D, 2,4,5-T or Silvex between the 1975 and,
say, 1977 time periods?

19v ^ 3

103

MR. WAGNER:

That he hasn't touched on?

MR. SCHULER:

That he hasn't mentioned

already, of course.
A

We have touched on a number of topics at various
times.

Q

I think we have covered them all.

Let me just ask you about the documentation.

Do

you have a CV, curriculum vitae, summarizing your
educational background, experience, training in
your profession?
A

No.

I haven't had a resume prepared since —
MR. WAGNER:

A

-- like almost 28 years.

Q

You haven't looked for a job in a long time,
that's right.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

He's not been job hunting.

Okay, in the notice of taking

deposition I had, and by the way, you spell your
name, K-A-R-L, correct?
A

Yes, sir.

Q

In the notice of deposition I had asked you to
produce any and all documents produced by you or
at your direction during the course of your
employment with Dow Chemical Company or its^
subsidiaries that pertain to any research,
analysis, formulation, study or production of the

104

chemicals 2,4-D, 2,4,5-T, Silvex or any product or
substance containing these chemicals or any
ingredients used in making these chemicals or any
contaminants or dioxins contained in any of these
chemicals or their ingredients.
Today you produced no documents,
correct?

You gave me the October of '78 report

that I already had.

Did you bring any of those

documents with you here today?
A

Well, all the documents are owned by the Dow
Chemical Company.

I have no documents that are

owned by m e .
Q

So the answer is, you did not bring any of those

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

documents here with you today?
A

That's right.

Q

You have not served, I understand from your
earlier testimony, as an expert witness in any
case, correct?

A

Correct.

Q

You have not issued any documents, reports,
articles or transcripts relating to any opinion
you might have ever formed regarding the cause of
soft tissue sarcoma or the toxicology or health
y

105

effects of 2,4-D, 2,4,5-T, Silvex, 2,4,5-TP or any
product or substance containing any of those
chemicals?
A

No, sir.

Q

You mentioned your status as, I think you told me
initially as senior scientist?

A

My official title within Dow Chemical Company is
an associate scientist.

Q

Are there rankings within the company by title,
and you get certain income, kind of like the
military or an organized entity like that?

A

Yes.

Q

So when you reach, you have a certain title, you

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

reach a certain level, you get a certain income
that goes along with that, would that be a fair
statement?
A

Yes.

Q

How long have you been with the company, the
number of years?

A

I joined the company in June of '65, so that puts
me at 27 years, nine months.

Q

j

Do you intend on staying with the company for the
time until retirement?

200

106

A

Yes, I do.

Q

When do you anticipate, if you do, retiring from
the company?

A

I have no plans for retirement at this point.

Q

Prior to coming here to this deposition today, did
you review any documents, other than obviously the
document we have marked as Plaintiff's Exhibit 2?

A

I reviewed one other letter that Allen showed me
that was essentially a letter written by my
manager at the time, I don't remember the exact
date on that letter, to an analytical manager
telling him we were going to be providing him with
some samples for analysis for various chlorinated

FORM LASER BOND A PENGAD/INDY 1-800-631-69B9

dioxins.

Those are the only two documents that

I've specifically reviewed for this deposition.
Q

Who is your manager who wrote that letter?

A

That was Dr. Mintz, Michael Mintz.

Q

What was the date of that correspondence?
MR. WAGNER:

I think he said he didn't

remember.
A

I don't remember the specific date.

It woujtd have

been in the period of, around 1976, plus or minus
a little.

201

107

Q

Prior to the time of this report that we have
marked as Plaintiff's Exhibit 2?

A

Yes.
MR. SCHULER:
that?

Did you have a copy of

Can I see a copy of that?
MR. WAGNER:

No.

MR. SCHULER:

You have a copy present

here today?

You're just not going to let me see

it?
MR. WAGNER:

I don't know if it's

present in this room.
Q

When did you see the

A

I saw it yesterday.

document?

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

MR. SCHULER:
a copy of the document.

For the record, I request
The copy of the

document's been refused and -MR. WAGNER:

What's the basis that I

would have to give you that document?
MR. SCHULER:

Because I asked it be

produced here today.
j

MR. WAGNER:
not his document.

It's a Dow document./ It's

If you would like documents

from Dow, send me a request to produce.

202

108

MR. SCHULER:

Well, I understand the

position that you've taken, but I disagree with it
100 percent, and particularly when the document is
present here today and could be discussed with
this witness.

To refuse to produce it, I think is

a violation of this request, and I'll seek court
relief on that.

I have no further questions,

thank you.
MR. WAGNER:

Before we let Aprille go,

let's make this part of the record.

Larry

Silverstein faxed the statement which turns out to
be an affidavit that he signed.
copy.

It was delivered here this morning, so

let's mark it as an exhibit.
FORM LASER BOND A PÉNGAD/INDY 1-000-631-6989

That's my only

From my review it

does not contain any information that you didn't
cover with him yesterday.
Why don't you take a minute to review
it, if you want.

We could probably have him come

over and answer questions about it, but as I say,
from my review of it, I think all those areas that
were mentioned were covered.
MR. SCHULER:
take a look at this.

/

Well, I'm not -- I can't
I mean, we had his

203

109

deposition yesterday.

This wasn't produced, and

I'm taking the position that it was wrongfully
withheld.
MR. WAGNER:

Well, he didn't have it

MR. SCHULER:

Well, he was requested to

produce it.
MR. WAGNER:

I know he was requested,

and I know it's here now.

If you want him, I'll

get him on the phone and see if he can come out
here.
MR. SCHULER:
me.

That's not good enough for

I was taking his deposition yesterday, and

I'm handed a four-page document with 16 paragraphs

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

today, and I'm not going to be put in that
position of doing this now, and when it wasn't
produced when it should have been produced, and
asking him questions about it.

We'll mark it for

the purpose of discussion, since we talked about
it at this deposition, as Plaintiff's Exhibit
Number 5.
(Plaintiff's Exhibit 5 was marked/for
identification.)
MR. SCHULER:

Is that it?

204

110

MR. WAGNER:

No questions.

AND FURTHER THE DEPONENT SAYETH NOT

FORM LASER BOND A PENGAD/INDY 1-800*631-6989

KARL KRÜMEL, Ph.D.

)

205

111

STATE OF INDIANA
ss :
COUNTY OF MARION

I, Aprille Rigsbee Lucas, RPR, Notary
Public in and for the County of Marion, State of
Indiana, do hereby certify that the deponent
herein was by me first duly sworn to tell the
truth, the whole truth and nothing but the truth,
in the aforementioned matter;
That the foregoing deposition was taken
on behalf of the Plaintiff;
That said deposition was taken at the
time and place heretofore mentioned between the

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

hours of 8:00 a.m. and 6:00 p.m;
That said deposition was taken down in
stenograph notes and afterwards reduced to
typewriting under my direction and thereafter
presented to said witness for signature; that this
certificate does not purport to acknowledge or
verify the signature hereto of the deponent;
I do further certify that I am a
disinterested person in this cause of action; that
I am not a relative or attorney of any of the

112

parties, or otherwise interested in the event of
this cause of action, and am not in the employ of
the attorneys for any of the parties.
IN WITNESS WHEREOF, I have hereunto set
my hand and affixed my notarial seal this 15th day
of March, 1993.

FORM LASER BOND A PENGAD/INDY 1-800-631-6989

My Commission Expires:
September 21, 1996

Ì

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

Page 1toPage 112

Associated Reporting, Inc.

(317)631-0940

CONDENSED TRANSCRIPT
PREPARED BY:

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Two Market Square Center
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Indianapolis, IN 46204
Phone: (317) 631-0940
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I

208

bsa

___________________ KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993_______
Page 1
STATE OF FLORIDA )
) SS:
COUNTY OF O RA N G E)
IN THE CIRCUIT COURT FOR ORANGE

(1)

(2)

(1)

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COUNTY, FLORIDA
(3)
(4)
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GO
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KIMBERLY MOYER, as Personal)
Representative of the Estate of)
ROBERT W. MOYER. II, Deceased,)
)
Plaintiffs, )Case No. Cl 89-8657
)Dlv: 32 Thompson
vs. )
)
DOW CHEMICAL COMPANY, et a l„ )
)
Defendants. )
The deposition upon oral examination of
KARL KRUM EL Ph.D., a deponent produced and

sworn
tu )

(12)
(13)
(14)
(15)

to before me, Aprille Rigsbee Lucas, RPR, a
Notary Public at large in and for the State of
Indiana, taken on behalf of the Plaintiff at
DowElanco, 9001 Purdue Road, Quad III,
Indianapolis, Marion County, Indiana, on March

10.
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1993, at 9:30 a.m., taken pursuant to the Florida
Rules of Civil Procedure in the above-captioned
matter.
ASSOCIATED REPORTING, INC.
TWO MARKET SQUARE CENTER
251 EAST OHIO STREET
SUITE 940
INDIANAPOLIS, INDIANA 46204
Page 2
APPEARANCES
FOR TH E PLAINTIFF: Richard D. Schuler, Esq.
Schuler, Wilkerson, Halvorson &
Williams, P.A.
1615 Forum Place
West Palm Beach, FL 33401
FOR TH E DEFENDANT Alan F. Wagner, Esq.
DOW CHEMICAL- Carlton, Fields, Ward,
Emmanuel, Smith & Cutler, P A
First Florida Bank Building
P.O. Drawer I90
Tallahassee, FL 32302
FOR THE DEFENDANT H. Roger Lutz, Esq.
HELENA CHEMICAL: Lutz, Webb, Bobo & Baitty, P.A.
Two North Tamiami Trail
Sarasota, FL 34236
INDEX
PAGE
DIRECT EXAMINATION,
Questions by Mr. Schuler 4
Page 3
EXHIBITS
Page
Plaintiff's Exhibit 1 - R&D Report dated 10-27-78 38
Plaintiff’s Exhibit 2 - R&D Report dated 10-27-78 45
Plaintiff's Exhibit 3 - 'Analytical Method' dated
12-16-79 75
Plaintiff's Exhibit 4 - “Analytical Method' dated
2-18-80 77
Plaintiff’s Exhibit 5 - Affidavit of Lawrence G.
Silversteln 109

(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)

(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)

(21)
(22)
(23)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)

(11)
(12)
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(1)
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(11)
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xm ax

Page 4
KARL KRUMEL. Ph.D.,
having been first duly sworn to tell the truth,
the whole truth and nothing but the truth,
relating to said matter, was examined and
testified as follows:
DIRECT EXAMINATION,
QUESTIONS BY MR. SCHULER:
0 Would you state your name, please.
A My name is Karl Krümel.
0 What is your professional address?
A My professional address is 1710 Building, the Dow
Chemical Company, Midland, Michigan, 48674.
O Are you employed?
A Yes, I am.
O By whom are you employed?
A By the Dow Chemical Company.
O What is your position with Dow Chemical Company?
A My title is associate scientist.
O As associate scientist, just in general, now, what

are your duties and responsibilities?
A Well, the associate scientist Is a generic title
for people in research who have reached a certain
level in the company. It doesn’t in any way
Page 5
define the Job.

Q Tell me a little bit about the structure, to give
me some understanding of how the research
department is organized. And if you would, could
you also tell me, and you don't have to be
completely thorough about this, but just tell me
in general what the stnicture is and the various
positions that are within the research department.
MR. WAGNER: I object as to breadth.
compound. You mean today?
MR. SCHULER: Right.
A Are you asking me about the structure of research
within the total Dow or within the structure
within my department, which is a small part of the
overall?
0 Let's start with your department.
A The department I’m in is agricultural chem icals
process research. This department, the name has
changed several times over the years that I've
been in it, but that’s the current name. Our
structure, we have a technical director. We have
two research managers, and these research managers
then control groups of on the order of 30
Page 6
technical professionals each. I happen to be in
one of those groups as a senior scientist in the
department.
O So there are roughly 62 or 65 people in the

department?
A In the current department, yes.
O Now, to expand that to the, to give me some idea

of how the department of agricultural chemicals
process research fits into the overall scheme of
things, what other departments are there, other
than that, if you know?
A Oh, goodness, there are a number of departments
located in Midland that support other a re as of Dow
R&D, you know, of the Dow Chem ical Com pany,
including pharmaceuticals, analytical, polymers,
resins.
O You're the only department that has to do with
agricultural chemicals in A In the Midland, area, yes.
J
MR. WAGNER: You meant research? of
course?
MR. SCHULER: Right.
O Are there other research departments that deal

Kt V1?
(317) 631-0940

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 7

(1)
( 2)

(3)

W
(5)

with agricultural chemicals in other areas of the
country?
A Well, we have small groups that will support the
production of ag chem icals in other locations
other than Midland, yes.

(7)

O That are right within the factories, themselves,
you mean?

(8)

A They’re within the plant area, themselves, yes.

(9)

O Who is the technical director presently?

(6)

(10) A The gentleman’s name is Jim Love, L-O-V-E.
(11) Q How long has he been technical director at the
(12) agricultural chemicals process research
(13)

department?

(14)

A H e’s been there since 1988.

(16)

A H is predecessor was, yes, the gentleman’s name is
Alex Vogel, V-O-G-E-L
O How long was he there, if you know?
A I can ’t give you the exact time Irame. It’s on
the order ol four years or so.

(15) Q Do you know who his predecessor was?
(17)
(18)

(19)

(20)
(21) Q Would that position of technical director of the
(22 )

(23)
(1 )
(2 )
(3)

(4)
(5)
(6)

(7)
(8)

(9)

agricultural chemicals process research department
have been in existence back in 1975, let’s say? __________
Page 8
A In '75, the organization was pretty much the same.
The name of the department at that point was
different.

Q What was the name at that time?
A Organic chem icals research.
Q And who was the head of the department back in

1975, if you recall?
A 1975, the technical director w as a gentleman named
Don Morehouse.
Q Were there also residents or research managers

(10)
(11) back in 1975?
(12) A Y es.
(13)
(14)
(15)
(16)

(17)
(18)

(19)

(20)
(21)
(22)
(23)
(1 )

O Do you recall who the research managers were in

1975?
A Well, I certainly recall my research manager at
that point, which was Michael Mintz, M-l-N-T-Z.
O Is Mr. Morehouse still with the company?
A No. He retired a number of years ago.
O Is he still in Midland or has he moved away?
A He moved - well, where he is today, I really
don’t know. He moved away to Florida, but I’ve
lost track of him.
Q How about Mr, Mintz, it is he still with the_________________
Page 9

company?

(2)

A Y es, he still works for Dow.

(3)
(4)

Q And what is his position now, the same?

(5)

A Oh, no, no, no. He’s off in another area. I
ca n ’t tell you exactly what his job is today.

(6)

O What is your educational background. Dr. Krumel?

(7)

A In 1 9 6 0 ,1received a Bachelor of Arts degree at
Grinnell College, Grinnell, Iowa; in 1962, a
Master in chemistry; in 1962, a Master of Arts in
chem istry from DePauw University, D-E-P-A-U-W, in
G reencastle; and then in 1965, Ph.D. in organic
chem istry from Michigan State University.
MR. LUTZ: What year was that?
TH E DEPONENT: 1965.
O After '65, what did you do?
A I joined Dow in June of '65, right out of college.
O So you have worked for Dow basically all of your

( 8)

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(11)
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working professional life?
A Correct, sin ce graduation from college.
O Trace for me, if you would, the positions that

( 1)

(2)
(3)
(4)
(5)
( 6)

w o rk e d ?

Q Yes, and the positions that you held.
A In 1965,1joined Dow a s a research chemist, which
was an entry-level position for a Ph.D. at that
time. I joined the benzene research lab, which
was part of the laboratory organization at that

(7)

t i m e k n o w n a s o r g a n ic c h e m i c a ls p r o d u c t i o n

(8)
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(12)
(13)
(u)
(is)
(16)
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(20 )
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research.
In 1969,1moved over to an area of
polymer chemistry, cellulose ether chemistry. The
department I moved into w as -

O)

P)
(3)
(4)
(5)

(6)
(7)
(8)
(9)
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(12)
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(u)
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' (i)
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0)
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(H)
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(22)

you've held at Dow, starting from when you began
work there after graduating in 1965.

(20 )
(21 )
(22 )

(23)

A From the standpoint ol the departments in which I

(23)

(2 1 )

XMAX

Page 10

0 I'm sorry, that last statement was?
A Cellulose, C-E-L-L-U-L-O-S-E, cellulose ether
chemistry.
0 Cellulose ether?
A Yes. And the name of that department changed a
couple of times during the time I w as there, but
in 19 75,1then moved into what w as then known as
organic chem icals research, and I’ve been in that
department, or whatever that department w as
renamed, since that time.
Q So I can save myself some time here, prior to
1975, would it be fair to say that you did not_______________
Page 11

have any experience, within Dow Chemical Company,
with the agricultural chemicals that the company
was producing?
A No, because I hired into benzene research, and
benzene research, at that time, one of their
responsibilities w as supporting the agricultural
chem icals busin ess at that time. The period of
time of ’69 to '75,1 had no involvement at all In
ag.
O Go back to '65, from '65 to '69, then, did you

have any involvement with polychlorinated phenols,
/ think they're called, those type of chemicals?
A The polychlorinated phenols, yes. In 19 6 6 ,1
began doing production research on dichlorophenol.

O Any others?
A And, of course, by association, I w as aware ol
what w as going on in the other chlorinated phenol
areas of research at that time.
0 To be more specific, did you produce any

documentation from 1965 through 1969 with regard
to any research on 2,4-D or 2,4,5-T or Silvex?
A No.
Q Did you work on any projects that involved 2,4-D,_________
Page 12
2,4,5-7 or Silvex during that time period?
A No.
0 Did you produce any research during that time

period, from '65 through '69, that had to do with
any of the component parts that went either 2,4-D,
2,4,5-T or Silvex?
MR. WAGNER: I object as vague.
A I’m sorry, would you rephrase the first part of
your question?
O Between '65 and '69, did you produce any research

at Dow Chemical Company on any of the component
chemicals that went into making 2,4-D or 2,4,5-T
or Silvex?
A Yes, I did.
O And which chemicals are those, as you recall?
A 2,4-dichlorophenol.
0 And that is involved with the production of 2,4-D?
A Yes.

O Did you have one or were there many projects
involving 2,4-dichlorophenal?

j

f

A It w as one major project.
0 And without getting too technical on me, can you
tell me basically, in laymen's terms, what the______________

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 13

(D project involved?
(2) A The project involved trying to improve the isomer
(3)
(4)

purity of the raw material, of the
2,4-dichlorophenol.

(5) 0 And did you produce a paper or papers regarding
(6) that?
A Yes.
(7)
(8) O Was the process that you were involved with
ultimately implemented commercially?
(9)
(10) A No.
(11) Q And do you recall the reason why?
(12) A Subsequently some additional work was done that
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
(22)
(23)

found something better.
Q And who did that additional work, do you recall?
A Let’s see, one of the gentlemen’s names was W.
David Watson. Dave Watson was the primary
researcher. He would have been the primary
researcher in that area.
Q Was there a fellow by the name of Brust or A Harry Brust, yes.
O Was he also working In that area In the process

for 2,4-dichlorophenol, or attempting to improve
the isomer from which 2,4-D is made? ___________________

(1)
(2 )
(3)
(4)
(5)
(6)
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(16)
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(21 )
(22 )
(23)

an expert on the toxicological impact of those
contaminants?
A That’s correct.
0 That type of research would be carried on by

others at Dow?
A Yes.
0 Between '65 and '69, did you do any research that

was connected with any Dow involvement with any
claims that either 2,4-D or 2,4,5-T or Silvex
caused various injuries or diseases?
MR. WAGNER: I object, over broad and
vague.
A Are you asking me did I consult with Dow
attorneys?
0 Yes, that would be part of it, I assume.
A No, I never did.

Q Did you ever testify in any form regarding 2,4-D
or 2,4,5-T or Silvex from, excuse me, from '65 to
‘69, again. I'm talking about?
A No.
O Did you ever relate any communications to any

governmental agencies regarding 2,4-D or 2,4,5-T
or Silvex or their component parts? _______________________

Page 14

(1) A By the time I got to know - well, I didn’t
(2) actually get to know Harry until I came back into
(3)
(4)
(5)

organic chem icals research in 1975. I’m aware of
what he did in y ears before that, but only because
I knew - 1got to know him when I came back into
the department. And he was not involved in the
dichlorophenol part, a s best I can recall.

(6)
(7)
(8) Q Between '65 and '69, though, he was not directly
involved in the research and development for 2,4-D
(9)
(10) a s far a s you know (11) A I don’t know what Harry Brust did in that period
(12) of time.
(13)
(14)
(15)
(16)
(17)
(18)
(19)

Q Between '65 and '69, did you have occasion In your

research to analyze or write about any potential
contaminants of 2,4-dichlorophenol or 2,4-D,
itself, such as any of the dioxins, TCDD or any of
the dioxins, for example?
MR. WAGNER: I object as to the breadth.
A Are w e specifically talking about polychlorinated
dibenzo-para-dioxins when we use the term dioxin?

(20)
(21) Q Yes.
(22) A Not that I recall.
(23)

d)
(2)
(3)
(4)
(5)

Q What about furans? I know that's a broad _______________
Page 15

statement, but did you do any papers or analysis
with regard to the presence o fA Again, polychlorinated dibenzofurans?

Q Yes.
A Not that I recall.
MR. WAGNER: He sounds like a scientist.
TH E DEPONENT: Well, I’m going to do
that.
O Did you do any toxicological research between '65

(6)
(7)
(8)
(9)
(10) and '69?
(11) A I have - no.
(12) Q Let me ask you a very general question here as
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
(22)
(23)

well, do you consider yourself, I know you're an
organic chemistry researcher, do you consider
yourself to have expertise in toxicology?
A No, I have no training whatsoever in that area.
O Again, a general question, which will save time

later on, as far as the, when I'm going to ask you
som e questions about the report you did, I think
in 1978, although the date is hard to make out
here, but with regard to any contaminants that you
ultimately may have dealt with in your research
with 2,4-D or 2,4-dichlorophenol, you would not be

XMAX

Page 16

Page 17
(1)
(2 )
P)
(4)
P)
(6)
(7)
(8)
(9)
do)
(11)
(12)
(13)
(14)
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(1)
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(6)
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(23)

A No.

Q Did you, and I'm going to open this up to the
entire time all the way to the present, did you
ever give a deposition in any any case involving
allegations of personal Injury as a result of
exposure to 2,4-D, 2,4,5-T or Silvex?
A This is my first deposition.
O This is your first deposition, period, you've

never given one before?
MR. WAGNER: You’re it

Q I have to get the answer from you, though. This
is your first one?
A Y es, sir.
O There has been testimony in this case that, I'm

not sure as I look back at It, the exact date, but
there was a meeting regarding contaminants found
in 2,4,5-trichlorophenol of various manufacturers,
I think either i n '64 or 65. You wouldn't have
attended that meeting, would you?
A Well, no, obviously not, because I didn’t join the
company until June of ’65, and I had no
Involvement whatsoever in the area of halogenated
phenols until after 1966._________________________________
Page 18
0 So you wouldn't have attended any meetings with

regard to the presence or absence of TCDD in any
of the Dow chemicals from 1965 to 1969?
A Correct. I’m sorry, would you ask that question
again? I want to make sure (THE REQUESTED MATERIAL WAS READ BY THE
REPORTER.)
A The question should probably be, I attended no
meetings, I was not involved in anything dealing
with 2,4-D, 2,4,5-T or Silvex.
O Nothing whatever during that time period?
A Correct.
0 Let's skip forward to your moving into the organic

chemicals research in 1975. Were you assigned
responsibilities when you went into that
particular department back in 1975, any
responsibilities with respect to 2,4-D or 2,4,5-T
or Silvex or their component parts with respect to
doing research?
i
A Yes, I was.
. t
0 What responsibilities were you assigned initially
when you first went into the department?
A When I first went to that department, I was___________

-

0

n

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10, 1993

BSA

Page 19
assigned the responsibility ol doing process
research tor the new 2,4-D plant that w as
scheduled tor start up in approximately two years
from the time that I joined the group.

0)
(2)
(3)
(4)
O And when you say process research for the new
(5)
(6) 2.4- 0 plant, 1975, when you went back to organic
chemistry research or the organic chemicals
(7)
(8) research department, 2,4-D was being made by Dow
(9) Chemical Company at that time?
(10) A Correct.
(11) O It was being made pursuant to a process that they
(12) had been using for a number of years, correct?
(13)
(14)
(15)
(16)
(17)
(18)
(19)

A That's also correct.
Q Do you know the history of the process of 2,4-D,
in other words, the process that was being used in

1975? When you went to the organic chemicals
research department, do you know, was there a name
for the process they were using at that time?
A Well, it w as just simply called the 2,4-D plant.
Q And what building was it located in?
A 489 building.

(20)
(21)
(22) O And there wasn't any specific name for the
(23)

process, who put the process together or anything

(1)
(2)

like that?

Page 22
(1)

A No, I don’t.

(2)

Q Do you know who might have, if anyone, done
research on the 2,4-D that was manufactured in
1975, to determine its purity or to determine
whether there were any contaminants in the 2,4-D?

(3)
(4)
(5)
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Page 20

(3)
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(5)

MR. WAGNER: I object, compound.
A Not to my knowledge. It w as just known a s the
2.4- D plant.
Q What was the purpose, if you recall, for

(6) attempting to put together a new process for the
manufacture of 2,4-D?
(7)
(8) A We developed som e new technology that w as much
more efficient, produced much higher yield, and
(9)
(10) produced isomer purity in the final product.
(11) O When you say we developed?
(12) A Our department.
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
(22)
(23)

(1)
(2)
(3)
(4)
(5)

O / understand, but were there certain individuals

that were responsible for developing that new
p rocess?
A Well, the scientists. David Watson, that I
mentioned before, w as the primary investigator in
improving the quality of our 2,4-diohlorophenol
from an isomer specific standpoint. Harry Brust
is the chem ist who developed the chemistry that
w as eventually Implemented in the 2,4-D process.
Q Is Mr. Watson still with the company, by the way?
A Y es.__________________________________________________________
Page 21
Q Is he in your department?
A No. He’s in another department. He’s located at
Midland.
O Do you know what department he's located in?
A The department is called design thermoplastics
research.

(6)
Q What about Mr. Brust, is he still with the
(7)
(8) company?
A No. Harry retired a number of years ago.
(9)
(10) O Is he still in Midland, or did he move away
(11) somewhere?
(12) A I believe he’s moved away, although I see him in
(13)
(14)
(15)
(16)
(17)
(18)
(19)

town every once in a while.
Q Did you know whether or not, with the process that

was being used in 1975, for the manufacture of
2.4- D, whether there were any problems, from an
organic chemistry standpoint, with contaminants
being found in the 2,4-D being manufactured, I'll
call it by the old process that was in existence,
1975?

(20)
(21) A No.
(22)
(23)

MR. WAGNER: I object, vague.
Q You don’t know one way or the other?____________________

(1)
(2 )
(3)
(4)
(5)

(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16 )
07)
(18)
(19)
(20 )
(21 )
(22 )
(23)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
d4)
(is)
(16)
(17)
(is)
(19)
(20 )
(21 )

MR. WAGNER: Calls for speculation.
A Could you be more specific?
Q Well, it's relatively specific. Let me see if I

can make it more clear. Do you know who the
individual was in the organic chemicals research
department, if anyone, who might have done
research on the 2,4-D being manufactured in 1975,
to determine whether there were any contaminants
in the 2,4-D?
MR. WAGNER: Same objection.
A No, I can ’t recall.
O Let me ask the question this way, maybe this will

make it more clear, was there anyone that you knew
back in 1975, in the organic chemicals research
department, that was responsible for doing the
basic research on 2,4-D back then?
A Well, Dr. Brust w as responsible for the research
on the new developing process. I did some_________
Page 23
research in the, a s it relates to the old process,
not specifically targeted at trace impurities.
Q In other words, you weren't just looking for trace

impurities; you were just doing research on it for
other purposes?
A For other purposes, yes.
Q Did you produce tapes that outlined your research

back in 1975?
A Yes, I would have.
0 Do you recall whether, in the course of doing your

research, you found any impurities in the process
for making 2,4-D in 1975?
A For me to answer that question properly, I gu ess
I’d like to know what impurities you’re
specifically asking about.
0 TCDD, for example.
A No.

Q No, you did not find TCDD?
A No, nor did we analyze - w as I responsible for
determining TCD D in that time frame?
0 You were not looking for that?
A Correct.
Q Do you know if there was anyone that was looking
Page 24

for TCDD, for example, in 2,4-D back in 1975?
A No.
Q You don't know, no, or A No, I don’t know.
Q How big was the department back then in 1975?
MR. WAGNER: Organic chemistry research?
MR. SCH ULER: Yes.
A More or le ss the sam e size. At this point I don’t
recall exactly how many people we had.
O What I'm getting at, do you have an idea of who

may have been involved in that type of research,
or you're just not sure who it was?
A I just simply don’t recall anyone doing any
research at that time, and Iwould, H it were
done, I’m sure.
O Okay, to get back to my earlier question, I asked

(22)

you about whether in your research I think you
found any TCDD. I know you weren't looking for i
these things, but in the course of your research
f
on the 1975 process, did you find any of the other
polychlorinated dibenzo-p-dioxins, did I pronounce
it properly?

(23)

A What you’re specifically asking me about is did we

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KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 25
look for these compounds in the old 2,4-D process,
in the 1975 time frame?

(1)
(2)
Q Correct.
(3)
w A No.

(1)
(2)
(3)
(4)

Q Let me change the question a little bit to, even

(5)

(6) though you weren’t looking for them, did you find
any of those?
(7)
(8) A No.
(9) Q Did you work with someone in doing your research
(10) on 2,4-D in 1975?
(11) A Within our department?
(12) O Yes.

(6)
(7)
(8)
0)
(1 o)
(11)
(12)
(13)
(u)
(is)
(16)
(17)
(18)
(19)
(20 )
(21 )
(22 )
(23)

(5)

(13)
(14)
(15)
(16)
(17)
(18)
(19)

A No. I w as doing the work. Excuse me, are you
asking about the old process work?
O The old process, that's right.
A Yes, that was done by me.
O You didn't have someone that worked with you in

the department, it was fust you?
MR. WAGNER: Asked and answered.

(20) A A s best I can recall at this point.
(21) O In your work on the old process, can you just tell
(22) me what your research did Involve back in 1975?
(23)

(1)
(2)
(3)
W
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)

A At that time, again, we were just - one of my________
Page 26
roles a s a process chemist is to make sure we’re
using the most modern, up-to-date technology and
chemistry that we can do. And my research was
essentially aimed at doing just that, making sure
the plant was operating, that the chemistry In the
lab w as operating most efficiently within the
boundaries in which we could operate in the plant,
maximizing yield, maximizing product quality, that
sort of thing.
0 Would you try different things in the laboratory

to see if you could improve the quality to
maximize yield and maximize purity?
A Correct.
Q And if they appeared to be, the things that you

did were improvements and appeared to be things
that could be incorporated into the process, then
that suggestion would be made, is that how it
worked?
A It would certainly be considered.

(20) Q Who would make the ultimate decisions as to
(21) whether a particular change in the process would
(22) be incorporated? I know there's probably a number
(23)

o f people it went through, but just give me a____________

(1)
(2)
0)
(4)

(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(u)
(15)
(16)
(17)
(is)
(19)
(20)
(21 )
(22 )
(23)

Page 27

(1) general idea how it worked.
(2) A At that time the, well, the ultimate - the person
ultimately responsible for the plant would be the
(3)
plant superintendent.
W
Q Who was the (5)
(6) A But the plant superintendent would work with
(7)

(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)

people in the agricultural chem icals production
department because we had some senior level
experienced engineers that were located in that
department, w hose responsibility it w as to
maintain high standards of technology from the
engineering perspective.
Q That was the agricultural chemical production

department, you say?
A Y es.

Q Who was the plant superintendent for the 489 2,4-D
process back in 1975?
A At the time I joined the group, the man’s name was
Bill Jon es, William Jones.

(20) Q Is he still with the company, to your knowledge?
(21) A A s far a s I know he is.
(22) Q Do you know where he is in the company, what
(23)

department?_______________________________________________

(1)
(2 )
(3)
(4)
(5)

(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(is)
(19)
(20 )
(21 )
(22 )
(23)

XMAX

Page 28
A I haven’t any idea at this point.
Q In the plant, would records be kept about the

process, in other words, the yields that were
being obtained, the quality of the product, would
that periodically be tested and records be kept on
that?
MR. WAGNER: 1975 time period?
MR. SCHULER: Right.
A During that time period, yes.
Q Do you know what other records that would be kept

in the plant, primarily?
A Well, they would keep operational records of how
the plant w as running, product quality, the
results of quality control testing, records on
plant maintenance and et cetera, et cetera.
0 Would the plant superintendent be specifically

responsible for the quality control testing?
A He’s the person who is in charge of the people who
do the work, yes.
Q Some of these questions. I'm sure, seem very basic

to you, but I need to know, do these plants run
continuously?
A Yes.____________________________________________________________
Page 29

Q 24 hours a day?
A Yes.
O And besides operational records and records

dealing with yield and purity and quality control
testing, are there any other types of records kept
in the plant back in 1975, I'm talking about?
A I think I covered the ones that certainly I'm
aware of.
Q Was it ever your function to go and review the

records in the plant to see how the plant was
doing?
A Oh, yes, I would, on a regular basis, review
records on how the plant w as operating and how the
product quality w as holding up. I didn’t have any
reason to review records on maintenance or
scheduling or things like that.

Q When you say product quality, and taking 2,4-D
specifically in 1975, and again, as generically as
you can, what would you look for to determine
product quality?
MR. WAGNER: I object to the form of the
question.
A We - well, we had certain specific indications_________
Page 30
that we - that the product w as required to meet
by our customers, and we would maintain a track of
that and try to maintain an awareness of how the
product quality w as related to the sp e cs that we
were - specifications that we were expected to
meet. And if problems or issu e s cam e up with
regards to meeting sp ecs, then we would attempt to
solve the problem or Issue.
Q What type of sp ecs are you talking about?
A A ssays, A-S-S-A-Y, the tracking of normal isomer,
isomeric impurities. We had several final product
quality control tests that we would monitor on a
regular basis.
0 When you talk about assays, what are you talking

about, what type of assays? You mean
concentration of the product?
A Well, the quality of the technical product, the
a ssay at that time w as expected to be 95jpercent
pure 2,4-D, so that’s what I mean by a ssa y. Now,
what I’m talking about Is the technical'2j4-D
assay, which is 2,4-dichlorophenoxyacetic acid,
A-C-E-T-l-C, acid.
Q And the spec at that time was 95 percent purity? _________

211
P 'a 3 *

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 31

(D A Yes.
(2 )

O And when you say 95 percent purity, was that in

(3)

what form, was that in liquid or powder?

(A)

A Powder lorm.
0 Was the powder put in suspension before the

(5)
(6)

(7)
(8)
(8)
( 10)
( 11 )

( 12)

(13)
(14)
(15)
(16)
(17)
(13)
(19)
(20 )
(21 )
(22 )

Page 34
(1)
(2 )
(3)
(а)

O Right.
A As best I recall, I’ve told you essentially
everything I did at this time.
Q From a chronological standpoint, how long were you

(5)

involved in the research in the old process before
you turned your attention or your responsibilities
were directed to doing research on the new
process?

product was shipped, or was it shipped both ways,
how did that work, if you know?

(б)

MR. WAGNER: I object to the form of the
question.
A It w as - we did supply, some of our materials
were supplied to the customer a s the acid form,
but then it w as supplied in a number of other
physical forms.
Q Depending on the customers' requirements, more or

(8)
0)
(10)
(11)
(12)
(13)
(ia)
(is)
(16)
(17)
d 8)
(19)
(20 )
(21 )
(22 )
(23)

less?
A Right.
O Now, when you said they were tested for isomeric

impurities, was there any test for the dioxins
that we discussed earlier, for example, TCDD?
A I simply don’t recall how that was handled in
those days.
O What about any of the other polychlorinated

(23)

dibenzo-p-dioxins, were there tests for any of the

(D

others?

(7)

Page 32
(2)

(3)
(4)

(5)
(6)

(7)
(8)
(9)

(10)
(11)
( 12 )

(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21 )
(22)

(23)

A Not that I specifically recall.
Q Same question with regard to the furans, were

there any tests for those?
A Not that I specifically recall.
0 What type of impurities, when you say isomeric
impurities, do you recall any that was tested for?
A We would, our quality control procedures at that
time did not require that we analyze for other
isom eric impurities.
Q / thought you told me earlier that there was

testing for isomeric impurities. Did I
misunderstand you?
A I'm trying to recall 18 years ago. If I said
that, I g u ess I must have misspoken. At that
time, the sp e c s that we were required to meet in
our quality control w as 95 percent a ssay , a 95
percent a ssa y . We had the ability to analyze for
other isom eric impurities, but that w as not an
official specification. That may be where we got
confused a little bit.

Q D oes that mean that it wasn't done or it was done
periodically or what, testing for isomeric _______________

(1)
(2 )
(3)
(а)
(5)
(б)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(is)
(19)
(20 )
(21 )
(22 )
(23)

Page 33
(1 )

impurities?

(1)
(2 )
(3)
(4)

(5)

MR. WAGNER: I object to the form of the
question.
A It w as more likely to be done on an irregular
basis, and most likely from a research standpoint.

(6 )

Q A s opposed to a quality control standpoint?

(6)

(7)

A A s opposed to a quality control standpoint, yes.

(7)

(8)

(8)

( 12 )

O You mentioned initially you did some research on
the old process for manufacturing 2,4-D, and at
some point you were given responsibilities to do
p ro ce ss research for what was potentially going to
be a new process, correct?

(13)

A Correct.

(2)

(3)
(A)

(9)

(10)
( 11 )

(1A) O Was there any other research, before we get to
(15)
(16)
(17)
(18)
(19)
(20 )
(2 1 )

(22)
(23)

that, that you did with regard to the old process?
I know I've focused on impurities, and you've told
me basically what you did, but was there any other
aspect of your research that we haven't covered
from the old process?
MR. WAGNER: This is 1975, before he
started working on the new one?
A A s it relates to the 2,4-0 acid process in the 489
building?__________________________________________________

(5)

(9)

(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(1 a)
(19)
(20 )
(21 )
(22 )
(23)

A Only a few months.
0 And when your attention was directed to the new

process, what was your initial assignment with
regard to that?
A Essentially to provide chemistry support to the
construction of the new plant, focusing on gaining
a personal understanding of the way the new
process w as going to operate.
0 Let me get some time parameters in here, too, so
perhaps this can save me some effort later on.

Did the new process -w a s it implemented?
A Yes.
O Can you tell me at what point in time the new

process was implemented?
A We started the new 2,4-D process in the spring of
Page 35
7 7 , 1think. I se e you’ve got my report. I
think it talks about May of 7 7 .
0 Okay, was it May of 77, is that when the process
was began?
A That’s when we started the production of 2,4-D.

Q And up until May of 1977, the old process was
being used?
A Yes.

Q Was the new process, did the new process, was that
put in the same building, 489?
A No. It w as a new structure.
0 What was the new building?
A 948 building - 948-949 building.
Q From your recollection, if you know, when the new

process was started in the spring of 77, was the
product, in May o f '77, was the product sold right
away or was there any delay in the sale of the
product?
MR. WAGNER: I object to the form of the
question, vague.
A I have no personal knowledge a s to when we
actually began - the old process continued to
operate for approximately 18 months after, a s best
Page 36
I can recall, after the start up of the new
process. So there w as a gradual phase in of
product from the new process, but I couldn't give
you any data at all, exactly when material began
to actually be sold from the new process.
0 That was going to be my next question, there was

an overlap then between the old process and the
new process?
A Correct.
O And that was roughly 18 months, you said?
A On the order of 18 months, yes.
O Was the old process eventually shut down in the

489 building?
A The old, yes, it was.
0 When you began your new responsibilities with

regard to research on the new process, did someone
else in the organic chemicals research department,
was someone else assigned to doing any work on
continuing with any work on the old process?
j
A I just simply don’t recall how that - the mind ■
has gotten kind of vague as to specifically what
was done, by whom, when, and all that.
Q Where there certain people within your department

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KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10, 1993

BSA

Page 37

0) in 1975 that were assigned to the 2,4-D process
(2) beside yourself?
MR. WAGNER: This is the new process?
(3)
MR. SCHULER: The new or the old.
W
A Well, Harry Brust w as certainly - continued work
(5)
(6) on the new process. At this point I’ll have to
admit I simply don’t recall who else.
(7)
(8) Q Let me ask you this question, and if you don't
know, just tell me and I'll move on, prior to
(9)
(10) 1975, when you became involved with organic
(11) chemicals research, do you know who was involved
(12) in the department, if anyone, doing research on
2,4-D?

(13)
(14)
(15)
(16)
(17)
(18)
(19)

A Harry Brust.
Q You said he's a chemist?
A Yes. And I know we had som e engineers involved in
that project, but I simply, at this point, don’t
remember who those individuals were.
O Let me show you the report that we've talked about

(23)

in this case, and I've highlighted some things.
I'm just going to ask you to identify it for now,
and if you have a copy of it, it will save me some
time.___________________________________________________________

(20)
(21)
(22)

(1)
(2 )
(3)
(4)
(5)
(6)
P)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(is)
(1 6)
d7)
(18)
(19)
(20 )
(21 )
(22)
(23)

Page 38

(1) A Yes, that’s my report.
(Discussion held off the record.)
(2)
(3)
(4)
(5)

(Plaintiff’s Exhibit 1 w as marked for
identification.)
MR. SCHULER: Back on the record.

(6) 0 Looking back at Plaintiff's Exhibit 1, here, this
is your report from October 27th, is that 1978?
(7)
(8) A Yes.
Q And you did this report for what purpose. Dr.
(9)
(10) Krumel?
(11) A The purpose w as to document some, essentially the
(12) research that Is described in the report.
(13)
(14)
(15)
(16)
(17)
(18)
(19)

Q That's your answer, I take it?
A D oes that answer your question?
0 / think so. There's some writing,! don't know,

maybe this was from a prior lawsuit or something,
but I've got some writing on top of mine that I
see you don't have on top of yours. Do you
recognize what that may be up there?

(20) A Well, the report w as obviously sent to somebody by
(21) somebody.
(22) Q But you don't recognize it?
(23)

A No. Steve, Steve, it m eans nothing to me.______________
Page 39

(1) Q In any event, this research was on the formation
(2) and removal of impurities in the 2,4-D process,
(3)
(4)
(5)

(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
(22)
(23)

correct?
A In the new 2,4-D process, yes.
Q And this was co-authored by Mr. R.F. Arnold?
A Ray Arnold is a laboratory technician who works
with me. I w as - his part of the project is he
ran the experiments or ran - ran many of the
experiments that are described in the report, but
I’m the one that’s responsible for the
interpretation of the data. Ray was not qualified
to do that.
O And this was sent to, or it said receiver's

signature, Peter Owen?
A Reviewer’s signature, Peter Owen was my immediate
supervisor. And the technique we use In report
writing at Dow is the authors submit the report to
the supervisor, and their supervisor has to sign
the report before it can be issued.
Q What was Mr. Owen's position?
A He was, a s I said, he w as my immediate supervisor
at that time.
Q Is he still with the company?________________________________

XMAX

Page 40

(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
0 o)
(11)
(12)
(13)
(14)
(is)
06)
(17)
(18)
(19)

(20)
(2 1)
(2z )
(23)
d)
(2)
(3)
(4)
(5)

(6)
(7)

(8)
(9)
do)
(11)
(12)
(13)
(H)
(15)
(16)
(17)
(is)
(19)
(20 )
(21 )
(22 )
(23)

A Yes.
Q Is he still in organic chemicals research?
A No. He’s off in another department. At this
point, I can’t tell you exactly what his job is.
Q Up at the upper right-hand comer of Plaintiff's

Exhibit 1, it says laboratory report code, OC,
slash, 78, dash, 85. Do you know what that code
stands for?
A O C is merely the designation for organic
chem icals. It was the designation used by our
library system to designate organic chem icals
research. The number, it just means it’s the 85th
report written in 1978, to come out of this
department.
0 And then below that, it's hard to make this out
because of the copy I have, but it appears to be a

lab number, is that right?
A Yes.
Q Let me A I beg your pardon?
Q Is it 05 or?
A 050.
Q And what is the significance of the 050 lab________________
Page 41

number, if any?
A That gets into some of the accounting and
recharging of research dollars within the company.
It has no meaning to the report, really, other
than just to designate. The 050 is a laboratory
number for accounting. T he problem number is a
method for internal recharging.

Q What do you mean by internal recharging?
A Well, how I’m paid, how my salary is paid.

Q And the problem number here is 9, six zeros?
A Correct, it h as absolutely nothing to do with the
report, itself.
Q With the subject matter?
A Yes.

G Looking down at the descriptive summary with
conclusions, let me just ask you a couple
questions about that. One of the findings that
you outline here is a new and unexpected class of
non-acetic impurities, correct?
A Mm-hmm.

Q Yes?
A Y es.
Q And you mention two of the major components were
Page 42

tetrachloroxanthone and octachlorospirobixanthene?
A Yes.
0 And what type of impurities are those, I mean -

maybe that's a bad question, but can you
categorize those impurities in any way?
MR. WAGNER: I object to the form of the
question, compound, vague.
A Well, xanthone is an accepted organic nomenclature
for a particular class of compounds.
Spirobixanthene, again, is the sam e thing, it’s
accepted nomenclature. What they are is organic
chem icals that were detected in the product.

Q In the final product of 2,4-D?
A That’s where we first observed them, yes.
Q And when you mention that the impurities were

causing problems in the subsequent formulation of
2,4-D as amine salts, what were you referring to,
what did you mean by causing problems? J
A The issue occurred as we stated before,^he plant
started up in May of '77. By that fall, what we
started observing, we have a quality control test
for our amines, where we mix a small amount of the
amine salts with water, shake them up, centrifuge

212
-p-AHO

8SA

(1)
(2)
0)
(4)

(5)

(6)
(7)

(8)
(9)
(10)
( 11 )
( 12 )

(13)

(14)
(15)
(16)
(17)
(18)
(19)
(20)
(2 1 )
(22 )

(23)

(1)
(2)
(3)
(4)

KARL KRUMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemicai - March 9-10,1993
Page 43
the sam ples and look at suspended solids, and we
have a certain amount of solids in that that’s an
acceptable spec.
T h e problem that you run into, we
started to see more of these solids, but where the
problem really came up w as when the formulated
product was applied in the field, we started
getting increasing customer complaints from
plugged spray nozzles. At which point we went
back and started looking specifically at those
solid s, and in these solids, that was where we
first observed some of the compounds, the
tetrachloroxanthene and the octachlorospirobixanthene.

O And this whole paper, if I understand it
correctly, was devoted to exploring the
possibility for attempting to control, minimize or
eliminate these impurities in the 2,4-D?
A Correct. It w as targeted at solving a customer
complaint issue.

Q Do you recall whether there was a specific
customer that did complain?
A I ca n ’t answer - I just simply don’t remember_________
Page 44
w here the specific complaints came from.
Q Do you remember how you got notice of the

complaint, that there was a complaint, and
assigned this project?

(1)

(2 )
(3)
(4)
(5)

(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20 )
(21 )
(22 )
(23)
(1)
(2 )
P)
(4)

MR. WAGNER: I object to the form of the

(5)

question, compound.
(6)
A I don’t recall the exact sequence of events. I
(7)
(8) believe people are mentioned in this report, a

(6)
m
(8)

(5)

(9)
(10 )
(11)
( 12)

(13)
(14)
(15)

(16)

(17)
(18)

(19)

J o y ce King, from formulations, in the 9001
building. It’s on page 8 at the bottom. She is
in our - or sh e w as in our formulations and TS&D
area at the time. She would be working with our
manufacturing supervision, who was working very
clo sely with our R&D supervision in my department.
S o the whole sequence of events I don’t
remember, but the bottom line came, I w as assigned
the job of getting involved in attempting to
understand the formation and how we could get rid
of them to solve a quality issue.

(20) Q Do you know whether the old process that, from
(21)
(22)

(23)

(D
(2)
(3)
(4)

(5)

(6)
(7)
(8)
(9)
( 10 )
( 11)

(12)
(13)
(14)

(15)
(16)
(17)
(18)
(19)

(20)

your earlier testimony, I understand was still
ongoing at this time, was evaluated for these
impurities, as well? __________________________________________
Page 45
A W e tested the samples, and none were found.
Q When you say we, who are you referring to?
A Again, our team, the we in this ca se would have
been someone from our analytical scien ces
department, and that someone w as most likely, as
best I can recall, Dale Humbert.
O Humbert?
A Who is listed a s a recipient on the back of this
report under 574 building, D. Humbert. He w as the
chief analytical scientist supporting this area.
Q And from an overview standpoint, this report, you

mention that the number of treatments and
potential solutions that you examined, none
appeared to be totally successful, correct?
MR. WAGNER: I object to the form of the
question.
A That answ er is - yes, that’s correct.
Q In my copy here, there's a blank that appears to

be filled in on the one you have, the last
paragraph. Can I see that for a second?

(21 )

MR. WAGNER: Sure.

(22 )

(Discussion held off the record.)

(23)

____________ (Plaintiff’s Exhibit 2 was marked for________

XMAX

Page 46

(9)

(10)
(11)
(12)
(13)
(14)
(is)
(16)
d7)
(18)
p9)
(20 )
(21)
(22 )
(23)

i d e n t if ic a t io n . )

MR. SCHULER: Back on the record.
Q Let me just follow through this report briefly

with you. My page 1 is a table of contents,
correct?
A Yes.
O Page 2 appears to be an introductory section?
A Yes.
0 And that's where you mention at the top that the

process, I think the word new is even blanked out,
anew process for preparing high purity 2,4-D was
started in May 1977 at the 943 building?
A 948.
Q Okay, it looks like 943 on mine, okay, 948

building. You mention that the high purity molten
acid is transferred by pipeline to the 489
building where it is formulated into esters and
water soluble amine salts, which would be the
final product, correct?
A Yes.
0 You mention that the impurities that you found

were never detected during laboratory or pilot
plant development work, correct? ______________________
Page 47
A Correct.
0 Again, there's a word missing, I've got to ask, or

there appears that there's a word missing, anyway.
In any event, you mentioned, also, in this first
paragraph, that the impurities were not found in
the old process, correct?
A Yes.
O And that was what you referred to earlier when you

said there was some testing done in the old
process, correct?
A Yes.
0 Who is ft McLachlan?
A He’s an analytical scientist in the sam e
department a s Dale Humbert.
0 Is he still there?
A I don’t believe he is. I have not - I’ve lost
track of him.
0 How about Mr. Humbert, is he still there?
A He’s still in the company. He's not in analytical
anymore, but I don’t know specifically where he
iS.
0 Mr. McLachlan, in any event, was the one who

analyzed precipitates and found the TCX and the
Page 48

(D
(2 )
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(is)
(16)
(17)
(18)
(19)
(20 )
(21 )
(22 )
(23)

OCSX?
A He’s the one that wrote the report.Who actually
did the work, I assum e Dick did, but I don’t know
that for a fact.
0 But that’s what you put in here, correct?
A Yes, that - yes.
Q And the chemical formulas for the TCX and OCSX are

outlined there, correct?
A Correct.
O You mention that the TCX from the screening

program at the plant showed levels of 200 to 500
parts p er million in the crude reaction mass, and
again, I'm missing words here. It says the
recycle A Recycle sodium dichlorophenate.

Q - solution and in the final product. Okay.
Levels of 1,000 to 2,000 parts per million were
found in the, and I'm missing -

j

A Would you want to just work off that, and we’ll - j
Q - were found in the perc solvent, and as much as ‘

10 percent in the still tars, perc still tars?
A Correct.
____________ MR. WAGNER: I object.________________________

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 49

(1) Q The toxicological significance of TCX and OCSX, Is
(2) that unknown to you?
(3)

A Only what’s reported in this report. I think on

(<) the next page, our page 6, is what I knew
toxicologically about this material.
(5)
(6) Q Where did you get the report on page 6?
A it should be referenced. It apparently is not (7)
(8) O So you don't know where that information comes
(9) from?
(10) A Not specifically, anymore. There’s a reference
(11) to, in the reference section on page 57, the very
(12) back of the report, reference two.
(13)
(14)

Q What reference are you referring to?

(15)
(16)

Q P. Keller?

(17)
(18)
(19)

Q Health and environmental toxicology?

(20)
(21)
(22)
(23)

A Reference number two.
A P. Keller, yes, that is from the A Yes, so -

0 Looking at that for a minute, on page 357 of
Plaintiff's Exhibit 2, it says P. Keller et al,
H-E-T, and some numbers, K, dash, 2372, dash,
parentheses, 18. Do you know what that stands
for? __________________________________________________________

(1)
(2)
(3)
(4)

(5)
(6)
(7)

incorporated in here by reference shows a
chloracnegeneric response in various
concentrations to both TCX and OCSX. correct?

(8)
(9)

MR. W AGNER: I object to the form of the
question.

(10)
(11)
(12)
(13)
(U)
(15)
(16)
(17)
(1 a)
(19)

A The answer to the question is yes, to the best of
my knowledge.
Q The diagram on page 7 is just a diagram of the

(20)
pi)

O At the bottom of page 8 you referenced earlier
some other workers, and one is S . Siegel, OCR?

(22 )
(23)

A Yes.
Q Organic chemicals research? _________________________________

(1)

A Yes.

(2)

O And was that someone who worked with you?

(3)
(4)
(5 )
(6)
(7)
(8)
0)
(10)
(11)

A That w as someone that was working alongside me,
yes. A s best I can recall, he w as working more in
the quality area directly with Joyce King and
Susan Shell.

process, would that be a fair statement?
A It is a very simplified diagram of the process,
yes.

Q Do you know, when referring to the top of page 8,
whether any data was obtained for long-term
effects of these impurities that you found?
A I don’t know.

Page 50

(1) A I have no idea.
(2) Q That would be the toxicology report?
(3)
(4)
(5)

A It is possible that that’s the toxicology report.

Q And you're thinking A I don’t know that for a fact.

(6) O Because it says HET?
A Correct.
(7)
(8) Q Going back to page 3, it talks about 11 other
minor components structurally similar to the
(9)
(10) above. When you say structurally similar to the
(11) above, what are you referring to there?
(12) A Without having seen reference one for many, many
(13)
(14)

years, I Just simply don’t recall.
O Besides the TCX and the OCSX, though, there were

(15)

other components that were discovered, as well?

(16)

A The compound shown a s 8-5, and that is shown on
page 4, and then on page 8 are two other
impurities that were found, but specif ically what
the 11 minor impurities refer to, I have simply
forgotten.

(17)
(18)
(19)

(20)
(21) O Go to page 4 fora second, the 8-5, you call this
(22) another significant impurity. What was the reason
(23)

for calling It that?__________________________________________

Page 53

Q Susan Shell was in the production end?
A Yes, she w as production supervisor.
Q Located in building 489?
A Y es, so sh e would have been production supervisor
of the ester and amines portion of the process.

(12)

O And Judy, w as it?

(13)
(H)
(is)
(i6)
07)
(is)
(19)

A Joyce.
O Joyce King was in the formulation end and located

in Building 9001?
A Yes.

(20)
(21)

Q You mention in the last paragraph above the
chemical symbols on page 8 that there were two
other impurities called complex one and complex
fwo, and you diagrammed those that were found,
also, correct?

(22 )
(23)

A Yes.
Q So we have, to keep track of all this, we have the___________

Page 51

(1) A B ecau se it w as detected in quantities that
(2) occasionally were comparable to what we were
(3)
(4)
(5)

(6)
(7)

seeing for the O C S X and the TCX.

Q Do you know the toxicological significance of 8-5?
A I'm not aware of any data on that compound
specifically.
O Had the page 6 initial screening for toxicity

(8) report that you incorporated In this, that was
research that you did not do yourself, correct?
(9)
(10) A No, sir.
(11) Q However, the report that you incorporated in
(12) Plaintiff's Exhibit 2 does appear to indicate

XMAX

Page 52
MR. W AGNER: Why don't we reask the
question. Now, I’m confused about what’s on the
table.
Q My question w as initially that the report that you

Page 54

(2 )

TCX, the OCSX, the 8-5, and the complex one and
complex two impurities, so far?

(3)
(4)

MR. W AGNER: I object to the form of the
question.

(I )

(5)
(6)
(?)
(8)
(9)
(10)
(11)

O Referenced in your report, correct?
A Yes.
O Do you know the toxicological significance of the

impurities, complex one

and complex two?

(12)

A No, I don’t. Incidentally, for correctness,
there’s a slight misprint on number four. The C
shown in the middle shows C L ; that should be CH .
This should be - may I?

(13)
(14)

chloracne response for different concentrations
and different doses of the TCX and OCSX, correct?

(13)

Q That's CH there?

(15)
(16)

A I only see, in this one, one concentration applied
several times.
O Well, correct me if I'm wrong, here, it looks to

(16)

(17)
(18)
(19)

me like there are two. One Is four grams per
kilogram and the other is five grams per kilogram.

(20) A Well, one is a tar sample that contains some TCX,
(21) som e O CSX, and but you asked me, I thought you
(22) asked me specifically about T C X ?
(23)

Q Well, I mentioned TCX and OCSX, as well.

(14)
(15)
(17)
(18)
(19)
(20)
(21)
(22)
(23)

MR. W AGNER: If you're going to correct
it MR. SC H U L ER : I'll correct it on this
one because it's marked up already. That should
be C H ?
J
T H E DEPON EN T: Yes.
j
MR. W AGNER: How in the world you can
remember that, I'll never know.
T H E DEPONEN T: Well, I just noticed it.

Q CH stands for?_______________________________________

______

213
y -

9 . ^

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

(1)
(2)
(3)

Page 55
A The C stands tor the chemical compound for carbon.
The H is the chemical symbol tor hydrogen. The C L
is the chemical symbol or chlorine, and that would
be an impossible structure.

(4)
O And the OH is the chemical symbol (5)
(6) A For the hydroxyl.
O Oxygen and hydrogen?
(7)
(8) A Yes.
(9) Q K.E. First, referring to page 9, what role did
(10) that individual have in this report, if any?
(11) A Ken First, at that time, was in process
(12) engineering, and i had actually even forgotten his
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
(22 )

(23)

(1)
(2)
(3)
(4)
(5)

involvement, but he did som e computer modeling of
rates of formulation based upon the data that I
generated, or that Ray Arnold and I generated.
And the contribution I think in his
report w as to - oh, goodness, I’m not sure what
page it’s on, but he talked about, if we
maintained a certain level In the recirculating
perc, we would maintain another level in the
product. It's in the report som eplace. I’m not
sure exactly what page that's on.
Q We'll get to that. I just wanted to know who that__________
Page 56
was. Let's refer to page 9, Dr. Krumel, for a

minute. At the bottom of page 9, after you
essentially have outlined the impurities that we
have already discussed, you decide to focus on
TCX correct?

(6) A Y es.
0 And you stated the reason for the focus on TCX,
(7)
(8) one of the reasons was that it was a major
impurity. What did you mean by that?
(9)
(10) A Of these - of the small amount of things that we
(11) found in the solids, it w as a major component
(12) Q By volume, you mean, or some other yardstick?
(13)
(14)
(15)
(16)

(17)
(18)
(19)

(20)
(21)
(22)
(23)

(1)
(2)
(3)
(4)
(5)

(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)

(17)
(18)
(19)

(20)
(21)
( 22 )

(23)

A Typically what we’re talking about would be by
weight percent within these traces of solids that
were found.
0 / want to ask you to skip over to page 21. One of

the comments that you made on page 21 is that a
recurring problem for the past several months was
how to explain the fact that the plant observed
TCX formation rates that were five times greater
than the lab. Did you ever find the reason for
that?
____________ MR. WAGNER: I object to the form of the_______
Page 57
question.
A No, we never really did, nothing more than what’s
explained In this report.
0 In the first sentence of the last paragraph, full

paragraph on page 21 of Plaintiff's Exhibit 2, you
mention that in addition to TCX, OCSX and 8-5 are
known to be formed measurable quantities during
the reaction to 2,4-D - maybe I didn't read that
properly. In addition to TCX, OCSX and 8-5 are
known to be formed in measurable quantities during
the reaction to 2,4-D. When you say measurable
quantities, can you tell me the relationship
between the three, perhaps reflected in percentage
as far as the ratio of the weights found?
MR. WAGNER: I object to the form.
A Without specifically reviewing data and numbers, I
just simply don’t recall, but we mentioned in the
report 200 to 500 parts per million of TCX was
found. M easurable quantities would, in that
context, would mean comparable numbers, but
specific data, I just simply don’t recall.
0 On page 28, referring you to 28, and you can't

tell because mine is the expurgated copy, here,

f

XMAX

Page 58
(1)
(2 )
(3)
(4 )
(5)
(6)
(7)
(8)
(9)
(10)
(1 1)
(12)
(13)
(u)
(is)
(16)
(17)
(18)
(19)
(20 )
(21 )
(22 )
(23)
d)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(n)
(12)
(13)
(u)
(is)
(16)
(17)
(is)
(19)
(20 )
(21 )
(22 )
(23)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
0 3)
(14)
(15)
(16)
(17)
(is)
(19)
(20 )
(21 )
(22 )
(23)

but in the middle paragraphs you mention some TCX
is formed in the reactor and was found throughout
the 948 building process. When you say that, are
you referring to the fact that the TCX was found
at various points in the process or actually in
the building, itself?
MR. WAGNER: l object to the form of the
question.
A It w as found in various process stream s. A s we
indicated before, it was found in the reactor
crude. It w as found in the recycle
dichlorophenate solution, and it w as found in the
recirculating perc, so it’s found inside the
chemical process, itself.
0 Was it found in the final product, 2,4-D?
A I think, back on page whatever, it w as indicated
that yes, we did find it in the product, itself.
0 Referring to the bottom of page 29, you make note

of the fact that the 8-5 impurity is not
efficiently removed with perc extraction, hence
most of what is made goes out with the product.
Why was that a concern?
____________ MR. WAGNER: I object to the form of the
Page 59
question.
A Again, because it is, the trace levels that were
in the product are insoluble in the am ines
formulating mixture and would again result in
small amounts of solids that I think we discu ssed
earlier.

Q In the table five above that statement you have
some numbers for initial and final as far a s TCX
and 8-5 in parts per million, correct?
A Yes.
0 What does that refer to, initial and final, in

that chart?
A I have to read the ch a rt What we did w as
simulate the process in the laboratory, and to
take a sampie of the crude sodium sait of 2,4-D,
extract with perchloroethylene, in the laboratory,
and analyze the sodium 2,4-D before and after
extraction with perchloroethylene, and these are
merely the results of those experiments.
0 Is the final referred to in the final product, or

is that at some other juncture that you extracted
the TCX and 8-5?
____________ MR. WAGNER: You mean the columns,
Page 60
final, is that what you're referring to?
MR. SCHULER: Yes.
A This would refer to the sodium. T his would not
refer to the final product, but rather to the
intermediate sodium 2,4-D.
O At the bottom of page 30 you refer to the 2,4-D

reaction as developed by H. Brust. Is that
referring to this new process?
A Correct.

Q At the bottom of page 31, you mention that
formation of the TCX cannot be limited to much
less than 60 percent per million. Is that with
reference to the final product of this new
process, or sodium or the amine version of 2,4-D?
MR. WAGNER: I object to the form of the
question.
A This refers to laboratory experiments which, a s .
you can see, were run at 72 hours at 160 degrees
in g lass equipment. This is not refering to
•
plant.
Q So this is the product that you were getting in

the laboratory?
A Correct.

______

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 61

(1) 0 Did you ever test the iinal product from the plant
(2) to determine a TCX concentration?
MR. W AGNER: I object to the form of the
(3)
question.
(4)
A The product in the plant was analyzed routinely
(5)
(6) for these compounds.
0 And is there information here in this report with
(7)
(8) regard to that, or would that be located in some
0) other report?
(10)
MR. W AGNER: I object to the form of the
question.
(11)
(12) A There may be a reference within the report here or
(13)
(14)
(15)
(16)
(17)
(18)
(19)

there. I don’t specifically recall talking about
specific plant data. All of the numbers reported
In various tables, to the best of my recollection,
are all laboratory generated numbers.
0 So you were using, you simulated the process or

reconstructed the process in the laboratory, and
the numbers in this report are with regard to the
product you produced in the laboratory?

(20)
(21) A Correct, other than the numbers that we discussed
(22) at the very beginning, where we said we found 200
(23)

to 500 parts in the reactor crude and In the____________

(1)
(2)
(3)
(4)

O Was there a specific number that was assigned to
subject matter, for example, like 2,4-D, w as there
a specific file or series of files pertaining to a

(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)

A Different coding system s were used at different
times. Now, whether there w as a coding system
specifically designed to 2,4-D, I don’t recall.

(15)
(16)
(17)
(is)
(19)
(20)
(21)

(22 )
(23)

Page 62
(1)
(2)

be generally higher than the laboratory data for
as far as the content of the impurities was
concerned?

P)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)

(5)

(6) A We observed that, i think I mentioned it a little
bit ago, where you were asking me, it’s on page
(8) 21, where the plant observed T C X formation rates
that were five times or so higher than laboratory.
(9)
(10) Q Referring to page 35, you make reference to an
(11) earlier report, and it's got a number, footnote
(12) 16. Is that the report that's listed as 16 in the
(7)

(13)
(14)

reference section on page 57?
A I recall the work. I do not recall the report.

(15) Q What's listed as 16 on page 57 has some numbers
(16)
(17)
(18)
(19)

behind it. Organic chemistry, I assume is the OC?
A Y es.
0 And then 78, dash, 17 stands for what, if you

know?

(20) A I g u ess I don’t remember specifically. The thing
(21) that confuses me a little bit is the LR, because
(22) that is a code that we used to use for letter
(23)

reports, which were a way of documenting results

(1)
(2)

back at that time. I think I mentioned earlier
the numbering code that we used. Well, we
mentioned it on this report, but the 78-17 LR, t
don’t specifically remember how we used to number
those.

(5)

(6) Q What about the 39, dash, 78?
A That, I’m not sure about that, either.
(7)
(8) 0 There's a reference in the reference section,
number 12, also, to some work done by, is it Dr.
(9)
(10) Brust?
(11) A Yes.
(12) Q And refers to organic chemicals, again, with a
(13)
(14)
(15)
(16)
(17)
(18)
(19)

(20)
(21)
( 22 )

(23)

long number, dash, 2, and then a 2-26-73. Do you
know what that refers to, number 12?
A That’s one of Dr. Brust’s research reports. I
can't tell you from the number exactly which one.
The date is the date that the report w as issued.
The numbering code is, the 0730013 is a coding
system that was used for a period of years.
C H E C K C H E C K C H EC K .
0 Any significance to that?
A Nothing a s far a s a - I don’t specificalloy
recall.

Q You don't remember whether there were specific
codes that were assigned to certain chemicals, for
example, to keep research, no matter what aspect
it dealt with, but in regard to a certain chemical
in that area that existed?
MR. WAGNER: l object to the form of the
question.

A I don’t specifically recall all that went Into how
they specifically assigned codes, because it
changed at times. And what w as used specifically
at the time this report w as issued, I don’t really
remember.

Q Was the research or the organization of the
product of the research computerized back in 1975?
A W as the research computerized in 1975?
Q I mean the organization of the reports? __________________
Page 65
A Oh, no, these were not done by, on computer.

Q But were they filed? Was there a computer index
of the reports, if you know?
MR. WAGNER: In 1975?
MR.SCHULER: In 1975.
A In 1975 w as there a computer? I don’t know for
certain.

Q At the bottom of page 36, or on page 3 6 1 should
say, you make a comparison in the first paragraph
between the two processes, the 489 building and
the new process in the 948 building, correct?
MR. WAGNER: I object to the form of the

(13)

(u)
(is)
(16)
(17)
(is)
(19)
po)
pi)

question.

A Are you talking about under item tour?

Q Yes.
A Well, the p rocess in 489 building did u se a step
involving the u se of bleach that w as not used in
the new process, that’s correct.

(22)
(23)

Q And were you making some type of an estimate as to
whether adding a bleaching step would improve or
reduce, help to reduce the impurities that were
found in the new process, is that what you were
doing there? _______________________________________________

(1)

Page 66
A Y es. It w as an option we wanted to consider.

Page 63

(3)
(4)

particular chemical like that?

(14)

(1) recycle, those were plant data.
(2) Q With the plant data that you mentioned, it would
(3)
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XMAX

Page 64

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Q And it is apparently submitted to somebody by the
name of K.E. First?
A That’s the sam e Ken First we discu ssed earlier.

0 And he estimated a cost of doing that at 500,000,
is that what that is?
A Yes.

Q So that wasn't pursued because of the - it wasn't
cost effective?
MR. WAGNER: I object to the form of the
question.

A Yeah, a s stated in the report, it w as dropped due
to the marginal benefits that we concluded.

Q At the top of page 38 you mention the capacity of
the 948 building up to that point in time, and I
just want to know, need to know the numbers you're
referring to there, it's 100 to 120 what p er day?
A It’s 100 to 120,000 pounds per day.
j
Q What, the new process?
f
A Y es.

Q Do you know at this time or, let me go back, do
you know as of May of 1977 whether the 948
building was running at that capacity? __________________

214
3^

~ot (j/

KARL KRÜMEL, Ph.D.- Kimberty Moyer Vs. Dow Chemical - March 9-10, 1993
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Page 67
A In May of ’77 when we started up?
0 Yes.
A No, it was not.
0 What about when this report was done in October?
A The date would basically refer to the date this
report was issued, so we’re talking about,
essentially now, October 1978. What the running
rate w as in October of '77, which is, I assum e,
the date you’re asking about?
0 Yes.
A I don’t know.
0 That's right, this report was October of 78, so

you’re referring to the full capacity as of
October of 78 ?
A Correct.
0 And in your statement in the next sentence with

regard to the impurities in the 2,4-D product is
what, 20 parts p er million of TCX?
A Yes.
O And 20 parts p er million of 8-5?
A P lu s or minus some. What the ranges are, I don’t
recall.
Q You mention in a couple of paragraphs down that
Page 68

(1)
(2)

(3)
(4)
(5)

Page 70
0 The acknowledgment section on page 56 of

Plaintiff's Exhibit 2 mentions a number of people,
some of whom you've already referred to, Dr.
Krumel, but let me ask you about some of the
others. Who is T. Evans?

(6)
(7)
(8)

A Tom E v a n s w a s an an alytical scien tist, a s w a s G ary
Jewett, a s w a s Penn , P-E-N-N, Schloem ann - well,
a s I indicated, for their an alytic support.

(9)
(10)
(11)

Q I just wanted to identify them. Did they all work
on some aspect of preparing this report that we
have marked as Plaintiff's Exhibit 2?

(12)
(13)
(14)
(15)
(16)

A They all would h ave provided input in the
analytical re su lts that w ere d escrib ed within the
report. I co uld n ’t identify for you sp e cifically
what e ach o ne of th o se individuals did at th is
time, but th ey w ere all part of providing the

(17)

analytical backup for this report.

(18)
(19)

0 Did any of them do any research on 2,4-D prior to

(20)
(2D
(22)

A Not that I recall.

the new process, the old process, we 'll call it?

(23)

Q I asked you about some of the documents listed on
page 57, the reference section. Who is
Mr. Dhingra, D-H-l-N-G-R-A?________________________________

further work is justified only if the levels of
impurities presently found in the product prove
unacceptable in the future from a toxicity,
environmental or performance standpoint. Do you
recall whethc- ■there was any further research done
in any of those areas to determine whether these
impurities were unacceptable?
MR. WAGNER: I object to the form of the
question.

(1)
(2 )
(3)
(4)
(5)
(6)

Page 71
A Y e s, Yog Dhingra.
Q Who is that?
A H e’s a ch em ist w ho w a s involved in the phenoxy
area during the tim e I w a s in the c e llu lo se ether
area. S o sp e cifica lly w hat h e w a s doing and w hat
he w as referring to in th is referen ce, I c a n ’t

(7)
(8)

tell you right now.
O Mr. Fern or Ms. Fem, whatever that is, do you

A No, I don't recall.
0 You did not do any research in those areas, I take

(10)

it?
A The work that we would have done in those areas
would have been continuing to work in the plant,
monitoring and making sure that we were, in fact,
operating within these ranges.

Q You mean the ranges of 20 parts per million?
A Y es.
0 Was there a quality control laboratory set up in

each building, for example, the 948 building for
2,4-D and the 489 building for 2,4-D?
A Yes.
Q And so the analyses that you referred to earlier__________
Page 69

with regard to quality control were performed
right there in the plant, if you will?
A Correct.

Q A s opposed to the organic chemicals research
laboratory?
A We did very, very few analyses ourselves, in our
department. We would rely on the quality control
laboratories, a s well a s the analytical scien ces
la b o r a to r y .

O Was there a quality control officer assigned, for

example, to building 489?
A I ca n ’t answ er how that w as - I don’t know how
that w as managed those days.
0 Was that a separate department in 1975, quality

control?
A The quality control work, during the time frame
we’re talking here, was done within the plants.
How the data w as managed in reference to a quality
control officer, oras you brought up,
I just - I
don’t know.

MR. WAGNER: Let’s take a quick break.
(R ec es s .)
___________ BY MR. SCHULER:____________________________

b

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know who that is, it's the next one down, number
14?
A That’s a m isprint. T h a t’s w hat I w a s afraid of.
You ca n - b ack to p age 3 1 , 1refer to Dhingra and
Fear, referen ce 14.

Q So that's Fear?
A The nam e sho u ld be F e a r, F-E-A -R , D en n is F e a r. He
w as an e n g in ee r w ho w a s very m uch involved in
p ro ce ss m odeling. Now, w e ’d h ave to look at the
report if you w ant to get sp e cifica lly a s to what
h e d id .

(22)
(23)

Q The work that you did in the organic chemical
research laboratory, was that originally committed
to what's referenced here in some places as a lab
book? _________________________________________________________

(1)
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(3)
(4)
(5)
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(7)

Page 72
MR. W AGNER: I object to the form of the
question, overbroad.
A O ur standard w ay of initially docum enting our
work, a s w e’re doing th e experim ents, is to write
them up in re s e a rc h data books. T h e re su lts of
our work d e scrib e d in th e se re se a rch data b ooks is
then sum m arized in th e se re se a rch reports.

(8)

Q So the summary, this research report would be the

(9)

summary of what's in the research data book for a
particular experiment?

(20)

pi)

(10)
(11)

A Co rrect, or a p articu lar project.

(12)

0 There’s a reference at the bottom where it talks

about laboratory notebook references, and it has
your name and Mr. Arnold?

(13)
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(15)
(16)
(17)
(18)
(19)
(20)
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(22)

A O C 417 and O C 6 40, th o se are co d e n um bers for the
data books. T h e p a g e s m erely d escrib e, s o in
research data b a ck O C 417 for R a y Arnold, you will
find the work that is sum m arized in th is report
j
described in p ag e s 109 to 150. And in data book f
640 from p ag e s 1 to p ag e s 73, and likew ise in m y
research data book, O C 559, you will find work
described in th is report on p ag e s 95 to 131. T h is

(23)

is t h e w a y w e h a v e o f r e f e r e n c i n g o u r r e p o r t s b a c k

BSA

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993
Page 73

(1) to the original data.
(2) Q All right. After this was completed, did you do
(3) any further research with regard to these
(«> impurities in the new 2,4-D process?
MR. WAGNER: I object to the form of the
(5)
question.
(6)
m A Not that I can recall.
(8) Q Did you do any further research into the old 2,4-D
(9)
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(1 1 )

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Q At some point in this report, this 2,4-D was
referred to as Rhone-Progil acid. Do you know
what that means?

(13)

A Y e s. Rhone-progil w as a company in Europe that
produced 2,4-D acid at that time. Their material
happened to be particularly pure, so we had a
sam ple of it that we used for research purposes
only.

(16)

(3)
(4)
(5)

MR. WAGNER: I object to the form of the
question.
A To my knowledge, there’s no connection.

(6) Q Did you, other than writing your report, and I
assume, let me go back and ask this question, I
(7)
(8) assume this report, that we have marked as
Plaintiff's Exhibit 2 here, was written for
(9)
(10) intercompany use?
(11) A Y es.
(12) Q Did you ever write any report for use outside the

(3)
(4)
(5)

A No. Mr. W isniew ski w a s definitely, he w a s an
analytical chem ist.

Q He may be with some company -

the level of purity that had been developed by
this Rhone-Progil company?

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(23)

company, to anyone outside the company?
MR. WAGNER: On any subject at any time?
MR. SCHULER: No, on this subject
A On this subject, no, I've not.
Q Did you ever communicate information to anyone

(14)
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A T h is would be a docum ent having been prepared
within the analytical departm ent, and no, I had no
Involvement in its preparation, nor do I reco g n ize

Q There's a sheet attached here to this Plaintiff's

(7)

(8)

Exhibit 4. It's very difficult for me to read,
and probably it will be for you, too, but can you
make out, it appears to say release rerouting
sheet. Have you seen a form like that before?

(9)

A I h ave no idea what th is is.

(10)
(11)
(12)

0 Have you ever testified in any form before the

Environmental Protection Agency, for example, or
the Department of Agriculture, regarding these
type of chemicals?

03)
(u)

A No, I h aven ’t.

(is)
(16)

Q Have you ever written any reports that were
furnished to the EPA that you're aware of?

07)

MR. W AGNER: On any subject?

outside the company regarding the fact that there
were these impurities in this new 2,4-D process
that were found and outlined in your report that
we marked as Plaintiff's Exhibit 2?

(is)

Q On the subject of these chemicals, 2,4-D, 2,4,5-T,

09)
(20)

A Not that I ca n recall at th is tim e.

pi)

Q Do you know who Marguerite Leng is?

A Not that I recall.
Q Do you know whether anyone else at Dow Chemical
Page 75

(22)
(23)

A Y e s , I know M arguerite.

Company communicated information in this report
that we marked as Plaintiff's Exhibit 2 to anyone
else outside the company at any point in time?

(1)

Silvex?

Q What is her position - well, let's start with is _______________
Page 78

she still with the company today?

(2)

A No, s h e ’s retired.

(3)

A Not to my knowledge.

(4)

Q What was her position when she was last with the
company, if you know?

Q Do you know a Mr. Wisniewski, D .F Wisniewski?

(5)
(6)
(7)

A S h e w as - 1 ca n ’t give you her exact title. S h e
w a s in the regulatory departm ent in so m e ca p a city,
but I don’t know exactly.

(8)

0 Do you know if scientific reports were provided to

(9)

her on a regular, continuing basis, particularly
regarding these chemicals?

you've seen this before, and you might show your
counsel there, too. Let me see the date on that.
A Decem ber 16th, 1979.
Q Have you ever seen that document before?
A Not that I recall.
Q You weren't involved in any of the research that

(20)
(21) went into the preparation of that document?
(22) A No, sir.
(23)

Q Well, I don't see your name on this one, either,
but let me ask you if you've seen that before?

(4)
(5)
(6)

(13)
(14)

(15)

A Well, W isniew ski worked in th e an alytical
department. W hat h is sp e cific scien tific
background training is, no, I don’t know.

Page 77

identification.)
.
Q Let me show you this document here and ask if

(16)

what his background was, Mr. Wisniewski's
background, I'm talking about scientific
specialty, obviously?

it specifically.
(P la in tiffs Exhibit 4 w a s m arked for
identification.)

(10)
(11)
(12)

(13)

MR. WAGNER:
Spiritually.
O - not with Dow Chemical Company. Do you know

(1)
(2)
0)

(6) A Dave Wisniewski.
Q What was his position back in '78 or '79, if you
(7)
(8) know?
A He w as an analytical chemist that offered support
(9)
(10) to the general phenoxy area. Specifically what he
(11) w as doing at that time, I can’t tell you.
(Plaintiff’s Exhibit 3 w as marked tor
(12)
(14)

MR. WAGNER: I object to the form of the
question.

MR. WAGNER: I object to the form of the
question.
A Not that I can specifically recall.

(23)

(22)

(3)
(4)

A Mr. W isniew ski p asse d aw ay a num ber of y e a rs
ago. So the right an sw er is no.

process after October of 1978?

Q And that's why you refer to it by that name?

(20)
(21)

toxicological oriented research. Do you know if
he's a toxicologist or not?

0 Is Mr. Wisniewski still with the company?

A Rhone-Progil, yes.
Q Was the new process for 2,4-D developed to reach
Page 74

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Page 76

Q Mr. Wisniewski appears to at least have done some

(is)
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(20)
(21)
(22)
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MR. WAGNER: I object to the form of the
question.
A T h e only reports that I would know would h ave been
distributed would h a ve b een, to w hom I ca n s a y th e
reports w ere distributed w ere th e o n e s that w ere
listed on the b ack co v er here, and if s h e isn ’t on
that list, then I ca n ’t an sw er, then I d o n ’t know
if s h e w as or not.
j

Q Have you ever been involved with her In terms of,
and I'm not just limiting it to these chemicals,
but have you ever been involved with her in the
sense that you submitted a copy of a scientific
report to her and she reviewed it for some ________________

V 'a

8SA

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10, 1993
Page 79

(1) purpose?
(2) A I don’t specifically recall having done that.
(3)
(4)

Q Have you ever been involved with her in any type
of work at Dow Chemical?

(5) A Only very much on the periphery. Marguerite
(6) happens to be a personal friend, and I know her
(7) more from that standpoint than the work
(8) standpoint.
(9) O Outside of being a personal friend of hers. I'm
(10) talking about whether you actually worked with her
(11) on any type of reporting or scientific work?
(12) A Not that I can specifically recall at this time.
(13)

Q And just so I'm clear on this, do you know whether

(14)

she ever edited any reports that you submitted?

(15)
(16)

A Not to my knowledge.
O Do you know an Andrew Watson?
A I know the name, but I don’t know the individual.
Q Would the function of determining the

(17)
(18)
(19)

(20)
(21)
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(23)

effectiveness of end product 2,4-D, for example,
for its ultimate purpose, killing weeds, would
that be done by another department other than
yours?
A Y es._________________________________________________________
Page 80

(1) Q What department would be involved in doing that?
(2) A Well, at that time the department w as known a s the
(3)
(4)
(5)

(6)
(7)

agricultural product department. In the 9008,
9001 building area, the person we mentioned
before, Joyce King is one who is more likely to
get involved In that type of activity.
0 Was she involved from the agricultural product

(8) standpoint with 2,4-D back in 1975?
A T he only time 1 specifically know that sh e w as
(9)
(10) involved with this project w as when we were
(11) working on the product, on the issue of xanthones
(12) and related compounds over the time frame
(13)
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(17)
(18)
(19)

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(23)

(1)
(2)
(3)
(4)
(5)

described in this report.

Q Have you been involved at all in the registration
process for 2,4-D, to your knowledge?
MR. WAGNER: i object to the form of the
question.
A The only involvement that I would have had is to
supply p rocess descriptions to the individuals who
actually - who prepare for reregistration
packages, and I have provided information on
occasion to those individuals.
Q Let me see if I understand this, process _________________
Page 81

description for reregistration packages, what
would that entail?
A Well, the reregistration - a small piece of the
reregistration process or package is to describe
the chem ical process for producing the product.
And I would - 1have in the past provided
information to that. I can ’t give you specific
dates off the top of my head when I’ve done that,
but I know I’ve done that.

(6)
(7)
(8)
(9)
(10) Q Did you do that in connection with 2,4-D?
(11) A Yes.
(12) O Can you give me an approximate time period when
(13)
(14)
(15)
(16)
(17)
(18)
(19)

you did that with respect to 2,4-D?
A Early to mid eighties time frame.
Q Can you tell me what individuals you dealt with,

in other words, who you furnished these process
descriptions to for the reregistration package?
A I don’t specifically recall at this time.
Q Was there a particular department that dealt with

(20) the registration process?
(21) A The ag chem icals product department did that, so
(22) it would be an individual in that department.
(23)

Q Is that department presently located in any______________

Page 82
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specific building?
A Weil, since the formation of DowElanco, the
organization is now very much different than it
was during the time we’re talking about here. All
of the activities that were out of the 9001
building and 9008 building are now here in
Indianapolis with DowElanco.
O Have you ever had any input into the labeling

process for 2,4-D?
A No.
0 Do you know whether the 2,4-D label ever reflected

the impurities that you found in your report of
October of 1978?
A Not to my knowledge.
O Do you know whether the 2,4-D label ever reflected

any impurities found in the product prior to
October of 1978?
MR. WAGNER: I object to the form of the
question, over broad.
A Not to my knowledge
Q Would the agricultural products department also

have responsibility for labeling,
to your
knowledge?__________________________________________________
Page 83
A I can’t answer that specifically, but I would
assum e yes.
0 Do you know, for example, back in 1975, any

individuals' names who might have had that
responsibility?
A No, I don’t - I don’t know any names sin ce that

was far removed from my involvement in the

(8)
P)
(10)
(11)
(12)
(13)
(u)
(15)

project.
O Back in 1975, and I apologize if I asked this

06)

MR. WAGNER: It was asked and answered.
I don't think he remembered it.
MR. SCHULER: I think he mentioned
Mr. BrusL
MR. WAGNER: That’s right.
A I did happen to think of one more individual, a
gentleman by the name of Quentin Hutchcroft.
Q Is he still with the company, Mr. Hutchcroft? ______________
Page 84
A No. He left the company many years ago. He w as a
colleague of mine, and he and I worked together on
an aspect of the process.
Q Anyone else that you recall?
A That's the only additional person that I can
recall that I didn’t mention earlier.
Q / think you testified that you, maybe I

(17)
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(22 )
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question or a version of it earlier, but I want to
be clear about this, back in 1975, besides
yourself, who else, if anyone, in the agricultural
chemical process or products research section had
responsibility for any aspect of the 2,4-D
research?

misunderstood you, but I want to be clear about
this, you haven't done any further research on
2,4-D after this 1978 project, is that correct?
A I was - 1w as the process chemist responsible for
2,4-D process research until approximately 1983,
1984, timefram e. I think you asked the question
in the context of specifically this report that we
have been discussing, and O Yes.
A - and to the best of my knowledge, I’ve not done
any work since that report.
J
Q When you say work since this report, you were
f

responsible, but there was no, once the process
got up and running, there was no further research
from your department on the 2,4-D process or
2,4-D, itself? ______________
______

XMAX

KARL KRÜMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

BSA

Page 85
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MR. W AGNER: I object to the form of the

(1)

question.
A Oh, yes, oh, yes.
O Can you give me an idea of what other research was

(2)

done on 2,4-D after October of 78 up until '83?

(5)

A We were - well, we did some further research on a
modified process over what was described for, I
think we discussed the plant in Aratu, Brazil,
there w as process research done in that area.
There w as process research done in the area of
other trace impurities in the process. We were
doing a lot of work during those days in the area
of related - related to waste brine treatment
clean up. Those are three key areas that I can
recall.
O Wasfe brine being a by-product of the process?
A Y es, one of the by-products of the p rocess w as an
18 to 20 percent sodium chloride stream.

Q And what else, anything else comes to mind?
A Those are the key areas of our research, and
continued support of the process. When plant
problems crop up now and then, and these can be
any one of a number of different things, that___________
Page 86
we’re constantly asked to provide technical
support to the plant, to the manufacturing staff.

O Have you done any research with regard to 2,4,5-T
or Silvex since 1975?
A Yes.

Q And can you give me some examples of research
you've done and the time period it may have
occurred?
A In addition to the 2,4-D acid process that w as run
in 489 building, we did have a process that
produced 2,4,5-T and 2,4,5 - well, Silvex esters.
We called that the direct ester process. And,
y es, I w as involved in sampling and evaluating
results in the areas of 2,3,7,8 TCDD and other
polychlorinated dibenzo-para-dioxins, and we did
som e research in that time frame about further
reducing those impurities from our product.

Q And when you say that time frame, you 're referring
to 1975,1976, somewhere around there?
A The peak time frame of 1975 to 1979, when the
direct ester process was shut down.

Q Did you generate reports?
A Yes.____________________________________________________________
Page 87

Q On that?
A Y es.

Q Do you have any of the reports with you today?
A No, sir.
MR. SCHULER: Are you taking the
position that Dow has them, and he doesn’t have
them, that's why you're not producing it?
MR. WAGNER: Correct, they're not his
reports.

Q From 1975 through 1979, did you find the presence
of TCDD in either Silvex or 2,4,5-T end product?
A Yes.
Q And do you recall at what levels you found it?
A Typically the levels could range in the .03 to .07
parts per million of 2,3,7,8 TCDD.
Q Was there a fluctuation from batch to batch?
A Yes.

Q Did you ever find the presence of TCDD at a higher
level than . 07 parts per million in any batch that
you sampled?
MR. WAGNER: I object to the form of the
question.
A I don’t recall specific data. When I tell you the_________

(3)
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Page 88
.03 to .07, those are ranges that I recall that we
would see in the product in that mid-1970 time
frame.
0 Can you give me a rough idea how many reports were

generated about that subject matter, the finding
of TCDD or other dioxins in 2,4,5-T or Silvex?
A I couldn’t give you an exact number or even a
close number at this point.
Q Those reports, I assume, were written and used for

intercompany purposes?
MR. WAGNER: I object to the form.
A Certainly anything that I wrote that would have
summarized results would have been done for
intercompany purposes. What happened to the data
beyond that point, I can’t comment.
0 Who else worked with you in this particular

analysis or research into the presence of these
dioxins in those end products?
A Well, Mr. Arnold would have provided technical
support, laboratory support to me. Mr. Siegel
that we mentioned earlier, has done work in that,
during, again, this 1975-1979 time frame.
Q Other than Mr. Arnold and Mr. Siegel, anybody else
Page 89

that you can recall?
A Not that I recall specifically at this time.
Q Was this, for lack of a better term, kind of a

continuing monitoring process when you tested
these chemicals for the presence of TCDD or other
dioxins?
MR. WAGNER: I object to the form of the
question.
A Right.
Q How frequently would you test these products for

the presence of those contaminants?
MR. WAGNER: I object to the form of the
question.
A In our direct ester process, I don’t recall the
frequentcy that we did at that time. This w as a
quality control lab, analytical lab function that
I w as only off on the periphery of with a c c e ss to
the data.

Q When you say the direct ester process, would you
also test the amine version of 2,4,5-T?
A I don’t recall that we produced an amine form of
2,4,5-T at that time.
Q What about Silvex, was that tested? ________________________
Page 90
A The Silvex esters would have been tested, a s would
the 2,4,5-T esters.
Q The amine formulation of 2,4,5-T was not

manufactured by Dow, you're saying from 75 to
79?
MR. WAGNER: I object to the form of the
question.

Q Or did I misunderstand you?
A I don’t recall that we manufactured the amine form
of those compounds at that time.
0 At some earlier time did the company do that, if

you know?
A Not that i know of specifically.
O Where would these records be kept from your

testing of these end products for TCDD or other
dioxins?
A Well, the records we’re talking about are records
that were generated, a s I said before, by ¿he
quality control labs and by the analytical lab, so
it would be within whatever, wherever their
documentation is maintained.
Q Would that be in the plant or some other place, if

you know?____________________________________________________

XMAX

KARL KRUMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10, 1993

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0)
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Page 91
A Some would be in the plant, and some would be
within our central reporting index.
MR. WAGNER: Was your question directed
to today or back then, Dick?
MR. SCHULER: During the period of 1975
to 79.
THE DEPONENT: Yes, that’s when I was
answering.
MR. WAGNER: I thought so.

Q During the period from 1975 to 1979, do you know

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A It would have been in that magnitude, but a
sp e cific num ber, I just don’t rem em ber.

(8)

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(16)
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0 Were there other locations back at that time that

1979 was furnished to the government with regard
to the dioxin contents of those end products?

(is)
(19)

A T h e su b sid ia ry produced 2,4-D for Dow in New
Zealand, Ivan W atkins Dow, W-A-T-K-l-N-S.

MR. WAGNER: Same objection.
A I am not aware specifically of Information that
w as submitted to the government on that subject.
Were you involved in the decision to shut down________
Page 92

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(22 )
(23)

Q Any other locations around the world?
MR. WAGNER: In 1975?
Q Yes, the 75-76 time period.

Q

production of Silvex and 2,4,5-T?
A No, I w asn’t.

Q Do you know who was involved in that decision?
A The managers of ag production and of the product
department w hose nam es - who the specific
individuals that would have met to make that
decision, I couldn't answer at this time.

Q Do you know who the individuals were that may have
been involved in making the decision?

A No. O nce the process w as shut down, it was shut
down, and being an organic chemist working in
research, I had no Involvement In the project.

Q Were you aware, between 1975 and 1979, of any

(17)
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(19)

hearings that were ongoing with regard to what's
known as a rebuttable presumption against
registration for either Silvex or 2,4,5-T?

(20)
(22)

A I knew about them, but I had no involvement in
them, and I couldn’t - don’t recall any of the
specific details at this time.

(23)

Q You don't recall furnishing any information that
was used in the course of those hearings?
A No, sir, no specific information that I recall.
MR. WAGNER: Let’s take a quick break.

W

(R ecess .)

(5)

BY MR. SCHULER:

(6 )

Q Back in 1975, was the 2,4-D that was manufactured

(7)

by Dow Chemical primarily sold in its amine form?

(8 )

MR. WAGNER: I object, no predicate as
to personal knowledge.
A It w as sold. I can’t comment a s to whether it was
sold primarily a s the amine formulation. We
certainly sold a significant quantity of it a s the
amine formulation, but I don’t know the balance of
esters, am ines and acids sold.

(9)
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(H )
( 12)

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O Do you have any knowledge of the total amount of
2,4-D sold on an annualized basis, for example,
back in 1975 and 1976?

produced the chemical on behalf of Dow?

A No. T h o se w ere it, th o se w ere the facilities.

Page 95

(5)

Q Do you know, and again, if you don't know this
information just tell me and I'll move on, but do
you know in what units the chemical 2,4-D was sold
in 75 and 76? In other words, was it sold by
the ton, by the pound, by the gallon?

(6)
(7)
(8)
0)
(10)

A It w as sold in a variety of different co n tain e rs;
g allons, five g allon s, 55-gallons, tan k c a rs ,
different p roducts w ere sold in different
co ntain ers, sp ecifically, you know, the sp e cific
b alance.

(11 )
(i 2 )
(13)
(u)

Q In 1975 and 1976, would you be aware of what the
five gallon container looked like?

(1)
(2 )
(3)
(4 )

MR. WAGNER: For?
MR. SCHULER: 2,4-D.

(15)

A A m ines, e s t e rs ?

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(19)
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O Amines.

(2D

(22 )
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Page 93

(3)

had, back in 1975 and '76, that produced 2,4-D
other than those?

Q Do you know whether any information from 1975 to

have any role in shutting down of the process?

(2)

Q Were there any other buildings that Dow Chemical

A No, sir. T h o se w ere the only p la ce s it w a s
produced at that time.

Q Did you have, once a decision was made, did you

( 1)

or not?

(u)
(15)

(12)

(2 1 )

A i d o n ’t r e c a l l t h a t n u m b e r a n y m o r e .

O Do you know if it was similar to the 948 building

MR. WAGNER: I object to the form of the
question.
A I don’t know.

(11)

(15)
(16)

(4)

(5)
(6)

MR. WAGNER: In Midland?
0 In Midland, yes.

A I can ’t give you a specific name.

(14)

Q What did building 489, what was its capacity, if
you know?

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A Y e s.

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whether there was any listing on the labels for
2,4,5-T or Silvex that those products contained
either TCDD or any other dioxin contaminants?

(11)

XMAX

Page 94

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MR. WAGNER: I object to the form of the
question, not specific.
A I h ave s e e n the c a n s , but after 17 y e a rs , to
recall exactly what w a s on the ca n and how it
looks, I don ’t.

0 Were the cans metal or plastic back then?
A Metal.

_________________________________________________

Page 96
Q And do you recall the color of the cans?
A Not anym ore.

0 Same question for Silvex, would you recall the

color of the cans? Was it sold in cans?
MR. WAGNER: I object, compound, no
predicate.

(7)
(8)

A Silvex, I c a n ’t recall sp e cifically the w ay Silv e x
w a s supplied.

(9)
(io>

0 Same question with regard to 2,4,5-T?
MR. WAGNER: Same objection.

(11)

A And the sa m e an sw e r a s for Silvex.

(12)
(13)

Q Do you know what the unit price was for a

(u)

A No, I don ’t rem em ber that.

(15)
(16)

O Who would know that information?

(17)

five-gallon can of 2,4-D back in 75 and 76?

A That would be information that would av a ilab le
fr o m th e c o m m e r c ia l fu n c tio n .

(18)

O Agricultural products division ?

(19)

A I couldn’t give you a number from personal
knowledge. It would be speculation.

A Y e s - well, D o w EIanco now, if th o se re co rd s stijf

(20 )

0 You mentioned that the, in your report that we

(19)

(20 )
e x is t .
(21 ) Q Do you have any opinions with regard to the
(22 )
toxicity of 2,4-D as it applies tc human beings?
(23)_______________ MR. WAGNER: No predicate as to

(2 1 )

( 22 )

(23)

marked as Plaintiff's Exhibit 2, that this 948
building at capacity could crank out 100 to
120,000 pounds a day, correct? ________________________

i

KARL KRUMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10, 1993

BSA

Page 97
(1)

expertise in that area. You mean his opinion

(2)

today?

P)
(4)
(5)
(6)
(7)
(8)

MR. S C H U L ER : Yes.
MR. W AGNER: Weil, the question is
whether or not you have an opinion. Go ahead.
A Well, a s an o rg an ic chem ist, not trained in
toxicology, I don’t feel I ca n render an opinion
on that.

(9)

O Have you participated in any other, had input in
any reviews that the EPA has instituted with
regard to the safety of 2,4-D?

(1 o)

(11)
(12)
(13)
(u)

(is)
(16)
(17)
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MR. W AGNER: I think it's been asked and
answered.
MR. S C H U L E R : I asked about Silvex and
2,4,5-T before.
MR. W AGNER: You're correct.
A I’m sorry, with the d ialog s MR. S C H U L E R : Could you read that back.

(19)

(The requested material was read by the

(20)
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(22)
(23)

REPORTER.)
MR. W AGNER: I object to the form.

(1)
(2)
(3)

(4)
P)

A No.

Q Back in 1975 and 1976, were you aware of any__________
Page 98

published literature that, I know you're not a
toxicologist, but I'm asking you in your capacity
as a scientist, were you aware of any published
literature with regard to the potential for
carcinogenicity of 2,4-D or Silvex?

(1)
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A F o r the potential of carcino genicity, no.

(7)
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Q Same question with regard to 2,4-D, same time
period?

(9)

A No.

(5)
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0 Do you, yourself, subscribe to scientific journals

(10)

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other than what may be available to you in the Dow
library?
A A s a m em ber of th e Am erican C h em ical Society^ I
re ce iv e their w eekly publication, C h em ical and
Eng ineerin g N ew s. O therw ise, all
of the
scien tific Journals that I read a re provided to me
through Dow.

Q Do you know a fellow by the name of Leonard or Len
Smith?
A Y e s.

Q And what is his position or was his position at
Dow?
A I d o n ’t know w hat h is position w a s at the time,________

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Page 99
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o v e r th e tim e fram e that w e’re talking about here.

Q Is he still with the company?
A H e ’s with D o w Elan co .

(1)
(2)
(3)

(4)

Q Here in Indianapolis now?

(4)

(5)
(6)
(7)

A Y es.
O Do you know what his position is?
A H e ju st m oved, an d I forget h is new title.

(5)
(6)

(8)
(9)
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(11)

Q When you were doing your analysis as reflected in

(12)
03)
(14)

A Y e s , I did. I u se d th e standard, good laboratory
p ra ctic e s that w e follow in our department.

(8)
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your report o f October of 1978, did you take
hygienic precautions in dealing with those
chemicals that are outlined in that report?
Q What kind of precautions did you take back in

1977-78, when you were working on this report?
A L ab coat, im p ervious rubber g lo ves, g la s s e s ,
g o g g les, all of o ur work w a s performed in a
properly ventilated hood, the standard precautions
that w e take with toxic and h azard o u s chem icals.

Q Do you wear any special type of pants, for
example, or does the coat come down pretty A It w a s a typ ical knee-length laboratory coat.

Q And do you wear any type of special shoes or boots ____

XMAX

Page 100

(7)

(19)

(20 )
(2 1)
(22 )
(23)

or anything like that?
A No.
0 When you say you work in a ventilated laboratory

hood, what does that look like?
A The typical laboratory hood is a bench top,
perhaps typically they’re six feet wide, about 30
inches deep, with air movement sweeping acro ss so
that we’re adequately protected.
Q The fumes are sucked up into the exhaust, if you

will?
A Yes.
0 Did you ever wear a respirator in dealing with any

of the materials outlined in your October 78
report?
A No.

Q Other than the research that we Ve discussed here
today involving 2,4-D and 2,4,5-T and Silvex, have
you done any other research with respect to those
chemicals that we haven't discussed here today or
touched on in your testimony?
MR. WAGNER: I object as to breadth.
A Yes.
Q What type of research? _______________________________________
Page 101
A Well, notably we did some research in the 2,4,5-T
area where we learned how to further reduce the
quantities of dioxins from the product. I think I
gave you numbers to the best of my recollection of
.03 to .07. We developed technology, again, I
can’t give you a concrete date, but in the ’77-78
time frame, to further reduce those levels in the
ranges of, again, a s best I can recall, .01, .02.
Q And what, do you recall the type of technology

that was developed or methods that were developed
to reduce the TCDD down to that level?
A The post treatment, prior to formulation, with
activated carbon.

Q I ’m not sure I understand - post final product A The technical product, before it is formulated
Into the final product, w as p assed through a bed
of activated carbon.
Q And the carbon helped to filter out some of those

impurities, at least down to that level?
A It removed the impurities down to this level of,
again, a s best I recall, .01, .02, .03, in that
range.
Q And to the best of your recollection, that would ___________
Page 102

have been in the 77 to 78 time period?
A Plus or minus a little, yes.
0 Who else would have worked on that project with

you?
A Sanford Siegel, in the laboratory.
O Who else would have been involved with that

project outside the laboratory as far as
implementation of the carbon filters are
concerned?
A That would have been, obviously, with the
engineers In the plant. Specifically who the
engineer or engineers were at this time, I don’t
recall.
O Was anyone from agricultural products involved

with that decision to approve the use of the
carbon filters, for example ?
A I don’t remember the decision p rocess tor specific
Implementation of all that.
|
0 But you were involved doing thelab work?
A I w as involved developing the technology, yes.

Q Any other research that you did with respect to
2,4-D, 2,4,5-T or Silvex between the 1975 and,
say, 1977 time periods? _________________________

________

217
V -3 5 0

KARL KRÜMEL, Ph.D.- Kimberty Moyer Vs. Dow Chemical - March 9-10,1993

BSA

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Page 103
MR. WAGNER: That he hasn't touched on?
MR. SCHULER: That he hasn't mentioned
already, of course.
A We have touched on a number of topics at various
times. I think we have covered them all.

(2)

A Yes, I do.
O When do you anticipate, if you do, retiring from

(3)
(4)
(5)

A I have no plans for retirement at this point.
0 Prior to coming here to this deposition today, did

( 1)

Q Let me just ask you about the documentation. Do
you have a CV, curriculum vitae, summarizing your
educational background, experience, training in
your profession?

(6)

A No. I haven’t had a resume prepared since MR. WAGNER: He's not been job hunting.
A - like almost 28 years.

( 10 )

Q You haven't looked for a job in a long time,
that's right. Okay, in the notice of taking
deposition I had, and by the way, you spell your
name, K-A-R-L, correct?

(13)
(14)

A Y e s, sir.

(17)
(18)
(19)

Q In the notice of deposition I had asked you to
produce any and all documents produced by you or
at your direction during the course of your
employment with Dow Chemical Company or its
subsidiaries that pertain to any research,
analysis, formulation, study or production of the________
Page 104
chemicals 2,4-D, 2,4,5-7, Silvex or any product or

substance containing these chemicals or any
ingredients used in making these chemicals or any
contaminants or dioxins contained in any of these
chemicals or their ingredients.
Today you produced no documents,
correct? You gave me the October of 78 report
that I already had. Did you bring any of those
documents with you here today?
A Well, all the documents are owned by the Dow
Chem ical Company. I have no documents that are
owned by me.
Q So the answer is, you did not bring any of those

(7)
(8)

(9)
( 11 )
( 12)

(15)
(16)

( 20 )
( 21 )
(22 )

(23)
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(2)

(3)
(4)
(5)
(6)
(7)
(8 )

(9)
(10)

( 11)
(12)

(16)

A That’s right.
0 You have not served, I understand from your

(13)
(14)
(15)
(16)

(17)
(18)

earlier testimony, as an expert witness in any
case, correct?

(17)
(18)

(19)

A Correct.
O You have not issued any documents, reports,

(19)

(15)

(20 )
(21 )

22)

(

(23)

documents here with you today?

articles or transcripts relating to any opinion
you might have ever formed regarding the cause of
soft tissue sarcoma or the toxicology or health_________

(20 )

(2 1)
( 22)

(23)

Page 105
(1 )
(2 )

(3)
(4)
(5)

(6)
(7)
(8 )

(9)
(10)
( 11 )

effects of 2,4-D, 2,4,5-T, Silvex, 2,4,5-TP or any
product or substance containing any of those
chemicals?
A No, sir.
Q You mentioned your status as, I think you told me

initially as senior scientist?
A My official title within Dow Chem ical Company is
an a sso ciate scientist.
0 Are there rankings within the company by title,

and you get certain income, kind of like the
military or an organized entity like that?

( 1)
(2)

(3)
(4)
(5)
(6 )

(7)
( 8)

(9)
( 10 )

( 11 )

( 12 )

A Y es.

(13)
(14)
(15)
(16)

Q So when you reach, you have a certain title, you
reach a certain level, you get a certain income
that goes along with that, would that be a fair
statement?

(13)
(14)
(15)

(17)
(18)

A Y es.
0 How long have you been with the company, the

(17)
(18)

(19)
(20 )

(2 1 )
(22 )

(23)

number of years?
A I joined the company in June of '65, so that puts
me at 27 years, nine months.
0 Do you intend on staying with the company for the

time until retirement?

XMAX

Page 106

( 12 )

(16)

(19)
(2 0 )
(2 1 )
( 22 )

(23)

the company?
you review any documents, other than obviously the
document we have marked as Plaintiff's Exhibit 2?
A I reviewed one other letter that Allen showed me
that was essentially a letter written by my
manager at the time, I don’t remember the exact
date on that letter, to an analytical manager
telling him we were going to be providing him with
some sam ples for analysis for various chlorinated
dioxins. Those are the only two documents that
I’ve specifically reviewed for this deposition.
O Who is your manager who wrote that letter?
A That w as Dr. Mintz, Michael Mintz.
Q What was the date of that correspondence?
MR. WAGNER: I think he said he didn’t
remember.
A I don't remember the specific date. It would have
been in the period of, around 1976, plus or minus
a little.____________________________________________________________
Page 107

Q Prior to the time of this report that we have
marked a s Plaintiff's Exhibit 2?
A Yes.
MR. SCHULER: Did you have a copy of
that? Can I see a copy of that?
MR. WAGNER: No.
MR. SCHULER: You have a copy present
here today? You’re just not going to let me see
it?
MR. WAGNER: I don't know if it's
present in this room.
Q When did you see the document?
A I saw it yesterday.
MR. SCHULER: For the record, I request
a copy of the document. The copy of the
document's been refused and MR. WAGNER: What's the basis that I
would have to give you that document?
MR. SCHULER: Because I asked it be
produced here today.
MR. WAGNER: It's a Dow document. It's
not his document. If you would like documents
____________from Dow, send me a request to produce.___________
Page 108
MR. SCHULER: Well, I understand the
position that you've taken, but I disagree with it
100 percent, and particularly when the document is
present here today and could be discussed with
this witness. To refuse to produce it, I think is
a violation of this request, and I’ll seek court
relief on that. I have no further questions,
thank you.
MR. WAGNER: Before we let Aprille go,
let’s make this part of the record. Larry
Silverstein faxed the statement which turns out to
be an affidavit that he signed. That’s my only
copy. It was delivered here this morning, so
let’s mark it as an exhibit. From my review it
does not contain any information that you didn't
cover with him yesterday.
Why don't you take a minute to review
it, if you want. We could probably have him£ome
over and answer questions about it, but as Ijfeay,
from my review of it, I think all those areas that
were mentioned were covered.
MR. SCHULER: Well, I'm not - I can't
____________take a look at this. I mean, we had his_______________

BSA

( 1)

(2 )

(3 )
(4 )
(5 )
(6)

m
(8)

(9 )
(10)
( 11)
( 12)

(13 )
(14 )
(15 )
(16 )
(17 )
(18 )
(19 )
(20)

(21)
(22 )
(23 )

(1 )

_______ KARL KRUMEL, Ph.D.- Kimberly Moyer Vs. Dow Chemical - March 9-10,1993

XMAX

Page 109
deposition yesterday. This wasn't produced, and
I’m taking the position that it was wrongfully
withheld.
MR. WAGNER: Well, he didn’t have it.
MR. SCHULER: Well, he was requested to
produce it.
MR. WAGNER: I know he was requested,
and I know it’s here now. If you want him, I'll
get him on the phone and see if he can come out
here.
MR. SCHULER: That's not good enough for
me. I was taking his deposition yesterday, and
I’m handed a four-page document with 16 paragraphs
today, and I’m not going to be put in that
position of doing this now, and when it wasn’t
produced when it should have been produced, and
asking him questions about it. We’ll mark it for
the purpose of discussion, since we talked about
it at this deposition, as Plaintiff’s Exhibit
Number 5.
(Plaintiff’s Exhibit 5 w as marked for
identification.)
MR. SCHULER: Is that it?__________________________________
Page 110
MR. WAGNER: No questions.
AND FURTHER THE DEPONENT SAYETH NOT

(2)

KARL KRUMEL, Ph.D.
(3)
(4 )
(5 )
(6)

(7)
(8)

(9 )
(10)
(11)
( 12 )

( 13 )
( 14 )
( 15)
(16 )
(17 )
( 18 )
(19 )
(20)
(21 )
(22)
(23 )

(1 )
(2)
(3 )
(4 )
(5 )
(6)
(7)
( 8)

(9 )
( 10 )

111
STATE OF INDIANA)
) ss:
COUNTY O F MARION)
I, Aprille Rigsbee Lucas, RPR, Notary
Public in and for the County of Marion, State of
Indiana, do hereby certify that the deponent
herein was by me first duly sworn to tell the
truth, the whole truth and nothing but the truth,
in the aforementioned matter;
That the foregoing deposition was taken
on behalf of the Plaintiff;
That said deposition was taken at the
time and place heretofore mentioned between the
hours of 8:00 a.m. and 6:00 p.m;
That said deposition was taken down in
stenograph notes and afterwards reduced to
typewriting under my direction and thereafter
presented to said witness for signature; that this
certificate does not purport to acknowledge or
verify the signature hereto of the deponent;
I do further certify that I am a
disinterested person in this cause of action; that
I am not a relative or attorney of any of the_________
Page 112
parties, or otherwise interested in the event of
this cause of action, and am not in the employ of
the attorneys for any of the parties.
IN WITNESS WHEREOF, I have hereunto set
my hand and affixed my notarial seal this 15th day
of March, 1993.
Aprille Rigsbee Lucas, RPR
My Commission Expires:
September 21,1996__________________________________

i

218

DANIEL THAU TEITELBAUM. M.D.
CLINICAL TOXICOLOGY
DRAWER 1070
P.O.B. 22557
DENVER, COLORADO 80222
p

-O J& H

I

4

V *-

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J

THE

DOW

CHEMICAL

COMPANY
IM S T O W

lU I L Q lN C

2030 OOW CCJ/rtA
M O L A M O . M «C h i C A M

4M A O

June 15, 1970

C

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<
»2b
to
»2b
C5

The Honorable Kelvin R. Laird
Secrecary of Defense
The Pencagon
Washington, D. C.

»

-

LO

t

\'

r :

Sir:
Subject:

!

Defoliants for che Desarroen: of Defense

Several weeks ago the Department of Defense announced the
temporary suspension of the use of Agent Orange (a mixture
of the n-butyl esters of 2,4-dichloroohenoxyacetic acid
and 2,4,5-crichlorophenoxyacetic acid) as a defoliant in
Southeast Asia. It has now come to our attention that the
use of Agent Orange may be «instituted.
There is abundant evidence chat 2,3,7,S -tecrachlorccibentop-c'ioxin occurring as an impurity in 2,4,5-T is highly
toxic. 2,4,5-T can be produced chat contains only minute
quantities of this impurity (less than one part per million),
and such a product is available to the government from various
sources. We at Dow are convinced chat 2,4,5-T containing less
than one part per million of 2,3,7,5-cetrachlorcdibenco-p-_
dioxin can be used safely. Certainly such a product is safer
in use than one containing larger quantities.
The Dow Chemical Company again recommends strongly that the
government sec appropriate specifications and controls to
insure that no 2,4,5-T be used if it contains more than one
part per million 2,3,7,8-tecrachlorociber.to-p-cioxin. More
specifically, we would make this recommendation with respect
cc the use of 2,4,5-x as a component of Agent Orange if it is
to be used as a defoliant in Vietnam. Such specification
should apply to stocks on hand as well as new procurement.

E X H I B I T II

\

(

i
r

»

l

i
I

b

-,

The Honorable Melvin R. Laird

Because of our scroag feelings in this xac:er, ve are
log copies of chls letter co chose listed below.
Dr. Lee A. DuBridge
Science Adviser to the President
The Honorable Clifford M. Bardin
Secretary of Agriculture

VCdVZV MOO

Page 2

The Honorable Elliot Richardson
Secretary of Health, Education, and Welfare
The Honorable Walter J. Hickel
Secretary of the Interior.

Yours very truly

Vice Présider

GJW:la

Í

UNITED STATES DISTRICT COURT
EASTERN DISTRICT OF NE W YORK

IN RE

M D L No. 381
(all cases)

"AGENT ORANGE"
Products Liability Litigation

ADDENDUM TO PLAINTIFFS'MEMORANDUM ON
THE APPLICABILITY OF THE LEGAL THEORIES
OF FAILURE TO WARN, CONCERTED ACTION,
ENTERPRISE LIABILITY AND ALTERNATIVE
LIABILITY

Plaintiffs submit the following material which was
inadvertantly omitted from their Memorandum and. should be
inserted after Page 15.
In a Dow document entitled "Report on the Chloracne
Problem Meeting on 3/24/65", dated March 29, 1965, it is clear
once again that all the participants at that meeting were fully
apprised of the fact that the

2,4,5-T they were manufacturing

was contaminated with dioxin.

It is further patently clear that

the method available for the detection of dioxin was completely
explained as well.

Expressed at that meeting was a serious

concern that the users of the finished contaminated product
were at greater risk than the plaint 2,4,5-T workers in view of
the fact that the multitude of safety precautions

by workers

j
were not available to them.

L. G. Silverstein, of the Biochemical

22.

Research Laboratories at Dow specifically recalled the afore­
mentioned concern and stated in that report at the bottom of
Page 4 that:
"The question of specification, quality
control specification that is, was raised
and we were asked if we could give levels
of dioxin contamination which were permissible
limits. V. K. mentioned that at present we
are using zero with a confidence of 1 ppm
in process samples. There was some discussion
on the problem of customers using finished
products under far less desireable conditions
of health control that we can provide our
workmen in our own plant."
Mr. Silverstein, in that document, further went on to state on
the bottom of Page 4 that:
"There seemed to be agreement among the
group that we could not afford to sell
contaminated products."
Thus, it is clear that by the end of that meeting, the represen­
tatives of Hooker Chemical Corporation, Diamond Alkali Company,
Hercules Powder Company and Dow knew full well that the products
they manufactured, which contained dioxin, should not be sold, yet
chose to disregard this knowledge when they proceeded to sell mass
amounts to the United States Government.
In a postscript to the aforementioned document, V. K.
Rowe stated:
"All participants seemed to appreciate
well the problem and all indicated that they
would return home and attempt to convince their
management to institute safety specifications
(really quality control) for their various
products in this area. All agreed that the
industry should meet its own responsibility. <
All were very appreciative of Dow's effort to/
steer them away from a danger area. Time will
tell whether we accomplished our mission, but
as of now I feel satisfied with our effort and
the reception it received."
-

2

225

-

£

b U'
2 *

Appended.hereto is a copy of the aforesaid document
entitled "Report on the Chloracne Problem Meeting on(r3 / 2 4 / 6 4 ^
dated 3/29/65 and authored by L. G. Silverstein, Biochemical

"A ret
1&HSI

Research Laboratory as Exhibit 1.

atu)
<

Plaintiffs respectfully submit the following information
which was omitted from its Memorandum because at the time of filing
we were not in possession of the transcript hereinafter referred
to.

The material which follows should have been inserted at the

end of Page 30b.
The Deposition of Robert R. Rumer, who was the Vice
President of the Monsanto Agricultural Chemical Division from
1965 to 1969 and also served as the General Manager of that same
division from 1964 to 1969 was held on November 18, 1983. (T-112)
Itjwas-1-earned that somewhere between 1965 arid 1967, Mr. Rowe
contacted Mr. William Allen,7 the individual in charge of Dow's
Agricultural Chemicals operations, (T-91), to ascertain if
"... Dow would be willing to sell or license Monsanto information
from Dow's process know-how to redice the impurities in the
trichlorophenol and produce a higher quality product. (T-88J
Mr. Allen flatly refused to share with Monsanto the knowledge,
they had regarding how to reduce the dioxin in Monsanto trichloro- ,
phenol because "... it wouldn't be in their interest." (T-91,92)
Thus, it is obvious that Dow, who was willing to share
the wherewithall to detect the level of dioxin contamination in
2,4,5-T, chose not to share with its competitors the means with

f

which to reduce the dioxin level of its competitors product.
-3-

v

Appended hereto are Pages 112, 91, 92, 88, 89 and 90
of the deposition of Robert R. Rumer taken on November 18, 1983,
as Exhibit 2.
Dated:

December 5, 1983
Respectfully submitted,

)
/

/

Plaintiffs' Management Committee
By: David J. Dean

Stephen J. Schlegel, Esq.
Benton Musselwhite, Esq.Thomas Henderson, Esq.

J

?27
*9

UNITED STATES DISTRICT C OURT
EASTERN DISTRICT OF NE W YORK

In re
"AGENT ORANGE"

MDL No. 381
(all cases)

Product Liability Litigation

ADDENDUM TO PLAINTIFFS' MEMORANDUM ON
THE APPLICABILITY OF THE LEGAL THEORIES
OF FAILURE TO WARN, CONCERTED ACTION,
ENTERPRISE LIABILITY AND ALTERNATIVE
LIABILITY

December 2, 1983
PLAINTIFFS' MANAGEMENT COMMITTEE
STEPHEN J. SCHLEGEL, ESQ.
Schlegel & Trafelet, Ltd.
One North LaSalle Street
Suite 3900
Chicago, Illinois 60602
BENTON MUSSELWHITE, ESQ. ''
Suite 517 - 609 Fannin
Houston, Texas 77002
THOMAS HENDERSON, ESQ.
Baskin & Sears
Frick Building
Pittsburgh, Pennsylvania 15219

228
V

U N I T E D STATES DISTRICT COURT
E A S T E R N D I S TRICT OF NE W YOR K
------------------------------------------------------------------------------ :-------------------------------- x

In Re
"Agent Orange"

MD L No. 381
(All Cases)

Products Liability Litigation
X

PLAINTIFFS’ MEMORANDUM ON THE APPLICABILITY
OF THE LEGAL THEORIES OF FAILURE TO WARN,
CONCERTED ACTION, ENTERPRISE LIABILITY AND
ALTERNATIVE LIABILITY

INTRODUCTION

Plaintiffs' Memorandum addresses the issue of whether

%

the legal theories of concerted action, enterprise liability,
or alternative liability may be applied here in the absence of
evidence enabling plaintiffs to identify which defendants'
tortious conduct caused the injuries complained of.

However,

plaintiffs do not solely rely on the aforementioned theories *

It is plaintiffs' position that:

(1) each defendant

breached its duty to warn the government of the dioxin hazards
to health known or which should have known by it to be

A

associated with its own dioxin contaminated

Orange

herbicide product and with the dioxin contaminated products
sold by the other defendants to the military;

j
t

■

(2) that

k .

229

X?

TABLE OF CONTENTS

Page
Introduction

i

FACTUAL BACKGROUND

1

I.

DEFENDANTS WERE KNOWLEDGEABLE ABOUT THE
MANUFACTURING PROCESS, DIOXIN AS A CON­
TAMINANT, DETECTION METHODS, RISK REDUCTION
METHODS AND HEALTH HAZARDS ASSOCIATED WITH
EXPOSURE TO DIOXIN
A.

B.
C.
D.

E.

F.

G.

H.

2

Prior to Becoming a "Government Contractor"
Dow had Invented, Patented, and Sold
Commercial Herbicides Containing a 50/50
Mixture of 2,4-D and 2,4,5-T

2

Dow was Knowledgeable About the Manufacturing
Process of 2,4,5-T and Its Toxic Impurities

4

Defendants were Knowledgeable About Detection
and Manufacturing Risk ReductionTechniques

25

Defendant Monsanto's Knowledge About
Manufacturing Process, Dioxin As Contaminant
Detection Methods, Risk Reduction Methods,
and Health Hazards Associated with
Exposure to Dioxin

29

Defendant Diamond Shamrock Corporation's
Knowledge About Manufacturing Process
Dioxin As Contaminant, Detection Methods,
Risk Reduction Methods and Health Hazards
Associated With Exposure to Dioxin

33

T.H. Agriculture and Nutrition'Company, Inc.
Knew About Dioxin as a Contaminant in 2,4,5-T
and Knew About Concomitant Health Hazards and
Failed to Warn the Military

40

The Military Was Uninformed of T.H.'s
Manufacturing Process and Its Capability
for Risk Reduction

50

T.H. Knew of Means For Detecting Dioxin And
Failed to Disclose Those Methods tQ the Military 53

U N I T E D STATES DISTR I C T COURT
E A S T E R N D I S T R I C T OF N E W YORK
------------------------------------ X

In Re
MD L No. 381
(All Cases)

"AGENT ORANGE"
Product Liability Litigation
---------------------- ------- X

PLAINTIFFS' MEMORANDUM ON THE
APPLICABILITY OF THE LEGAL THEORIES
OF FAILURE TO WARN, CONCERTED ACTION,
ENTERPRISE LIABILITY AND ALTERNATIVE
LIABILITY

December 1, 1983

PLAINTIFFS' MANAGEMENT COMMITTEE.
Mr. Stephen J. Schlegel
Schlegel & Trafelet, Ltd.
One North LaSalle Street
Suite 3900
Chicago, Illinois 60602
Mr. Benton Musslewhite
Suite 517 - 609 Fannin
Houston, Texas 77002
Mr. Thomas Henderson
Baskin & Sears
Frick Building - 10th Floor
Pittsburgh, Pennsylvania 15219

231

9

chloracne appeared at the Ingelheim plant and 18 cases appeared
at the Hamburg plant.

The problem became so serious that

production was halted at the Ingelheim plant in December of
1954.

In the spring of 1955, production was halted at the

Hamburg plant.

The plants were closed.

To test for toxicity in the plants, rabbits were
placed on each of the floors with the doors and windows
closed.

All the rabbits died within five days.

Autopsies

showed pronounced liver changes and liver necrosis.

By

June of 1955, Dr. K.H. Schulz of the University Skin Clinic in
Hamburg-Eppendorf had found that the "chloracne inciters" were
present in the phenol and the 2,4,5-trichlorophenolate
solution.

Dr. Schulz further determined that the

anisóle fraction was the carrier of the chloracnegenic
substance.

In 1956, Dr. Schulz identified the offending

substance as 2,3,6,7-tetrachlorodibenzodioxine.

Because C.H. Boehringer was having such difficulty
with chloracne in the manufacture of 2,4,5-TCP, it sought
outside help.

C.H. Boehringer was put in touch with Dow.

On January 27, 1955 Dow wrote to Boehringer,
"[Ejnclosing a data sheet describing the hazards due to
toxicity and precautions for safe handling and use of
j

i

2,4,5-tr ichlorophenol and answered seven specific questions?'
regarding experience in our own plant."

- 6 -

In the course of

1. C a u s t i c H y d r o l y s i s

a. A solution of caustic (believed to be
sodium hydroxide) in methanol was
formed;
b. The caustic and methanol were mixed
with tetrachlorobenzene;
c. The solution of caustic and methanol
and tetrachlorobenzene were placed in a
reactor under pressure and heat.
2. Preparation of Sodium Salt of 2,4,5-TCP
a. Distillation of methanol under heat;
b. Distillation of water under heat;
c. Driving off of trichloroanisole under
heat;
3. Coupling Sodium 2,4,5-tricholophenate and
Monochlorpacetic Ester

In 1945, Dow conducted the first rabbit skin test on
the trichlorophenol process material.

At that time the caustic

insoluble oil from the 2,4,5-TCP process was found to cause
acneform dermatitis on the rabbit's skin.

As early as 1945,

Dow knew that exposure to trichlorophenol process materials -•
could cause acneform dermatitis.

In 1952 Dow went from a "batch"

process to a "continuous" process.

By 1956, Dow learned of the

particular substance in the 2,4,5-TCP

and 2,4,5-T which was

responsible for the acneform dermatitis.
Knowledge of the toxic contaminant in 2,4,5-TCP was

,

learned by Dow from the C.H. Boehringer Sohn Company of
Germany.

In 1951, C.H. Boehringer began experimenting with the

production of 2,4,5-TCP. Between 1952 and 1954, 19 cases of serious

-5-

y

In the manufacture of its commercial 50/50 mixtures of
2,4-D and 2,4,5-T, Dow developed internal specifications.
Those specifications dealt with the manufacturing processes and
the compositions of the final products.

m

addition to product specifications, Dow developed "accepted
quality control procedures" and "quality requirements."

Prior to selling "Agent Orange" to the United States
Military, Dow was thoroughly familiar with commercial 50/50
mixtures of 2,4,5-T and 2,4-D.

Prior to selling "Agent Orange"

to the United States military, Dow had developed internal
specifications and quality control programs for the production
of commercial herbicides containing a 50/50 mixture of 2,4,5-T
and 2,4-D.

As the result of direct manufacturing experience

since 1948 of commercial products containing 2,4,5-T, Dow
developed a tremendous expertise with respect to that
particular phenoxy herbicide.
B.

Dow was Knowledgeable About the Manufacturing
Process of 2,4,5-T and Its Toxic Impurities
Though Dow has withheld as proprietary and confiden­

tial the specific manufacturing processes it utilized from 1948
to 1970, it is generally known that Dow produced 2,4,5-T
through the following process:
i

234
0

(
U N I T E D S T A T E S D I S T R I C T COURT
E A S T E R N D I S T R I C T OF N E W Y ORK
------------------------------:------------ X

In Re
"Agent Orange"

M D L No. J81
(All Cases)

Products Liability Litigation
X

PLAINTIFFS’ MEMORANDUM ON THE APPLICABILITY
OF THE LEGAL THEORIES OF FAILURE TO WARN,
CONCERTED ACTION, ENTERPRISE LIABILITY AND
ALTERNATIVE LIABILITY

INTRODUCTION

Plaintiffs' Memorandum addresses the issue of whether
the legal theories of concerted action, enterprise liability,
or alternative liability may be applied here in the absence of
evidence enabling plaintiffs to identify which defendants'
tortious conduct caused the injuries complained of.

However,

plaintiffs do not solely rely on the aforementioned theories4

It is plaintiffs' position that:

(1) each defendant

breached its duty to warn the government of the dioxin hazards
to health known or which should have known by it to be
associated with its own dioxin contaminated Aaer>+- Orange

j

herbicide product and with the dioxin contaminated products
sold by the other defendants to the military;

(2) that

235

B.

C.

The Facts and Circumstances of this Case also
Warrant the Imposition of Liability Upon the
Defendants Under the Theory of Enterprise
Liability

103

The Facts and Circumstances of this Case
Also warrant the Imposition Liability Upon
The Defendants under the Theory of
Alternate Liability

109

CONCLUSION

113

i

236

f.

President and Director of Research for Dow, gave a statement
before a subcommittee of the United States Senate Committee on
Commerce.

Mr. Johnson stated:

Since 1950 we have been keenly aware of the
possibility of a highly toxic impurity being
formed in 2,4,5-trichlorophenol as a side
reaction under conditions of elevated processing
temperatures..-We also knew that if the impurity
was present in the 2,4,5-trichlorophenol it could be
carried forward to the end product, 2,4,5-T.
A review of Dow's history of 2,4,5-trichlorophenol (hereafter

" 2 ,4,5-TCP") and 2,4,5-T production confirms that statement.
Dow began making 2,4,5-TCP in mid-1946.

In 1948, Dow

registered its first 2,4,5-T product under the Federal Insecticide,
Fungicide and Rodenticide Act.

Since 1948, Dow has manufactured a number of products
containing by volume (minus inert ingredients) a 50/50 mixture
2

of 2,4,5-T and 2,4-D.
50-50.

/

One such product was Brush Killer

Absent inert ingredients, that product contained a

50/50 mixture of 2,4,5-T and 2,4-D.

In

addition to Brush Killer 50-50, Dow also manufactured Brush
Killer LV 2-2, Tippon 2-2, Verton CE, and Veon Brush Killer,
each of which is approximately a 50/50 mixture of 2,4-D and
f

2,4,5-T.

I

2/

Dow patented Tippon 2-2 and Brush Killer 50-50.

"Agent Orange" was a 50/50■mixture of 2,4,5-T and 2,4-D.
-3-

I.

DEFEN D A N T S WERE KNOWLEDGEABLE ABOUT THE
M A N U F A C T U R I N G PROCESS, DIOXIN AS A CON­
TAMINANT, DETECTION METHODS, RISK REDUCTION
M E T H O D S AND HEALTH HAZARDS ASSOCIATED WITH
E X P O S U R E TO DIOXIN.

A.

Prior to Becoming a "Government Contractor,"
Dow had Invented, Patented and Sold Commercial
Herbicides Containing a 50/50 Mixture of
2, 4-D and 2,4,5-T___________________________

Dow admits to have known about a highly toxic impurity in
1/
2,4,5-T since 1950.
.On April 15, 1970, Julius E. Johnson, Vice17 The record suggests Dow's earlier knowledge.
1. ’ .1937--Four hundred (400) lumber workers using Dowicide H
(tetrachlorophenol), some of whom developed among other things,
comedones, cysts and pustules (chloracne), urinary disturbances,
skin leisons lasting seven years and marked hyperkeratosis;
2.

1937-- Twenty-one (21) workers at a Dow plant which manufactured
-tetrachlorophenol, some of whom developed the same symptoms as
the 400 lumber workers;

3.

1949-- Ten (10) workers exposed in Nordheim, W. Fahlen in the
manufacture of 2,4,5-TCP, some of whom developed neuralgic
pains, heart disorders and chloracne;

4.

19 49_-- One hundred seventeen (117) workers exposed in the manu­
facture of 2,4,5-T and 228 family members and medical personnel
dealing with the exposed workers, at a Monsanto plant in Nitro,
West Virginia some of whom developed chloracne, liver damage,
vomiting, papable liver and tiredness;
'
‘

5.

1954-- Thirty-one (31) workers at a C.H. Boehringer plant exposed*
in the manufacture of 2,4,5-TCP and 2,4,5-T, some of whom developed
liver damage and chloracne;

6.

1956-- Twenty-nine (29) workers in a Diamond Alkali (now Diamond
Shamrock) plant exposed in the manufacture of 2,4,5-T some of whom
developed porphyria cutanea tarda, hyperpigmentation and hirsutism;

and
7.

1964-- Forty (40) plus workers in a Dow plant in Midland, Michigan
’ exposed in the manufacture of 2,4,5-T, some of whom developed
chloracne and complaints of tiredness, weakness, and depression ■
with some reduction in hemoglobin and red cel counts. Some workers
with metaplastic changes were examined.
93R

-2-

F A C T U A L BACKGROUND

In order to address the issues of failure to warn and
applicability of the theories of concerted action, enterprise lia­
bility and alternative liability, it is necessary to review in his­
torical sequence, the factual record as it has been developed to date.
The record is far from complete, but enough is already known upon
which the Court may reach a preliminary judgment that the conduct,
transactions and relationships between the defendants (horizontal)
and between the defendants and the Government (vertical) are such as
to warrant a finding that defendants have breached their duty to warn
and that one or more of the above theories of liability are applicable
in this case.

It is likely that additional discovery will, -if any­

thing, buttress the appropriateness of applying these theories.

We begin the review of the historical record with an
examination of the knowledge and conduct of the defendant Dow
Chemical Company, a key player in the events which followed
and a linchpin connecting many of the horizontal and vertical
relationships between the defendants and the Government in
connection with the sale of the dioxin-contaminated Agent
Orange herbicides which caused plaintiffs' injuries.

Where necessary to present the full context of factual
statements in this part of plaintiffs' ~..uv, a limited number/of
documents have been appended which have previously been used as
exhibits or referred to in plaintiffs' prior submissions or in

239

depositions of the defendants and Government witnesses.
0

l il ^

^ ol

Instead, they conspired secretely and persistently to
deceive the military and other government agencies about the
matters hereinafter detailed which were of profound importance
to the health of American soldiers and to the national security
let alone to the American people generally.

The -defendants

used every device available to keep their dioxin problems
confined to their inner circle and to keep the military and
government agencies in the dark - secret meetings, confidential
documents, misrepresentations, half truths, suppression and
withholding of data and technology, task and trade association,
fronts and position papers, ad hoc committees, and a myriad
of other regrettable activités, which, if they had not occurred,
might have led to military decisions which would have prevented
the injuries inflicted by defendants.

The full story is

now told.

i

240.
iv

O

214

alternative liability, enterprise liability, and that, should
the Court deem it necessary to address the defendant identifi­
cation causation issue, the defendants may be held jointly and
severally liable under any of these three theories.
In the detailed factual background statement which follows,
a tragic hitherto unrecorded chapter of the Vietnam war is told
of the misdeeds of chemical war contractors which injured American
and allied soldiers.
The defendant chemical companies owned or controlled
virtually all of the Agent Orange herbicide production capacity.
They supplied to the military, the sole source purchaser
over 99% of the herbicides contracted for and received over 99%
of the purchase price paid. (Exhibit 1)
Each’of the defendant’s herbicides was contaminated with
dioxin, in varying degrees and violated their contractual
obligations to the military.

Each defendant knew its product

was contaminated and hazardous to human health.

Each defendânt

knew that the other defendants * herbicides were dioxin contaminated
and hazardous.

Each knew, with varying degrees of expertise, how

to eliminate or reduce the dioxin.

None ever warned the trusting,

less expert, military, or informed it of the dioxin problem and
the means of its avoidance or elimination.

iii

j*

each defendant's breach of duty to warn was a substantial
factor leading the military to decide to mix and deploy the
dioxin contaminated Agent Orange herbicides supplied by
defendants, which caused plaintiffs' injuries; and (3) that
consequently defendants are liable as tortfeasors -jointly
and severally for such injuries without any burden on the
part of plaintiffs to identify and prove which defendant caused
their injuries.

If this Court agrees that the defendants' breach of
their duty to warn carries such legal consequences, it need
not decide with regard to the failure to warn issue, whether
the theories of concerted activities, enterprise liability or
alternative liability need to be applied on the identification/
causation issue.

However, so that the Court may be in a position

to consider the legal implications of all these theories,
plaintiffs present herein a comprehensive historical record of
defendants' conduct in the manufacturing and sale of dioxin
contaminated Agent Orange herbicides to the military for use
in Vietnam, focusing on the realtions between the defendants
and with the military and other government agencies during the
period of the Vietnam era.
i

Plaintiffs believe that this historical record fully
supports any and all of the theories of concerted activities,

242
0
11

I.

T.H.'s Participation in the Conspiracy

J.

Thompson Chemical Was Knowledgeable About
The Manufacturing Process, Dioxin as a
Contaminant, Detection Methods, Risk Reduction
Methods, and Health Hazards Associated with
Exposure to Dioxin
56

K.

T.C. Knew that a Highly Toxic Impurity
Was in its TCP and 2,4,5-T

56

Hercules Incorporated Was Knowledgeable
About The Manufacturing Process, Dioxin
As a Contaminant, Detection Methods, Risk
Reduction Methods and Health Hazards
Associated with Exposure to Dioxin

59a

L.

II.

DEFENDANTS' MISREPRESENTATIONS OF THE SAFETY OF
THEIR HERBICIDES TO OTHER GOVERNMENT AGENCIES

III. THE DEFENDANTS SUPPLIED DIOXIN CONTAMINATED
HERBICIDES WHICH WERE MIXED TOGETHER BEFORE
BEING SPRAYED IN VIETNAM MAKING IMPOSSIBLE
IDENTIFICATION OF WHICH DEFENDANT’S HERBICIDE
CAUSED INJURIES TO PLAINTIFFS
IV

V.

DEFENDANTS' JOINT ACTION TO PREVENT GOVERNMENT
PRODUCTION OF 2,4,5-T and 2,4-D

55

60

73

75

THE MILITARY WAS NOT AS KNOWLEDGEABLE AS THE
DEFENDANTS A30UT THE MANUFACTURING PROCESS, DIOXIN AS
A CONTAMINANT, DETECTION METHODS, RISK REDUCTION
METHODS AND HEALTH HAZARDS ASSOCIATED WITH
EXPOSURE TO DIOXIN
77

VI. UNDER THE PRECEDING FACTS AND CIRCUMSTANCES, EACH
DEFENDANT'S BREACH OF ITS SEPARATE DUTY TO WARN
MAY BE CONSIDERED THE "CAUSE IN FACT" OF PLAIN­
TIFFS' INJURIES, AND THE PROBLEM OF SEPARATE
DEFENDANT IDENTIFICATION THEREFORE DOES NOT
EXIST; BUT IN ANY EVENT, THE DEFENDANTS MAY
BE HELD JOINTLY AND SEVERALLY LIABLE UNDER
THE THEORIES OF CONCERTED ACTION, ENTERPRISE
LIABILITY AND ALTERNATIVE LIABILITY
A.

The Facts and Circumstances Warrant Application
of the Concerted Action Theory as a Basis for
Defendants' Joint and Several Liability

82

96

243
O ' .3-

attempting to identify the cause of the chloracne, researchers
at C.H. Boehringer identified tetrachlorodibenzodioxine
in 1956.

As a result of C.H. Boehringer1s identification

of dioxin as the chloracnegenic agent in 2,4,5-TCP, C.H.
Boehringer instituted certain process changes to prevent the
formation of dioxin.
Since Dow had provided C.H. Boehringer information in
1955 concerning the chloracne problem, C.H. Boehringer sent to
Dow, on February 11, 1957, information on the preparation of
trichlorophenoxyacetic acid in a manner to avoid the formation
of "chlorakne exciters."
information was sent by C.H. Boehringer to all known producers
3/
of chlorophenol.
1° April, 1957, Dr. Schulz reported his findings with
respect to 2,3,7,8-tetrachlorodibenzodioxine together with
Professor Kimmig in "Die Naturwissenshaften" 44:337-338
(1957).

In the article, Kimmig and Schulz

described the appearance of workers at C.H. Boehringer's plants
who had been exposed to the trichlorophenol containing the
2,3,6,7-tetrachlorodibenzodioxine which they believed to be the
culprit:
The appearance of the illness was
characterized by a scattering of comedones,
pustules, small sebum retaining cysts in the
regions of- the face, neck, breasts, back, and
extremities. Damages to liver functioning
was determined in individual cases.
3/
—

j
f

This suggests that the other defendants knew at the time that
Dow did, how to avoid the formation of the toxic impurity that
was causing the chloracne problem.
-7"

Kimmig

and

Schulz.

(noted the "high general toxicity" oE the

compound and found upon autopsy of exposed rabbits "severe
necroses as well as diffuse adiposis of the liver."
states:

The article

"It was also possible to isolate a tetrachlorodibenzo-

dioxane, identical to the synthesized model substance, from the
by-products resulting in the industrial pressure'phenol
process."
Dow either had a copy of the Kimmig and Schulz article
in 1957 or should have had a copy of that article in light of
their extensive dealings with C.H. Boehringer.

in Ccptcnber,

1362, Dow made a two-week pilot plant run using an approximate
24% caustic solution diluted with water.
4/
was raised.

Again, the temperature

In July, 1963, Dow shut down building 199, where 2,4,5-TCP
was manufactured, to install new equipment to increase Dow's
capacity to hydrolyze tetrachlorobenzene to 2,4,5-TCP using
the 22% caustic solution.

After reopening, Dow was "running at

the limit of (its) hydrolyzing capacity".
existing plant to (its) limit."

Dow was "pushing (the)

"Whenever production is increased

it is usually done by increasing the temperature of the synthesis
run."

4/

The caustic insoluble oil from the production of 2,4,5-TC^
nub studied by the Biochemical Research Laboratory of Dowr
and found to be an active chloracnegen.

2 ,&

-8-

0

2-

O n J u l y 3, 1963, an event occurred w h i c h illustrates

that Dow and.the defendant Hercules were both fully aware of
the hazards associated with the use of 2,4-D and 2,4,5-T.

On

that date, Dr. John P. Frawley, Hercules’ Chief Toxicologist,
wrote to V.K. Rowe, Chief Toxicologist for the Dow Chemcial
Company, to discuss the hazards associated with the use of
2/4,-D and 2,4,5-T.

The letter reaas in part as follows:

••Dear V.K. :

-

■

Several weeks ago I mentioned to Don McCallister that Dr.
Jack Leary of U.S.D.A. has approached Hercules and Monsanto
with a request to conduct subacute dermal toxicity studies on
at least one chlorinated phenoxy herbicide.
On June 27th, I had an opportunity to review this request
with Leary and I will try to report to you the background.
Undoubtedly you have seen the clinical reports of four cases
of neuropathy which allegedly have been caused by 2,4-D salts
and esters.
(Archives of Internal Medicine, Vol. 3, 1963,
pp. 133-134; J.A.M.A. November 7, 1959 pp. 1306 to 1389) In
.addition, I have heard of one previously unreported case involving a product liability claim which was successfully defended by a formulator. To my knowledge, Leary has not
heard of this case...
On the basis of these reports Leary feels that the hazards
associated with the use of 2,4,-D and 2,4,5-T products should
be understood more thoroughly. He specifically wishes to
know whether repeated dermal exposure of animals to the free
acids and the various salts and esters will cause peripheral
neuropathy or the other related symptoms. He plans to make
-an informal request of each manufacturer to study at least
one such product... Frankly I believe Leary's request is
reasonable. It could have been made in the form of a.demand
and not a request, and certainly could have involved far more
extensive design. I believe it is desirable for you. Bill
Hunt and myself to confer on the desirability of conducting
such studies and to consider carefully the design and the
selection of minimum number of these products for such
study...
I also suggest that we handle such discussions by
requesting NACA to appoint an ad hoc toxicology sub-committee
consisting of the three of us- After we have crystalized our
own thinking we can invite others to serve as we see fit a|id
can negotiate with USDA as a technical committee...
r
Since Dow is generally regarded as the largest manufacturer
of phenoxy herbicides, I suggest that you serve as Chairman
of this committee...
Sincerely,
John P. Frawley, P.H.D.
i—v.■;o f Tnvicoloqist. . .

2

0

(

This

letter reveals three significant facts.

First,

the United States Department of Agriculture as early as July,
1963, was relying upon the phenoxy herbicide industry to make
the studies necessary to determine whether phenoxy herbicides
were toxic to humans.

Second, both Dow and Hercules had seminal

knowledge of problems associated with consumer use of 2,4,5-T,
and third, in order to insure against any adverse findings,
NACA (National Agricultural Chemical Association), an industry
operated lobbying group would appoint industry representatives to
"negotiate" with USDA so that the design and study of toxicity
and potential hazards to human health would be minimal and not
5/
get out of hand.

Incredible as it may seem, given its extensive knowledge
of health hazards associated with the use of 2,4-D and 2,4,5-T
in 1963, Dov; affirmatively misrepresented to the United States
military:
(V7)e have been manufacturing 2,4-D and 2,4,5-T
for over ten years. To the best of our knowledge,
none of the workmen in these factories have shown
any ill effects as a result of working with these
chemicals.
5/

L

From this seminal undertaking later emerged in the years 1965,
1966, and 1967, an industry-wide conspiracy whose sole functionwas to defraud the military and the government by concealing
from them the knowledge which and the phenoxy herbicide
industry possessed about dioxin as a ccr't-**^ipoison i|i
2,4,5-T and its potential hazards to human health.
r

-IP-

Dow made that representation knowing about the prior
occupational health problems in its own and other chemical
company plants, and knowing about C.H. Boehringers' horrifying
experiences with chloracne

and liver damage in 1954.

Apparently Dow thought in 1963 that the military would
be interested in Dow's industrial health history in the manu­
facture of 2,4,5-T as a benchmark of safety.
As the result of pushing its production capacities to
the limit where the temperatures employed were increased, workers
in the Dow plants began to experience chloracne.

In August of

(1 9 6 4 ) Dow utilized vapor phase chromatography to detect dioxin
in the waste oils.

The waste oils were fractionated, dioxin

isolated and identified.

Dow then proceeded to synthesize

dioxin in the laboratory.
internally a confidential memorandum on an analytical method
for "The Determination of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
in 2,4,5-Trichlorophenoxyacetic Acid by Gas-Liquid Chromatography

The analytical method was for detection of dioxin
in 2,4,5-T, the end product and not only for 2,4,5-TCP, the
intermediary.

Dow apparently thought it was necessary to

analyze its end product.

-1 1 -

0

Thus, by November, 1964, the Dow Chemical Company
had identified dioxin as the toxic compound causing chloracne,
an admittedly hideous disfiguring disease.

This identifi­

cation of dioxin as the causative factor in the known health
problems as set forth in the November 30, 1964 memorandum on
the stationary of "The Dow Chemical Company", titled
i

"The Determination of Compounds Capable of Causing Chloracne \
in 2,4,5-Trichlorophenol Process Samples By Gas-Liquid
Chromatography."

This memorandum describing the methods

and means for detecting dioxin was later to be distributed
to those attending the secret March 24, 1965 "dioxin"
conference, described infra.

Dow sought to advise the

other manufacturers of 2,4,5-T that Dow knew their
products were contaminated.

Dr. R.C. Dosser of Dow pointed out to Mr. E.T.
Upton of T.H. (Defendant T.H. Agriculture & Nutrition, Inc.),,
in a telephone conversation on or before January 12, 1965:

-1 2 -

/

[t]hat if a compound, found in 2,4,5-T acid
or its esters, proved to be damaging that
this might lead to a flurry of successful
claims by users of the herbicide who
allegedly had been injured by it.

On February 18, 1965, Dow held an internal "Exciter"
Problem, Meeting.

Minutes of that meeting state:

Otis introduced the meeting by indicating
that recent information indicates "Exciter"
components may be present in Dow
2,4,5-trichlorophenol. Bioproducts is
concerned about 2,4,5-T acid, esters,
formulations, silvex, ronnel, and Erbon.
This meeting is to review status of our
..knowledge of this subject, potential hazards,
possible effect on Dow image, legal
implications, and need for possible
quarantine. These basic decisions are to be
made without consideration of economic impact.

As a result of that meeting, Dow determined to meet with
the other producers of 2,4,5-T.

In February, 1965, Dr. Frawley, Chief Toxicologist of
defendant Hercules learned from V.K. Rowe, Dow's Chief Toxicologist
that 2,4,5-T was contaminated with an acnegen.

This

is the

toxic impurity which was more accurately identified by Dr. Rowe
at the secret conference called March 24, 1965 at Dow.'s headquarters
in Midland, Michigan.

Prior to March 1, 1965, V.K. Rowe of Dow contacted the

1

Medical Director (Emett Kelly, M.D.) and Assistant Medical Director
at Monsanto and the Chief Toxicologist at Hercules (John P. Frawley)
concerning dioxin contamination.

0
-13-

On March 19, 1965, Dow entered into a letter agreement
with C.H. Boehringer, concerning the disclosure of processes
and/or apparatus and/or production information regarding the
prevention of incidence of chloracne arising out of the production
of 2,4,5-T.

The agreement provided for C.H. Boehringer to

disclose to Dow technical know-how designed to prevent the
occurrence of chloracne.

The documentation and information

was submitted within a covenant of secrecy.

The agreement

was to come into force December 7, 1964 and be valid for a
period of ten years until December 6, 1974.

The importance

of secrecy was emphasized in the following provisions:
"You agree to keep any documents concerning
the process as well as all verbal or written in­
formation and data strictly secret. You will bind
your collaborators who get knowledge of this
information, documents and data to the same
obligation as that assumed by Dow by requiring
them to execute an individual commitment.
The obligation of secrecy hereunder shall not
apply to any item of information disclosed hereunder
which:
1.

Dow can demonstrate was known to Dow and
in its possession prior to disclosure by
Boehringer on or after December 7th, 1964, or

2.

Is now or hereafter becomes generally available
to the public without fault of Dow, or3

3.

Dow can demonstrate was obtained by it in good
faith from a third party having a bona fide right
to make such disclosure."

We do not know at this time w*'e+-v>“'-

the extent to ^hich

or at what time if ever, the existence of this agreement was made
known by Dow to the other defendant chemical companies or the
Government.

-14-

O n M a r c h 19,

1965, V.K. Rowe of Dow wrote an identical

letter to Eitmefct Kelley, M.D., Dr. J. Wilkenfeld of Hooker
Chemical Corporation, Mr. Raymond Verhoeze of Hooker Chemical
Corporation, Mr. Francis Kennedy, Plant Manager of Diamond
Alkali Company, Dr. Ed Chandler, Technical Services, Diamond
Alkali Company, and Dr. John P. Frawley.

That letter stated:

[I] am inviting each of you to come to
Midland to discuss the toxicological problems
caused by the presence of certain highly
toxic impurities in certain samples of
2,4,5-trichlorophenol and related materials.

Our discussions will deal only with
toxicological and analytical aspects of the
problem. We will not discuss manufacturing
know how, sales, or anything else not dealing
with the problems of health.
See, Exhibit 2.

The meeting occurred on March 24, 1965.

Present at that meeting were:

Dr. Wilkenfeld and Raymond

Verhoeze of Hooker Chemical Corporation, Mr. Francis Kennedy
and Dr. Edward Chandler of Diamond Alkali Company, and Mr. C.L.
Dunn and Dr. John P. Frawley of Hercules Powder Company.

At

the meeting "V.K- Rowe recapped the Dow situation in terms of
the problem and the initial studies by Toxicology and
Environmental Research Laboratory regarding the in-plant
situation.

He expanded this in general terms to the study of

end products, ours and other peoples."

See. Exhibit

3.

a

f

number of the attendees at the March 25, 1965 meeting drafted
memos to file.

Those memos are worth reviewing in their

entirety.

-15-

A memo

to f i l e

f r o m E.L.

Chand l e r

of

D i a m o n d A.

Company notes, among other things:
The Dow people state that they intend to set
a limit of zero with sensitivity of plus or
minus 1 ppm on this material. They have
analyzed materials from other companies,
including our company, and have found amounts
as high as 10 ppm in 2,4,5-T acid (end
product) and 20 to 30 ppm in phenates.
They have made a single application to the
ears of test rabbits and have found that 20
ppm will not give folliculitis. Forty ppm
does give a slight effect, and 100 ppm is
severe. They have made repeated applications
of from 10 to 100 ppb, and 25 of these
treatments do not cause a response; however,
1000 ppb (1 ppm) gives a slight response with
nine applications and a severe reaction with
11 applications.
They conclude, therefore, that 1 ppm with
repeat exposure can create a real problem.
See, Exhibit 4

(Emphasis added).

It is clear that Dow believed

in 1965 that 1 ppm with repeated exposures presented a
significant health hazard.
C.L. Dunn of Hercules Powder Company also prepared a
memo to file.

In that memo Mr. Dunn notes, "Rowe expressed

concern that carry-through of toxic materials into final
formulated herbicide products may occur unless precautions are
taken.”

See, Exhibit 5 , p. 1.

On page 2 of that memo to file

is found: "Evidence that the chloracnegens may be systemic.";
and "Hooker and Diamond people were quite aware of chloroadhe.
One of the Hooker people said that some cases are believed to
relate to exposures occurring 20 years before."

On page 4

D

9-

o f tha t m e m o

to file Mr.

Dunn

recorded

the det e c t i o n limits

for

Dow's gas chromatography:'- "2,4,5-TCP - 1 p.p.m." and "2,4,5-T
acid - 1 p.p.m."

See, Exhibit 5 , p. 4.

On page 5 is found:

"Competitor products - Dow has examined all manufacturer's
2,4,5-T products.

Some have "surprisingly high" amounts of

chloroacnegens.

This defined as 10 p.p.m. in 2,4,5-T acid, and

up to 30 p.p.m. in 2,4,5-trichlorophenate."

Id.,’p. 5.

Similarly, J. Wilkenfeld of Hooker Chemical Company
recorded the information he had received at Dow on March 24,
1965.

Dr. Wilkenfeld noted:
Work with rabbits with washing after
exposure, sometimes as soon as 15 minutes
after application, did not stop the
development of the chloracne and single, oral
dose toxicity tests (not (?) m 50) resulted
in the death of some rabbits at 17 micrograms
per kilo. Peripheral liver cell necrosis
occurred in some rabbits where the washing
was done.

The current inplant working limit is "no
response" with less than one ppm by
chromatography considered safe. When they
were having difficulty, chloracne causers
were in the order of 20 - 30 ppm.
See, Exhibit 6

(parenthetical unclear).

Not a single

government representative was invited to attend the March, 1965
meeting.

Dow nor any of the other defendants has produced any

evidence suggesting that the information conveyed by Dow to the
other defendants at the March 24, 1965 meeting was conveyed to
any government representative or more properly, a high-ranking
military official.

255
-17-

O

'

Defendants other than Do w were also c o m m u n i c a t i n g with

each other as to their chloracne and dioxin problems.

On April 9, 1965, Dr. Frawley (Hercules) sent a memorandum to Mr. C.L. Dunn.

in the memorandum, Dr. Frawley refers to

obtaining information from Monsanto,
"...regarding the problems they and Badische
have had on chloracne..."
He then goes on to report that,
"...from the data provided, a sample which
contained 5 ppm of the Dioxin would be acutely
toxic. Whether this refers to death or liver
damage is not clear..."
ê

On June 24, 1965, V.K. Rowe of Dow's Biochemical
Research Laboratory wrote à letter to Ross Mulholland, Manager,
.Bioproducts, Dow Chemical of Canada.

In that letter, Mr. Rowe

stated
As you well know, we had a serious situation
in our operating plants because of
contamination of 2,4,5-trichlorophenol with
impurities, the most active of which is
2,3,7,8-tetrachlorodibenzodioxin. This
material is exceptionally toxic; it has '
tremendous potential for producing chloracne
and systemic injury.
If it is present in the
trichlorophenol, it will be carried through
into the T acid and into the esters and hence
into formulations which are to be sold to the
publicJ One of thethings wnich we want to
avoid is the occurrence of any acne in
consumers. I am particularly concerned here
with persons who are using the material on a

18-

daily, repeated basis such as custom operators
may use it. If this should occur, the whole
2,4,5-T industry will be hard hit and I would
expect restrictive legislation, either barring the
material or putting very ridged controls upon it.
This is the main reason why we are so concerned
that we clean up our own house from within, rather
than having someone from without do it for us. In
this way, we can approach the problem in an orderly
manner. If the producers and handlers of this material
will cooperate, there is no reason why we cannot get
this problem under strict control and thereby hopefully
avoid restrictive legislation; in other words, let us
practice good citizenship.

We are not in any way attempting to hide our
problem under a heap of sand, but we certainly
do not want to have any situations arise which
will cause the regulatory agencies to become
restrictive. Our primary objective is to avoid
this.

I trust that you will be very judicious in
your use of this information. It could be
quite embarrassing if it were misinterpreted
or misused.

See, Exhibit 7, (emphasis added) .

In keeping with the desire

to maintain secrecy, V.K. Rowe wrote as a postscript, "under no
circumstances may this letter be reproduced, shown, or sent to
anyone outside of Dow.”

Id.

Later, a telephone conversation took place on July 9,
1965 between Dr. John P. Frawley, Chief Toxicologist for Hercules,
.f
and Earl Farnham, a Dow Company executive, who, according to this
memorandum, was calling Dr. Frawley on behalf of Dow Vice-President,
Donald Baldwin.

The document dated July 12, 1965, and marked

"Confidential", reads as follows:

_ 1 O _

(Exhibit 8)

The documents reveal that the chemical companies were all
aware that their dioxin level in Agent Orange was totally unaccep­
table and a potential health hazard.

No such communication or

any of the information described above was ever transmitted by
any chemical company to the Government or the military, even
though the chemical companies knew that the dioxin level of
some of the- herbicides ranged from 20-140 ppm, and they all knew
that their contaminated herbicides were being mixed together in
drums before use in Vietnam.

Silence and confidentiality were the code words utilized
to conceal the knowledge which these defendants had amassed con­
cerning the potential health hazards associated with the contaminated
Agent Orange herbicides.

It is clear from the record that no one in the military
was advised of the contamination of the defendants' Agent
Orange herbicides with dioxin and of the concomitant health
hazards until March 6, 1970.

On that date, representatives of Dow provided a briefing
to representatives of the United States military.

The subject of

that briefing was dioxin as an impurity in 2,4,5-TCP and 2,4,5-T.
At thai. briefing, Dow representatives presented the following^
information on 2,4,5-T:

-2 1 -

258

Since 1950 it has been known that
2,3,7,8-tetrachlorodibenzo-p-dioxin is an
impurity associated with
2,4,5-trichlorophenol (TP). The latter
material is used in the manufacture of 2,4,5
T. Dioxin is a highly toxic material...In
1964, Dow closed their plant which
manufactured 2,4,5T due to widespread acne
among plant workers. Dioxin and other
impurities were found in the 2,4,5T. The
plant was cleaned and the manufacturing
process was changed to eliminate the dioxin
and other impurities. The Dow 2,4,5T now
contains less than 0.5 ppm of dioxin.
See, Exhibit '9.
The deposition of Dr. Robert Darrow is instructive on
the level of the United States military's knowledge with
respect to dioxin as late as March of 1970.

Dr. Robert Darrow

attended the meeting on March 6, 1970 at the Pentagon with Dr.
Charles Minarik as representatives of the Crops Division at
Fort -Detrick.

During examination by defendant’s counsel, the

following transpired:

Question: Can you recall a meeting which
took place on or about March 11, 1970, at
which various representatives of Dow met with
Gen. William Sloan (sic) and various others
concerning Agent Orange?
Mr. O'Brien:

(Objection)

Mr. Krohley: (question rephrased)
Mr. O'Brien: (Objection)
Answer: I was at a meeting with Dow's
representatives but I don't recall the date
of it. The name General Sloan doesn't
register with
l :«. not sure.

-2 2 -

.
/

Question : Do you recall what if anything you
said at that meeting.
Answer : I just listened.
anything.

I didn't say

Question: Do you recall what if anything Dr.
Minarik said at that meeting?
Mr. O'Brien:

Same Objection.

Answer : The presentation was given by the
Dow people. That was it. They presented
information.
Question: Anyone at the meeting, Dr. Darrow,
did they say in words or in substance to the
Dow representatives why didn't you tell us
about this before?
Answer : I think the feeling was there but
I'm not sure it was said. We were surprised
when we got the information at this time.
Question:
Answer :

By "we" who are you referring to?

Dr. Minarik and myself.

Question: Do you'recall what if anything was
said in that regard by anyone at the meeting?
Answer: No specific comments, no. In other
words , this represented information that we
were receiving for the first time in this
respect on the dioxin situation.
Question: Where was that meeting held?
you recall that?

Do

Answer: It was in the Pentagon. It was" in
Washington, D.C., in the Pentagon.

1

-23-

260
V' ^

Without any doubt, Dow and the other defendants in
this litigation had conspired to withhold information from
the United States military concerning dioxin contamination
of the Agent Orange herbicides.

On June 15, 1970, Dow wrote a letter addressed as
follows:
The Honorable Melvin R. Laird
Secretary of Defense
The Pentagon
Washington, D.C.
See, Exhibit 10.

In that letter, Dow advised the Secretary

of Defense that Dow's Agent Orange contained one part per million
of dioxin and that "certainly such a product is safer in use
than one containing larger quantities".
Thus was culminated a period of relationship between
the government and defendants which began with Dow's misreresentations in 1963 of the safety of its herbicides and ended
in 1970 after a continued conspiracy of silence and failure
to warn, with admissions of their high toxicity, and the fact
higher dioxin levels meant greater safety hazards.

It is clear also that during the period of time of their
relationship with the military, the defendants also withheld from
the military their considerable knowledge about detection and
manufacturing risk reduction techniques.

-2 4 -

f

C.

Defendants were Knowledgeable About Detection
and Manufacturing Risk Reduction Techniques

Risk reduction requires a problem, method for investiga­
ting the problem, remedial action and a method for monitoring
to prevent recurrence.

The "highly toxic impurity" problem

defined itself in 1937 when 400 lumber workers developed
chloracne.

The method for investigating the problem was

animal testing which Dow did not undertake.

The remedial action

was a change in the

Plaintiffs are unaware

manufacturing process.

whether such a change was made.

As of 1941, the method for

monitoring to prevent the recurrence was the rabbit skin test.

In 1964, the problem was the same.

The method for

investigating the problem was gas liquid chromotagraphy and
sample preparation techniques.

The remedial action, at least

with respect to Dow was the purchase and implementation of C.H.
Boehringer technology to produce 2,4,5-TCP and 2,4,5-T with less
6

than one ppm of dioxin.

The method for monitoring the problem to

prevent recurrence was liquid gas chromatography and

separation

techniques pioneered by Dow.

§_/ The C.H. Boehringer technology called for, among other
things, reducing the temperature of the reactor (autoclave)
to a maximum of 175 degrees centigrade; no more than 20
atmospheres (hereinafter "atms") of pressure in the
> I
reactor; rinsing salt deposits from the reactor after each
use; cessation of the introduction of sodium hydroxide if
the temperature or pressure in the reactor went above the
maximum; distillation of methanol under heat and 5 atms
until temperature at head has risen to 88-90 degrees
centigrade with a cessation of distillation when
tr ichloroanisole appears; maximum temperature of 11-5
degrees centigrade in the sump phase to prevent excess
water evaporation from the phenolate solution; addition of
water before driving off the trdchloroanisole solution
■fnr- imartf narripr of dixion) bv steam. /

362

T h e r e can be no d o u b t that Dow was familiar wit h risk

reduction techniques of a detection and manufacturing nature
and the Dow had total discretion in the decision of whether to
employ those techniques.
The military placed no restrictions on the -defendants
with respect to their manufacturing processes.

Dow had clear

discretion in the choice of processes to use.

Dow well under­

stood that the process used determined the amount of dioxin in
the 2,4,5-T.

Dr. B.B. Holder, Medical Director, Medical Depart­

ment of Dow admitted:
In 1964 at the trichlorophenol production area
a process alteration was made changing the
temperature and pressure levels previously
used. It was well understood by all involved
that we had to be extremely careful in process
changes to prevent the formation of excessive
chlorinated dioxins and similar toxic compounds.
Dow was fully aware of process alternatives.

In fact, to lower

the dioxin contamination of its 2,4,5-TCP and 2,4,5-T, Dow purchased,
in 1965, parts of a 2,4,5-TCP process from C.H. Boehringer.
had absolute freedom to do so.

Dow

Dow was so concerned about end

product contamination that on May 4, 1965, it established a
specification requiring a gas liquid chromatographic analysis
of all 2,4,5-T leaving the plant.

Had the military known that

different temperatures, pressures, alcohols, and phenolate water
content resulted ir* different levels of dioxin contamination,^ there
can be no doubt, the military would have required the safest
method.

26

Nothing

speaks more clearly

to the effect of d i f f e r e n t

processes on the level of dioxin contamination and to
defendants' knowledge on that subject than the lolloping excerpt
from an internal document:
Chlorophenol and derivatives producers
are Dow, Monsanto, Hercules, Diamond and
Hooker- Dow and Hooker isolate and distill
the trichlorphenol prior to sales and use,
and analyses of samples of their sales
products show no exciter present. It is
suspected that Hercules also distills the
trichlorophenol as samples of their 2,4,5-T
acid shows no exciter. Diamond and Monsanto
do not isolate the trichlorophenol to purify
it. but nako ail derivatives from the sodium
salt. Analysis of Monsanto's 2,4,5-T acid shows
3 - 8 ppm. exciter, and analyses of Diamond’s
sodiumtrichlorophenate shows 8 - 2 4 ppm. exciter.
Clearly, different manufacturing processes resulted in
different levels of dioxin contamination and Dow and the other
defendants were clearly aware of that fact.

Of equal clarity

is the fact that the military was ignorant of this matter.
The evidence indicates that the military did not know indepen­
dently and was not informed by the defendants of the relationship
between process selected and level of dioxin.

A particularly irrational instance of "cover up" was in
the defendants' withholding from the government of the technology
necessary to analyze the products and to detect its deadly impurities.
The Air Force was working on a method of analysis, gas chromotrography
which it hoped would prove more effective than the army's infrared
spectrography, analysis and preliminary tests looked promising.
The government was well behind the defendants in developing this
technology, however.
-27-

In a Hercules memorandum marked "confidential" and dated
September 5, 1967, from M.A. Taves, Synthetic Research Division,
to Mr. J.M. Eagan, Synthetic Department, the government procedure
(infrared) was described as "very tedious" and possibly was
inaccurate.

The report states that "they apparently are not

aware of the components which we knew to be present."

The

memorandum conjectures that the government would probably
be receptive to adopting Hercules' analytical method, but
Taves cautioned, "we must carefully compare both methods
because it is possible that their method may be giving
beneficially higher analysis, particularly on 2,4-D, than
our own method."

4

4

-28-

D u r i n g the years that the defendants supplied contaminated

herbicides to the military, Dow was not the only defendant possessed
of expertise as to dioxin hazards and means of risk reduction.
While their expertise may have varied in depth and time acquired,
each of the defendants failed to warn the military of what
defendant knew about its and other defendants' products and
sooner or later became a party to the conspiracy to conceal or
misrepresent the matters which the military needed to know in
order to make informed choices and decisions as to herbicide
procurement.

We turn next*to an historical review of the conduct of the
other defendants.

DEFENDANT MONSANTO'S KNOWLEDGE ABOUT
MANUFACTURING PROCESS, DIOXIN AS
CONTAMINANT,DETECTION METHODS, RISK
REDUCTION METHODS, AND HEALTH HAZARDS
ASSOCIATED WITH EXPOSURE TO DIOXIN

Perhaps the most malevolent participant in the Chemical
Company conspiracy to withhold from the Government and the
general public the toxic effects of the dioxin content in their
2,4,5-T is the Monsanto Chemical Company.
It was in 1949, at their Nitro, West Virginia plant

j

that Monsanto was first alerted to the existence of a contaminant
present in their 2,4,5-T process.
upset",

As a result of the "process

(Monsanto's term), workers participating in the refinement

of sodium trichlorophenol (the precurser of 2,4,5-T) were exposed

to the product.

Ultimately, more than 200 workers in the 2,4,5-T

department began to develop manifestations of toxic exposure.
Multiple workers' compensation claims were filed in which
there were made acute complaints of liver damage, peripheral
nerupathy, chloracne and severe systemic effects.
Monsanto's extensive knowledge of the health problems associa­
ted with 2,4,5-T exposure is further illustrated by the communication
from Elmer Wheeler, a key Monsanto employee, in which he discussed
an incident at Badische, the German manufacturer of 2,4,5-T.
Referring to a November, 1953 process disruption similar to that
of the Nitro incident four years before, Mr. Wheeler acknowledged
that approximately 50-60 cases of Badische worker health problems
occurred following the incident. Stated the Monsanto hygienist,
not only did Badische 2,4,5-T workers show "horrible skin eruptions"
but that "In addition to the skin manifestations, their men
reported all the additional symptoms as experienced in our workers,
i.e. fatigue, vertigo, loss of libido, painful joints, etc."
Through the 1950's Monsanto continued to be alerted to the
problem of worker 2,4,5-T exposure.

A 1955 confidential memorandum

acknowledged widespread employee toxic reaction.

It stated, "You

also know that the 2,4,5-T problem has not been solved and chloracne
remained ar the outstanding problem of the Nitro plant in dealing
with hourly personnel".

(Exhibit 11 ).

267
-30-

Throughout the '50's, the worker illness problem in the
2,4,5-T plant became so acute that the workers refused to labor
in that environment.

Monsanto was required to pay an hourly bonus

to those volunteer workers who did subject themselves to the
health problems which were rampant in the 2,4,5-T .factory.

In

the 'SO's as production increased, worker health problems became
even more frightening.

As a matter of fact, James Springgate,

who became Plant Manger of Nitro in '64 was required, as part
of his job, to review Monsanto worker health complaints and
estimated that over 100 workers complained of chloracne during
the period from *64 to '68.

Significantly, the Plant Manager

estimated that there were more 2,4,5-T Monsanto employees who
complained of health problems in the period of '60 to '64 than
the 100 he estimated in the next four years.
In 1964, Monsanto sent to Dow for analysis, Monsanto's
2,4,5-T.
ppm's.

The dioxin content of the sample showed three to ten
(As high as this amount was, it was nowhere near the

huge amount of toxic contamination of the Monsanto product that
further analysis was about to reveal.).

On the 24th day of

February, 1965, the Medical Director, Kelly, spoke to his Dow
counterpart, V.K. Rowe.

Rowe acknowledged that Dow had 20 cases

of chloracne and admitted that he was sure that dioxin was the
cause.

(Exhibit 11a) .

The Memorandum clearly reveals that Dotf's

motivation for its secret March meeting was hardly salutory;
since Dow suggested a "crash meeting with all the producers” in

-30a-

an attempt to eliminate the contamination before the "PHS
got into the act."

Of course, the Public Health Service

couldn’t get into the act unless they found out about the
toxic contaminant, a discovery that the conspiring chemical
companies mightily tried to avoid.

It was only one month

later that V.K. Rowe wrote the infamous March 19 secret
communication to certain 2,4,5-T manufacturers in which he
alluded to the dioxin content of 2,4,5-T as "certain highly
toxic impurities".

(Exhibit 2 ).

In February of 1965 Monsanto and Dow shared information
concerning their mutual problems.

By that time, it was known

by both companies that dioxin was the contaminant in their
product.

Therefore, as supported by the sworn admission of

Monsanto employees as well as the annexed documentary evidence,
Monsanto knew:
a)

of the continuing acute health problems to
which their 2,4,5-T employees had been
subjected for the past 17 years,

b)

that other chemical companies, both here and
abroad had similar pblems, and

c)

that the health problems to which Monsanto
had personal knowledge not only included
chloracne, but also involved:
1.
2.
3.
4.

fatigue
vertigo
loss of libido
painful joints

2693 q3
-30b-

M o n s a n t o ’s 2,4,5-T was enormously toxic.

In a September

14, 1965 interdepartmental memo which was then filed in the
"Confidential Folder," Monsanto admitted that "during April,
1965, production of TDD rose to an all-time high and remained
much higher than its previous norm-current - 50 ppm normal - 10
ppm".

(Exhibit lib).That amount was 50 times greater than the

one ppm dioxin which Dow claimed was safe (although plaintiff's
evidence establishes that even 1 ppm is toxic).
Monsanto did not remove this acknowledged enormously
toxic contaminant from its 2,4,5-T.

In a confidential communication

dated almost four years later, Monsanto acknowledged that their
1968 experience showed a content of 40 ppm and that even in
1969, their contamination ranged from 5 to 7 ppm.

(Ex.11c).

So serious was the problem that in 1968, after the medical
director was informed that there had been no new chloracne cases
since October of the previous year, he responded to that information
by asking, "I don’t want to be cynical, but are there any employees
in the department who don't have chloracne already?"

(Ex.lid).

As was reported in the confidential Monsanto final report
on 2,4,5-T terminating January of 1969:
"The incidence of chloracne has been almost universal
among personnel engaged in the manufacture of 2,4,5trichlorophenol (TCP) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The most severe cases have occurred
in individuals involved in the clean up of uncontrolled
autoclave batches (hydrolysis of tetrachlorobenzene). How­
ever, cases of varying severity have occurred consistently
among operators primarily employed around the 2,4,5-T work
up equipment - filteration, acidification, drying, etc."

2P
-31-

270

Monsanto was able to isolate dioxin as the toxic ingredient
when it first began to produce Agent Orange, and Monsanto knew
for 20 years before 1969 that the 2,4,5-T that they produced
contained toxic impurities that were clearly and dramatically
hazardous to humans.

Their knowledge emanated from their own

personal experiences, from the reports of industrial problems
from other chemical companies producing the same product and from
confidential exchanges from the manufacturers.

There is no question that Dioxin was viewed by Monsanto
and all other defendants as highly toxic.
dioxin contaminated 2,4,5-T sold

They knew that the

by them to the Government was

being mixed together and used in Vietnam.

But Monsanto never

informed any governmental officer with regard to the risks of
dioxin contamination associated with Agent Orange or the methods
of dioxin control; nor did Monsanto ever warn the Government
with regard to the causal relationship between 2,4,5-T exposure
and serious injury.

In their Verified Answer to the Plaintiffs'

Interrogatories, Monsanto has admitted that they were not respon­
sible for, participated in, or familiar with any warnings td the
United States Government with regard to the risks of dioxin
contamination associated with Agent Orange, or with the methods
of dioxin control.
R.Emmet Kelly, M.D., for many years the Director of th|
Monsanto Medical Department and the person whose responsibility
it was to investigate and supervise Nitro workers' complaints,
in his deposition, acknowledged the causal relationship between

271

2,4,5-T exposure and claims of peripheral neuropathy, nerve
demyelination, chloracne, and even "the possibility of liver
T

__

»1

/
0

Thus, Monsanto's conduct clearly marks it as a prime
participant with the other defendants in their efforts to
conceal and misrepresent the hazards associated with the
herbicides they were selling to the Government.

E.
DEFENDANT DIAMOND SHAMROCK CORPORATION'S
KNOWLEDGE ABOUT MANUFACTURING PROCESS DIOXIN AS
CONTAMINANT, DETECTION METHODS, RISK REDUCTION METHODS
AND HEALTH HAZARDS ASSOCIATED WITH EXPOSURE TO DIOXIN.
1.

Documents submitted by Diamond Shamrock Corporation and

testimony of the Defendant's own witnesses graphically demonstrate
that there was an enormous amount of information exchanged relating to
the contaminant involved herein, its manufacture, its means of
analysis, .methods of elimination, and last, and perhaps most
importantly, knowledge by the defendants of the extent of
contamination in the product sold to the government by Diamond.
2.

The historical experience of Diamond Shamrock

Corporation with 2,4,5-T is encapsulated in communication from Richard
W. McBurney, M.D., dated March 27, 1963, addressed to Mr. Frank W.
Jarvis, Vice-President.of Diamond Shamrock Corporation, labeled
Chloracne— Confidential.

(Diamond Shamrock,

Exhibit 12

This letter

refers to a building of ancient vintage where 2,4,5-T acid processing
actually takes place and advises that it is in this building that the
"workers are easily contaminated by vapors in the air. Paragraph 4,
page 1, admitss
"As long as this plant has been in operation, there has been
a chronic problem in the employees hired— of a condition
referred to as chloracne."
j

}

*

At one time, approximately 40 of the 72 workers in the plant
were affected by chloracne. Paragraph 5 of page 1 states, "It is my
impression and the impression of the management (Newark plant), that
these byproducts are those of a chlorinated ether and are a result of
the reaction of caustic soda on 1,2,4,5—tetrachloro benzene as used in
the making, of the

2,4,5-T."

3.

This concern expressed by Dr. McBurney, however, does

not begin and end with the problem of chloracne in the production
workers- Rather, 'as may be seen on page 2 of his letter, there was a
growing concern about a medical condition known as porphyria cutanea
tarda. This is a disease of the blood forming elements of the body in
which the hemoglobin of the red blood cells is broken down and,
essentially, the spleen, liver, and kidneys are effected to a greater
or lesser extent, depending upon the ingestion of such a chlorine ted
benzene. One of the physicians working on behalf of Diamond Shamrock
at the Newark plant. Dr. Bleiberg, conducted a test on four men who
had suffered the longest from chloracne only to find that two of these
men had positive porphyn reactions in their urine.
4.

Eugene Bak in the mid 1960's became production manag

of the Diamond Shamrock Newark plant (page 27,:lines 17-25).

Bak

testified at his deposition on January 27, 19B3 that he was-advised of
health problems with the workers in the Newark plant when he first
came to Newark and reported to Francis Kennedy, Plant Manager (page
39, lines 16-23; page 21, lines 2-10).

f,. :■

He testified that he felt

chloracne was a serious health problem when he became production
■manager (page 40, lines 19-23). He admitted that certainly half the
workers in Acid and T-Ester Building were effected by chloracne (page
59, lines 11—25; page 60, lines 1-17). He conceded that the
management suspected that the health hazard also included porphyria
among the workers at Newark and that there was some positive findings
in the urine specimens of these workers (page 66, lines 10-25; page
67, lines 1-25; page 68, lines 1-3).

He testified that chloracne and -

liver problems existed in the Newark plant and he was concerned about
it (page 68, lines 4-23). The plant manager for Diamond Shamrock at
Newark considered chloracne to be a serious health problem while
functioning in that capacity (Deposition of Francis Kennedy, page 48,
lines 16-24; page 50, lines 3-8).

Mr. Bak admitted that the same

products were sold to the public that were suspected to cause ,
chloracne in workers (page 74, lines 15-25; page 75, lines 1-4)".
5.

Mr. Bak also admitted that these same products were s

overseas as Agent Orange (page 75, lines 5-9).

Given the admitted

knowledge of Diamond Shamrock's production manager, it is shocking

t573

consider the complete lack of disclosure to the Government of the
information possessed by Diamond Shamrock (page 105, line 2):

’Q

Q: At any time during those years 1965 through 1968, did
you personally ever advise the United States Army of the
contaminant in the TCP process stream?“
A:

I have not personally.

Q:
Did anyone to your personal knowledge on the part of
Diamond Shamrock ever advise the Army of that?
A:

.1 don't know."

6.

Having

established

the existence of and knowledge of

health hazards, not only in the production stages of the product, but
in the final product itself, consider the interchange of this
information between Diamond Shamrock and the other defendants in this
law

suit.

February
the

The deposition testimony of Edward Lee Chandler, taken on
8, 1983, indicates that in 1957, Chandler became manager of

technical

service

department of Diamond Shamrock which was a

liaison between the technical development of products and the sales of
(pa- 30, lines 19-25; pg. 31, lines 1-2). Diamond Shamrock
Exhibit 13 is an interoffice memorandum addressed to Mr. R. A. Guidi,
dalrsrd— 5uly 9, 1962, from Mr. Edward Lee Chandler. At that time, Mr.
Guidi was the manager of the Newark plant. The letter clearly
illustrates Diamond Shamrock's concern with the loss of two sizeable
customers, Riverdale Chemical and Quaker City Tree, both of whom
complained of chloracne problems with the use of the final products
sold to them by Diamond Shamrock. The dermatological problem was so
severe

to the employees of these companies that Diamond lost them as

customers.

i

-35-

274

Diamond's knowledge of the health hazards associated
with the use of its products was unquestionably established
by a serious outbreak of chloracne among users of their
2,4-D and 2,4,5-T in Columbia, South America.

This problem

was described by Lex Creamer, Diamond's representative, who
forwarded a report to Diamond's New York office on March 18,
1965 (Exhibit 13a).

As his report indicates, in one area

alone twenty people were affected with most of them being
hospitalized for months.

He also indicated that the horses

were badly affected with loss of hair, skin lesions and in
one case death.

7.

Considering Diamond Shamrock's concern over the loss of

customers because of health hazards and the use of their esters, it is
not surprising that we see Francis Kennedy and Edward Lee Chandler on
a list of invitees to the now infamous Dow-Midland Conference of March
24, 1965, by letter from V.K. Rowe of Dow Chemical dated March 19, 1965.
In that invitation Rov/e directly addresses the toxicological problems
caused by the presence of certain highly toxic impurities in certain sam-.
pies of 2,4,5-T. He does not confine these problems to any single company,
but rather admits that the probl-em was industry-wide and that the

j
4

-35a-

275

purpose of the meeting itself was to deal with the toxicological
and analytical aspects of this problem.

It is indisputable that

as of that date, Dow had possessed a method of analysis which it .
was willing to share with the invitees throughout the industry,
but not with the military.

Dr. Chandler never denied receiving

this letter from Rowe, or in fact speaking to Rowe prior to his
attendance at the meeting.
meeting.

He readily admitted attending this

He did, however, deny any accurate recollection of what

took place at the meeting in Midland (Chandler deposition, p. 96) .
In interoffice correspondence from E.L. Chandler to John Cort, Jr.
dated March 25, 1965 with carbon copies to Francis R. Kennedy,
Manager of the Newark Plant, and others (Exhibit 14 ), it is
obvious first, that Dow Chemical was sharing with the rest of the
industry the severe health hazards; secondly, Dow advised the industry
that they had identified the causative agent as dioxin; thirdly,
Dow had developed a new analytical method with a sensitivity level
of 1 ppm; fourthly, Dow advised the industry of its intention to set
a limit at that time of 1 ppm dioxin on this material; fifthly,
Chandler admits that Dow had analyzed materials from other companies
including Diamond Shamrock and found amounts as high as 10 ppm of
dioxin in the 2,4,5-T acid.

The last paragraph in this exhibit

reconfirms the purpose, industry-wide, of the Midland meeting of
March 24, 1965, where Mr. Chandler concludes ’’the purpose

of
j

this meeting was designed to help us solve this problem before
outsiders confuse the issue and cause us no end of grief.

Dow is

sending the test results of our material to us incidentally and this
will further check our techniques, etc."

-36-

Having considered the

0

3£>

universiality of the health problem of 2,4,5-T esters and the
need throughout the industry to cooperate to some extent to
alleviate this problem, what steps if any, did Diamond Shamrock
take to eliminate the contaminant dioxin from the T ester which com­
prised half of the Agent Orange product?

Kennedy returned to the

Newark Plant after attending the Dow conference at Midland on March
24, 1965 with the knowledge that there was a problem involving
dioxin that had to be solved (Kennedy deposition, p. 135, line 1-17).

8.

The dioxin contamination of Diamond's herbicides caused

it to lose customers, in particular, Dow.

On April 6, 1956 the following memorandum was sent from
J.C. Kelly, Diamond's sales shipping coordinator in Division
headquarters of its Ag-Chem Division in Cleveland, to J.O. King,
sales manager in that division, regarding Dow's refusal to purchase
Diamond's production:
April 6, 1966
"Mr. J.O. King

Mr. J.C. Kelly

Dow Chemical Company
On March 21, we directed a sample of our Technical
2,4,5-T Acid to subject account.

In talking with

Ken Hanson on April 4, he advised that they would
not be in a market for our material.

Apparently,

they feel that our material could conceivably re­
create a chlor-acne problem at Midland and, as such,

j

would not entertain the purchase of our present pro­
duction.
J. C. KELLY
JCK/im
cc.

Mr. F.R. Kennedy - Newark
Mr. R.A. Guidi"

9.

There is no doubt that Diamond had considerable knowledg

of dioxin risk reduction techniques.

An interim report, January 9,

1967 of experimental work for TCP purification, reveals their
awareness of Dow’s studies regarding identification of the com­
pounds causing chloracne and analytical procedures used to quan­
titatively identify the dioxin contamination.

Diamond also knew

what needed to be done to eliminate or reduce dioxin, and that this
could be accomplished in several ways including alteration of the
TCP condensation reaction or utilizing engineering techniques to
remove dioxin from process streams after they have been reduced.
10.

It is significant that from the time Dow gave Diamond

Shamrock the means of analyzing its product in March of 1965, it was
not until September of 1967 that a purification column was installed
on the production floor and put into use.

Despite such installation,

and perhaps most significantly, by Diamond Shamrock's own analysis
from January to March of 1968, it was running 3.8 ppm dioxin ^nd
related compounds in its 2,4,5-TCP.

-38-

In October through December

1968, it ran 9 ppm.

Nevertheless, production continued, ai.

product was sold to the government.

In the affidavit of Franc

R. Kennedy, sworn to March 27, 1980, he speaks eloquently of the
government's need for Agent Orange, but is absolutely silent on
Diamond Shamrock's need for purification of a contaminated product
that it knew that it was selling to the government without disclosure
of the contamination problems.

What effect, if any, did the

performance of Diamond Shamrock corporation have on the defendants?
Did the concern expressed by Dow in the Midland meeting in March
of 1965 terminate its concern regarding the contaminant which it knew
at that time was industry wide?

Or in fact did the purported concern

for this serious health problem continue among the various defen­
dants well beyond the Dow conference?

An answer to that can

clearly be seen in a confidential memorandum of J.P. Frawley, dated
July 12, 1965, of the Hercules Powder Company which relates to a
telephone conversation dated July 9, 1965 with Mr. Earl Farnhan
of Dow Chemical Company .

Mr. Farnhan was convinced

that no one else in the industry had done anything to remove the
contaminant from their. 2,4,5-T.

Mr. Farnhan further stated that

Dow was extremely frightened that this situation might explode.
Mr. Frawley quotes Mr. Farnhan as stating that Dow "aware that their
competitors are marketing 2,4,5-T which contains alarming amounts of
acnegen and that if the government learns of this the whole industry
will suffer.

They are particularly fearful of a congressional

investigation and excessive restrictive legislation on the manu­
facture of pesticides which might result."

-39-

Obviously, it was not the intention of Hercules, Dow and others
to disclose a problem of health to its customer, the United States
Government, but rather to try and induce the industry at large to
"clean-up" ("cover-up?") its product before the government found
out about the health hazard.

It is hard to conceive of greater

evidence of the conspiracy of silence where, as here, the
industry admittedly knew of a serious health problem, unknown to
the government, than Mr. Farnhan's own words of precaution that
Dow is fearful if the government learned of the alarming amounts
of acnegen, the entire industry would suffer.

F. T.H. Agriculture and Nutrition Company, Inc.
Knew About Dioxin as a Contaminant in 2,4,5-T
and Knew About Concomitant Health Hazards and
Failed to Warn the Military.________________

Much of what is known about the defendant T.H. Agriculture
and Nutrition Company, Inc., formerly known as Thompson-Hayward
Chemical Company, Inc., (hereafter "T.H.") is the result of a
deposition of Edwin T. Upton and a review of T.H.'s produced
documents. Mr. Upton was deposed on April 7
and 8, 1983 and T.H. produced documents totaling approximately
18,000 pages.

Counsel for T.H. represented to counsel for

plaintiffs that no confidential or proprietary documents were
withheld.

Mr. Upton's deposition, in conjunction with the

documents, clearly shows that T.H. knew about dioxin in itjs end
product (hereafter variously 2,4,5-T, 2,4,5-T ester and isooctyl
ester 2,4,5-trichlorophenoxyacetic acetate) and knew about
concomitant health hazards.

Mr. Upton's deposition and T.H.'s

documents further establish that neither Mr. Upton nor anyone
- 1-

m

n

MTirnDfl H i o mi 1 i t a r v .

-in-

£ 80

Edwin T. Upton first worked for T.H. on a full-time
basis as a chemist beginning in 1946. (Upton Tr. at 27.)
From Chemist, Mr. Upton progressed to Chief of the Quality
Control Laboratory, Chief Chemist, and finally Laboratory
Administrator.

Id. at 27, 44.

From 1946 to 1947 Mr. Upton

worked on formulating usable forms of 2,4,5-T.

Id. at 29.

In experimenting with formulations, Mr. Upton made an informal
literature search resulting in a paper which was presented
at a regional American Chemical Society meeting in 1946 or
19 47.

Id^. at 29.

In preparing that paper he reviewed a number

of patents on the use of phenoxy herbicides.
Those patents were reviewed prior to 1955.

Id_. at 30.
I_d- at 31.

In

1946 or 1947, Mr. Upton developed for T.H., a successful
formulation of 2,4,5-T.

Id_. at 32-33.

Between 1946 and 1947,

Mr. Upton also worked on products containing a mixture of
2,4,5-T and 2,4-D.

_Id. at 35.

Through Mr. Upton's efforts, T.H. developed, in the
early '50's, a herbicide which was a 50/50 mixture of
2,4-D and 2,4,5-T.

That product was called DED WEED 50-50

BRUSH KIL. (Upton Tr. at 36).

T.H. also manufactured 3-3

BRUSH KIL.

That product was a 50/50 mixture of 2,4,5-T

and 2,4-D.

(Upton at 41).

i

-41-

T.H. established specifications for 2,4,5-T.

Id. at

49.

Those specifications "were established in the late *40s.

Id.

Beginning in 1950 or 1951, T.H. began manufacturing 2,4,5-T

according to those specifications.

Jd. at 51.

2,4,5-T was

manufactured from approximately 1950 to some time before 1960
at a plant in Kansas City, Kansas.

Some time after 1960, a new

plant was opened in Turner, Kansas.

In manufacturing the end

product, isooctyl 2,4,5-trichlorophenoxyacetic acetate, T.H.
began with trichlorophenol purchased from the Dow Chemical
Company.

The 2,4,5-trichlorophenol was converted to sodium

2.4.5- trichlorophenate.

In a separate process, monochloro-

acetic acid was esterified with isooctyl alcohol to make
isooctyl monochloroacetate.

The two intermediates, sodium

2.4.5- trichlorophenate and isooctyl monochloroacetate were
Lv.' ,: :; '

coupled to make the end product, isooctyl 2,4,5-trichlorophenoxyacetic acetate.

JEd. at 76.

From 1947 when he was a chemist until 1974 when he was
the Laboratory Administrator, Mr. Upton remained responsible in
a "hands on" or supervisory capacity for the analytical testing
of raw materials, intermediaries and finished products.
44, 81.

at

From 1947 to approximately 1965, T.H. utilized the

official Agricultural Chemist Association method (Parr Bomb)
for determining gross amounts of chlorine in the 2,4,5-T.
Upton T r . at 82.

Beginning in 1964 or '65, T.H. began using an

infrared spectrometer for determining the gross compos:* *•ion_
its 2,4,5-T.

Ici. at 84.

The infrared spectrometer continued

to be used until Mr. Upton left T.H. in 1974.

at 85.

1962 or 1963, T.H. obtained a gas chromatograph.

Id. at 87.

-42-

In

From 1963 when T.H. obtained its gas chromatograph until
the

middle of 1964 that gas chromatograph was not used to deter­

mine impurities in 2,4,5-T.

Id. at 88,89.

From 1963 until the

middle of 1964, T.H.'s gas chromatograph was not utilized to
determine the amount of inert ingredients in the 2,4,5-T being
manufactured by T.H.

Id. at 89, 90.

On December 3, 1964, Dr. David Groth of the Regional
Health Reserach and Training Facility in Cincinnati, Ohio,
wrote to Mr. Upton.

In that letter, Dr. Groth indicated

that he was interested in the "determination of the toxic compound
present in the commercially available 2,4,5-tri.chlorophenoxyacetic acid which is sold as the iso-octyl ester." David Groth
further indicated that Kimmig and Schultz had published a paper "which
gave evidence that the skin and liver toxicity were not (emphasis in
original) due to the 2,4,5-trichlorophenoxyacetic acid, but probably
from some by-product which is present in very small quanities."
From his reading of Kimmig and Schultz, Dr. Groth stated
' hat he thought to be the responsible compound and drew a
schematic of that compound.

Of greatest importance, he noted

as a result of his lack of knowledge, "however, there is no
conclusive evidence that this, or any other specific compound,
is responsible since no one has yet separated the various

1
compounds present in commercial 2,4,5-T."

Apparently,:in

the hope of being able to separate those compounds, David Groth
requested E. T. Upton of T.H. to send him samples of isooctyl
ester 2,4,5-T manufactured by T.H.

283

After letters and conversations with employees of the
Dow Chemical Company - which were the direct result of David
Groth's letter - E..T. Upton sent samples of T.H.'s 2,4,5-T and Dow's
trichlorophenol to David Groth.

In a letter of January 14,

1965 which accompanied the T.H. samples, Mr. Upton wrote "we
would appreciate very much receiving a copy of your analytical
method, which I assume is based on gas chromatography for
determining the 2,3,7,8-tetrachlorodibenzo-p-dioxin."
Apparently, Mr. Upton was aware that gas chromato­
graphy could be utilized to determine the existence of 2,3,7,8tetrachlorodibenzo-p-dioxin in the 2,4,5-T.
To assure himself that he would be advised if Dr.
Groth discovered anything, Mr. Upton wrote a second letter
dated February 17, 1965 in which he stated: "We are very much
interested in your study of the toxicity of the by-products
present in commercially available 2,4,5-trichlorophenoxyacetic
acid esters.

For our information, please send us a copy of

your analytical method for the determination of the 2,3,7/8tetrachlorodibenzo-p-dioxin in technical 2,4,5-T esters."

See,

Exhibit 4 (emphasis added).
Unfortunately, David Groth was never able to determine
that, in fact, 2,3,7,8-tetrachlorodibenzo-p-dioxin_was the subst-r.. . I»» commercially available 2,4,5-T causing liver damage
and chloracne.

As explained by David Groth in his letter to

Mr. Upton of February 26,. 1965:

284
-44-

I had hoped by this time I would have been
able to give you some results on our tech­
nique. However, due to a shortage of funds
we have not yet purchased the thin-layer
chromatography apparatus that we plan on
using for the separation.
In previous correspondence I mentioned some
articles which referred to the toxicity of
2,4,5 trichlorophenoxyacetic acid and
possible toxic contaminants. The principal
(sic) article is by Kimmig in Dermatologica
115;540-546. 1957. So far, that is the
present state of our knowledge on the
subject.

Like Kimmig and Schultz in 1957, David Groth was only able to speculate
that 2,3,7,8-tetrachlorodibenzo-p-dioxin was the possible toxic
contaminant.

However, Mr. Upton, others at T.H. and others at

Dow Chemical Company were keenly aware that David Groth was
groping for answers to a serious industrial and end user helath
problem.

Representatives of Dow, T.H. and of the other defendant

Chemical companies had the answers Dr. Groth was seeking. Those
answers were, never provided to him.

Mr. Upton never wrote to Dr. Groth after David Groth's
letter of February 26, 1965.

Mr. Upton never informed

Dr. Groth of information Mr. Upton had concerning 2,3,7,8tetrachlorodibenzo-p-dioxin, its relationship to 2,4,5-T and
intermediaries, and analytical techniques for determining the
presence of dioxin.

Upton Tr. 225, 226.

While David Groth was

never able to determine whether dioxin was a contaminant in
2,4,5-T, the same cannot be said for Mr. Upton and others at
T.H.

285

David Groth's initial letter of December 3, 1964 was
the catalyst for a number of events. After receiving David
Groth's letter, Mr. Upton discussed the contents of that letter
with Lindley S. DeAtley, Vice-President of Research and Develop­
ment for T.H. Upton Tr. 102. Within a matter of days, Mr.
DeAtley wrote a letter dated, December 11, 1964 to Dr. R.C.
Dosser, Laboratory Director for the Dow Chemical Company. In
that letter, Mr. DeAtley stated: "As we have corresponded and
talked about the purity of trichlorophenol and related compounds
on several occasions, I thought you would be interested in the
attached letter of December 3, from Dr. David H. Groth of the
Public Health Service.” (Emphasis added.) When Mr. Dosser
failed to respond, Mr. DeAtley wrote another letter of Decem­
ber 28, 1964 stating: "... we feel we must reply to the letter
of December 3 from David H. Groth ..." (Emphasis added).
Mr. DeAtley never received a written response from Dow.
Rather, Dr. R.C. Dosser of Dow called Mr. DeAtley on January 12,
1965 and "pointed out" that:
"[I]f a compound, found in 2,4,5-T acid or its esters,
proved to be damaging that this might lead to a
flurry of successful claims by users of the herbicide
who allegedly had been injured by it. Also, he said
that although he did not know our method of proces­
sing Dow's tricholophenol, his chemist suspected
that by some procedures, the toxic compound might be
formed in processing through the sodium salt of the
phenol to the sodium salt of the acid.

t
-46-

286
9

Dr. Dosser, of Dow, was clearly aware of alleged "user"
injuries.

T.H. was advised of those end user injuries at this

time, if it did not have previous knowledge.

Dr. Dosser, of

Dow, also informed Mr. DeAtlev of T.H. , that Dow had developed
an analytical technique for detecting dioxin and had been
utilizing animal tests (the rabbit ear test) which had a sensi­
tivity of about one part per million.

Id. None of this infor­

mation was conveyed to Dr. Groth at the Public Health Service
though he had clearly expressed his interest. Upton Tr. 225,
226.

Representatives of Dow and the representatives of T.H.

were well aware of his interest.
When Mr. Upton responded to David Groth's letter on
January 14, 1965-two or more days after Dosser's conversation
with DeAtley - Mr. Upton failed to inform Dr. Groth of the
information provided by Dr. Dosser, of Dow, to Mr. DeAtley,
of T.H. Upton Tr. 225, 226.

As noted earlier, Dr. Groth wrote

to Mr. Upton on the 26th of February, 1965 and advised him that
due to budgetary constraints, Dr. Groth would not be able to pur­
sue his research.

Upon receiving Dr. Groth's letter, E.T. Upton

or others at T.H. clearly could and should have imparted to Dr.
Groth all of the information they independently possessed and
learned from the Dow Chemical Company.

i

287
0'

As a result of the February 19, 1965 meeting. Dr.
r^eS e . Lewis, who worked for T.H. as its Industrial Hygiene
•-visor, visited Dow.

« 'In his alleged Report on.the Chloracne

Problem, Dr. Lewis noted:

Because of the past experience at
Thompson-Hayward it would seem that two
general approaches need to be made to the
problem. First, because of the use of some
material which was probably heavily contami­
nated with dioxin and other C.A. (chloracne)
producting agents, it would seem important
to sample (using the wipe sample method) the
environment of the synthesis area to make
sure that there is no residual contamination
with these agents....It would seem highly
desirable to go to the use of coveralls and
showers as mandatory, as well as monthly
inspection of these individuals for skin
lesions and on an occasional, perhaps 2 to 3
months, check on blood tests for their liver
function.

%

In discussing this with Mr. Rowe (Chief
Toxicologist at Dow) it was also thought
that it might be wise to do an occasional
sample of the final product of the operation
here with V.P.C.
(believed to stand for
Vapor Chromatography) for dioxin and
maybe(?) occasional rabbit test.
<■ (emphasis added except the last; parentheticals
added excePt -the last).

If the cover letter is an indication.

Dr. Lewis' alleged report was written prior to April 26, 1965.
Dow and T.H. were clearly concerned about end product contami­
nation and hazards to users.

j

By February 19, 1965, and certainly by April 26, 1965
T.H. had a store of information concerning dioxin and analytical
methodology.

Nonetheless, neither E.T. Upton nor any other

288
-49-

representative of Thompson-Hayward Chemical Company wrote to
Dr. Groth after his letter of February 26, 1965 in which he
indicated an inability to obtain answers to his questions.
Upton Tr. 225, 226.
G.The Military Was Uninformed of T.H.'s
Manufacturing Process And Its Capability
For Risk Reduction.

In his first letter to Mr. Upton, Dr. Groth requested
"any information you can give us concerning the manufacturing
process, ie. starting compounds, reactions and possible
by-products."

In responding to Dr. Groth's request, Mr.

Upton directed Dr. Groth to open literature on 2,4-D manu­
facturing processes.

Mr. Upton did not direct Dr. Groth to

open literature on 2,4,5-T manufacturing processesT
inference of conspiratorial silence again arises.

The

In addition,

Mr. Upton was undoubtedly reluctant to divulge trade secrets.
When Dr. Dosser of Dow requested information on T.H.'s manu-.
facturing process, T.H. again was willing only to direct the
inquirer to published literature.

From the published literature,

neither Dow nor the military could have known T.H.'s manufacturing
process.
The military's lack of knowledge as to the manufacturing
process is important because "the type of manufacturing process
used affected the level of dioxin contamination and that by
exercising discretion as to the process, the defendants

-50-

c o n t r o l l e d the extent of the d i o x i n h a z a r d . ”

See,

In Re Agent

Orange,' 534 F.Supp. 1046, 1957 (E.D.N.Y., 1982).
By admission, some of the material used in the manu­
facture of T.H.'s 2,4,5-T was "heavily contaminated" in the
mid-'60s -

According to Mr. Upton, by 1970 or

•71 tests of T.H.'s 2,4,5-T esters showed a lower level of
contamination of up to two parts per million (hereafter "ppm").
Upton Tr. at 143.

Samples taken from excess stocks of T.H.'s

"Agent Orange" in 1973 from an inventory at Gulfport, Missis­
sippi may belie those low 1970 or '71 figures.
The Gulfport samples showed a contamination level of from
0.7 to 4.1 ppm.

Unfortunately, the date upon which T.H. manu­

factured the Agent Orange samples taken at Gulfport has not yet
been determined.

From the rate at which Agent Orange was being

used, however, the Agent Orange sampled was probably manufac­
tured by T.H. in the late '60s or early '70s.
From the mid-'60s when T.H.'s isooctyl ester 2,4,5tricholorophenoxyacetic acetate was "heavily contaminated” to
the late '60s or early '70s when T.H.'s Agent Orange contained
lower but still hazardous levels of up to (and perhaps higher
than) 4.1 ppm. Gene Douglas, a T.H. chemist, under Mr. Upton,
attempted to discover where dioxin was being produced in T.H.Js
plant and to remove the dioxin with activated car’>on.
.

Whether an activated carbon clean up process was instituted

and the levels of dioxin in this herbicide during 1960-1969,
will only be known after plaintiffs have had the opportunity to
complete their discovery of T.H..

In a d d ition to looking at an activated carbon clean up

process, Gene Douglas conducted experiments in 1967 to determine
the relationship between pressure/temperature and the production
and amount of dioxin.

From those experiments, Mr. Douglas clearly

learned that over a certain temperature, dioxin formed and that
the higher the temperature the more dioxin was produced.

With

that knowledge, Gene Douglas would have been remiss if he had not
suggested that the sodium trichlorophenate be dried at a lower
temperature.

He might also have suggested that the wet ester be

dried at a lower temperature and that the excess unreacted phenol
be driven off with steam instead of heat.

Whether those suggestions

were made and implemented will also not be known until plaintiffs
complete their discovery.

Clearly, T.H. knew of methods for reducing the level of
dioxin in its end product.

T.H. also knew from 1965 and perhaps

before 1965 of the dangerousness of dioxin and T.H. knew that the
level of hazard increased with the level of dioxin.

There has been

no proof, on the other hand, that the military knew about T.H.’s
original manufacturing process.

There has been no proof that the

military experimented with a pressure/temperature dioxin relationship
There has been no proof that the military experimented with an acti­
vated carbon clean up process.

Nor has there been any proof by T.H.
j

any of the defendants that the military was told about the foiregoing.
7/

Whenever production is increased it is usually done by in­
creasing the temperature of the synthesis run." The higher
temperature resulted in increased dioxin in the waste and in
the end product.

->

-

Finally, neither T.H. nor the other defendants has put in any
proof that "the government had knowledge equal to theirs (about
the above discussed risk reducing techniques) and that even with
that knowledge the government imposed no requirement or restriction
with respect to the manufacturing process or the level of dioxin
contamination."

The evidence points instead to T.H.'s failure

to disclose these techniques to the military, just as it failed to
warn them of the hazards associated with the dioxin contaminated
herbicides it was selling to the Government.

H.

T.H. Knew of Means For Detecting Dioxin
And Failed To Disclose Those Methods to
the Military._________________

T.H. clearly learned from the Dow Chemical Company (if
they did not already know) how to use gas chromatography for
the detection of dioxin in trichlorophenol, sodium trichlorophenate and later 2,4,5-trichlorophenoxyacetic acetate.

From

discussions with H. Gill of Dow, Mr. DeAtley and Mr. Fuhlhage
clearly knew about the use of gas chromatography for detecting
dioxin.

Mr. DeAtley and Mr. Fuhlhage learned about Dow's

detection method prior to February 23, 1965.

T.H. never informed

Dr. Groth of their knowledge concerning the use of gas chromato­
graphy even after Dr. Groth's letter of February 26, 1965 wherein
he alerted T.H. that he had not been able to purchase a gas chroma­
tograph and devise a method for separating the compounds.

Whether

or not T.H. and the other defendants had a duty to test their

292
V
o

products using gas chromatography, they had a clear duty to
£/
advise the military of its availability.
Use of a gas chromatograph to identify dioxin and deter­
mine the levels of contamination is a risk reduction technique.
Knowledge of gas chromatography (and the rabbit ear test) before
and after 1965 is important.

Under the contracts for the

procurement of "Agent O r a n g e t h e defendant chemical companies
were required to utilize the Parr Bomb method and when it became
available, mass spectrometry.

Upton Tr. 222.

Neither of these

methods is capable of detecting trace amounts of impurities. Neither
of those methods can detect dioxins. Id. at 223,224.
A government inspector was frequently present when T.H.
conducted its Parr Bomb and later, mass spectrometry tests. Though
present, that inspector could not learn about the presence of
dioxin in the 2,4,5-T esters through either the Parr Bomb or
mass spectrometry tests.

T.H. and the other defendants in

similar situations had a clear duty to divulge to those
government inspectors the availability of a better method for
the detection of dioxin and determination of levels of con­
tamination.

That did not occur in T.H.'s case.

During Mr. Upton’s deposition, he stated that during
the testing of the final 2,4,5-T product, a Mr. Block, who he
believed to be a government inspector, was present. Upton Tr .j
8/ Defendants also had a duty to tell the military about the
rabbit ear test which had been in existence since at least
1941 for detecting acnegens to 1 ppm.

at 221.

The test method employed was the Parr Bomb.

tography was not utilized.

Gas chroma­

Though Mr. Block was present during

numerous tests of the 2,4,5-T end product, Mr. Upton never told
Mr. Block about gas chromatography or the existence of dioxin as
a contaminant in 2,4,5-T.

Upton at 224, 225.

Nor is there any

evidence that anyone at T.H. informed the military of gas chroma­
tography as a method for detecting dioxin.
I. T.H.'s Participation In The Conspiracy

The evidence indicates that T.H. entered that conspiracy,
as early as December 11, 1965 with Mr. DeAtley's letter to Dow,
two.years before T.H. produced its first Agent Orange for the
■

“

military.
Dr. David Groth's letter of December 3, 1964
was the catalyst for a series of meetings and conversations
between January and March of 1965 involving most of the defen­
dants in this litigation on the subjects of dioxin and hazards
to workers and end users.
T.H. clearly participated in those conversa­
tions and meetings.

Out

of those conversations and meetigs came a conspiracy of silence
Though Mr. UDton had the ability to inform Dr. Groth,
|
of the Public Health Service, of dioxin, gas chromatography,
risk reducing manufacturing procedures and health hazards
^

associated with dioxin, he did not do so.

Upton at 225, 226.

294
-55-

Though Mr. Upton had the opportunity on numerous occasions to
inform the government inspector, Mr. Block, of dioxin, its
hazards and of availability of gas chromatography and alterna­
tive manufacturing processes, Mr. Upton did not do so.
224, 225.

jrd.

at

Furthermore, the Court should note that T.H. has not

produced evidence indicating that anyone at T.H. informed the
military of the foregoing.

A conspiracy of silence reigned.

.7 . T h o m p s o n r v u M i r v . wive; ^jnFT.T'nni’ABL*; a b o u t

THE MANUFACTURING.PROCESS ,> DIOXIN AS A
CONTAMINANT, DETECTION METHODS, RISK
REDUCTION METHODS-, AND HEALTH HAZARDS
ASSOCIATED WITH EXPOSURE TO DIOXIN.
Thompson Chemical Company also had far more knowledge
about the manufacturing process than military decision makers.

There can be no question that over numerous years as a
manufacturer of TCP and 2,4,5-T, T.C. was fully aware of the manu­
facturing process for those compounds.

T.C. knew that in the synthesis

of tetrachlorobenze to TCP, heat and pressure were utilized.

T.C.

knew that in the distillation of water, alcohol and anisole, heat
was employed in the production of 2,4,5-T, the end product.

T.C.

was thoroughly familiar with the manufacturing process for 2,4,5-TCP
and 2,4,5-T.

K. T.C. Knew That A Highly Toxic. Impurity Was In Its
TCP and 2,4,5-T
____

As a manufacturer of TCP, T.C. may have been informed in 1956
by C.H. Boehringer Sohn that a TCP or 2,4,5-T process that used heat

C.H. Boehringer Sohn had experienced horrendous outbreaks of
chloracne with liver damage in some cases in two separate plants.
To assure that other manufacturers of TCP and 2,4,5-T did not ex­
perience similar incidences, C.H. Boehringer Sohn sent in 1957,
"Information of the reaction conditions under which no chloracne
results to all known producers of chlorophenol." Plaintiffs have
established that The Dow Chemical Company, as a manufacturer of
TCP, received such information from C.H. Boehringer Sohn.

As a

manufacturer of TCP (a chlorophenol), T.C. probably received the
same information in 1957 from' C.H. Boehringer Sohn, as to a toxic
impurity arising under certain conditions in the manufacture of
TCP and 2,4,5-T.
Dr. K.H. Schulz of the University Skin Clinic in Hamburg
reported in "Die Naturwissenshaften" 44: 337-338(1957), what he
believed to be the contaminant in the TCP and 2,4,5-T being
manufactured by C.H. Boehringer Sohn.

Had anyone at T.C. read

that article, he or she would have been alerted to the possible
presence of dioxin in T.C.'s 2,4,5-T and TCP.

Though he did

not start with T.C. until approximately 1965, Mr. M.S. Buckley
may have read Dr. Schulz's article.

Thompson Tr. p.43, 50.

Regardless of whether T.C. received information from Boehringer, or the Naturwissenshaften article, T.C. was undoubtedly aware c
a number of industrial exposure incidents in which workers manufacturin
TCP ar.3 2,4,3-T experienced chloracne, liver damage in some instances,
and maladies involving the nervous system. See, generally,
tetrachlorodibenzo-para-dioxin in the Environment, Robert W.
Baughman (unpublished dissertation for the Harvard Department of

296
-57-

Chemistry, 1975j . An awareness of those incidents would have alerted
T.C. to the presence of a highly toxic impurity in TCP and 2,4,5-T.
If T.C. had not learned of the existence of a highly toxic
contaminant in TCP and 2,4,5-T through C.H. Boehringer Sohn, Dr.
Schulz* article in 1957 or through knowledge of industrial worker
exposures, T.C. clearly came to learn about dioxin from its own
experiences with employee injury. Some time prior to February 3,
1967, employees at T.C. experienced cases of severe chloracne. For an
unexplained reason, Mr. M.S. Buckley of T.C. was sufficiently well
informed to call The Dow Chemical Company to inquire of recommended
treatment for the exposed. Mr. W.J. McCoy of Dow recorded in a memo
to file his conversation with Mr. Buckley of T.C. :
Mr. M.S. Buckley of Thompson Chemical phoned Howard Sheldon
February 2, indicating that he believed they have a severe
chloracne problem with some of their employees. He indicated
that they already have two men affected and believe that they
may have two more employees that appear to be affected as
well. They are using Hooker's tetrachlorobenzene to make
their trichlorophenol.
Buckley was asking if Dow would have any recommendations for
medical treatment for their employees.
Thompson Tr. 31.

Thus, T.C. knew about dioxin as a contaminant in

TCP and 2,4,5-T as early as 1956 and certainly no later than the end
of 1966.
The military placed no restrictions on T.C. with respect to
its manufacturing processes.
of processes to use.

T.C. had clear discretion in the choice

See, Thompson, TR. 38.

T.C. well understood

that the process used determined the amount of dioxin in the 2,4,5-%.
When M.E. Buckley of T.C. called Dow to discuss T.C.'s chloracne'
problem, Mr. Buckley "started talking about the chemistry of this
material.

Apparently, Mr. Buckley knew the chemical origins of dioxin

and knowing that, knew that alternative manufacturing processes existed
-58

T.C. was fully aware of process alternatives. T.C. had absolute

freedom to select the manufacturing process.

Had the military known

that different temperatures, pressures, alcohols, and phenolate water
content resulted in different levels of dioxin contamination, there
can be no doubt, the military would have required the -safest method.

As previously shown, different manufacturing processes
resulted in different levels of dioxin contamination and while
T.C. and the other defendants were clearly aware of that fact, the
military was ignorant of this matter because T.C. did not warn the
military of the relationship between process selected and level
of dioxin.

Thus, T.H. also was part of the conspiracy of

silence to conceal from the military.

The facts of presence

of dioxin, associated health hazards, and risk reduction processes.

298
-59-

L - HERCULES INCORPORATED WAS KNOWLEDGEABLE
ABOUT THE MANUFACTURING PROCESS, DIOXIN
AS A CONTAMINANT, DETECTION METHODS, RISK
REDUCTION METHODS, AND HEALTH HAZARDS
ASSOCIATED WITH EXPOSURE TO DIOXIN.

Hercules sold the product known as "Agent Orange" to
the military beginning sometime in July, 1965.
The "orange" was a mixture composed of equal volumes of
2,4-D and 2,4,5-T.
Sometime in February, 1965, Hercules learned from another
defendant, Dow Chemical Company, that a previously identified
acnegen (chloracnegen) was a contaminant in 2,4,5-T (Frawley dep. 35)
That beginning sometime in June, 1965, Hercules knew that
the 2,4,5-T which it was selling to the military was contaminated
with dioxin (Frawley depo. 24; 67).
Hercules learned from Dow in March, 1965 that the acnegen
was dioxin (Frawley depo. 37) , and that dioxin had the capacity
to produce physiologic

and systemic injury at a very low dosage

(Frawley depo. 47).
Hercules knew that unless dioxin was removed from inter­
mediates such as trichlorophenol it would carry though to the
finished product. (Frawley depo. 65, 70).

-59a-

;

299

0

Hercules produced dioxin contaminated herbicides which
were ultimately sold to the military for use in Vietnam.

Although

the evidence as to the dioxin content of Hercules' herbicides is
disputed by T’ercules, it was sufficient to persuade this Court to
recently reconsider and deny Hercules' Motion for Summary

Judgment.

The evidence included:
1.

The Hercules internal memorandum (Ex.14a)/ reporting
that Dow's sampling showed an excess of 2 ppm. dioxin
in Hercules product as late as 1966;

2.

The fact known to Hercules that Dow was purchasing
Hercules' contaminated 2,4,5-T for sale to the
military in order to fulfill Dow's contracts for
delivery of Agent Orange;

3.

The Gulfport, Mississippi sampling which revealed
that 5 - 10% of the Hercules samples tested contained
dioxin in the range of 14 - 16 parts per million;

4.

Hercules knowledge since the 1950's of dioxin
formation in its 2,4,5-T and 2,4-D manufacturing
i

process ;
5.

Hercules knowledge of chloracne problems experienced
by its. plant employees during the period 1950 - 19l>9.

-59b-

300
V

Hercules never informed any agency or department of
Government, particularly the United States military to whom
it sold "orange", that the product it was selling to the military
was contaminated with dioxin.

That Hercules never disclosed to any agency, or any
department of Government much less did it notify the military to
whom it was selling the dioxin-contaminated "orange" the information
it had obtained both from industry and independent sources concerning
the toxic effects of exposure to dioxin and its potential hazard
to human health including disfiguring skin

diseases, liver damage

and systemic diseases. (Frawley depo. 78-79; 87-88; 90-91; 93-94;
95; 104-107; 110-111; 113-114; 115; 130-133; 138).

Hercules processes for manufacturing 2,4,5-T were at all
times proprietary.

(Frawley depo. 71-72).

Hercules never disclosed the details of its manufacturing
process to the military or to any agency of government at any of
the times relevant to this litigation. (Frawley depo. 28).

-59c-

301

II.

DEFENDANTS' MISREPRESENTATIONS OF
THE SAFETY OF THEIR HERBICIDES TO
OTHER GOVERNMENT AGENCIES

Concurrently with their conspiracy of concealment
and failure to warn the military, defendants also attempted to
silence any criticism of dioxin contaminated 2,4,5-T and to
obtain the United States Governments' approval of the contami­
nated herbicides whech they were selling to the military.

De­

fendants formed what came to be known as a "joint industry task
force on phenoxy herbicide tolerances" whose sole purpose was to
persuade the pesticide regulation division (PRD) of the United
States Department of Agriculture (USDA) to declare various
phenoxy herbicides, including 2,4,5-T,. as toxicologically safe.
The technical term used was "negligible residue tolerance."
On or about August 23, 1966, the Task Force held its
first meeting at the Madison Hotel in Washington, D.C.
Members of the Task Force included representatives of
Defendants

Diamond-Shamrock,

Chemical . Co.,

Hercules,

Inc.,

Monsanto Co.; Dow

and Thompson-Hayward, later to be joined by Thompson

Chemical Corporation and Uniroyal, Inc.
The

Task Force was convened under the aegis of the National

Agricultural
organization

Chemicals Association, a chemical industry activist
owned, operated, managed and controlled by the chemical

industry.

elected

j

Mr. George E. Lynn, an executive of Dow Chemical Company was
Chairman while Mr. C.L. Dunn, an executive of Hercules, was

302

elected Vice-Chairman.
-60-

The minutes of the August 23, 1966 meeting
revealed that the National Agricultural Chemicals Association
had called the meeting at the request of an unidentified member
company.

The purpose of the meeting as set forth in the minutes

was to ascertain if the companies present wished to form a Task
Force and work jointly in an effort to secure negligible residue
tolerances for phenoxy herbicides.

Put another way, its purpose

was to persuade the United States Department of Agriculture to
declare phenoxy herbicides such as 2,4,5-T safe (nontoxic to
humans and animals), notwithstanding the mass of information
which each other concerning the toxicity of 2,4,5-T to humans.
The member companies meeting decided that the task force
would be foremd,
"...to work with the Food and Drug Administration and
the United States Department of Agriculture for the
purpose of securing the establishment of tolerances
for existing no-residue registrations of phenoxy her­
bicides (— 2,4,5-T— )."
One of the activities delineated in the minutes is as
follows:
"— 2 Each member of the task force will compare and
submit to the Chairman a listing of the toxicological
and residue information which his company has on each
of the herbicide chemicals involved..."
The next meeting of the task force which occurred on

j

September 27, 1966 at the Jefferson Hotel in Washington, D.C. r
was attended for the first time by a representative of Thompson
Chemical Corp.

Consequently by September 27, 1966, defen­

dants Dow Chemical Co., Thompson Chemical Corp.,
Diamond-Shamrock, Monsanto Co., Thompson-Hayward, and Hercules, m e .
- 6 1 -

303
3b

were now members of the industry Task Force. Significantly, by this
time, all defendants were aware of dioxin contamination of 2,4,5-T and
the fact that it carried through to the end product posing a hazard to
consumers.
Hercules Chief Toxicologist, Dr. John P. Frawley, had by
this time not only received information from Dow, but also from
Monsanto and Badische in Europe concerning their problems with dioxin
contamination arising out of the manufacture of trichlorophenol.
They were also aware of potential hazards to human health
based upon the March 24, 1965 dioxin conference (supra) as well as the
subsequent contacts by Dow with other companies to inform them of the
frightening implications of their continued manufacture of dioxin
contaminated 2,4,5-T as per the Frawley memorandum dated July 12,
1965.
At

the

September

26,

1966

meeting,

the subject of

"toxicological and residue data" arose and it was decided
"— that each member of the task force -is to send to Dr.
Popham, any and all toxicological and residue data which he
may have relative to phenoxy herbicides. . ."
The Task Force engaged a Dr. Popham whom later minutes would
describe as formerly with the Agricultural Research Service of the
United States Department of Agriculture. He was, in effect, to become
the Task Force's point man for purposes of deceiving the government
concerning the nature and extent of the toxicological data which was
locked within the phenoxy herbicides industries' confidential files.

On October 25, 1966, the Task Force again met, this time at
the offices of the National Agricultural Chemicals Association in
Washington,
D. C.
The minutes reflect that the

304
-62£)-% 3 C *

Agricultural Research Service of the United States Department of
Agriculture, appointed Dr. L.L. Danielson of the Crops Research
Division "— to work with the Task Force — " The minutes further
describe that Dr. Danielson
"— is going to search the USDA files for any residue data
that is available and Dr. Popham will work with him to
collate it with what the Task Force already has. — "

to

Dr. Danielson was to search the USDA files
determine whether those files had any information on the toxicity

of the herbicides under consideration including 2,4,5-T. What Dr.
Danielson and his superiors at the USDA did not know was that current
toxicological data on the toxicity of 2,4,5-T was safely reposing
within the Task Force companies who had solicited the USDA's
“assistance." As will be seen (infra) the USDA had not an inkling of
the problem of dioxin contamination of 2,4,5-T as the Task Force
conspirators well knew.
The minutes"of the January 18, 1967 meeting of the Task Force
reveal that Dr. L.L. Damelson of the Agricultural
'Department had, by that time, been apparently retained as a part-time
"consultant."
How this squared with his duties at the US Department
of

Agriculture

and a possible conflict of interest is unclear.

It

seems not to have presented any problem to the task force.
At

that

meeting the committee “discussed" the fact that a

point needs to be made with both the FDA and PRD/USDA that there is
considerable public interest involved in the continued use of 2,4-D,
etc-,

(including

2,4,5-T)

and

that in view of all the data now

available, the agencies should extend themselves to consider and act
favorably on the Task Force's proposition that the negligible residue
tolerances should be established for all current registered uses.
None
producers
with the
animals

of

i
the data obtained by Hercules or any 'of the other

from Dow concerning the toxicological hazards associated
use of the product and the adverse impact upon laboratory
as

reported by Dow at the March 24, 1965 conference

305
-63-

O '* * 1

and in the other'communications between the defendants ever found
its way into the petition.

On March 28 of 1967, Mr. George E. Lynn, an executive of Dow
Chemical then Chairman of the industry Task Force composed a report
detailing the activities of the Task Force including
the individuals who would be cooperating with it in establishing a
negligible residue tolerance.
The report shows that several
representatives of the USDA including the Administrator of the
Agricultural Research Service were invited to cooperate with the Task
Force.
The report further indicates that Dr. George W. Irving, Jr.,
administrator of the Agricultural Research Service of the USDA and Dr.
James L. Goddard, Commissioner of Food and Drugs, were invited to
"cooperate'' with the Task Force in this project "by supplying such
technical assistance and data as would be appropriate with the public
interest."
The
of

report further shows that the committee in the presence

representatives of the USDA and the Food and Drug Administration

made it a point to stress:
."that in view of the wide use of these herbicides by the
American farmer for food production, the Task Force felt the
USDA and the FDA also had a vital interest in the continued
availability of these essential herbicides..
One

of the objectives of the Task Force as described in the

memorandum was to:

Î

306
-64-

O '5

. "collect all available data from private and published
sources with respect to toxicity . . . pertinent to the use
of any and all phenoxy herbicides— "
"— The probable sources of such data being
(a) Agricultural Research Service, USDA;
(b) industry (data
registrations);

used

in support of no residue

(c) state experiment stations;
(d) scientific literature;
(e) Food and Drug Administration, USDHEW.
Significantly, the kind of "industry" data to be supplied was
not

left to speculation.

It was to be only that data which could be

"— used

in support of no.residue registrations — " As will be seen,
any belief that the U. S. Department of Agriculture or the
Department of Health, Education and Welfare might have had about
' industry supplying its current data or directing USDA to its
scientific literature would at the time of submission of the petition
turn out to be a sham. As will be further seen (infra)-, not only did
industry not report the state of its current knowledge about dioxin
contamination of 2,4,5-T, but deliberately submitted antiquated
literature none of which was critical of 2,4,5-T much less containing
any mention of an acnegen or a chloracnegen and certainly not dioxin.
By
the minutes,

the time of the April 20, 1967 meeting, as reflected in
the Task

Force learned that

!

. . . the FDA's concept of a negligible tolerance is in a
range of 0.1 -ppm but 0.2—0.3 ppm is not out of line if data
justifies it. . ."
Of
contamination

course,

the

0.1 ppm etc., has no reference to dioxin

since

the

USDA at that juncture has absolutely no

knowledge from the Task Force about the problem of dioxin
contamination of 2,4,5-T. One would expect that, given defendants
claimed knowledge by USDA, FDA and HEW of the dioxin contamination
problem

and

its

307

potential to human health, at least one of these
-65-

0' 3 ^

minutes would have shown some discussion and perhaps even a
disclosure to these agencies or their representatives at the
meeting about the potential hazards-

The minutes contain no such

reference The minutes contain a schedule of the diffèrent phenoxy
herbicides and opposite 2,4,5-T all defendants,except Uniroyal
appear to have contributed towards the fee for putting the
petition together and the filing.

They each appear to have

been assessed the sum of $1,100.00.
On May 11, 1967, the National Agricultural Chemicals
Association on behalf of the task force informed Hazelton
laboratories by letter, that it had been selected to prepare
the petition to have 2,4,5-T declared safe to.humans, animals
and crops.

The fraud and deception continued with the

following empty promise described in the third paragraph of
the letter to Hazelton:
"The industry Task Force will turn over to
Hazelton all of the information on the above mentioned
phenoxy herbicides which it has gathered from various
sources with respect to animal toxicity and crop
residues..."
An examination of the studies concerning animal toxicity
submitted with the petition reveals in substance that 2,4,5-T
is as safe as drinking water.

Of course, the V.K. Rowe studies of

1950 were included, showing 2,4,5-T to be safe while the V.K.rRowe
studies of 1965 showing toxicity to humans and animals as discussed
at the secret March 1965 dioxin conference were conspicuously absent.

308
-66-

The Task Force minutes of October 17, 1967 report

"considerable discussion was given to possible handling of
the use of. these herbicides on rangeland. The high
application rates involved, up to 6 pounds per acre, could
result in high residues on the treated forage immediately
after application. . ."
Significantly, the military only used 3 pounds per acre in
Viet Nam. The/ Committee then had to consider the problems associated
with application of 6 pounds per acre of 2,4,5-T. The minutes reflect
that there was discussion of possible approaches such as
". . .requesting a sufficiently high numerical tolerance,
requesting that the use be declared a "non-food use," and
using label statements specifying a minimal time interval for
grazing the treated range and/or for slaughtering cattle
which have grazed the land. . .“
The Committee then decided as a better solution
. . to list this use under a new heading "Forest Grass,
Pasture, Range. . ."
It was also decided to include in the
. . . petition the notation which appears in the 2,4-D entry
in the USDA summary of registered agricultural pesticide
chemical uses under the "Pasture: Clover, Grass" item to the
effect: "Do not graze dairy animals on treated areas within
seven days after application."

ability

Nothing appears to have been beyond the imagination and
of this resourceful group of conspirators. With a spray rate

of 6 pounds per acre the only way to overcome the toxic residue was to
have the USDA increase the tolerance level. Of course, at this-- point
there is still no mention by industry of dioxin contamination to the
product and its potential hazard to human health. The fact that the
Task Force did not wish to permit the dairy animals to graze on
treated areas for at least seven days after application demonstrates
some consideration for animals when weighed against the fact that no
one told the military to keep the soldiers out of the sprayed areas
for

at

lease one week.

The
Danielson
the

minutes

i

further reflect that at 12:00 noon, Drs. L.L.

and D.L. Klingman of the Agricultural Research Service of

USDA joined the group-

Dr. Klingman is quoted as discussing the

spraying of range lands with herbicides and that many more acres would
-67-

^A

be benifited if they were sprayed.

He is further quoted as urging

• that the task force seeked to obtain clearance for
this use so that farmers and ranchers could continue to
utilize these valuable tools. ."
However,

his

part-time consultant
further when he

associate
to

from

the USDA, the'' occasional

the task force, Dr. Danielson, went even

"promised to assist the task force in every way possible and
proper in obtaining regulatory clearance for these materials
so as to keep them available. Specifically, he and Dr.
Klingman promised to consult their files in an effort to
locate any pertinent data which would be helpful to the task
force in its efforts to obtain tolerances."
It is clear that the minutes do not reflect any knowledge by the
USDA, FDA, HEW that any of these phenoxy herbicides, including
2,4,5-T are toxic.

Significantly,

for the first time, Uniroyal Chemical joined

the Task Force by E.A. Hafner in attendance.
On

November

27, 1967 on the stationery of Hercules, Inc.,

C.L. Dunn, Chairman of the industry Task Force wrote to Dr. Harry A.
Hayes, Director of the Pesticide Regulation Division of the United
States
National

Department of Agriculture.
Agricultural

In substance, he stated that the

Chemicals Association Industry Task Force on

phenoxy herbicide tolerances .had assembled petitions requesting
tolerances to cover uses previously registered on a "no-residue"
basis. What this means is that previously, the phenoxy herbicides had
been registered with the USDA as.having a no residue toxicity. Now,
the

industry

was seeking by its petition, to establish a toxicity

tolerance for these very same herbicides.

^

Mr. Dunn went on to misrepresent on page 1 of the letter:

"There is no hazard to animals as evidenced by
the extensive use of these materials for more than a
decade, nor is the presence of residues in meat or
milk a regulatory problem..."
Nothing was said in that letter about the animal studies
conducted by Dow; nor that Dow had determined that dioxin was
a contaminant in 2,4,5-T which carried through unless extracted,
carried through to tne end product, nor that Dow had alerted all
producers of 2,4,5-T to the potential hazards associated to humans
exposed to dioxin contaminated 2,4,5-T; nor that Dow had set an
internal specification of 1 ppm of dioxin contamination based
upon their experience with laboratory animals; nor that Dow had
expressed to the producers at the March 24, 1965 meeting that
their analysis of their competitors 2,4,5-T showed what fate
described as "surprisingly high amounts of the acnegen" which
they identified as-dioxin; nor was there any mention of the
telephone call of the substance of knowledge gained by Dr. Frawley "
from the telephone call received from Earl Farnham of Dow Chemical
Company on July 9 of 1965 alerting Dr. Frawley to the fact that
Dow was frightened that the whole industry might explode and
that there might be governmental intervention by way of a
Congressional investigation and a banning of pesticides because
of what Dow perceived as "alarming amounts of acnegen" in their
competitors' 2,4,5-T; nor any disclosures by Mr. C.L. Dunn who
attended the secret dioxin conference with Dr. John Frawley on
4

i

behalf of Hercules and was copied on the memo Dr. Frawley wrote
recounting his conversation with Farnham of Dow.

At no time did

the so-called industry Task Force on phenoxy herbicides

69

ake disclosure- to the USDA or FDA people in attendance at
heir meetings of the common knowledge which they had all
cquired beginning in November, 1964 when Dow had devised a
eans for the identification of dioxin in 2,4,5-T.
On November 27, 1967 on the stationery of Hercules, Inc.
r. C.L. Dunn, acting in his capacity of Chairman of the Task
orce wrote to Dr. Harry Hayes, Director of the Pesticide
egulation Division of the United States Department 'of Agriculture
nforming him that the industry Task Force had assembled petitions
equesting tolerances on the phenoxy herbicides.

The fourth

aragraph of Hr. Dunn's letter continues the misrepresentation
nd fraud when he states:

"there is no hazard to animals as evidenced by the extensive
use of these materials for more than a decade — “
On

that same date, November 27, 1967, Mr. Dunn wrote to the

Force informing them that both he and Don McCollister (Dow) were
ouraged by the apparent unconcern of the USDA
"for the farmer users of phenoxy herbicides. In addition.
Dr- Anderson seemed quite opposed to a cooperative program.
He expressed sensitivity to criticism by G.A.O. Investigators
who recently complained about USDA developing data
subsequently used by a manufacturer -for registration,
purposes. — "
On December 8, 1967, the conspirators submitted to the
>etition control branch of the Food and Drug Administration of
:he Department cf Health, Education and Welfare a petition to
:a

2,4,5-T declared safe.

The cover letter is on the staticn-

jry of National Agricultural Chemicals Association, signed
:. L. Dufm, Chairman.

by

The petition consists of seven sections.
-70-

a-g.

S e c t i o n C reads as follows:

"full- reports of investigations made with respect to
the safety of the pesticide chemical. — "
An examination of the bibliography in support of the Task Force
claims a lack of toxicity

shows that not one study critical

of 2,4,5-T was cited.
Instead, these defendants submitted to the unsuspecting
gullible and ingenuous USDA, Food & Drug Administration, and HEW,
studies by V. K. Rowe, McCollister and Spencer of Dow Chemical Company
dated 1950, all of which had been negated by Dr. Rowe's "startling"
confirmation of dioxin as the toxic chloracnegen in November, 1964 and
Dow's subsequent experimentation with dioxin contaminated 2,4,5-T upon
laboratory animals, none of which work found its way into the open
scientific literature much less into the FDA petition.
Subsequently, the Task Force received a letter dated
April 8, 1968 from the Department of Health, Education and Welfare
f

to Mr. C. L. Dunn, Chairman of the Task Force, informing Mr.
Dunn that the toxicology data submitted by the industry was in­
sufficient especially with respect to the fact that there would
be a carry over into meat and milk.
The petition was subsequently withdrawn along with the
petition which sought to have 2,4-D declared safe also.
Defendants' efforts to disparage any claims of the toxicity
of dioxin did not cease, however. When the National Cancer Insti­
tute which commissioned the so-called "Bionetics Report" released
its findings concerning the potential health hazards of dioxin
contaminated 2,4,5-T, Dr. John Frawley, Chief Toxicologist of

\

Hercules, sought to belittle the ignorance of the National Cancer
V.

313

Institute about the toxicity of dioxin. In a letter dated
November 25, 1970 responding to a letter from his counterpart
in England, Dr. John C. Higgins, of the Hercules Powder Company
of England, Dr. Frawlev made the following caustic and critical
disparagement of the National Cancer Institute's knowledge of
dioxin and its toxicity:
"-- the Government Agency sponsoring the study (NCI)
was not familiar with the toxicity of the dioxin and
allowed publicity on the results without consultation
with better informed government or industrial scien­
tists. -- "
He reserved his most severe criticism for the surgeon general when,
in that same letter to Dr. Higgins, he wrote:
"-- on the basis of this single observation in mice, the
Surgeon General (who has never in the past gotten involved
in safety evaluations) declared before a Congressional
Committee that even pure 2,4,5-T presented an imminent
hazard to the health of the public. This triggered the
banning of 2,4,5-T for all household and several indus­
trial uses ..."
It was not until 1979 that the Environmental Protection Agency
(hereinafter "EPA"), although knowing that some manufacturers
produced 2,4,5-T with less than 1PPM, instituted deregistration
proceedings against 2,4,5-T. The EPA's Prehearing Brief on The
Risk Associated with the Registered Uses of 2,4,5-T and Silvex
concludes:
"In sum, the data on toxic effects in animals and
humans together with the data on exposure potential .•
establish that the continued use of 2,4,5-T and Sil­
vex contaminated with TCDD (dioxin) pose risks of
adverse effects on human health.
(parenthetical added).
Though the EPA is undoubtedly concerned with the health .
hazard dioxin in 2,4,5-T presents to those who manufacture it,
the focus of EPA's concern is the user, the innocent bystander
and the environment.

Since EPA apparently believes that less

than 1PPM is unsafe. Tfc-? inescapable inference is that defen­
dants' conspiratorial conduct, misrepresentations and failure j
to warn were responsible in substantial measure for the EPA's
delay in commencing deregistration proceedings.

314
-72-

f
III.

THE DEFENDANTS SUPPLIED DIOXIN CONTAMINATED
HERBICIDES WHICH WERE MIXED TOGETHER BEFORE
BEING SPRAYED IN VIETNAM MAKING IMPOSSIBLE
IDENTIFICATION OF WHICH DEFENDANT'S HERBICIDE
CAUSED INJURIES TO PLAINTIFFS.

The defendants' dioxin contaminated herbicides were
supplied in drums not bearing the defendants' corporate name.
They were mixed together before spraying:

A description of

"standard operating procedures" is contained in an official
Q/
U.S. Air Force Technical Report— , (pp. 1-15, 15).
Each of the 11 different companies that manufactured
military herbicides packed them in new ICC 17C 55-gal 18 gauge
steel drums for shipment to Southeast Asia.
Each herbicide drum was marked with a three-inch colorcoded band around the center to identify the specific military
herbicide.

This marking was initially a 12-inch band, but was

changed to a 3-inch band in March 1966.
About 10 out of every 10,000 drums shipped were received
in a damaged or defective state.
rate of 0.1 percent.

This represented a damage

About 50 percent of these damaged drums

leaked as a result of punctures or split seams.

There were

caused by improper loading and defective drums.

Forklifts

operated by Stevedores also caused punctures.

Redrumming was

accomplished at the ports.
About 65 percent of the herbicide was snipped uo the 2Qth
Ordnance Storage Depot, Saigon, and 35 percent was shipped to
9_/ "The Toxicology, Environmental Fate and Human Risk of Herbi­
cide Orange and its Associated Dioxin" Alvin L. Young, et al.,
October 1978.

31

-73-

0

7«

the 511th Ordnance Storage Depot, Da Kang.

Under the normal

handling procedures, drums were unloaded at Da Nang and Saigon
from the cargo vessel directly into semi-trailers and were
placed in an upright position.

The-trailers were driven to

the various units of the 12th Air Commando Squadron (primarily
at the bases of Da Nang, Phu Cat, or Bien Hoa) for disposition.
Normally the contents of the drums were transferred into
blocked F-6 trailer tanks through a suction tube without remov­
ing the full drums from the semi-trailers.

Each F-6 trailer

held 4,298 gal or about 78 drums of herbicide.
Vihen the herbicide was pumped from the drums into the
F-6-trailers about 0.5 to 1.5 gal remained in the drum.

Hence

the drum was placed on a drain rack and the "drippings" were
collected from many drums in a pan-tvpe receptacle and used for
spraying base perimeter areas.

316
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IV . DEFENDANTS' JOINT ACTION TO PREVENT
GOVERNMENT PRODUCTION OF 2,4,5-T AND
2,4-D
The defendants together comprised virtually the entire
2,4-D and 2,4,5-T industry.

As we have demonstrated, they acted

conspiratorially or in concert to conceal from or .misrepresent
to the government the hazards associated with their products.
In addition, to guard their dominant market position, they acted
jointly to prevent the government from constructing and placing
in operation at Weldon Springs, a plant for the production of
2,4,-D and 2,4,5-T.
authored

This is evidenced by a document

by M. F. Wilkerson, Diamond's Marketing Manager, re­

flecting the industry decision taken by the defendants at a
meeting October 4, 1963 of the Task Force created by the National
Agricultural Chemical Association (NACA), attended in person or
by representation by defendants, Monsanto, Hercules, Diamond,
Dew & Thompson-Hayward.
The document reviewed the industry capacity "as secretly
submitted", to produce both 2,4-D and 2,4,5-T as opposed to the
purchase patterns of the military.
Although the production data submitted by each defendant
was coded to preserve secrecy, Mr. Wilkerson estimated their
respective capacities:

i

317
-75-

"A bit of upside-down reading gave the following breakdown of the partici­
pating rrembers' capacities. These were coded but are exact. I have attached
Company names which may or may not be, with the exception of Diamond, asso­
ciated correctly with the capacity number.
2,4,5-T
5.5 MM - Hercules
3.0 Mi - .Diamond
12.0 KM - Dow
7.2 MM - Monsanto
4.5 Mi - T-Hayward

2,4-D
5.0 KM - Hercules
12.0 MM - Diamond
40.0 MM - Dow
24.0 MM - Monsanto
14.0 MM - Chitxnan

TOTALS 95.0 MM
32.2 MM
T-Eayward acknowledged they produced no 2,4-D as did Chitman for
2,4,5-T.
This group's best estimates for total annual domestic requirements of
D and T were:
2,4-D - 55 MM lbs.
2,4,5-T - 18 MM lbs. _
Hooker acknowledged they new have TCB'capacity to supply all producers,
an the basis of these estimates, except for Dow (who produce their own) and
T-Hayward (who are presently being supplied TCP by Dow. )"
The task force then adopted the following position:
"SUMMARY OF POSITION
The group of phenoxy herbicide producers at their meeting of October 4, 1968
after estimating the capacity of the domestic industry to produce 2,4-D and
2,4,5-T; after estimating as accurately as possible the dcræstic civilian
consumption of these products and the military requirement based upon the
stated needs and current delivery schedules, concluded that there is sufficient
domestic production of 2,4-D to fully meet both the civilian and military
requirements, and that the production of 2,4,5-T would meet a substantial part
of both the civilian and military need. It was concluded that the questions
which prompted the Government Officials to make the decision to construct and
place in operation a plant at Weldon Springs to produce both 2,4-D and 2,4,5-T
have changed, and that the industry should request an opportunity to explore
these data with the Government.
It was further concluded that even if it is assumed that the military will
require the full amount of its needs as heretofore estimated, that there
would be a very substantial over-production of both 2,4-D and 2,4,5-T if the
Weldon Springs plar^. in <~>p'?-'=ated at full capacity. This raised questions¿of
serious inport to the domestic industry which should be thoroughly
explored with the Government.

318
-ic,-

V

V.

THE MILITARY WAS NOT AS KNOWLEDGEABLE
AS THE DEFENDANTS ABOUT THE MANUFAC­
TURING PROCESS, DIOXIN AS A CONTAMINANT,
DETECTION METHODS, RISK REDUCTION
METHODS AND HEALTH HAZARDS ASSOCIATED
WITH EXPOSURE TO DIOXIN

The disparity of knowledge between the defendants and
the military was enormous.

It is a significant factor giving

rise to the defendants' duty to warn the military of the hazards
accompanying use of their herbicides known to the defendants,
and the duty to inform the military of the means of risk elimi­
nation or reduction as this Court noted in 534 F. Supp- 1046, 10 55:
"A supplier should not be insulated from liability
for damages that would never have occurred if the
military had been apprised of hazards known to
the supplier. A supplier, therefore, has a duty
to inform the military of known risks attendant to
a particular weapon that it supplies, so as to
provide the military with at least an opportunity
fairly to balance the weapon's risks and benefits."
The good sense of imposing a duty to inform is readily
apparent.

Such a duty does not interfere with the military's

prerogatives by requiring suppliers and courts to second-guess
the military's decisions.
rogatives by

Indeed, it enhances those pre­

helping to ensure that suppliers will share their

knowledge and expertise with governmental decisionmakers.

Nor •

does such a duty cause delays in supplying needed ordnance the suppliers are obligated merely to share knowledge and
expertise already in hand.

319
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In o rder for kno w l e d g e about hazards to have helped the

military "fairly to balance a weapon's risks and benefits," it
must have been possessed by individuals who were in positions
of sufficient authority and responsibility to act on that know­
ledge ■

If the decisions in question were those regarding

whether and how to deploy Agent Orange in Southeast Asia and
which of the various forms of the Agent to employ, knowledge
about hazards must have been possessed by a decisionmaker
relatively high up in the chains of command and authority.
Moreover, for the knowledge to have informed that relevant
decisionmaker, it must have been possessed by him in a cohesive
manner so that he would be in a position to integrate it into
a. meaningful whole.
It is not sufficient for military contractors to share
information with anyone at all or with individuals so far down
the relevant chains of command and authority as to render the
information useless as a means of increasing the rationality of
the

policy decisions being reached by the appropriate decision­

maker at the appropriate level in the chain of authority.
Nor is it sufficient if the information consists of
isolated bits and pieces of knowledge, scattered both vertically
and horizontally throughout the governmental bureaucracies and
shared in piecemeal fashion, with one person in government being

■i
informed as to another aspect.

The first of these threats to r

rational decisionmaking might be termed the threat of vertical
nonintearation.

Both defeat the objective of- rational

320
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decisionmaking by. preventing knowledge about hazards from being
available to those attempting, in the Court's words, "fairly
to balance the risks and benefits."
In their prior submission, "Plaintiffs' Memorandum
Concerning the Government Contract Defense Phase of the 'Agent
Orange' Products Liability Litigation: A Management Plan for
the Discovery Phase”, June 8, 1982, plaintiffs addressed the
legal implications of the question of who in the government
must have known, and noted that under the relevant case law,
including that of the product liability field, the following
rules apply in determining the issue of knowledge imputation
or information transference:
1.

Inter-Agency imputation of knowledge is wholly

impermissible and intra-agency imputation use narrowly limited
(pp. 22-68).
2.

Information transference must be targeted to

the appropriate decisionmaker and focused to alert to danger
(pp. 22-31).
It is clear from the record that judged by these
standards, the defendants have breached their duty to warn
and inform the responsible governmental decisionmakers.
Apart from the question of who (ie. the high level
rational decisionmaker) in the government should have possessed
the information defendants had and withheld, is the issue of
what information would rational governmental decisionmakers
have wanted the chemical companies to share with them in order
to be "fairly to balance the risks and benefits, II given the

levels, and the third focusing on risk avoidance.

The fourth

type of information is more judgmental than factual, consisting
of the conclusions, however, that the chemical companies had reached
regarding the risks presented by Agent Orange.
Finally, there is the question of "when?" —

ie., the

relevant time frame within which the government must have had
knowledge about the hazards associated with Agent Orange?
Consistent with the concept of informed and rational
decisionmaking, the crucial time for the government to have
had knowledge of the hazards was the time during which decisions
were made regarding the purchase and deployment of Agent Orange
in southeast Asia.

The key to understanding the relevant time

frame is the. objective that the military not be forced unneces­
sarily to act on inadequate information.

Thus, suppliers of

the chemical herbicides were obligated to share whatever relevant
information they possessed at the

time of sale and were obligated

to share additional information.as it became available to them
throughout the period during which those herbicides were being
used by the government.
The discovery to date establishes that these chemical
companies were in a position, at little or no cost, and indeed
had the duty, to draw the hazard and risk avoidance pieces together
and timely warn and share them with the responsible government^
authority who made the decisions that directly and drastically
affected the welfare of the plaintiffs.

The defendant companies

322
-81-

9

failed to do this.
of officials

Defendants'elaborate discovery of hundreds
have at most produced bits and pieces of in­

formation about the hazards of dioxin in general scattered use­
lessly

across the length and breadth of various federal

bureaucracies.

Thus, defendants have also failed in their duty

to warn and inform the responsible governmental decisionmaker
as to the specific facts the military needed to know in order
to make an informed decision.

V...

à

323

VI.

UNDER THE PRECEDING FACTS AND CIRCUMSTANCES,
EACH DEFENDANT'S BREACH OF ITS SEPARATE DUTY
TO WARN MAY BE CONSIDERED THE "CAUSE IN FACT"
OF PLAINTIFFS' INJURIES, AND THE PROBLEM OF
SEPARATE DEFENDANT IDENTIFICATION THEREFORE
DOES NOT EXIST; BUT IN ANY EVENT, THE
DEFENDANTS MAY BE HELD JOINTLY AND SEVERALLY
LIABLE UNDER THE THEORIES OF CONCERTED ACTION,
ENTERPRISE LIABILITY AND ALTERNATIVE LIABILITY

Because of the manner in which the defendants sold Agent
Orange to the Government, and the manner in which the Government
then utilized it so as to expose the plaintiffs to its effects,
it is unlikely, no matter how firmly it is established that
Agent Orange in fact caused the plaintiffs' injuries, that any
plaintiff will be able to identify with certainty which one or
more of the defendants actually produced the specific batch of
Agent Orange to which he was exposed, to his detriment.

Rather,

because the defendants put no company-identifying marks on the
barrels of Agent Orange they sold to the Government, and the
Government treated the product generically, the most that
plaintiffs will be able to prove is that they were all injured
by Agent Orange, virtually all of which was produced by the
defendants.

To go further than this, and to require each

plaintiff to identify the specific defendant or defendants
whose Agent Orange caused his injury, would present impossible ■
problems of proof.
At one time in the law, perhaps, such problems of proof
might have been fatal to a plaintiff's case.

Th^ demands of

modern society, however, have brought chancre to the law of
causation and liability.

The courts have clearly recognizecf

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324

that if they are to continue to serve the ends of justice in
an evolving society, the rules of lav; they apply must also
evolve.

As the Supreme Court of California put it, in con­

sidering the similar problems of proof of causation and lia­
bility facing a plaintiff in a products liability action
involving the drug DES:
"In our contemporary complex industrialized
society, advances in science and technology
create fungible goods which may harm consumers
and which cannot be traced to any specific
producer. The response of the courts can be
either to adhere rigidly to prior doctrine,
denying recovery to these injured by such
products, or to fashion remedies to meet
these changing needs. Just as Justice Traynor
in his landmark concurring opinion in Escola
v. Coca Cola Bottling Company (1944) 24 Cal.
2d 453., 467-468, 150 P.2d 436, recognized that
in an era of mass production and complex
marketing methods the traditional standard of
negligence was insufficient to govern the
obligations of manufacturer to consumer, so
should we acknowledge that some adaptation of
the rules of causation and liability may be
appropriate in these recurring circumstances
Sindell v. Abbott Laboratories, 607 P .2d 924 , 926 (Cal. 1980,.) .
Or, as Judge Meyer of the New York Court of Appeals more
succinctly put it in another products liability action involv­
ing DES, "Products liability law cannot be expected to stand
still where innocent victims face 'inordinately difficult
problems of proof.'"

Bichler v. Eli Lilly & Co., 55 NY2d 576,

580; 450 NYS2d 776,779 (N.Y. 1982).

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,

325

Thus, Court as well as commentators have proposed means which
permit recovery by plaintiffs under circumstances such as these,
where the conduct or product of a specific defendant out of a
group of potentially liable defendants cannot be identified
as the "cause in fact" of the plaintiffs' injuries.

Such

proposals involve application of principles of "concerted
action", "enterprise liability", "alternative liability",
and, more recently, "market share liability".— ^
10/ The Court in Sindell v. Abbott Laboratories, 607 P.2d 924
(Cal. 1980) developed the market share liability theory
as a specific modification of the alternative liability
theory to surmount the rational difficulties in applying
the alternative liability theory in cases where not all or
substantially all potentially liable parties are named
as defendants. Since, as Exhibit 1 to this Memorandum
.clearly demonstrates, virtually all potentially liable parties
are named as defendants here, the problems presented in
Sindell, and the specific solution of market share liability
devised by the Sindell Court to overcome them, do not
apply. Plaintiffs, therefore, do not discuss the market
share liability in this memorandum.

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nn

Plaintiffs believe that the lengthy factual statement
fully supports the theories of concerted action, enterprise
liability and alternative liability.
addressed seriatum.

These arguments will be

However, there is good reason to examine

at the outset the implications of the failure to warn theory
as it has developed in this case.

On its own it is dispositive

of the problem of defendant identification.

The plaintiffs have presented facts in this case estab­
lishing that the defendant chemical companies failed to warn the
government about a broad range of risks related to the use of
Agent Orange.

Plaintiffs submit that the very special nature

of the breach of the

duty

to warn issue as it arises in

this case moots the issue of causation as it relates to the
identification of which defendant should be deemed responsible
for which plaintiff's harm.

As we shall demonstrate, each

defendant individually in the truest sense of the word was a
"cause in fact" of the entirety of the harm.

It will be helpful to focus on the nature of the failure
to warn claim.

Plaintiffs contend that each of the defendants

failed to warn of risks which they either knew or should have
known about.

These break down into various categories.

First,

plaintiffs contend that the defendant failed to share with the

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327
V ' ^

United States Government information concerning the possible
hazards attendant to the use of dioxin contaminated Agent Orange.
What suspicions did they harbor or should they have had that the
herbicide caused a broad range of diseases?

The defoliation project

subjected soldiers to doses and exposure to the herbicide hereto­
fore unknown to mankind.
backyard.

This was not spraying a bush in one's

Thousands of gallons of the defoliant were to be

sprayed from the air to defoliate jungles.

Thus, any test results,

experiments, suspicions and conclusions however tentative should
have been shared with the government with total candor.
have shown that this did not occur.

Second,

Plaintiffs

was a long

history of industrial accidents that indicated that problems of
dioxin contamination were related to the manufacturing process.
These accidents took place over a rather long period of time.
Some were.. o£ .consi.de.rabl e severi±.y. They

have been noted in

the factual introduction to this memorandum.

The disastrous results of these industrial accidents '
caused the defendants to discuss the need for extraordinary
precautions in the cleanup to assure that dioxin was avoided
or removed from the workplace and to protect the workers in
the cleanup process.

There was no assurance that the dioxin

which was the cause of these industrial catastrorh°s was avoided
or removed from the final product.

Plaintiffs have demonstrated

328
-8 6 -

that defendants failed to fully inform the government of these
industrial accidents, the precautions and methods discussed or
used to avoid the formation of or rid the plants of dioxin and
most important of the terrible consequences to those injured as
a result of exposure to the dioxin.

Finally, plaintiffs have shown that defendants had
information concerning their ability and non-ability to deter­
mine the level of dioxin contamination in the final Agent Orange
product.

Some defendants knew much about their ability to test

for dioxin and their ability to control its presence.

Others

knew that they were unable to test for the presence of the
dioxin contaminant and that their quality control techniques
were erratic at very best.

The evidence establishes that the

defendants failed to inform the government about their analytical
and testing capabilities and the methods available to them to
control the risk by instituting alternate methods of manufacture
that would significantly reduce or eliminate the dioxins or their
inability to control the risk in that their quality control techni­
ques were such that they did not know how to evaluate or control
r

the dioxin level that was in their product.

329
-87-

f

At first blush, it would appear that plaintiffs are
presenting a classic failure to warn case that would require
conformance to normal causation principles-

However, on

reflection it is clear that there is something very different
about this failure to warn case.

Warnings serve two purposes.

The standard failure to warn case serves the purpose of risk
reduction.

Most products raise the spectre of some element

of danger if the products are not used properly.

A warning

can reduce the probability of harm (thus effecting the riskutility balance) by alerting the user to risks that may even­
tuate should the user not follow the prescribed instructions.
Alternately, a warning may inform a user that he belongs to a
special class of persons who should not utilize a product at
all or utilize it with special precautions.
warning is very common in drug cases.
are

desianed to

achieve

a

This form of

Both forms of. warnings

¡reduction of risk since

they permit the user to intelligently respond to risks that
attend the use of the suspect product.

There is, however, another category of failure to warn
cases.

In that type case, the contention is not that the defen­

dant failed to warn so that risk could be reduced, but that
the risk level is constant and there is little that can be
done by the user to reduce the probability of harm.

The function
#A
of the warning in this second genre of product cases is to inform

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330

the user of risks attendant to the use of a. product so that the
user can decide whether he/she wishes to expose himself/herself
to an irreducible risk.

This class of failure to warn

cases is very closely analogous to the informed choice medical
malpractice case.

The issue in those cases is not the conduct

of the defendant per se, but rather the failure to give the
patient sufficient information so that the patient

can. make

an informed and knowledgeable choice as to whether to expose
himself to a given therapeutic procedure.

See e.g. Canterbury

v. Spence, 464 F. 2d 772 (DC Cir) cert denied 409 US 1064
(1972); Cobb v. Grant, 8___ Cal 3d 229, 104 Cal Rptr. 505, 502
P. 2d 1 (1972).
The product liability analogue to these informed choice
medical malpractice cases is exemplified by such well known
cas.es as Davis v. Wyeth Laboratories, 339 F. 2d 121 (9th Cir.
1968); Reyes v. Wyeth Laboratories, 498 F. 2d 1264 (5th Cir.
1974) cert denied 419 US 1096. Cunningham v. Charles Pfizer &
Co. Inc., 532 P. 2d 1377 (Okla. 1974).

In these cases use of

polio vaccine was attended with a small but irreducible risklevel which could not be affected by production.

In Davis v.

Wyeth Laboratories, Judge iderril recognized that he was faced
with this problem:
"There are many cases, however, particularly in the
area of new drugs, where the risk, although known
to exist, cannot be ... narrowly limited and where
knowledge does not yet explain the reason for the
risk or specify those to whom it applies. It thus

l

applies in some degree to all, or at lease a sig­
nificant portion, of those who take the drug.
This is our case; there seems to be no certain
method of isolating those adults who may be
affected adversely by taking Type III Sabin
vaccine.
In such cases, then, the drug is fit and its
danger is reasonable only if the balance is struck
in favor of its use. Where the risk is otherwise
known to the consumer, no problem is presented,
since choice is available. Where not known, how­
ever , the drug can properly be marketed only in
such fashion as to permit the striking of the
balance; that is, by full disclosure of the
existence and extent of the risk involved."
39S F. 2d 121, at 129.
The function of the warning in this case the court con­
cluded was not to reduce the risk but instead to provide the
plaintiff with the opportunity to decide whether to expose
himself to a risk which could not be further reduced by any
action on his part.

The Court noted:

"When, in a particular case, the risk qualitatively
(e.g., of death or major disability) as well as
quant itaf ively, on balance with. the. end sought to be achieved, is such as to call for a true choice
judgment, medical or personal, the warning must be
given." Id. 399 F. 2d at 129-130 (emphasis added)
Also see Model Uniform Product Liability Act. Sec. 104
(c)(3), Twerski, Old Wine in a New Flask-Restructuring Assump­
tion of Risk in the Products Liability Era, 60 Iowa L. Rev. 1,
44-46 and Twerski, Weinstein, Donaher and Peehler, The Use and
Abuse of Warnings in Products Liability - Design Defect Liti­
gation Comes of Age, 61 Cornell L. Rev 495, 517-521 (1976).
The importance of the stated distinction is that it
affects the causation issue in a most interesting fashion.

-90-

'If

332

V

the question is asked how responsible is each defendant for
not sharing the totality of all the risk information which it
knew or should have known about, the asnwer is clear.

The

failure of each defendant to warn the government was respon­
sible for the ignorance of the government and contributed, not
only to the use of each defendant's product, but to the very
decision to use Agent Orange as a defoliant at all.
That decision was not a divisible one.

There is -thus joint

and several liability in the most classic and traditional
sense.

The reason that this informed choice argument

resolves the identification problem is that the focus
has switched from the nuance of each defendant's product
to the defendants' collective and individual responsibility
for failing to inform the government so that it could make
a decision with all the information before it.

Since the

decision was non-divisible and was contributed to by
everyone's failure to warn, the liability ought
to be joint and several as well.

As long $ the failure to

deliver the requisite information was a substantial factor
leading to the decision to deploy Agent Orange, the plaintiffs
have fully discharged their burden on causation.

Concurrent

tortfeasors do not have the luxury of the but-for argument
in this context.

See, Anderson v. Minneapolis St. P. & St.

M.R.R.

C o . , 146-Minn.

Chicago

430,

179 N.W.

45

(1920), Kingston v.

& N.W.R. Co., 191 Wis. 610, 211 N.W. 913 (1927).

The facts

of this case support the conclusion that the

failure to discharge one's own duty to warn must be viewed in
the context of the

government's decision to utilize Agent

Orange as a defoliant.

The defendants were not lone rangers

in this case, totally unaware of each others activities.

The

facts point to a heavily concentrated industry with a high
degree of special expertise with regard to the manufacture
and use of herbicides.

This highly concentrated industry

dealt with a dizzying array of government agencies.

From time

to time bits and pieces of knowledge were in the possession of
one person or another in one government agency or another. The
information that was available to the defendants was or should
have been put together by the defendants in a coherent fashion
so that the responsible persons, in the..responsible government
agencies were delivered the total risk picture.

We shall

demonstrate at trial that this was never accomplished.
The defendants had full knowledge that the Agent Orange that
went to Vietnam was to be loaded in planes to be mixed and
sprayed without discrimination as to which defendant's product .
was being utilized.

The consequences of the dangers if the

suspicions and fears about dioxin turned out to be true were
staggering.

Hundreds of thousands of soldiers would be exposed

to the risk.

If we hypothesize that a government well aware of

the risk would have or well might have decided against the
defoliation then it would seem clear that the aforementioned

facts,if proven, strengthen the argument that each bears some
responsibility for that final decision.

The relationships

between the manufacturers and their knowledge of how the product
was to be deployed add to the strength of the argument that they
cannot easily separate themselves into fragments for the purpose
of causation.

Whether or not the aforementioned facts do or do

not amount to concerted action they are clearly a oredicate for
the proposition that the breach of the duty to warn cannot be
isolated.
Finally,and as a separate argument,plaintiffs

note that

several defendants had specific knowledge not only of the dioxin
contamination of their ovm product but of the rather substan­
tial problems that other defendants had with the dioxin content
in their product.

So much so that defendants were called

together to discuss the problem.

The government was the con­

spicuous uninvited guest to that meeting.

Once the -defendants

became aware of the problems that existed with regard to the
manufacture of dioxin contaminated Agent Orange the question is
did they have a duty to warn the government not only about their
own product but the problems that were being faced industry wide.
An argument could be made ,

given the long standing relation­

ships between such defendants as Dow and Hercules with the
government, that ei’en if they had decided not to manufacture and
sell Agent Orange to the government they would have had a duty
to disclose to the government the information that they had
1

-93-

335
fl'3'

discovered about the products of other chemical companies were
manufacturing the product at a highly toxic level.

The relation­

ships between these defendants and the government was not that
of pure strangers.

This is not the classic case of a stranger

who refuses to come forward and rescue another.

Long standing

relationships in which the parties have come to trust each
other's judgment may be a predicate for the imposition of an
affirmative duty to act.

See, e.g. Prosser, Wade and Schwartz,

Cases and Material on the Law of Tort, pp. 440-442 (Seventh
Ed. 1982).

Relationships having far less moment have been

held to trigger a duty to act affirmatively.

See, Connelly v.

Kaufmann & Baer Co., 349 Pa. 261, 37 A. 2d 125, (1944); Parvi
v. City of Kingston, 41 NY2d 553, 344 NYS2d 161, 362 NE2d 553
(1977); Hutchinson v. Dickie, 162 F. 2d 103 (6th Cir. 1947).
However, this case is not one where defendants were
uninvolved in the manufacture and sale of Agent Orange.

They

were selling to the government and were looked to by the
government as the most important source of information with
regard to herbicides. Dean Prosser has noted that the imposi\
tion of a duty is a matter of good common sense:
"It should be understood at the outset that there
is no magic in 'duty'. It is merely a word with
which the court states its conclusion that there
is no liability; and it means whatever the court
wants it to mean in the particular case. No
general formula ever has been devised to state
when there is, and when 'J crc- is not, a duty in
negligence cases; and it is very likely that none
will ever be. This is because consideration of
social policy vary depending on the precise issue

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336

before the court and social policy questions always
underlie the duty issue." Prosser, Wade and Schwartz
p. 404 (Sixth Ed. 1S76)
The court thus must determine whether the conditions in
this case support the imposition of such a duty.

We believe

that given the relationship between the government and the
defendants, the high foreseeability that danger to hundreds of
thousands of soldiers would result if the information was not
shared, the common use of the Agent Orange in Vietnam through
indiscriminate mixing, and the highly specialized knowledge
that existed within the chemical industry that a duty to inform
the government of the other defendant's problems is established
beyond peradventure. When one adds to this the "take charge"
aspect of Dow and other defendants with regard to the informa­
tion that was to be disseminated and the attempt to jealously
guard it from public view,the duty issue simply disappears.
Once a defendant has decided not to stand aside but to act
affirmatively,the duty to act reasonably under the circumstances
is firmly established.

Restatement (Second) of Torts Sec. 32;

Parvi v. City of Kingston, 41 NY2d 553, 362 NE2d 960 (1977).
The implications for the causation issue once a duty
has been established to warn the government of the dioxin con­
tamination that existed in other defendants' products is
obvious.

If the duty to warn is as we have set forth, then

there can be no argument that responsibility should be limited
to the individual defendant.

By hypothesis the breach of the

-95-

337

duty to inform the government was specifically directed to the
highly toxic product of a co-defendant.

It was that very

product which was deployed in Vietnam.

There is thus no

causation issue left to decide.

The very product which caused

the harm was allowed to be deployed because the defendants not
only failed to warn of the dangers which were indigenous to
their product but that which the entire industry was selling.
i

Once the duty issue is resolved causation is resolved as well.
Each defendant who did not reveal that which it should have
revealed bears direct responsibility for the harm caused by
the product of the other defendants which they knew to be
more highly toxic then their own.
Should the Court require still further grounds for
holding the defendants jointly and severally liable, however,
ample such grounds exist under any or all of the theories of
concerted action, enterprise liability and alternative liability,
discussed seriatim below.

V7arrant--A.pp-li--eation.
i3of the
Concerted Action Theory as
a Basis for Defendants* Joint
and Several Liability_

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Concerted action among two or more defendantsresulting

in injury to a plaintiff is a fact situation under which joint;

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and several liability has historically been imposed.

Hall v. E.I.

/
DuPont de Nemours & Co., Inc., 345 F.Supp. 353, 371 (E.D.N.Y. 1972);/
-96-

c

1 Harper & James, The Law of Torts §10.1 at 697-93 (1956);
Prosser, Joint Torts and Several Liability, 25 Calif. L.Rev.
413, 429 et seq. (1937); See also In re Beverly Hills Fire

i

i

Lititgation, Civil Action No. 77-79, Order 215, p.8 (S.D. Ohio, j
-i ^ **<-<- ■ •, /
filed November 14, 1979) (Order attached as Exhibit 16 ;
0
s']
’
hereinafter referred to as "Beverly Hills"). The elements of
the concerted action theory are prescribed in Section 876 of
The Restatement of Torts, which provides in part as follows:

I
Ii

(

For harm resulting to a third person from
the tortious conduct of another, a person
is liable if he . . . (b) knows that the
other's conduct constitutes a breach of
duty and gives substantial assistance or
encouragement to the other so to conduct
himself, or (c) gives substantial assistance
to the other in accomplishing a tortious
result and his own conduct, separately
considered, constitutes a breach of duty
to the third person.

With respect to this theory, Prosser states that:

{
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"(T)hose who, in pursuance of a common
''
pl an or design to coramit a tortious
act, actively take part in it, or further it by cooperation or request, or
who lend aid or encouragement to the
wrongdoer, or ratify and adopt his
acts done for their benefit are equally
liable with him. (P) Express agreement is
not necessary, ana all that is required
is that there be a tacit understanding . . . "

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Prouser, r.aw of Torts §46, p.292 (4th Ed. 1971); See also
Sindell v. Abbott Laboratories, 607 P.2d at 932 (Quoting Prosser);!

•<? ' 3 ^ 1
-97-

and Hall v.

DuPont,

345 F.Supp.

at 371

(Quotinq Prosser) .
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' ,‘Three elements are necessary to prove a case of joint
and several liability for concerted action in a products lia-

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bility casei
First., plaintiffs must establish a causal relation

!

I

between the plaintiffs’ harm and the targeted defendants.
Second, the plaintiffs must prove that defendants in

!

the group participated by cooperative or concerted activities

I

to cause this harm.

i

Third, plaintiffs must show that the defendants in the

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group have by their actions or omissions contravened a legal

i
standard of care.

See Hall v. DuPont, 345 F.Supp. at 371;

Beverly Kills, Order at pp. 8-9.

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<•*

Expanding upon these elements somewhat, and consider,tne;n each in turn,
. , „,
,
,
, .
m g /it is clear from tne Smdell and Hall cases that plain­
tiffs are not required as part of their proof of causation
to identify the injury-producing party.

In Hall v. DuPont,

for example, the Court noted that "the issue o'f who ’caused'
the injury is distinctly secondary to the fact that the group
engaged in joint hazardous conduct." 345 F.Supp at 372.
Of course, the plaintiffs must still identify the injury- !
.?

producing product, but under the concerted action theory,

Ij

i

the tortious event is considered to be the express or tacit
agreement among the defendants to commit a culpable act.

j

Beyond

identifying the injury-producing product, plaintiffs must only

-98-

9

show that each defendant was a substantially contributing
factor in producing, promoting and placing the defective pro­
duct into the stream of commerce.

Sheiner, DES and a Proposed

Theory of Enterprise Liability, 46 Fordham L.Rev. 963, 983.
(1978).
dant.

i

This proof links the harm done to a particular defen­
Thus, the fact that a specific injury-causing party is

unknown does not prevent a plaintiff's recovery.

Beverly Kills,

Order at pp. 10-11.

S

To establish that defendants are a substantial factor
in plaintiffs' injuries,

|
}
;

therefore, it is necessary for plain-

tiffs to show that all defendants in the group manufactured

'

and promoted similar defective products. Id., at p. 11; Hall v.
DuPont, 345 F.Supp. at 374.
By placing a defective product into the stream of commerce
and promoting it, the manufacturer increases the public usage
of the product.

This, in turn, compounds the chance of injury

caused by the product.

Thus, each defendant v/ho produced and
i

promoted the defective product in concert with others shares

j

in the responsbility for plaintiffs' injuries.

j

Id.

■
Under the facts and circumstances of the present case,

'I

it is evident that if plaintiffs can identify Agent Orange as
the defective and injury-producing product, and furtncir establish

■i

concerted action among the defendants with respect to its
production and promotion and to failure to warn the government

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of the risks attending its production and use, ..then there
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\ causation.
will be little if any remaining question regarding

No defendant disputes, for example,/that Tt~si^Iied Agent Orange
to the government during the relevant period. /'Vie will turn
our discussion, therefore, to the more substantial matter of
concerted activities.
In addition to satisfying the causation requirement,

<J1 /d
ry

>

plaintiffs must also establish that the targeted defendants
acted by cooperative or concerted activities before the theory
of concerted action will be imposed.

Hall v. DuPont, 345

F.Supp. at 371; Beverly Hills, Order, p. 11.
Generally, all this means is that there must be at least

f

some tacit agreement or understanding among the defendants.
»

Prosser, Law of Torts, §46 at 292.

In the products liability

arena, and in this case, the tacit agreement or understanding
among the defendants must be to market and promote a defec­
tive product, or to fail to warn of undue risks or dangers
known to or foreseeable by them.

Beverly Hills, Order at p. 13;

Hall v. DuPont, 345 F.Supp. at 372.\

__________

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The preced-i-ng factual materials^.together with the
Exhibits attached :
‘£è^hò^~fciemQi^nduin, clearly establish the
té
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y
existenceAV TÏot"‘
‘not 3ust
~just of
of'concerted
activity or tacit agreement,
cone

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but of an actual, ongoing and pervasive conspiracy among the '
defendants to market and promote Agent Orange, a product known

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-100-

342

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by them to be dangerous and defective, and t© actively conceal«^
A.

such dangers and defects from both the government and the
general public.

The evidence further discloses substantial

sharing among the defendants of information relating to the
risks and dangers attending the production of

and exposure

to Agent Orange.
To briefly recapitulate some of this substantial evidence
of conspiracy and cover up, the plaintiffs would direct the
Court especially to the long history of industrial accidents
involving Agent Orange-related materials; Dow's 1963 misrepresen­
tation to the military that it was unaware of any problems
associated with the production or use of Agent Orange; the March

! fK ^
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24, 1965 conference among the defendants at Dow headquarters

/

in Midland, Michigan, at which the defendants were all in

;

attendance or upon which they were briefed; the K.A.C.A.,-task

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force formed by the defendants to study the production methods

'
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and effects of exposure to Agent Orange-related products; the
Ad Hoc Committee formed by Dow and Hercules to, in effect,

-•

lobby the government in favor of Agent Orange-related products;

i
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the Boehringer agreement; the sharing among the defendants of

\

analytical and dioxin detection knowledge; Dow's sampling

!

and testing of other defendants' products, and reporting to them

]

of its results; the withholding from the government of effective

■i

analytic techniques for testing for toxic contamination of Agent
Orange, despite the knowledge that the government's techniques
were insufficient; the successful drive by

-1 0 1 -

the defendants to

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Plaintiffs ^i/ould only refer the <
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fulfLv/in/section VI /of/'this Mei
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spi
peqts/ thei/ proc^dct liability cl a
mil7'ri^

pr-riHiirr-f-g 1 i-frb i 1 i_fcy-f?a §

Suffice it,to say that,

for present purposes, the matter of the defendants' breach of
some applicable standard care, whether that standard be of
strict liability, negligence, or conduct warranting imposition
¿ 1

of punitive damages, will not be a stumbling block to imposing
liability upon the defendants under the theory ‘of concerted acti­
vity.
The plaintiffs have therefore alleged and substantiated
,'Q
aru ample—ba-s-is ~for invoking—tbe ^concerted activity liability
doctrine against the defendants, and for holding them jointly
and severally liahle. to. the, plaintiffs.B.
As / A

‘1

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The Raots-^ni^troAfiistances--.
of-~this— Ca-se-aiso-Warrant—the
Imposition of Liability Upon
the Defendants Under the Theory
of Enterprise Liability

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.The facts and circumstances of the present case also

if
arrants application of the theory of enterprise liability as

Z

means of bridging the gap of causation between the injury-

causing product and the particular defendants.

-103-

3 ^ 3 7

*

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6 ^

.Enterprise liability blends the theories of concerted
activity, discussed supra, and alternative liability, discussed
infra, although it is based primarily on the latter of these.
Sheiner, supra. 46 Fordham L.Rev. at 974:
"Under enterprise liability, the plaintiff
must prove there is a high probability
that (his) injury was caused by the tortious
behaviour of some one of the defendants—
a modification of alternative liability.
In addition, (the plaintiff) must show
thatdefendants concertedly adhered to a
dangerous, industrywide safety standard
in their manufacture of the injury-produc­
ing product. Evidence of these two ele­
ments will shift the burden of proof on
causation to the defendants.
Enterprise liability would impose joint
and several liability in a situation which
occurs with increasing frequency in our
highly industrialized society. Fungible
products with delayed and dangerous effects
cause injury, but the instrmentality and
agent producing the specific injury are
unidentifiable.36" id.
The theory of enterprise liability was suggested by the
Court in Hall v. DuPont, 451 F.Supp. 353.
The theory^pf enterprise-—3riab.il ity proceeds— from a
/*
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determination of''fairness: .as between an innocent victim and
/
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members.of an/industry who* are negligent or who have joint ’
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control of the risks/ the latter should bear the cost of
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the injury. Enterprise liabilityis proposed as an eqpitable
/
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method of allocating theSe risks in a manner both affording
/
/
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/
/
/
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the plaintiffs an opportunity to recover' and protecting the
■defendants against“ unjust' loss

/

-104-

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In the Fordham Law Review article, Schiener suggests seven

: 'S ~ .

requirements for imposition of enterprise liability.

These re-

|

quirements are as follows:
1.

There existed an insufficient, industry-wide

j
I

standard of safety as to the manufacture of the
product.
2.

Plaintiff is not at fault for the absence of evidence
identifying the causative agent, but rather, this
absence of proof is due to defendant's conduct.

3.

A generically similar defective product was manu­
factured by all the defendants.

b

4.

Plaintiff's injury was caused by this defect.

5.

Defendants owed a duty to the class of which
plaintiff was a member.

6 . There is clear and convincing evidence that plain­
tiff's injury was caused by a product made by one
of the defendants.

For example, the joined de-

j
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fendants accounted for a high percentage of such
defective products on the market at the time of
plaintiff’s injury.
7.

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All defendants were tortfeasors.

Scheiner, supra, 46 Fordham L.Rev. at S95. Once plaintiffs prove
these things, the burden of proof as to causation shifts to
defendants, each of which can exonerate itself only by showing
that its product could not have been the one which injured the
particular plaintiff.

Id.

346
'Q "3> 1 ^

-105-

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Plaintiffs submit th&t each of' these seven requirements
are met, here,\ and—thatrinTtposirtien—of eriterprxs^tj-ability -upon

/

ther-d5iendah"ts— xs— LIierefor e~proper,.

A./

\

First, there was no real industry standard of safety
for the manufacture, testing and use of Agent Orange-related
products.

Certainly, knowledge of the danger of dioxin contami­

nation was there, as was the technological ability to detect and
reduce the magnitude of its incidence.

But these cannot be

considered "standards" in any real sense, for the reason that
the defendants largely

ignored them.

t

Even those defendants who

\'

apparently did make some efforts to monitor and reduce the in­
/
/

cidence of dioxin contamination in their products cannot be
considered to have formulated or adhered to an adequate standard

of safety, for the evidence suggests that any level of dioxin con­ f'":

i}:

tamination can have serious effects when exposure is prolonged

\
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or repeated.

And for the infantry in Viet Nam, prolonged, repeated

exposure was probably the norm.

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thera£cuce_exirs±ed. /

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Second, the plaintiffs are not at fault for their

1

inability to pinpoint which defendant, or defendants caused
J

their specific injuries.

the manner in which Agent Orange was distributed to and .utilized
by the government.

L-

This inability is due, rather, to
/
/

Whether or not the defendants are at fault

as between plaintiffs and defendants, the latter .j

in this

should bear this risk.

See, e.g., Sindell v. Abbott Laboratories,

607 P .2d at 936.

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Third, the requirement that a generically similar
fective product be manufactured by all the defendants is
met in this case.

All the defendants manufactured generically

\ similar Agent Orange-related products; all of cheir products
| suffered from dioxin contamination to one degree dr another;
j none of the defendants labeled their containers, making it im­
possible to tell one defendants’ product from another’s once

I delivered into the government's possession; and the government
in fact treated the products generically, mixing the products.

■AS*-*L■
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indiscriminately^ The—re^pairement of
dé~feeti-vc prtjdrncb—i-s—the-re-fo'fe~met-.-

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p.

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Fourth, there is substantial evidence both that plain- 1

tiffs’ injuries were caused by the dioxin contaminated Agent

i:

Orange, and that the government utilized this contaminated

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product in consequence of the defendants’ failure .to warn.
ts fa x Jt
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T-'/Ct'/ ‘f - r f ji ' i A * - r o f
forueth xequireni
requiremetheyef-ore—met.
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Fifth, as discussed more fully above, the defendants
both owed and breached their duty of care to the plaintiffs,
those ultimately and foreseeably exposed to Agent Orange, in
failing to remedy or warn of the known dangers of dioxin contam­
ination-

The fifth requirement of enterprise liability is there­

fore- satisfied.

c*c-

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of

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Sixth, there is clear and convincing evidence that the
plaintiffs’ injuries were caused by a product made by one of
'/ s&s <■■(.■ A / iji
the defendants. Exhibit 1 to th-i-s Memerahdiim establishes that

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defendants accounted for over 99% of the Agent Orange market,
both in terms of gallons and dollars sold-

This case is there­

fore distinguishable from Sindell, in which the Court declined
to apply either enterprise or alternative liability theories
because of the absence as parties of significant members of
the affected industry, and the sixth requirement of enterprise
liability is easily met. — ‘;-=~ c- e '~

7

A--.. -4

^

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-fSeventh, all defendants are tortfeasors in the present case.
All of them manufactured defective products; all of them knew
the others’ products were similarly defective; all of them knew
the government and the public were unaware of the existence of
the defects; all of them knew the government relied upon their
jcollective and individual representations as to the product's

Ii

safety; yet none of them effectively eliminated or warned of
the known defects, as a consequence of which the plaintiffs

X-*

were injured. ^ a
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This, all of the requirements for imposition of enterC ~ l.

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prise liability outlined by Scheiner have been met in the present

,y~> /.r~c^j' ix
case/j

Consi.derati ons._t>f--fund^me nt a-l-fai-rness-require -that—th e

liable defendants, having,.control of the risks* and not the'

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nocent .-plaintiffs, bear the consequences of plaintiffs’ inf*
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ability to identify with specificity
the defendants wljiich
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caused their respective injuries. Imposition of enterprise}
l
liability upon the defendants' fulfills such considerations of
\

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fundamental fairness, and application of enterprise liability
in__thia-TTase is'therefore~warrantedi----

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FACTS-RND CIKeWiSTftNeES-OF
THE-TAi
THIS -eASE-ALSO" WARRANT THE
IMPOSITION LIABILITY UPON THE
DEFENDANTS UNDER THE THEORY OF
ALTERNATIVE LIABILITY.________

One final theory of liability advanced by the plaintiffs
:is that of alternative liability. The theory of' alternative
i
;liability applies "where negligence on the part of [several]
, defendants is clear, and it is only the issue of causation
which is in doubt, so that the choice must be made between
letting the loss due to failure of proof fall upon the innocent
plaintiff or the culpable defendants.”
§41, p. 243 (4th Ed. 1971).

Prosser, Law of Torts,

The theory of alternative liability

I is adopted in Section 433 B(3) of the Restatement of Torts,
! which provides that:

i

I

Where the conduct of two or more actors is
tortious, and it is proved that harm has been
caused to the plaintiff by only one [or more]
of them, but there is uncertainty as to which
one lor more] has caused it, the burden is
upon each such actor to prove that he has not
caused the harm.
Thus, as under the enterprise liability theory, where the
alternative liability theory is applicable, the burden of proving

l

1 causation shifts to the independently acting defendants.
The classic case applying the alternative liability
¡theory is Summers v. Tice, 33- Cal. 2d 80, 199 P. 2d 1 (1948) .
In Summers, the plaintiff was injured when two hunters
negligently shot in his direction.

It could not be determined

Which of them had fired the shot which actually caused the injury

350
109

9'

to the plaintiff's eye, but both defendants were nevertheless
held jointly and severally .liable for the whole of the damages.
The California Court reasoned that both were wrongdoers, both
were negligent toward the plaintiff, and that it would be unfair
to require plaintiff to isolate the defendant responsible, because
if the one pointed out were to escape liability, the other might
also, and the plaintiff-victim would be shorn of any remedy.
In these circumstances, the Court held, the burden of proof
shifted to the defendants, "each to absolve himself if he can."
Id., p. 86 , 199 P.2d p. 4.

The Court stated that under these or

similar circumstances a defendant is ordinarily in a "far better
position" to offer evidence to determine whether he or another
defendant caused the injury, or, if not, then as between the
defendants and the innocent plaintiff, it is the former who should
bear the consequences, of any lack of evidence concerning causation.
Relying principally upon the ruling in Summers, the
Plaintiffs in Sindell v. Abbott Laboratories likewise sought
to impose alternative liability upon the defendants for their
manufacture of the defective product DES.

The District Court,

however, rejected plaintiffs' claims in this regard and refused
to apply the theory of alternative liability

upon the facts

\ before it, distinguishing the holding in Simmers from the case
\
before it as follows. In Summers, all the parties who were
\
. j
\ or could have been responsible for the harm to the plaintiff
!were joined as defendants.

In contrast, the Plaintiffs in Sindell,

351
-110-

named only five of the approximately two hundred manufacturers
of DES as defendants.

Thus, while on the one hand, there was

certainty in Summers that the defendant who actually caused
plaintiff's injury was among those to be held jointly liable,
and a fifty percent probability that either of the defendants
was responsible for plaintiff's injuries, on the other hand,
there was no rational basis in Sindell upon which to infer that any
of the five named defendants caused plaintiff's injuries, since
any one of the two hundred companies which manufactured DES
might have made the product which injured the plaintiff.
Accordingly, the Court in Sindell refused to apply the theory
of alternative liability.
The clear implication of the Court's analysis in SindèTT
is that if the market in that case had been smaller and more
cohesive, and if all or practically all potentially liable
manufacturers had been joined as defendants, the case would

^

have fallen squarely within the holding in Summers v. Tice and the
theory of alternative liability would have applied.

In this

regard, the present case is far more analogous to the situation
in Summers than in Sindell, for here, virtually all potentially
liable manufacturers are named as defendants.

As in Summers,

the question in this case is simply which of the named defendants
caused plaintiff's injuries.

Unlike the situation in Sindell,

the possibility that the named defendants will be held liable
for the acts of those outside the group and not named as defendants

-1 1 1 -

is r e m o t e to non-existent.

For the foregoing reasons, therefore.

application of the theory of alternative liability is warranted
and the defendants may be held jointly and severally liable
on such grounds.

■j ... o i i r

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is remote to non-existent.

For the foregoing reasonsf therefore,

application of the theory of alternative liability is warranted
and the defendants may be held jointly and severally liable
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on such grounds.
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CONCLUSION

The reasons for defendants' conduct are not yet fully
clear.

Was their failure to act as they should have due to

a desire to maximize profits?

What additional costs, if any, were necessary to
eliminate the dioxin contaminant from their product?

Why

didn't defendants who had cost plus contracts with the
military, spend whatever sums were necessary to eliminate
the dioxin from their products?

The discovery that remains to be completed may answer
these questions.

What is clear, however, is the "cover up"

mentality that pervaded defendants' activities during the
Vietnam era, and well beyond.

We append hereto as Exhibit 15 , a letter dated September
15, 1977 from the President of Dow Chemical to all Dow U.S.A.
supervisors.

The letter speaks for itself and provides further

evidence of the continuing conspiracy of silence.

That letter

states the fundamental corporate position with respect to its
responsibility to outsiders, to a great portion of whom that
company sells products for profit.

■

355

WMÊMMSt

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d St a t e m e n t of Dr. R i c h a r d Clapp
T a k e n b y R. D. S c h u l e r o n 27 A u g u s t 1993

P.A.

Recorded Statement of Dr. Richard ClaoD
Schuler:

This is Richard Schuler, it's August 27th, 1993,
I'm on the telephone with Dr. Richard Clapp.

Dr.

Clapp, do I have your permission to to record
this?
Clapp:

Yes you do.

Schuler:

Okay, now, uh you were going to tell me about some
comments with regard to the recent material I sent
to you.

Clapp:

That's right.

It was a Federal Express package

dated August 18th but it was the transcript of
Kenny Crump's deposition that was in Moyer v. Dow
and I don't see the date here on the deposition
but I think you know which one I'm talking about.
Schuler:

Right.

It's the only one.

Clapp:

Okay.

Um, the first thing is this question about

the potency factor calculating on page uh thirtysix, line twelve.

You asked him about a

calculation of a cancer potency factor.
Schuler:

Okay.

Clapp:

Which he had done.

Um, and let's see if I

can get the little page earlier if he says
what it's for.

Um, well in any case, I think

it's important when he uses his cancer

358

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d Sta t e m e n t of Dr. R i c h a r d Clapp
T a k e n b y R. D. S c h u l e r o n 27 A u g u s t 1993

P.A.
2

potency factor which isn't here in the
deposition, uh to know exactly which it is
and how it differs from the potency factors
used both by the EPA and by the Agency for
Toxic Substances and Disease Registry for
Dioxin. Here, I think we 1re talking about
Dioxin.

And uh,

Schuler:

Okay.

Clapp:

Those agencies both have cancer potency factors
that they've used and have been peer reviewed and
have become, you know, part of the um the database
on which prudent findus would rely, I would say.

Schuler:

Okay.

Clapp:

And so, uh, that I think you might ask does he
know what the EPA and the ATSDR potency factors
are and why his is different.

Schuler:

Okay, that's the EPA...

Clapp:

Yeah,

Schuler:

What was the other agency again?

Clapp:

It's, the initials are A-T-S-D-R.

Schuler:

A-T-S-D-R.

Clapp:

Right.

I think they actually just incorporate the

EPA's but they both put out statements about the
toxicity of or the carcinogenicity of uh Dioxins
that I think are different from Dr. Crump's.

3 «3*^
C '&

Schuler, Wilkerson, Halvorson & Williams,
Recorded Statement of Dr. Richard Clapp
Taken b y R. D. Schuler on 27 August 1993

P.A.
3

Schuler:

Okay.

Clapp:

I mean this is just my suggestion, you may not
need to bring this u p .

Schuler:

No, I think that's a good suggestion.

Clapp:

Okay, and then on page forty-one, there's a
reference to somebody that he had worked for or
reported to at the Council of Environmental
Quality and he gives the name David Bermaster,
spelled, B ..line eleven,
B-E-R-M-A-S-T-E-R.

I think that's actually David

Bermaster spelled B-U-R-M-A-S-T-E-R, who's a
friend and colleague here in Boston.
Schuler:

Okay.

Clapp:

So if there's anything that, um, you needed to
know about Dr. Crump's work for David Burmaster,

Schuler:

Okay.

Clapp:

I could find it out or you could find it out.

Schuler:

Okay, that's good to know.

Clapp:

Um, and that's also on this question of
carcinogenicity.

Schuler:

Carcinogenicity, okay.

Clapp:

Um, let's see, this case in Colombia, South
Carolina I believe if I'm working for the
plaintiff’s firm, you should know in that same
case, this is on page forty-three,

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d Sta t e m e n t of Dr. R i c h a r d Clapp
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
4

Schuler:

Okay.

Clapp:

Uh, and he's working for the defendant's,

in

Colombia, South Carolina, their issues are
trichloroethane in water.
Schuler:

Okay.

Clapp:

Um, let's see what else I found here.
talked earlier about Dr. Schultz.

I think we

He refers

several times to Dr. Carl Schultz who is another
industry guy that I run across.
Schuler:

Right, well I've taken his deposition in this
case,

Clapp:

Oh, you have, I see.

Schuler:

yeah, and I think you should have that.

I feel

virtually certain I sent it to you.
Clapp:

Maybe you did.

Yeah, I didn't bother go back to

look through that stuff but probably you did.
Schuler:

Yeah.

Clapp:

There's a couple of references to a Dr. Squire and
one of them is on page fifty-one.

Schuler:

Okay.

Clapp:

And then later I think it actually comes up again.
I'm not going to be able to find the second
reference, but Dr. Squire, this actually is a key
thing I think, Dr. Squire re-analyzed slides from
an animal test done by a man named Kociba, K-O-C-

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
5

I-B-A.
Schuler:

Right.

Clapp:

And it's a real serious question about what was
done in that re-analysis and I think that
certainly the the pathologist that I know, and
there is a guy I know who is a pathologist,

Schuler:

Okay.

Clapp:

who's looked at Squire's re-analysis..and he
thinks it was improperly done.

And that for one

thing it included uh re-designating some slides as
um non-tumors that were first designated as tumors
and the re-analysis was suppose to only include
designating things that were considered sort of
premeoplastic lesions as non-tumors.
Schuler:

Okay.

Clapp:

So it went beyond the scope of the re-analysis as
it was laid out and it raises the question as to
why the did that. They weren't even suppose to be
looking at that second group of slides, um and I
think that, itself, has not really been accepted
the Kociba, uh sorry, excuse me the Squire re- .
analysis has not been accepted broadly as an
appropriate re-analysis of the Kociba, um
findings...

Schuler:

Okay.

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d Sta t e m e n t of Dr. R i c h a r d Clapp
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

Clapp:

P.A.
6

by the general scientific community, it's only the
industry side that says that uh Squire re-analysis
is what you should rely on.

Schuler:

Oh, I see.

Clapp:

I certainly wouldn't and I don't not that you're
asking me to.

I'm not a toxicologist, but I think

that if there I were a toxicologist in this case
that you had gotten, they would probably say the
same thing.

So I think it's, maybe again it's

worth your knowing that Squire's re-analysis is
not the all and end-all on this question of how
toxic uh TCDE is to animals.
Schuler:

Okay. Yeah, that is important.

Clapp:

Crump seems to rely on that heavily.

Schuler:

Okay.

Clapp:

Uh, let's see what else I have here this is not
the way you wanted to spend the last hour or two
of your work day, but.

Schuler:

Oh, no, no. no, that's quite all right.
to be here for a while longer, so uh.

I'm going
I like to

get things done.
Clapp:

All right.

Schuler:

No, I'd rather be fishing, but uh [laugh], or
playing golf I guess.

Clapp:

Yeah, there you go.

I think it's probably hotter

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C l a p p
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
7

here than it is where you are I think it's ninetyfive in Boston today.
Schuler:

Yeah it's hotter [laugh] than here, it's about
eighty-eight here I think...it's still pretty warm
though [laugh].

Clapp:

Yeah, that's true.

So we'll wait till the sun

get's a little lower before we go out to the golf
Schuler:

That's right [laugh].

Clapp:

Uh let's see, there was some back and forth on
page eighty-four.

You were sort of, it looked

like, about to nail down where he got his exposure
as to whether it was a sprayer or as a driver and
he finally said he received all of that exposure
while they were spraying and I think there1s
something inconsistent in there and I urge you to,
um, have Mike Ellenbecker look at that.

I think

there's something, if it's through what he says in
there I think there making some inconsistent
assumptions, either he or Nick, one of the two.
Schuler:

Okay, I going to, um, I think I've already sent or
it's in the process of being sent that same
package to Ellenbecker, yeah, this exposure.

Clapp:

And also on page, this is a very small point but
on page one hundred five, he said he thinks
anastrosarcoma is a soft tissue sarcoma but he's

>

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

P.A.
8

not a hundred percent sure,
Schuler:

U n , hun.

Clapp:

It's not.

He's a hundred percent wrong actually

about that.
Schuler:

Okay.

Clapp:

Um, and that's probably not a major point on his
side either itjust happens to be a
factual error.

Schuler:

Okay.

Clapp:

This stuff about his risk assessments and the
parts you know the uh, the uh risk assigned ten to
the eighteen or whatever the heck he comes up with

Schuler:

Yeah.

Clapp:

It's all, in the deposition it's all impenetrable
to me, I'm sure the pages where he lays it out are
where the numbers are, but, uh at some point
somebody should look at those numbers because I
think they're absurdly low ... the risks that he
estimates are absurdly low.

Schuler:

Well the, wasn't there attached to what I sent you
a copy of um of his numbers?

Clapp:

No.

Schuler:

Okay, well let me, I will send you, send a copy of
Crump analysis exhibits to Dr. Clapp, okay. You
did have some papers there, preliminary though,

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d St a t e m e n t of Dr. R i c h a r d Clapp
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
9

supposedly they were that lay these numbers out...
Clapp:

Right.

Schuler:

that I can send to you.

Clapp:

I'd be curious to see them because it's, you know,
amazing to me that he's making such statements.

Schuler:

Yeah.

Clapp:

Urn, yeah here's the second reference to the Kociba
studies it's on page one twenty-two, and um, again
their using these life-time risks of cancer based
on the Kociba studies...

Schuler:

Right.

Clapp:

and I assume that means the re-analysis of this
Kociba study by Squire, which I think is faulty.

Schuler:

Okay.

Clapp:

So if his risk assessment these life-time risk
calculations are resting on that on Squire's re­
analysis of the Kociba studies as he seems to be
saying on page one twenty-two at the bottom, then
I think h e 's on a house of cards or whatever
foundation I'm saying cause I think that the
Squire re-analysis has been picked apart as not
valid.

Schuler:

Okay.

Clapp:

Um, and also the assumptions about numbers of

;

stages of the carcinogenic process I think also

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

P.A.
1 0

there there would be plenty of room for argument
about that the way he lays it out.
Schuler:

The wah he analyzes it.

Clapp:

Yeah. Uh, I guess I think those are the main
things that I really say the sort of key point is
this Kociba stuff and the degree in which he
relies on it, I think is very vulnerable there.

Schuler:

Okay.

Well I'll go back and when I do my own

adaptation and when I get ready for his remaining
part, his deposition I'll load up in that area...
Clapp:

Yeah.

Schuler:

and see what I can get at 'em.

Clapp:

Yeah, I can send you some, by then, whenever it is
I think even if it's now or when..

Schuler:

It's not going to be until, you know, either midSeptember or October so it's a ways off.

Clapp:

By then there may be a new report out from the EPA
on their reanalysis of Dioxins that that deals
with this question of Kociba and uh re-analysis of
Squire by Squire.
it to you.

If that's available I'll send

You can use it.

Schuler:

Oh, I would love it.

Clapp:

.. let you even use it.

It's in draft now, I have

the draft you know the EPA stamps it not for
situation or quotation but if it's in final form

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

P.A.
1 1

you could read it right into the record cause it
will be, I think, a contradiction to what um Crump
was saying.
Schuler:

Yeah, oh I'd love to see that.

Clapp:

Okay.

Schuer:

Uh, maybe you could even send me a copy of the
draft.

Clapp:

Yeah, I will.

Schuler:

I've got, I actually do have the draft of that EPA
that nine-volume or ten-volume assessment, is it
in there?

Clapp:

Yeah, it would be in the "Dose Response" chapter.

Schuler:

Okay, all right.

When did you say they're going

to come out with the final one?
Clapp:

The final version of the Chapter Seven of that is
being reviewed on September 7th, and I think, you
know, whatever the Federal Register says thirty
days after that their suppose to have the final.

Schuler:

Okay.

Clapp:

Of that chapter and then these other chapters are
coming in different times but the whole thing is
all delayed but it's due to be done by the end of
this year.

Schuler:

Okay.

Clapp:

And that's going to help our side.

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C l a p p
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

Schuler:

P.A.
12

Yeah, I noticed that the, what is it, the uh
National Science Foundation, was that it?

Clapp:

National Academy of Sciences.

Schuler:

National Academy of Sciences, yeah.

Clapp:

They come out strongly on soft-tissue sarcoma.

Schuler:

Yeah, they really did.

Clapp:

That's their number one cancer actually for the
Agent Orange and Dioxin contamination.

Um and the

guy who wrote that chapter said that you know even
since we had done our Vietnam Veteran's report in
1990 a lot of new stuff has come in that just
strengthens the case, so it gets stronger all the
time actually on soft-tissue sarcoma.

That’s what

he said and that's what the report reflects I
think.
Schuler:

Yeah I think it does too and it seems to me what
this case is boiling down to and I anticipate
getting a trial date, I thought we were going to
get one in September but they switched judges on
us at the last minute and uh so this judge is
telling me that we got to move to set it and I
have moved to set it and now he's telling us we'll
probably get a trial date in the spring so I
anticipate a trial date this spring and I'm
sticking to this as hard as I can because I need

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C l a p p
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
13

to get this case tried.
Clapp:

Right.

Schuler:

You know it's just been around too long, Bob's
passed away and his widow, you know, really could
use the help so.

Clapp:

Yeah.

Schuler:

I'm urn, I'm really leaning on trying to get this
case wrapped up and uh you know Dow has taken the
position .. they wrote me a letter or I guess or
solicited a demand from me of some months ago, I
sent them a demand I sent them demands earlier so
I renewed my demand and I got the recent medicals
in which were like seven or eight hundred-thousand
dollars in medical expenses and sent them up their
and they asked me if I wanted to mediate this case
and I said fine if you're willing to do it and
then they know I've never heard from them so
they... I don't know whether it's a communication
problem with... I don't know if this is the way
they usually are in cases cause they seem to, they
seem to say one thing in one moment and then they
change their mind or they go the other direction
in another moment.

Clapp:

No.

Schuler:

Uh, you probably had more experience in cases with

Schuler, Wilkerson, Halvorson & Williams, P.A.
Recorded Statement of Dr. Richard Clapp
Taken b y R. D. Schuler on 27 August 1993

14

them then I've had but..
Clapp:

Right, well it always seems like there’s different
law firms involved at the local level and then
perhaps Dow Corporate law office gets involved and
changes things that the local people are trying to
set u p .

Schuler:

Yeah.

That -- that's one of my impressions.

That

may be happening.
Clapp:

Yeah.

Schuler:

Cause I knew, I know they do have some kind of guy
inside, some kind of house counsel that's
monitoring this..

Clapp:

Yeah.

Schuler:

but, uh, it just makes it tough to you know to
take the for their worth..

Clapp:

Right.

Schuler:

And they probably do that by design I guess, like
to. .

Clapp:

Yeah, that's my impression of these guys.

The Dow

people and then [inaudible] is even worse.

Their

involved with another set of pesticides.
Schuler:

Yeah,

Clapp:

They're completely un-trustworthy.

Schuler:

Yeah.

And I noticed that...were you involved in

that case up in Canada with the soda, the Sprayers

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a tement of Dr. R i c h a r d Clapp
T a k e n b y R. D. S c h u l e r on 27 A u g u s t 1993

P.A.
15

of Dioxin Association?
Clapp:

No.

I know about it, but I wasn't personally

involved in it.
Schuler:

Yeah.

Clapp:

I met Jerry White for example and ..

Schuler:

Oh did ya?

Clapp:

Yea.

Schuler:

Cause I had conference with Jerry.

I went up

there and went through a lot of their documents
and everything.
Clapp:

Yeah.

Schuler:

They settled that case I understand..

Clapp:

Right..that1s my understanding too.

Schuler:

Did you hear anything about the settlement or what
their..

Clapp:

I didn't, I think what and woman who told me was
Jane Saganoff, do you know her?

She's a uh, she

works with Barron and Bud and I think I might have
given you her name because of some other expert
that she had deposed a juror facing [inaudible]
Schuler:

Yeah, I don't recall talking with her, but uh..

Clapp:

She had hear about the settlement and she I think
said that it was a substantial settlement.

I

can't remember the dollar she mentioned the dollar
amount.

Uh, but Jerry White, you know, he wanted

372
q

- H ^

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d S t a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. Schu l e r on 27 A u g u s t 1993

more.

P.A.
16

He wanted people to go to jail or

something.
Schuler:

Oh, yeah, yeah.
Corporation.

He wanted New Brunswick Power

They were funding the case because

they reached a preliminary settlement with them
and part of the settlement was that they would
fund the case against Dow.
Clapp:

Yeah.

Schuler:

and the manufacturer.

So they had like ah, an

unlimited pocket there.

Their lawyer, they

apparently can't have contingency fees in Canada
so their lawyer was charging by the hour and had
burned up an incredible amount of legal fees I
know that, I remember I was really surprised and
uh, but he wanted, even though New Brunswick was
funding this thing, he really had an ax to grind
with the power corporation.
Clapp:

Yeah.

Schuler:

I guess because that was the local target and

Clapp:

That was, I guess his disappointment was that he
didn't get somebody behind bars as a result of all
this.

Schuler:

Yeah, yeah.

Clapp:

But, uh, I don't know.

Personally I think some of

these families got some help and that's a pretty

Schuler, Wilkerson, H a l v o r s o n & Williams,
R e c o r d e d St a t e m e n t of Dr. R i c h a r d C lapp
T a k e n b y R. D. Schuler on 27 A u g u s t 1993

P.A.
17

good settlement.
Schuler:

Yeah, that's enough.

Clapp:

So that's all I could .. THE END

All right.

374

MOYER V .

DOW
ANNOTATION OF DEPOSITION OF RICHARD W. CLAPP
TAKEN ON APRIL 17. 1992

4/12

My profession is epidemiology with emphasis on community
environmental exposures and diseases.

4/17

Epidemiology is the study of the patterns of diseases and
the causes of diseases, usually in humans.

5/2

Maybe the term is "environmental epidemiology" and the
source of exposure would be from something in the air or
in the water, or in some cases it would be the workplace
or where people live.

5/7

C.V. marked as Exhibit No. 1.

7/6

I'm employed by John P. Snow, Incorporated which is a
public health consulting company; primarily government
contracts in the area of child health, family planning,
AIDS prevention; and in my group, environmental health.

7/20

About a third of my personal work is involved with
litigation support.

8/2

My work is primarily for plaintiffs and occasionally for
government agencies.

8/16

I was contacted by Mr. Schuler, I'm guessing it was a
year ago last fall.

8/19

I was asked to review the epidemiologic literature about
exposure to herbicides and their contaminants and this
cancer, soft tissue sarcoma.

9/3

I have been asked to render an opinion as to scientific
causation. I am not a medical doctor, so I will not be
rendering an opinion about the cause of Mr. Moyer's
disease.

9/15

There is significant evidence in the literature.
The
weight of the evidence in the literature supports the
association between specific herbicides and their
contaminants and soft tissue sarcoma.

10/5

I am not in a position to say that as a result of being
exposed to herbicides while working for Orange County,
that Mr. Moyer now suffers from soft tissue sarcoma "and
the resulting complications of having that disease.
I
think that is a medical opinion.

10/16

I recognize the list of articles that was attached to
answers to interrogatories dated 1/3/92. I prepared that

list.
11/3

Other than the articles on that list, there is an
exchange between Dr. Fingerhut and Dr. Collins that was
in a journal called "Epidemiology" in 1992. It doesn't
change my opinion. It buttresses it.

12/5

In my view, the articles on this list are the most
reliable in making the determination of whether there is
an association between exposure to 2,4-D or 2,4,5-T or
any of its contaminants and soft tissue sarcoma.

12/8

Ranking or weighing a publication in terms of its
reliability is a judgment process that involves
consideration of the design of the studies, who it was
they were studying, the information about the disease and
the exposure, the degree they have been carefully
characterized, the size of the study, how many cases were
involved, and the methods of statistical analysis,
whether they seem appropriate to the data.

12/22

The interpretation that the authors gave the data are of
less importance, but is something that I take into
consideration.

13/5

The size of the population
important criteria.

13/13

You would tend to give more weight to the larger study
that has more precision.

14/9

I think a study of sufficient size can determine
scientifically an increase of as little as ten or twenty
percent over an expected number of disease end points in
a population.

14/16

If it is a rare disease, you might need a very large,
hundred-thousand size population to show up a ten or
twenty percent increase.
A more common disease, say
heart disease, you might be able to detect a ten or
twenty percent increase in half that or less.

15/1

I was asked to pay particular attention to 2,4-D, 2,4,5-T
and 2,4,5-TP, which is sometimes called Silvex, and their
contaminants.

15/5

Initially, I think Diquat was on the list to consider,
but that's not anything that I have been paying attention
to recently.
■

15/12

I did not reach any conclusions with respect to the
health effects of exposure to Diquat, hydrothol, Hydeout,
2

studied

is

one

of

the

Roundup or Rodeo.
15/22

I believe some chlorinated dioxins have been found as
contaminants of 2,4-D, and this is getting into an area
that is not an area of my expertise: toxicology.

16/10

A dioxin is a chemical that has a particular structure,
where it's made up of two benzene rings connected with
oxygen bridges and then a number of chlorine atoms
attached.

16/16

Contaminants of 2,4,5-T:
in particular, an isomer of
dioxin that's called 2,3,7,8-TCDD.

16/23

I don't have the specific dioxin, but there are dioxin
contaminants of 2,4,5-TP as well.

17/8

Risk assessment is not within my field of expertise.

17/12

With respect to the 2,4-D specifically, I believe the
literature supports the assertion that people who are
exposed to 2,4-D in the context of work or other ways are
at an increased risk of cancer.

18/22

My opinion assumes that there is an increased risk of
cancer for those people who are exposed to 2,4-D and that
there is no threshold for exposure to carcinogens.

19/2

I always assume in my work that exposure to a carcinogen
always results in some increased risk of cancer.

20/6

It's basically the question of whether the studies of the
human populations exposed to 2,4,5-T and other herbicides
show they are at increased risks of cancer, in
particular, soft tissue sarcoma. My conclusion is that
there is evidence in the scientific literature that
persons so exposed are at increased risks for that
cancer.

20/20

I am not in a position to say how much increased risk
someone has by being exposed to any particular level of
2,4,5-T.

21/2

The opinion that I have been asked to express about
2,4,5-TP is basically the same as with respect to 2,4,5T.

21/10

When I mentioned 2,4,5-T I said soft tissue sarcoma, jaut
I deliberately did not say soft tissue sarcoma whefa I
talked about 2,4-D.

21/15

I think the literature suggests most strongly with 2,4-D

there is an increase for cases of non-Hodgkin's lymphoma.
There is almost no situation where there is pure 2,4-D
exposure without other chemicals.
It's very hard to
sort.
22/12

I have no opinion about cases other than non-Hodgkin's
lymphoma with respect to 2,4-D.

22/16

Non-Hodgkins lymphoma and soft tissue sarcoma are two
different types of cancer, but they have some important
similarities.
Both seem to be related to a patient's
immune status.

22/22

If their immune status is suppressed in some way because
of the drugs they have been taking, there is an increased
risk for those patients of both of those cancers.

23/3

The epidemiological definition of "confounder" is the
substance or the exposure that is associated with a
disease and also with the other exposure that you are
interested in.

23/13

The AIDS Virus, HIV is associated with one particular
soft tissue sarcoma called "Kaposi's sarcoma."

23/18

I think immunosuppressive drugs, the types of drugs that
are given to patients who have gone through a kidney
transplant, for example, are at increased risk of soft
tissue carcinoma.

24/1

Soft tissue sarcoma is very rare.
one percent of the cancer deaths.

24/7

I think the highest rate is in children.

24/19

Currently, if you include the Kaposi's sarcoma, the
highest rates of occurrence are from San Francisco. If
you exclude San Francisco, there is no other area that is
high.

25/17

The risks to the general population of cancer death are
one out of three, roughly. That is a lifetime risk.

25/23

The risk of cancer, not cancer death, is somewhat higher
than that, perhaps one out of two and a half, now. These
numbers are going up. Cancer is a more frequent disease
and more common cause of death.

26/7

About half a million people in the U.S. die of canceir a
year.
I would expect roughly one percent, or 5,000 of
those to be by virtue of soft tissue sarcoma.
4

It represents about

378

27/24

I would expect some portion of these 5,000 deaths to be
the result of exposure to herbicides, but I couldn't tell
you what that portion might be.

31/20

Say it is three per hundred thousand. Then you will need
33,000 people of our age to look at in order to expect to
see one soft tissue sarcoma.

32/3

If it turned out that there were two soft tissue sarcomas
out of those 33,000, you would compute what is called a
relative risk of that 33,000, and it would be 2.0 So the
number would be twice as many as you actually expect in
that population.

32/13

There is a formula to determine whether or not that
increased relative risk is simply the result of chance.

32/20

You look at the number of people and the size of the
excess, and you put those into mathematical terms, and
it's called a chi square result, and you see whether the
chi square exceeds the level of statistical data. If it
does, the probability is that the finding was a result of
chance.

33/9

Before you can conclude that the increase is due to
something
other
than
chance,
there
are
other
considerations that an epidemiologist would take into
account. The biological plausibility of the association,
whether it is consistent with thé findings from other
studies, that kind of thing.

33/17

Those are the most important ones. Whether the study was
properly done, and for example, the exposure preceded the
disease.

33/21

The simplest definition of relative risk is the incidence
of disease in an exposed population divided by the
incidence of the disease in an unexposed population.

34/3

If that ratio produced a one, that would tell us that
there is no difference between the incidence in the
exposed and the unexposed.

34/14

I don't think there is an answer to how big the relative
risk has to get before you would say there is more likely
than not an association between the substance and the
disease.

35/22

In order to conclude from a 1.1 an association between
the substance and the disease, you would normally need a
very large population.
5

36/2

10,000 or more I would say.

37/6

There may be studies that conclude that there is no
increased risk of cancer as a result of exposure to
2.4.5- T for a particular study population.
I don't
believe any make that as a global conclusion.

37/12

For the particular study population in New Zealand, there
may be studies that conclude no association between 2,4-D
and soft tissue sarcoma.

37/15

No, I don't believe any make that particular conclusion
about 2,4,5-TP.

37/19

There are a couple of articles where
mentioned as part of the mix, but not
focusing on 2,4,5-TP.

37/24

The difference chemically between 2,4,5-T and 2,4,5-TP is
beyond my area of expertise, but in general, there is
propinic acid added to the 2,4,5-TP.
It is the P
molecule.

38/7

So far as I know, there are no studies on specifically
whether 2,4,5-TP causes cancer.

38/14

There are studies where humans are exposed to a mix of
chemicals and 2,4,5-TP is part of that mix. There are
studies of 2,4,5-TP that is also contaminated with
chlorinated dioxin.
There are numerous studies where
people are exposed to substances that include chlorinated
dioxin.

39/4

The common thread with TP is dioxin contaminants which
are common to other chemicals as well.

39/24

I really don't have an opinion on whether it is the
dioxin that finds itself in the 2,4,5-T and not the
2.4.5- T itself that causes the increased risk of cancer.
I think the two in combination, the dioxin in combination
with the 2,4,5-T, and the dioxin with the contaminants.

40/4

Beyond that I don't have an opinion as to which is
more important. They may be important together or
they might be important individually, and I can't
sort that out in my area of expertise.

41/2

My literature review leads me to conclude there is;-an
increased risk of cancer, and specifically non-Hodgkin's
lymphoma, as a result of exposure to 2,4-D. I am not in
a position to say whether or not there is an increased
risk of soft tissue sarcoma as a result of the exposure

2,4,5-TP is
specifically

6

380

to 2,4-D, or any other specific cancer.
41/14

It depends on which list you use as to how many types of
cancer there are. My list is about ninety. I think that
is a middle-of-the-road number.

42/3

If you are talking specifically about questions of
observation or investigator bias or recall bias, I do not
share those concerns or criticisms of the early works of
Dr. Lennart Hardell.

42/17

My understanding of those criticisms are that they center
on possible investigator bias on the patients' part,
recall bias, inability to remember certain things.
I
believe Dr. Hardell and his colleagues adequately address
those in the initial studies and in subsequent studies.
I do not agree with the blanket statement that those
early studies are agreed to be flawed.

43/8

In the area of the study of 2,4-D or TCDD or 2,4,5-T I
wouldn't say there is any one person particularly
persuasive in the epidemiological field.
I definitely
would include Dr. Hardell, Dr. Eriksson and Dr. Fingerhut
now as three very persuasive epidemiologists.

44/4

The precise meaning of a negative relative risk is that
the risk or the incidence of disease in the exposed
people is lower than in the unexposed people.

45/2

I see that the largest study on this table that I am
reading from, the paper "Scientific Solutions," is by
Wickland and Holm. It's 3,054,620 and exposure is to a
mixture, but I'd have to go back to the article to see
what the mixture was.

45/10

I don't have a specific number in mind for the expected
relative risk that is associated with exposure to 2,4-D.
It's different for different studies. It's greater than
one in the aggregate.

45/14

It's based on combining several studies where they have
technically focused on 2,4-D.
One in particular by
Sheila Zahm. It's a 1990 article, but it was relative
risk of 1.5 for non-Hodgkin's lymphoma.

46/2

I don't have a reference for the specific chemicals, 2,4D, 2,4,5-T or TP.
They are always mixed with other
chemicals.
I

46/10

A meta-study or meta-analysis is where you combine the
data of a bunch of separate studies.
You effectively
increase the size of the study by looking at groups of

1

38 i

numbers aggregated together; you get the larger numbers.
46/20

I have not tried to do that in determining the
association between 2,4,5-T, 2,4,5-TP or 2,4-D and soft
tissue sarcoma.

47/3

The basic problem is that the different studies are not
entirely comparable to one another. So it is an
apples/oranges type of problem. You can't throw them all
into one mix and get a believable or credible result.

47/10

Some are called “case control studies" and the others are
what are called "cohort studies".
They have given
assumptions in how you do those studies, and you can't
take the numbers from one study and simply add them to
the numbers from another.

47/24

A cohort study is where you look at a group of people who
work in some occupation or in some industry, and then
follow them through time and see how many diseases and
what type of diseases the people in that cohort got.

48/23

In a case control study, instead of starting out with
some sort of workers, you start out with patients with a
specific disease, and then you select people who are like
the patients but don't have the disease.

49/22

The advantage of a cohort study is so you can get a
better understanding of exposure at the outset.
You
define the exposed group by some agreed upon criteria at
the outset of the study, and then follow them through
time.

50/5

The weakness of the cohort study is if you are looking at
a rare disease, it may take a long time for enough of
those diseases to show up, and sometimes cohort studies
go on longer than the investigators do.

50/12

The principal advantage of a case control study is that
you can study a rare disease by going someplace a lot of
those patients are diagnosed and assemble a sufficient
number of cases to do the study rather quickly.

50/17

Its weakness is that you are depending on people's recall
or recollection of what their exposures were, because
they had it prior to their getting the disease.

51/8

When I say that people exposed to 2,4-D from my review-of
the literature have an increased risk of cancer, that
assumes that 2,4-D is a cancer causing agent, it is a
carcinogen.
8

382

51/18

A carcinogen is some substance that causes cancer in
exposed humans.

53/6

When I say that 2,4-D is a carcinogen what I mean is that
exposure to 2,4-D increases the risk that someone will
get cancer as a result of that exposure.

53/16

I think I take all of the articles into consideration in
forming my view, but I don't have a particular ranking in
mind.

54/3

I was asked to render an opinion in a case that never
went to trial about 2,4-D.

54/23

This was a person who sprayed 2,4-D on his farm in Kansas
and was diagnosed with and actually died of non-Hodgkin's
lymphoma.

55/3

I worked for the Plaintiff.

55/19

I think it was about a year ago.

56/1

No other cases where I have testified specifically about
2,4-D. I have testified about Agent Orange, a component
of 2,4-D.

56/7

I have never testified about 2,4,5-T, excluding Agent
Orange, or about TP.
I have testified about 2,3,7,8TCDD.

56/17

The first time was in Times Beach, Missouri —
was contaminated with dioxin, 2,3,7,8-TCDD.

57/6

The second TCDD case was a patient who died of soft
tissue sarcoma and was exposed at a trucking terminal
where he worked in St. Louis to dioxin in the soil —
TCDD contaminated soil.

58/3

None of the Times Beach people contracted the disease.
My testimony was simply that they were at an increased
level of getting the disease.

60/7

No.
I don't believe that the association between the
increased risk of cancer and exposure to Agent Orange is
by virtue of the T component. I think it's the mixture.

60/9

The contaminant is TCDD and varieties of dioxins.

60/12

I testified about Agent Orange at Congressional Hearings.
I think the first one was in June of 1990 and a year
later, perhaps August of 1991.
9

His name was Mr. Sloan.

the soil

62/3

We have a separate transcript file.

63/11

I have testified in two cases involving exposure to
herbicides or pesticides. One was a group of workers at
a pesticides plant that made a chemical called DBCP, and
I testified at a San Francisco state court regarding the
exposure to DBCP and particular cancers.

63/17

The second one was people or children in a school
district whose water was contaminated, and that they
would be at an increased risk of cancer as a result of
that exposure.

64/10

Other substances I have been concerned with in my
testimonial experience:
electromagnetic radiation,
diesel exhaust fumes, a substance called ethyl acrylate
and trichloroethylene.

64/24

I have not testified for a defendant in these cases.

65/5

I testified about TCE just once. It was in Denver, and
it was, I believe, called Renoid vs. Martin Marietta.
Dr. Teitelbaum was on the other side.

65/15

I testified in one diesel case.
That was a man in
Florida who actually had lung cancer, was a non-smoker,
and had worked in a railroad yard where he was exposed to
diesel emissions from the railroad — from the engines.

66/1

It was Smith v. Amtrak.

66/14

I testified in one plexiglas case. That's a man who was
exposed to a spill of the chemical ethyl acrylate coming
out of a tanker truck in his front yard, and it was in
Louisiana.

66/20

The man's name was Washington and the defendant was a
trucking company, but I forget the name of the trucking
company.

67/18

I am not aware of any association between EMF and soft
tissue sarcoma.

67/21

I have testified just once on EMF. I was working for the
New Jersey Department of the Public Advocate. The were
objecting to an electric utility company's plan to put a
power line through three residential neighborhoods.

69/2

My correspondence with Mr. Schuler contained lettrers
transmitting documents.
A letter from me transmitting
the literature lists.
Fax Sheets, that type of thing,
and a couple of bills.
10

69/16

I received Mr. Moyer's medical records from Mr. Schuler.

70/5

I reviewed them to verify the diagnosis of soft tissue
sarcoma.

70/11

I thought it would be important to know in general
whether this was a case about soft tissue sarcoma.

70/16

I just glanced at the depositions and statements.
didn't read them carefully.

71/5

The document we did for the Agent Orange Task Force for
the veterans groups definitely talks about the cancers
which we believe are caused by certain exposures and soft
tissue sarcoma.

72/5

I don't believe the epidemiological studies associate the
length of exposure or the overall dose with the risk of
increased likelihood of cancer.

72/11

Some of the studies do talk about exposure of two years
or less. I believe in particular Dr. Hardell's and Dr.
Zahm's.

72/18

Some of Hardell and Zahm's studies concern exposure for
a total of one year or less.
It is usually a group
that's exposed one to six years, and whatever it is.

73/4

When you say "one year or less" in general that means
covering some number of days, but certainly not five days
a week all year long.

73/8

Dr. Fingerhut and I are colleagues.
We discuss
scientific things over the phone, at conferences.
She
works at the National Institute for Occupational Safety
and Health in Cincinnati.

73/23

To evaluate these publications, I think it's the
generally accepted method in the epidemiological field to
consider the study design, the size of the study, the
definitions of exposure and disease as they are described
in the study, the statistical analysis, and any other
knowledge that I might have about the plausibility of the
exposure that they are talking about being related to the
disease.
Then forming an opinion based on what I
consider the aggregate strength of the evidence.

74/24

I gave the Fingerhut studies a lot of consideration
because it was a carefully defined group who were known
to have been exposed to TCDD.

75/10

I think I gave relatively little weight to a small study
11

I

385

by Cook and others where they looked at one particular
plant.
75/20

I think the series of studies by Dr. Hardell and Dr.
Eriksson I gave a lot of consideration to. I think they
are, in the aggregate, very persuasive.

76/1

And in a sort of obvious way, my own work, two of which
studies are on the list, looking at veterans in
particular.

76/13

One text I used in teaching is Epidemiology in Medicine
by Hennekens and Buring, but I wouldn't call it the
single authoritative text.

76/19

There is one by Checkeway, and I believe it is called
Research Methods in Occupational Epidemiology.

77/19

There is one other text, Environmental Epidemiology, and
it's a committee of authors of the National Academy of
Sciences that wrote it, but I don't know if it's good,
bad or indifferent.

78/7

In the general field of epidemiology,
Buring are authoritative.

78/11

I think Dr.
epidemiology.

78/14

Dr. Fred Li, who works in Boston at the Dana Farber
Cancer Institute, I consider an authority in cancer
epidemiology.

80/17

To consider how much weight to give a study when looking
at whether the exposure to TCDD would cause an increased
risk of cancer, it depends how intense the exposure is,
and how long you are going to follow them.

81/13

In instances where people who worked in a plant where
there were very few controls on exposure and people who
were wet from exposure to some chemical, or where there
had been an accident and people got very large doses,
even if it were for a very short period of time, I think
a cohort study of 500 would be worth studying.

82/9

The size of a group for a study would depend on the
particular circumstances.

82/11

There was a cohort study in Massachusetts, I believe it
was something like thirty people in this one plant had
very high exposure to asbestos.

Hardell

12

is

an

Hennekens

authority

in

and

cancer

82/17

I was part of that study, and there were very significant
findings in cancers related to asbestos exposure.

83/13

The list of confounders that should be considered when
determining whether or not there is an association
between an exposure to 2,4-D, TCDD, or 2,4,5-T and an
increased risk of cancer are: immunosuppressive drugs;
family history of those cancers or other diseases;
radiation, by which I mean the ionizing kind, the x-ray
type radiation; possibly dietary history.

84/4

I think ionizing radiation,
almost any cancer.

84/20

Some people are exposed at work to ionizing radiation,
either because they work in an x-ray department,
administer radioactive drugs, or they work in a nuclear
power plant or in a nuclear submarine.

85/6

There is radon and potassium 40 that comes from the soil.
There is also ionizing radiation that comes from the sun
or elsewhere in space, so-called cosmic radiation.

86/13

I think people who live in Florida and Boston are at
increased risk of cancer more than the rest of the
country.
In Florida, it might well be because of
sunlight exposure, in Boston, it might be because of the
old industrial history, air pollution or ground or water.

89/21

As I sit here today, I do not have an opinion one way or
the other as to whether any of these subject chemicals
listed in my subpoena increase the risk of cancer.

91/17

I have had discussions with Drs. Hardell and Eriksson
about their work.

92/3

I have talked with Dr. Zahm about her work in Kansas and
Nebraska and other places.
She also testified at some
Congressional hearings that I testified at.

92/13

I talked to Dr. Teitelbaum at those same hearings.

93/4

I have not had any of these conversations specifically
with reference to this case.

93/11

Dr. Hardell and I usually send faxes and articles back
and forth. I don't believe I kept those cover sheets.

94/21

I only know Mr. Nesbet by reputation and he certainly has
a good reputation.

95/12

John Graham directs a center at Harvard School of Public

particularly,

can

cause

13

387

Health.

It's called the Center for Risk Analysis.

95/23

I don't agree with his work.
conclusions.

96/11

I think that the weight of Dr. Graham's evidentiary
review process undervalued Dr. Zahm's work. Her work is
convincing.

96/15

Dr. Zahm was a member of Dr. Graham's task force and I
know she disagrees with the conclusions of the task force
as well.

97/16

Undoubtedly, there are experienced people in the field
who disagree with the view that I have about 2,4-D, yes.

97/24

I can't think of anyone that I would consider my
professional equal who disagrees with my conclusion that
2,4-D, 2,4,5-T, 2,4,5-TP or that 2,3,7,8-TCDD increases
one's risk of cancer if exposed to it.

99/4

I am sure there is still disagreement, but I think that
2,4,5-T is pretty broadly accepted in the field to be
carcinogenic in humans.

101/10

By identifying certain textbooks as authoritative in
epidemiology, that does not mean that I agree with all
the statements made therein.

101/16

And by identifying certain individuals as possible
authorities in the field of cancer epidemiology, that
does not mean that I agree with all the statements made
by these individuals.

I don't agree with his

14

388 '

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

-A i

[10 ] professor of envi­
[17] Q. My pages are
ronmental health sciences unnumbered.
at [11] the University of
[18] A. Right.
South Carolina.
[19] Q. So why don't you
[12] Q. You gave me or point out for me [20 ] the
a c t u a l l y
your
two publications, for
[13] counsel for Dow and e x a m p l e , t h a t y o u
Occidental gave me what
[2 1 ] added?
[14] appears to be a cur­
[22] A. Okay. Right unriculum here. Let me show d e r
the
w o r d
[15] it to you.
[23] p u b l i c a t i o n s ,
[16] A. Well, let me
Schulz, Lee and Mathews,
g i v e y o u a new one
[24] absorption and dis­
[17] that's a little more tribution of subcutane­
updated from that.
ously [25] implanted sil­
[18] Q. That's what I icone gel P/H 3200 in
female rats.
was just going to ask
[19] you. [20] Let's go
- Page 7 ahead and have this new
[I] Q. What does the P/N
[2 1 ] curriculum marked as stand for in [2 ] that?
Plaintiff's 1 to his
[3] A.
It's just part
[2 2 ] d e p o s i t i o n .
number.
[23] (PLF. EXH. 1, Resume
[4] Q. All right. What
for Carl 0. [24] Schulz,
is
the
o t h e r
was
m a r k e d for
[5] publication you've
[25] identification.)
added?
- Page 6 [6 ] A. Bates, Schulz and
[1] BY MR. SCHULER:
L e e ,
1 9 9 3 ,
[2] Q. Let me try and
[7] developmental toxici­
s a v e s o m e t i m e . Do
ty evaluation of the
[3] you go by Dr. Schulz?
[8 ] mammary implant mate­
Is that-rial, silicone gel P/N
[4] A. Yes. That's fine.
[9] 3200, implanted sub­
[5] Q. Let me save some cutaneously in rats.
time and ask you [6 ] what
[10] Q. And are those
differences there are
the two publications
b e t w e ^ n t he r e s u m e
[I I ] you're referring to?
[7] that I have and this
[12] A. Yes.
new resume that you hand­
[13] Q. What presenta­
ed [8 ] me and we marked tions, now, have you
as Plaintiff's 1?
[14] added in the resume?
[9] A. I have added two
[15] A. The first one is
new publications [10 ] on called "Stealth
the top of page 3 and I
[16] Poisons: Chemicals
think
one
new
That Damage the Central
[1 1 ]
presentation on the[17] Nervous System."
top of — I don't know Presentation to the Carowhat [1 2 ] page that is,
linas [18] Brain Injury
^ but two new presentations
Symposium. Charlotte,
^ a t the [13] top of the North [19] Carolina.
■page that starts out pre­ April 29, 1993. [20] And
sentations .
the other is "Absorption
[14] Q. Okay.
and [21] Distribution of
[15] A. That's the only Subcutaneously Implanted
difference I'm [16] aware
[22] Silicone Gel P/N
of.
3200 in Female Rats." The
A. WILLIAM ROBERTS & ASSOCIATES

2

SCHULZ, CARL O.
[23] Society of Toxicolo­
gy 32nd Annual Meeting.
New [24] Orleans, Louisi­
ana. March 18, 1993.
[25] Q. All right. And,
otherwise, the
- Page 8 [1] resume is the same?
[2] A.
I think so. I
believe so, yes.
[3] Q. The publications
that you have [4] added,
the two that involve sil­
icone gel, don't [5] have
anything to do with herb i c i d e s
or
[6] pesticides; correct?
[7] A. That's correct.
[8] Qi And the same with
the p r e s e n t a t i o n s
[9] regarding stealth
poisons and implanted
[10] silicone gel; right?
[11] A. That's correct.
[12] Q.
I noticed, in
looking
at y o u r
[13] resume initially,
that you've testified
before [14] the FDA re­
garding silicone gel; is
that [15] correct?
[16] A. That's correct.
[17] Q. And were you
h i r e d to do t h a t by
[18] any particular trade
or industry group or
[19] individual or what?
[20] A. By a manufacturer
of
silicone
[21] mammary implants.
[22] Q. Who was the man­
ufacturer of that?
[23] A. McGhan Medical
Corporation of Santa
[24] Barbara, California.
[25] Q. Have you testified in silicone gel
- Page 9 [1] cases before?
[2] A. No, I have not.
[3] Q. Have you reviewed
individual cases [4] for
any manufacturers?
[5] A.
I have had pre­
l i m i n a r y interviews
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
1

2
4
5

- Page 1 IN THE CIRCUIT COURT OF
NINTH JUDICIAL CIRCUIT IN
AND FOR CHANGE COUNTY,
FLORIDA
KIMBERLY MOYER, AS PERSONAL
PRPITESEMI'AMUVH C F tffiR ESTATE
CF ROBERT W. MOYER, II,
DECEASED,
Plaintiff,
V S.

CI 89-8657
DOW CHEMICAL COMPANY, OCCIDENTAL
9
CHEMICAL CCRECBAIICN, MONSANTO
AGRICULTURAL PRODUCTS OCMPANY,
HELENA. CHEMICAL OCMPANY, AND
10
SOUTHERN MILL CREEK PRODUCTS CO.,
11
INC.,
12
Defendants.
DEPOSITION OF:
CARL O. SCHULZ,
14
Ph.D.
15
DATS:
March 5, 1993
16 TIME:
9:32 A.M.
LOCATION:
Law Offices of
17
Nexsen, Pruitt,
Jacobs fi
18
Pollard
1441 Main Street
! ! I:
Columbia, SC
19
20
TAKEN BY:
Counsel for the
Plaintiff
WANDA K. CECIL
21
REPORTS} BY:
Court Reporter
Ccmputer-Aided Transcription By:
A. WILLIAM ROBERTS, JR., S
ASSOCIATES
Charleston, SC
Columbia, SC
25
(803) 722-8414
(803) 731-5224
___________
1
2

APPEARANCES OF COUNSEL:
ATTORNEYS FCR THE PLAINTIFF
KIMBERLY MOYER, AS
PERSONAL
3
REPRESENTATIVE CP THR
ESTATE
OF ROBERT W. MOYER, II,
DECEASED«
SCHULER, WILKERSON,
HALVCRSCN S
5
WILLIAMS, P.A.
BY: RICHARD D. SCHULER
6
1615 Forum Place
West Palm Beach, FL
33401
7
(407) 689-8180
ATTORNEYS FOR THE DEFENDANTS
9
DOW CHEMICAL OCMPANY and
OCCIDENTAL CHEMICAL
CORPORATION:
CARLTON, FTEIDS, WARD,
BMANUEL,
11
SMITH S CUTLER, P.A.
BY: ALAN F. WAGNER
12
First Florida Bank
Building
P. O. Drawer 190
13
Tallahassee, FL 32302

15

BAITTY, P.A.
17
18
21
SCRIPT)

(904) 224-1585
ATTORNEYS FOR THE DEFENDANT
HELENA CHOIECAL COMPANY:
LUTZ, WEBB, BOBO &
BY: H. ROGER LUTZ
TWO North Tamiami Trail
Sarasota, FL 34236
(813) 951-1800
(INDEX AT REAR CF TRAN­

- Page 3 [1] STIPULATION [2] It is
stipulated by and among
[3] Counsel that this
deposition is being taken
in [4] accordance with
the Rules of Civil Proce­
dure; [5] that all objec­
tions as to Notice of
this [6] deposition are
hereby waived; that all
[7] objections except as
to form are reserved un­
til [8] the time of tri­
al; and that the witness
does [9] not waive read­
ing and signing of this
[10] deposition. [11] *
* * * * * * * *
* * * [ 12] C A R L O .
SCHULZ, Ph.D.,
[13] being first duly
sworn, testified as fol­
lows: [14] EXAMINATION
[15] BY MR. SCHULER:
[16] Q. Would you state
your name, please?
[17] A. Carl O. Schulz.
[18] Q. What is your
address, Mr. Schulz?
[19] A.
2500 Hayward
Street, Columbia,
[20] South C a r o l i n a
29205.
[21] Q. By whom are you
employed, sir?
[22] A. COSAR, Incorpo­
rated.
[23] Q. What is your
position with COSAR,
[24] Incorporated?
[25] A.
I'm the president.__________________
- Page 4 [1] Q. What is COSAR,
Incorporated?
[2] A. It's my own inde­

A. WILLIAM ROBERTS & ASSOCIATES

1

SCHULZ, CARL O.
pendent consulting
[3] practice in toxicolo­

gy-

[4] Q. Do the letters
s t a n d for a n y t h i n g ?
[5] COSAR, is it an acro­
nym?
[6 ] A. No. Well, the
C-O-S is my [7] initials,
but it doesn't really
stand for [8 ] anything. I
just liked the sound of
it.
[9] Q. Okay. How many
employees does [10] COSAR
have?
[11] A. Two of us.
[12] Q. Yourself and who
else?
[13] A. An assistant.
[14] Q. What is his or
her name?
[15] A. Junko Brown.
[16] Q. How do you spell
that first name?
[17] A. J-u-n-k-o.
[18] Q. And is that a
man or a woman?
[19] A. It's a woman.
[20] Q. When you say you
have this [2 1 ] consulting
business, do you operate
this from [2 2 ] the ad­
dress that you gave me or
do you operate [23] the
business from some other
address?
[24] A.
No. I gave you
my home address. [25] My
office is at 2231 Devine
Street.________________
- Page 5 [1] Q. And that's in
Columbia?
[2] A. In Columbia. Yes.
[3] Q. And is that the
o f f i c e s of C O S A R ,
[4] Incorporated?
[5] A. Yes.
[6 ] Q. Do you have any
o t h e r b u s i n e s s e s ’or
[7] activities of an em­
ployment nature that you
are [8 ] engaged in?
[9] A. Well, I'm also an
adjunct associate
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
[6] with defense attor­
neys preparing for poten­
tial [7] litigation in
silicone mammary inplant
cases, [8] but that has
never gotten to the point
of [9] discussing specif­
ic cases and specific
issues.
[10] Q. And the defense
a t t o r n e y s
are
[11] representing what
manufacturers, if you
know?
[12] A. One is-[13] MR. WAGNER: Dr.
Schulz, if you [14] have
not — if you have been
r e t a i n e d o n l y as a
[15] consultant, as op­
posed to someone to tes­
tify as [16] an expert, I
don't believe you're re­
quired to [17] reveal for
whom you are consulting.
[18] You can if you want
to, and I don't [19] know
if t h e l a w y e r s t h a t
you-re dealing with
[20] would have an objec­
tion to it or not, but. .
•

[21] THE WITNESS: I can't
r e m e m b e r
the
[22] lawyers' names,
frankly, who I've talked
to.
[23] BY MR. SCHULER:
[24] Q. Okay. My ques­
tion, though, was do
[25] you know who the
manufacturers were that
they__________________
- Page 10 [1] were representing?
[2] A.
Yes. One was
McGhan
Medical
[3] Corporation and the
o t h e r
i s
[4] Bristol-Myers-Squibb.
[5] Q. All right. Let me
just go through [6] your
background a little bit
here.
[7] Ja . Uh-huh.
[8 ] Q.
I was a little
A. WILLIAM ROBERTS

&

bit c o n f u s e d by the
[9] summary or the nota­
tion here regarding your
[10] degree. Now, you got
your Ph.D. in organic
[11] chemistry; correct?
[12] A. That's correct.
[13] Q. Do you have a
degree in toxicology,
[14] too, as such?
[15] A. Not a degree,
no.
[16] Q. Okay. If I un­
derstand your resume
[17] correctly, though,
you became a postdoctoral
[18] fellow in environ­
mental medicine at Johns
[19] Hopkins School of
Hygiene in 1971, 1972;
[20] correct?
[21] A. Correct.
[22] Q. And you equate
e n v i r o n m e n t a l
[23] medicine to toxicol­
ogy?
[24] A. Well, toxicology
was
an
area
of
[25 ] specialization within the Department of
- Page 11 [I] Environmental Medi­
cine at the School of
Public [2] Health at that
time.
[3] Q. All right. And
then from 1970 —
[4] actually, before
1971, when you had this
[5] fellowship, after
your postdoctoral time in
[6] chemistry, you began
employment in effect;
[7] correct?
[8] A. That's correct.
[9] Q. As a research
chemist?
[10] A. No. As a toxicologist.
Well,
[II] research chemist —
l e t ' s see. I got my
[12] doctorate in chemis­
try and was a chemist and
[13] then decided I wanted
to
become
a
[14] toxicologist. So in

ASSOCIATES

SCHULZ, CARL O.
'71, I left Union Carbide
[15] and went to Johns
Hopkins and retrained in
[16] toxicology, as a
postdoctoral fellow.
[17] Q. I understand.
[18] A. Okay.
[19] Q. So you got your
degree in [20 ] chemistry,
you worked as a research
chemist for [2 1 ] a couple
of years?
[22] A. Right.
[23] Q. Went back and
did postdoctoral work
[24] in toxicology and
then started out as a
[25] research associate,
I g u e s s , at J o h n s
Hopkins;______________
- Page'12 [1 ] correct?
[2] A. Yes.
[3] Q. And that was for
two years, and [4] then
you worked for the Center
for O c c u p a t i o n a l
[5] Safety and Health,
Stanford Research
[6 ] Institute. Is that a
private corporation?
[7] A. Yes, it is.
[8 ] Q. And what did you
work on in your [9] two
years at that institu­
tion?
[10] A.
SRI had a contract
from
the
[11] National Institute
of Occupational Safety
and [12] Health to devel­
op what are called crite­
ria [13] documents, which
are the scientific bases
for [14] establishing
standards for occupation­
al [15] exposure to chem­
icals in the work'place.
[16] And I was senior
toxicologist on [17] that
project, developing the
t o x i c o l o g y
[18] information tha
went into these criteri
[19] documents for a num­
ber of compounds.
MICROCopy ^

&

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

^
^

]

[20] Q. Did any of those cides we're concerned
compounds include
with in
[21] the herbicides that
- Page 14 we're involved with in
[1] this case?
this [22] case?
[2] A. No.
[23] A. No.
[3] Q. And then you —
[24] Q. What types of
it l o o k s l i k e , a n d
c o m p o u n d s are y ou
[4] correct me if I'm
[25] talking about in wrong, that you stayed
that-with [5] the Food and
- Page 13 Drug Administration, but
[1] A. A variety of in­ were in a [6] different
d u s t r i a l compounds.
branch?
[2] Methanol, methyl
[7] A. That's correct.
parathion, malathion,
[8] Q. Okay. You went to
[3] isopropyl alcohol,
the
Bureau
of
[9] Veterinary Medicine,
carbaryl. I can't
[4] remember. Another b i o l o g i c a l p r o g r a m
dozen or so industrial
[10] specialist?
[5] chemicals.
[11] A. Right.
[6] Q.
So that was a
[12] Q. Correct?
private company that
[13] A. Yes.
[7] had a contract with
[14] Q. Was that a
the government?
transfer at your request
[8] A. Correct.
[15] or was that a promo­
[9] Q. And then you
tion?
spent two years there
[16] A. It was a promotion
at
their
[10] and moved to the
Food and Drug Administra­
[17] request. At this
t i o n , [11] Bureau of
point in the history of
Foods; correct?
the [18] Food and Drug
Administration, we were
[12] A. Correct.
[13] Q. And what were
[19] implementing some­
your duties there?
thing called the biore­
[14] A. I was a petition search [20] monitoring
review [15] toxicologist.
program, which involved a
When individuals or com­ series of [21] standards
panies [16] submit appli­ and inspections to ensure
cations to the Food and the quality [22] and in­
tegrity of toxicology
Drug [17] Administration,
in this case, it was new d a t a s u b m i t t e d to
animal [18] drug applica­
[23] the Food and Drug
tions. For drugs to be Administration. [24] So
used in [19] food produc­ the Bureau of Veterinary
ing animals, I reviewed
[25] Medicine asked me to
the [20] toxicology data head up their compliance
that they submitted with
- Page 15 their [21] petition to
[1] and enforcement pro­
make a determination
gram for the laboratory
whether that [22] would
— [2] toxicology labora­
be safe for human health tory part of that pro­
to use that drug [23] or gram.
chemical in food animals.
[3] Q. What, essential­
[24]
Q.
Okay. Any ofly, were you dealing
your work
there
[4] with as far as the
[25] involve the herbi­
A. WILLIAM ROBERTS & ASSOCIATES

4

SCHULZ, CARL O.
animals were concerned,
[5] though?
[6] A. Well, we were
c o n d u c t i n g
[7] inspections of toxi­
cology laboratories that
[8] were conducting tests
that would be submitted
[9] to the government in
support of the safety of
[10] food animals — food
additives in animal drugs
[11] and to make sure
that they were in compli­
ance [12] with the regu­
lations .
[13] Q. Did any of that
w o r k i n v o l v e the
[14] herbicides that
we're concerned with in
this [15] case?
[16] A. No.
[17] Q. All right. 1978,
then, to '82, [18] still
in the Food and Drug Ad­
ministration. [19] Looks
like now in the Bureau of
Drugs. And it [20] says,
chief, gastrointestinal
and c o n t r a c e p t i v e
[21] d r u g p r o d u c t s
branch. Was that another
[22] promotion?
[23] A. Yes, it was.
[24] Q. And what was the
reason for your [25] move
there?
- Page 16 [1] A. Well, the initial
program had been [2] set
up that I was administer­
ing in the Bureau [3] of
Veterinary Medicine and
an o p p o r t u n i t y c a m e
[4] for me to advance and
become a branch chief,
[5] which is also an in­
crease in grade and sala­
ry, [6] so I took it and
went to the Bureau of
Drugs [7] and was in
charge of this branch of
about 12 [8] people in
the over-the-counter drug
review.
[9] Q.
Gastrointestinal
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
and c o n t r a c e p t i v e
[10] drug products, those
types of things, you said
[11] over-the-counter,
a n t i a c i d t y p e dr u g s
and-[12] A.
Antiacids.
Right.
[13] Q. -- oral contra­
ceptives for women?
[14] A.
No. Because
that's a prescription
[15] drug. The o n l y
non-prescription contra­
ceptive [16] drug that we
evaluated was spermicidal
gels and [17] creams and
sprays.
[18] Q. And you were
t h e r e
f o r
[19] approximately four
years?
[20] A. Yeah. There's a
m i s t a k e ;- t h e r e
I
[21] notice on — now,
that I see that, that
would [22] have been un­
til 1981, of course, be­
cause I left [23] there
to go to Clement Associa t e s . It w a s j u s t
[24] about three years.
[25] Q. And did any of
your work there________
- Page 17 [1] involve the herbi­
cides? [2] A. No.
[3] Q. All right. '81,
you went to [4] Clement
Associates, Inc. What is
Clement [5] Associates,
Inc.?
[6] A. Clement Associ­
ates is a consulting
[7] firm in Washington
that does environmental
[8] occupational toxicol­
ogy and risk assessment.
[9] Q. A private corpo­
ration?
[10] A. Yes.
[11] Q. And, back in
1981, who was running
[12] Clement Associates,
Incorporated?

[13] A. Well, when I
went to work there the
[14] president was John
Colojefski.
[15] Q. How big a company
is
Clement
[16] Associates, Incorpo­
rated?
[17] A. Well, at that
time, it probably had
[18] about 60 employees,
I would guess. Now, it's
[19] been absorbed into a
much larger corporation
[20] and I've somewhat
lost track of both their
[21] exact corporate
identity and their size.
[22] Q. Who was your
boss
at C l e m e n t
[23] Associates?
[24] A. When I began
t h e r e it w a s J o e
[25] Rodricks.
- Page 18 [1] Q. And you said you
were in the [2] division
of life sciences?
[3] A. That's correct.
[4] Q. What other divi­
sions did they have?
[5] A. Well, there was
an
engineering
[6] division; and I think
those were the only two
[7] essential program
divisions. There might
have [8] been a division
of administration and
[9] management or some­
thing like that, but
[10] engineering and life
sciences were the two
main [11] program parts.
[12] Q. And what were
your
duties
and
[13] responsibilities as
associate director of the
[14] division of life
sciences?
[15] A. Well, I super­
v i s e d t h e s t a f f of
[16] about eight or a
dozen staff scientists
and [17] assistant staff
scientists in a variety

A. WILLIAM ROBERTS & ASSOCIATES

5

SCHULZ, CARL O.
of [18] contract activi­
ties, primarily for the
federal [19] government.
[20] Q. Was Clement Associates,
Inc.,
[21] mostly a government
contractor working on
[22] different projects
for the government?
[23] A. At that time, we
w e r e p r o b a b l y 95
[24] percent government
contracts and about 5
[25] percent private.
- Page 19 [1] Q. And in '81 to
'82, as a s s o c i a t e
[2] director of the divi­
sion of life sciences,
did [3] you have occasion
to work on any herbicide
[4] projects?
[5] A.
I think so. I
don't know exactly
[6] when, at that point,
my in vo lvement with
[7] herbicides began. It
began within the first
[8] two years or so that
I wo r k e d at Clement.
[9] Probably — I can't
place it exactly. Proba­
bly [10] about 1982 when
I began heavy involvement
with [11] the phenoxy
herbicides.
[12] Q. What was your
first involvement
[13] with phenoxy herbi­
cides, as you recall it?
[14] A. We submitted a
proposal
to t h e
[15 ] Veterans Administration in response to a
[16] request for proposal
to perform a literature
[17] search and review on
scientific literature and
[18] the potential health
effects of herbicides
that [19] were used in
Vietnam.
[20] Q. And did you ge
that contract?
[21] A.
Yes, we were
awarded that contract
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[22] in -- again, I'm
thinking 1982. It was a
[23] three-year contract.
We re-competed it in 1985
[24] or so and won it for
three more years and then
[25] a one-year extension
on that. So I believe
- Page 20 [1] that we had the con­
tract for seven years, is
my [2] recollection.
[3] Q. Was the first
work product that you
[4] were involved in with
r e g a r d to p h e n o x y
[5] herbicides published
around 1985?
[6] A. Well-[7] Q. At the conclusion
of this [8] three-year
contract?
[9] A.
No. We did it
every
year.
We
[10] p u b l i s h e d a
two-volume summary every
year once [11] we began
the contract. And I think
the first [12] one cov­
ered through 1981 or the
middle of 1981, [13] so
it would have been publ i s h e d in ' 8 2 , I
[14] think.
[15] Q.
So the first
p u b l i c a t i o n of t h e
[16] literature summary
would have been around
1982?
[17] A. Yeah. It says
b a c k in h e r e .
I
[18] think I've got them
all listed. Okay. I'm
[19] mis-remembering, as
I tend to do. 1984 was
the [20] first publication that I did. We completed it [21] in '83.
That's right. I'm remem­
bering now.
[22] Q.
So the first
publication that you
[23] were associated with
involving phenoxy
[24] herbicides was in
1984?

[25] A. Correct._______
- Page 21 [1] Q. And that was the
o n e l i s t e d h e r e on
[2] your resume that says
Veterans Administration,
[3] 1984. Synopsis of
Scientific Literature on
[4] Phenoxy Herbicides
and Associated Dioxins,
[5] Number 1, Volumes 1
through 4?
[6] A. Well, yes. The
volume right above
[7] it, too. The way
these work is we pub­
lished a [8] two-volume
set, in that case in '84,
it would [9] have been 3
and 4; 4 being an anno­
tated [10] bibliography,
3 being a critical review
of the [11] literature.
And then we summarized
those in [12] what we
called a synopsis or a
lay
l a n g u a g e
[13] summary, which was
published the same year.
So [14] what you have,
basically, is three vol­
umes came [15] out every
y e a r , if y o u w i l l .
[16] Two, 8 1/2 by 11
books, one being [17] an
annotated bibliography
and one the critical
[18] review. And then the
smaller, little pamphlet
[19] like that the VA
produces, which were de­
signed [20] to be a sum­
mary of those volumes,
but written [21] in a way
that educated lay people
could read [22] them and
understand them.
[23] Q. Okay. So if I
understand
you
[24] correctly, the con­
tract and the product of
the [25] contract with
the Veterans Administra­
tion over
- Page 22 -

A. WILLIAM ROBERTS & ASSOCIATES

6

SCHULZ, CARL O.
[1 ] the years has been
e s s e n t i a l l y
a
three-volume [2] output,
the annotated bibliogra­
phy, the [3] critical
review and the summary
pamphlet I'll [4] call it
for lack of a b etter
word?
[5] A. Synopsis. Yes.
[6] Q. Synopsis?
[7] A. Yes. Right.
[8] Q. Okay.
[9] MR. WAGNER: Every
year, not in [10] total.
I don't know if there's a
[11] miscommunication.
[12] MR. SCHULER: Pardon?
[13] MR. WAGNER: It's
every year, not [14] in
total.
[15] MR. SCHULER: Right.
[16] Q.
You up date it
from year to year?
[17] A. Yes. Well, it's
a whole new [18] document
each year. In that — in
the period [19] that we
had this contract, approximately
300
[20] relevant articles
were published every
year. [21] We wouldn't up
date — in other words,
each [22] volume is a new
and separate document
that [23] contains none
of the literature of the
previous [24] years, ex­
cept if we referred back
to it to make [25] a com­
parison, you know, or
extension in the_______
- Page 23 [1] critical review part.
[2] Q.
Okay. So each
year,
you would
[3] review the new arti­
cles that came out in the
[4] prior year?
[5] A. That's correct.
[6] Q. So each install­
ment of this would [7] be
approximately 300 new
articles
to
be
[8] r e v i e w e d a n d
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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
synopsized?
[9] A. Correct.
[10] Q. Have you done
any original research
[11] on phenoxy herbi­
cides that's been pub­
lished?
[12] A. No.
[13] Q. As far as the
b i b l i o g r a p h y that
[14] you've done and the
review of the articles
and [15] research that
has been published, just
from [16] your experience
now, 300 articles a year
on [17] phenoxy herbi­
cides, is that a relatively
active
[18 ] investigation based
on the number of articles
[19] or how would you
describe it?
[20] A. I would say it's
b e e n o n e of t h e
[21] major research ef­
forts of the last ten
years.
[22] Q. And the average
has been around [23] 300,
give or take, in each of
the
years
that
[24] you've been in­
volved?
[25] A.
Yes. That's
pretty accurate, I______
- Page 24 [1] think. 300 is a good
number. It was higher
[2] than that, dropped
down a little bit, and
came [3] back up again.
In fact, in the middle of
this [4] somewhere, I
published a paper that
had a graph [5] in it of
papers per year and so
forth.
[6] Q. Those are arti­
cles from the product
[7] of research from all
over the world; correct?
[8] A.
Yes, yes. The
nature
of
our
[9] contract was that we
r e v i e w the w o r l d ' s

[10] literature.
[11] Q. Did you ever go
back and look back
[12] beyond your initial
e n g a g e m e n t in 1982,
[13] roughly, to deter­
mine and look back
[14] retrospectively to
see whether, say, in the
[15] prior decade from
1972 to 1982, whether
there [16] had been that
much research activity
regarding [17] the phe­
noxy herbicides or wheth­
er, at some [18] point,
there was a dramatic increase
in
the
[19] research?
[20] A. Well, I looked
at that. What [21] you'll
notice is that the first
year that we [22] had the
contract, the first pub­
lication was [23] Volumes
3 and 4. Volumes 1 and 2
were produced [24] by
another contractor under
an ini t i a l c o n t r a c t
[25] from the Veterans
Administration. And their
- Page 25 [1] mandate in their con­
tract was to review all
the [2] literature pub­
lished up through 1981.
See, [3] when we got it,
it became a yearly up
date; but [4] they were
to go back as far as they
could find [5] anything.
And
[6] Q. Could I stop you
for one second?
[7] A. Yes.
[8] Q. Who was that com­
pany that did that?
[9] A. The name of that
c o m p a n y was c a l l e d
[10] JRB Associates, and
they were in Washington
at [11] the time. I don't
think they exist any
more.
[12] Q. Who was the ind i v i d u a l , if y o u

A. WILLIAM ROBERTS & ASSOCIATES

7

SCHULZ, CARL O.
[13] know, at JRB Associates who had the
[14] responsibility for
that?
[15] A. I don't have any
idea. I don't [16] think
I ever knew.
[17] Q. You ever talk
with anyone of JRB?
[18] A. No. They were,
of c o u r s e , b i t t e r
[19 ] that they lost the
contract to us, so. . .
[20] Q.
So there was
a-[21] A.
But I did have
th eir V o l u m e s 1 and
[22] 2, which I still
have. And, o v e r the
years, of [23] course,
it's been incumbent on me
to evaluate [24] the com­
pleteness and accuracy of
the work they [25] did.
And, in general, it was
fairly complete.________
- Page 26 [I] There's some omis­
sions, which we [2] tried
to pick up. And, actual­
ly, we included [3] in
that first set of volumes
we did, 3 and 4, [4] we
included some earlier
l i t e r a t u r e w h e n we
[5] identified it and saw
that it wasn't in Volumes
[6 ] 1 a n d 2 a n d we
thought it was important.
We [7] put it in 3 and 4
even though it was pub­
lished [8] prior to the
era of coverage of our
review. [9] So I'm fairly
c o n f i d e n t that the
[10] review, through the
last year we did it, was
[II] quite complete.
[12] Q. To go back to my
original question,
[13] though, since you've
looked at Volumes 1 ancK q c
2, [14] that was the ini^_
tial volumes 1 and 2 done 3 3 ^
by [15] JRB Associates,
can you give me some kind
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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
of an [16] idea, looking w a s n ' t you. E i t h e r
backward from 1982 to
[22] that or you've dis­
whatever [17] year they covered the-went back to, what type
[23] A. Foundation of
of activity [18] in terms youth.
of number of articles per
[24] Q. -- Ponce de Leon
year or any [19] way you
f o u n d a t i o n
want express it?
[25] somewhere. But is it
[20] A. I'm sorry. Yes. anybody related to you?
I lost the track [21] on
- Page 28 that. No. Clearly, there
[1] A. No.
was not [22] significant
[2] Q. Spells the name
research, published re­ the same.
search [23] interest in
[3] A . Y e s . Well,
this area much before the Schulz, spelled the way
[24] late '70s. [25] I
[4] I spell it, it's is
would say that Volume 1 the most common surname
and 2_________________
in [5] Germany. So it's
- Page 27 not surprising.
[1] bibliography covering
[6] Q. Smith?
everything before the
[7] A. Yeah. It's the
[2] middle of '81, I S m i t h of G e r m a n y .
w o u l d say p r o b a b l y
[8] But, no, I don't.
there's — [3] I'm just
[9] Q.
So you're not
guessing, but approxi­ related to the Schulz
mately 500 [4] articles
[10] of K i m m i g and
in that first volume bib­ Schulz?
liography. So [5] prior
[11] A. No..
[12] Q. Okay. And the
to the middle of '81,
o n l y 500 a r t i c l e s
1950s a r t i c l e that
[6] total were published.
[13] you're referring to,
[7] Q. Going back all do y o u r e c a l l t h a t
t h e w a y to t h e ' 4 0 s
[14] specifically?
[15] A. No. I'm just -[8] or-[9] A. Well, it depends.
I'm h e s i t a n t even
I mean, probably [10] the
[16] there. I can't, now
earliest papers specifi­ as I think back, remember
cally on dioxins was
[17 ] when ‘articles rele­
[11] 1957. Health effects vant to the health ef­
of phenoxy herbicides, I fects of [18] phenoxy
[12] can't remember the h e r b i c i d e s , per se,
earliest paper, but prob­ started to appear. [19] I
ably [13] in the '60s or didn't think about that
^
so, early '70s maybe.
in p r e p a r a t i o n for
?? [14] Q. Going back to
[20] today.
the article that you
[21] Q. Okay. But in any
[15]
referenced in '57. event, the [22] articles
That wasn't
the
that you're referring to,
* [16] Kimmig-Schulz-the '57 [23] article on
dioxin and the '60s arti­
[17] A. Schulz. Yes.
[18] Q.
I was going to cle on the [24] health
effects — early '60s, I
ask you a b o u t that
[19] today because I think you [25] said —
noticed-health effects of phenoxy
[20] A. It's not me.
herbicides,
[21] Q.
I figured it
A. WILLIAM ROBERTS & ASSOCIATES

8

SCHULZ, CARL O.
- Page 29 [1] they're all in that
Volume 1 and 2 that we've
[2] been talking about?
[3] A. Yes.
[4] Q. Do you have copies
of
the
JRB
[5] Volumes 1 and 2 in
your library?
[6] A. Yes, I do.
[7] Q. How big a tomes
are we talking [8] about
here?
[9] A. Well, they're —
probably each [10] volume
is 300 to 400 pages.
[11] Q. Did they do just
the bibliography [12] and
annotation to the bibli­
o g r a p h y or d i d t h e y
[13] also do a-[14] A. They did a crit­
ical summary, too.
[15] Q. Did they do a
synopsis, also?
[16] A. No. The synopsis
was a new thing [17] in
our contract. And, if you
look,
the
first
[18] synopsis I did was
Volumes 1 through 4. So I
[19] went back, and for
the lay language thing,
[20] synopsized the two
volumes that summarized
the [21] two volumes that
JRB did, as well as the
first [22] two that we
did.
[23] Q. Do you recall
any
p u b l i s h e d
[24] research — and if
you don't recall just
tell [25] me so. I real­
ize that I'm probably
testing________________
- Page 30 [1] your memory here. But
do y o u r e c a l l a n y
[2] published research in
the 1950s that originated
[3 ] out of Dow Chemical
Company that related to
the [4] health effects of
phenoxy herbicides?
[5] A.
No, I don't reMICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
call.
[6] Q. What about in the
1960s?
[7] A. I don't recall,
but there could [8] have
been. I just don't remem­
ber.
[9] Q. Would the summary
volumes
of
the
[10] scientific, pub­
lished scientific litera­
ture in [11] this area
investigate those pub­
lished articles [12] that
originated out of indust r i a l r e s e a r c h , as
[13] well as independent
scientific research?
[14] A.
If they were
p u b l i s h e d in t h e
[15] publicly available
domain. And not even
[16] necessarily pub­
lished, if they were — I
think [17] we did a pret­
ty good job, at least
after we [18] took over,
of identifying documents
not [19] published in
normal scientific jour­
nals, so to [20] speak,
that we could get our
hands on.
[21] Q. Okay. Whei^ you
f i r s t
becartTe
[22] involved with this
project in your associa­
tion [23] with Clement
A s s o c i a t e s , was the
search that [24] you did
-- and I looked at, I
t h i n k , o n e of t h e
[25]
versions of what
you've done and I think
it was
- Page 31 [1] a later version. But
were the searches that
[2] you did of the scien­
tific literature both
[3] manual, as well as
computer?
[4] A. That's correct.
[5] Q. And just — you
d o n ' t h a v e to g e t
[6] into great detail,

but how w o u l d you
[7] essentially do the
manual search? By going
to [8] some library some­
where or how did you do
that?
[9] A. Very typically,
a l t h o u g h the normal
[10] approach was to
start with the computer
data [11] base search of
the common data bases,
M e d - L i n e [12] a n d
Tox-Line, specifically.
[13] You would identify,
from that, a [14] large
number of relevant arti­
cles which you [15] would
get the hard copies of.
Then, typically, [16] you
would look in the biblio g r a p h i e s of t h o s e
[17] to find references
to other articles that
you [18] may have missed.
So that was part of the
[19] manual searching.
[20] Part of the manual
searching would [21] be
looking at something
called
Current
[22] Contents, which is
just a compilation of the
[23] tables of contents
of all the scientific
[24] journals in the
field, and you'd have
certain [25] journals
that you'd screen the
table of_______________
- Page 32 [1] contents for, every
month as they come out,
[2] l o o k i n g for it.
[3] And then there were a
few other [4] printed
current literature things
that you look [5] at. One
that we used quite a bit
in the early [6] days was
something put out by the
National [7] Cancer In­
stitute. No. Chem Ab­
stracts. [8] Chem Ab­
stracts Service would put
[9] out these monthly or

A. WILLIAM ROBERTS & ASSOCIATES

9

SCHULZ, CARL O.
weekly publications that
[10] would just compile
the abstracts relevant to
a [11] certain area, like
c a r c i n o g e n e s i s or
[12] reproductive ef­
fects, and we'd scan
those, too, [13] for ar­
t i c l e s r e l e v a n t to
d i o x i n s or p h e n o x y
[14] herbicides.
[15] Q. I know you've
described what you've
[16] done, but what was
the overall reason for
the [17] contract, if you
know, let by the Veterans
[18] Administration?
[19] A. Well, it was
man dated by public
[20] law, and I can't
remember what law that
was [21] now, passed in
about 1979 or something,
that [22] had a number of
provisions in it for the
[23] Veterans Administra­
tion to investigate the
[24] possible link be­
tween exposure to herbi­
cides in [25] Vietnam and
long-term health effects
in Vietnam
- Page 33 [1] veterans. [2] And one
of t h e
specific
[3] specifications that
Congress put in that
[4] legislation was that
the VA review and — I
[5] don't know whether it
the mandated publication,
[6] but it said review
and maintain and up date
a [7] file of all litera­
ture relevant, scientific
[8] literature, medical
literature, relevant to
the [9] health effects of
the herbicides that were
used [10] in Vietnam. So
the contract grew oqt of 39r
a [11] congressional man­
date.
[12] Q. And that mandate
grew out
of t h e

394

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
[13] what, concern aris­
ing about the health ef­
fects [14] of Agent Or­
ange on the Vietnam vet­
erans?
[15] A. Correct.
[16] Q. Were you in­
volved, during your time
[17] with Clement Associ­
ates, with any other
[18] projects, other than
this one?
[19] A. Relevant to phen o x y h e r b i c i d e s or
[20] just-[21] Q. Any project.
[22] A. Oh, many pro­
jects. Many other
[23] projects.
[24] Q. That did not
involve
phenoxy
[25] herbicides?
- Page 34 [1] A. That's correct.
[2] Q. Can you give me
some examples of [3] some
of the things you recall
you were involved
[4] with during that, I
think, 1981 to 1985?
[5] A. Yes. We had a —
in the early [6] first
two of those years or so,
we had a [7] contract
with the Office of Pesti­
cide Programs [8] at EPA
to review data that was
submitted to it [9] in
support of the safety of
p e s t i c i d e
for
[10] registration of pest i c i d e s
or
re-registration [11] of
pesticides.
[12] Q.
Pesticides re03 f e r r i n g to i n s e c t
[13] killers?
^ [14] A. Everything. Insect
killers,
[15] fungicides, wood
preservatives.
[16] Q. Okay.
[17] A. So forth. And,
of course, that [18] will
raise the question. Herb i.c i d e s c o u l d h a v e

[19] been covered under
that, but I don't recall
[20] that while I was
involved with that pro­
ject, I, [21] or any of
the people I supervised,
reviewed any [22] data on
a herbicide that was one
that we used [23] in
Vietnam or is relevant to
this case.
[24] Q. Okay.
[25] A . So i t 's , I
think, coincidental that
- Page 35 [1] it didn't have that
involvement.
[2] Q. Did you publish
anything as a [3] result
of that contract?
[4] A. No, no. That was,
of
course,
all
[5] confidential work for
EPA.
[6] Q. Okay. What other
projects
do y o u
[7] recall that you
were-[8] A. We had-[9] Q. -- involved in
during that-[10] A. Yeah.
[11] Q. Let me finish my
question.
[12] A. I'm sorry.
[13] Q.
-- during that
four-year period
[14] from '81 to '85?
[15] A. We had a major
c o n t r a c t from the
[16] Occupational Safety
and Health Administra­
tion. [17] They had —
before I went to work at
Clement, [18] they had
p u b l i s h e d something
called
the OSHA
[19] carcinogen policy.
And it was a notice and
[20] they invited com­
ments, and we reviewed
the [21] comments to the
notice, and helped draft
a [22] final order for
the OSHA carcinogen poli­
cy.

& A. WILLIAM ROBERTS & ASSOCIATES

10

SCHULZ, CARL O.
[23] Q. Okay.
[24] A. What other?
[25] Q. Anything else?
- Page 36 [1] A. Yes. There were
many more, but [2 ] what
can I think of. We had
another
small
[3] contract from OSHA to
evaluate occupational
[4] exposure to formalde­
hyde in the work place.
[5] Had a contract from
— several [6 ] contracts
from EPA sequentially to
investigate [7] risk as­
sessment methodology used
for -- b o t h [ 8 ] for
prioritizing pollutant
c h e m i c a l s
for
[9 ] standard development,
a n d f o r all a c t u a l
[10 ] standard development
itself. [1 1 ] I worked on
private contracts in
[1 2 ] that time.
[13] Q. Can you remember
the names of any [14] of
the companies that you
w o r k e d
w i t h ,
[15] c o n t r a c t e d for
Clement's services?
[16] A. I remember one.
We
did
a —
we
[17] investigated the
link between aspirin and
[18] Reye's syndrome for
the Aspirin Foundation, I
[19] b e l i e v e it w a s
called. But a trade, you
know, [20 ] organization.
[21] Did some work for
Tampax [22] Corporation
on a strategy for estab­
lishing the [23] safety
of their medical device
products.
[24] Q. Is that in conn e c t i o n with the
[25] toxic shock?______
- Page 37 [1] A.
No. It was in
c o n n e c t i o n ,
[2 ] basically, with the
implementation of the
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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
1976 [3] medical device
amendments, which would
require [4] them to sub­
mit data to the Food and
Drug [5] Administration
to establish the safety
of all [6 ] of their prod­
ucts. And we just out­
lined for [7] them the
kind of te s t i n g they
might have to do [8 ] and
a proposal so they could
go to F D A a n d say,
[9] here's what we pro­
pose to do. What do you
[10 ] think?
[11] Q.
In your work
with Clement, did you
[1 2 ] have any contracts
or did the company have
any [13] contracts that
you were aware of with
any [14] herbicide manu­
facturers? Dow Chemical
or [15] Diamond Shamrock?
[16] A. No. Certainly
not. And we [17] probably
— particularly in those
early years, [18] when we
— when we had the EPA
contract from [19] Office
Pesticides, we were legally prohibited
[20 ] from any contractual
e n g a g e m e n t w i t h any
[2 1 ] pesticide manufac­
turing company. So I know
we [2 2 ] didn't then.
[23] We didn't have that
contract after [24] about
1982 or '83. I vaguely
recall
we had a
[25] contract with, I
think, W.R. Grace; and
they__________________
- Page 38 [1 ] won't have been a
phenoxy herbicide
[2 ] manufacturer. I think
we did, in those later
[3] years, have some; but
nobody would be — not a
[4] Dow. Never a Dow.
Never
a Diamond
Shamrock-[5] Q. Chevron?

[6] A. -- while I was
there. Now, I'm [7] going
to stop. Did have a con­
tract indirectly [8] with
Dow. It was actually with
something [9] called the
III, the International
I s o c y a n i d e
[10] Institutes and the
— our contract or our
[11] project officer was
Larry Rampy, who was an
[12] industrial hygienist
at Dow Chemical Company.
[13] And we reviewed the
NTP, National Toxicology
[14] Program bioassay of
toluene diisocyanate for
[15] them.
[16] MR. SCHULER: Did you
get that, [17] toluene
diisocyanate?
[18] T H E W I T N E S S :
D i i s o c y a n a t e . You
[19] can flag these and
I'll spell them for you
at [20] the break. But-[21] MR. LUTZ: We haven't
even started [22] yet.
[23] THE WITNESS: Yeah.
Let's see. [24] Lost my
train of thought. No oth­
er — no work [25] for
phenoxy herbicide manu­
facturers^_____________
- Page 39 [1] BY MR. SCHULER:
[2] Q. Let me just ask
you a question with
[3] regard to -- your
contract or Clement's
[4] contract was with
III?
[5] A. Yes.
[6] Q. And your project
m a n a g e r was this
[7] fellow from Dow—
[8] A. Right.
[9] Q. -- that you men­
tioned?
[10] A. Yes.
[11] Q. And the toluene
d i i s o c y a n a t e was an
[12] element of what type
of product, if you know?
[13] A.
It's a major

A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
b u i l d i n g b l o c k for
[14] manufacturing poly­
ester resins.
[15] Q. Okay. All right.
[16] MR. WAGNER: I must
say,
that
was
[17] impressive that you
were able to regurgitate
[18] that.
[19] THE WITNESS: He
stumbled a little.
[20] MR. SCHULER: My organic
chemistry
[21] background canes to
the fore.
[22] Q.
If you need to
take
a break
on
[23] occasion, we can-[24] A.
I'll let you
know.
[25] Q.
Just let me
know.__________________
- Page 40 [1] A. Okay.
[2] Q. My last area of
q u e s t i o n i n g , I was
[3] trying to ask if you
knew
if C l e m e n t
[4] Associates, Inc., had
any contracts with any
[5] herbicide manufactur­
ers . I t h i n k y o u ' v e
[6] answered that. [7] Is
there anything else that
you can [8] recall that
you wish to add to that
answer?
[9] A. No.
[10] Q. And I think you
b a s i c a l l y g a v e me
[1 1 ] the background of
some of the other pro­
jects [1 2 ] that you re­
member during your time
at
C l e m e n t
[13] Associates. Did most
of the projects involve
[14] review of litera­
ture, that type of thing
and [15] analysis of sci­
entific literature? I
think [16] there was onftQQ
or two that you mentioned
that [17] you did some 3 9 5
pro formas for the EPA
and things [18] of this

y

MICROCopy

9

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY___________________
nature for clients to
submit to the [19] EPA;
correct?
[20] A. Yes. It was all
literature
and
[2 1 ] writing and — we
did no laboratory work or
had [22 ] no research fa­
cilities that would have
allowed [23] original
research.
[24] Q. Okay. You men­
tioned, I think, who
[25] your initial boss
was at Clement Associates.__________________
- Page 41 [I] Can you tell me, if
there have been a series
of [2 ] them, who the oth­
er people were that su­
pervised [3] you?
[4] A. Oh, boy.
[5] Q. And if there's a
whole bunch of [6 ] them,
just give me the main
people
that you
[7] worked with.
[8 ] A. Yeah. After Joe
R o d r i c k s l e f t , it
[9] w o u l d have b e e n
D i e t r i c h ,
D-i-e-t-r-i-c-h. And
[10 ] I can't remember his
first name. That's kind
[I I ] of embarrassing, I
think,.„not to know your
[12] boss' name. There
were some odd things go­
ing [13] on organization­
ally at Clement at that
time. [14] Gary Dietrich,
that's his name. Gary
Dietrich, [15] and I sup­
pose that he was my di­
rect supervisor [16] the
remainder of the time I
4 was there, a l t h o u g h
O
[17] we kept reorganizing
^
and shifting titles.
[18] One other name, who
was probably — [19] may
■have been my direct su­
pervisor at one point
[20] or another was Jay
Turim, T-u-r-i-m.

s

[21] Q. Okay.
[22] A. That's basically
covers it.
[23] Q. You mentioned
that
C l e m e n t
[24] Associates was pur­
chased by another company
or [25] was absorbed into
another company; is that
- Page 42 [1] correct?
[2] A. That's correct.
[3] Q. What company was
it absorbed into?
[4] A. It was purchased
by a company [5] called
ICF.
[6] Q. What does that
stand for?
[7] A.
I don't know.
Before that — we [8] was
purchased in about 1983
by a strange [9] company.
I don't know the name of
it. And [10] then in
about 1985, late 1985,
Clement was [11] bought
by ICF International,
which still exists
[12] and that's their
parent company now. And
it's [13] in Vienna, Vir­
ginia, and I don't know
what ICF [14] stands for.
[15] Q. Vienna, Virgin­
ia, is the l o c a t i o n
[16] now of-[17] A. Uh-huh.
[18] Q. — where the old
Clement would be?
[19] A. Yes. What's left
of
it.
It's
a
[20] division of ICF.
[21] Q. Does that divis i o n s t i l l do t h e
[22] government contract
type of work?
[23] A.
I don't think
so. My r e c o l l e c t i o n
[24] is they do almost
exclusively private work
now.
[25] Q. All right. You
left Clement
- Page 43 -

A. WILLIAM ROBERTS & ASSOCIATES

12

SCHULZ, CARL O.
[1] Associates; correct,
in 1985?
[2] A. Well, I left them
gradually.
[3] Q. Okay. Tell me
about that.
[4] A. In 1983, I felt I
was spending way [5] too
much of my time doing
administrative
[6 ] functions and not
nearly enough doing the
[7] actual scientific
work that I was qualified
to [8 ] do. [9] And I ap­
proached the management
of [10 ] Clement and said,
I'd like to establish a
new [1 1 ] relationship
whereby I consult to your
clients, [1 2 } but on an
hourly basis, and I'd
like to [13] establish my
own independent consult­
ing [14] practice, not in
competition with yours.
And [15] they were very
generous and very willing
to do [16] that. [17] And
that's the relationship
that [18] existed from
'83 to '85 when I was
what was [19] referred to
as a senior toxicology
adviser at [20 ] Clement.
In that period, about 80
percent of [2 1 ] my time,
chargeable time was spent
working on [2 2 ] Clement
projects in Clement's
offices; but I [23] did
-- I was, in a sense,
w e a n i n g m y s e l f aw a y
[24] from the company at
that point.
[25] Q. Okay. So in
1983, you started this
- Page 44 [1] COSAR, Inc.?
[2] A. Right.
[3] Q. And did primarily
consultations [4] with
Clement and then started
to do some [5] outside
consulting, as well; cor­
rect?
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[6 ] A. That's correct.
[7] Q. When did you be­
gin m e d i c a 1 / 1 ega 1
[8 ] consulting work, I'll
call it, or working with
[9] attorneys?
[10] A. I think we provided some —
we
[11] provided litigation
support while I was still
[12] at Clement. And did
some of that and then
it's [13] been a part of
my business ever since.
[14] MR. WAGNER: Before
you move into [15] legal
cases, could we take a
quick break?
[16] MR. SCHULER: Sure.
[17] (A recess tran­
spired. )
[18] BY MR. SCHULER:
[19] Q. Let's see. I
think we were talking
[20] about your employ­
ment with Clement and
then [21] your beginning
of COSAR, Incorporated,
a n d
y o u r
[22] medical/legal in­
v o l v e m e n t or m e d i ­
c a l
/ l e g a l
[23] involvement — your
consulting with lawyers.
[24] A. Uh-huh.
[25] Q. When did you
first get involved in
- Page 45 [1] consulting in litiga­
tion type matters in
terms [2] of chronologi­
cally? Can you tell us?
[3] A.
Probably around
1983, sometime [4] right
in the middle of my em­
ployment with [5] Clement
Associates.
[6] Q. 1983?
[7] A.
I'd guess that.
Yes.
[8] Q. And can you recall
the
first
[9] instance of your in­
v o l v e m e n t ? Was it a
[10] herbicide case or
was it some other matter?

[11] A. No, it wasn't
herbicides. It was a
[12] case involving DDT
contamination in Alabama.
[13] Q. Do you have
s o m e w h e r e a list of
[14] your case involve­
ments, in cases where
you've [15] testified,
either deposition or tri­
al?
[16] A. No.
[17] Q. I mean, it would
save some time. [18] You
know, if you've got the
i n f o r m a t i o n
[19] somewhere and have
it, it'll save me some
time [20 ] in questioning.
[21] A.
I've got the
information. And, in
[2 2 ] fact, last night, I
made a little handwritten
[23] crib sheet to cover
the last five years.
[24] Q. Okay.
[25] A. I brought that
with me._______________
- Page 46 [I] MR. WAGNER: I told
him that you [2 ] were
curious about that.
[3] MR. SCHULER: Yes, we
like to know [4] those
things.
[5] Q. Can I just take a
look at that—
[6 ] A. Sure.
[7] Q.
-- quickly and,
again, it'll [8 ] probably
save me some time if I
can just glance [9] down
here.
[10] A. I'll tell you,
r i g h t o f f t h e bat,
[I I ] almost none of them
are phenoxy herbicide or
[1 2 ] dioxin.
[13] Q. Okay. Well, that
was probably [14] going
to be my first question.
Are any of [15] these
cases phenoxy herbicide
cases?
[16] A. I'm working on
one other active

A. WILLIAM ROBERTS & ASSOCIATES

13

SCHULZ, CARL O.
[17] case.
[18] Q. Presently?
[19] A. Uh-huh.
[20] Q. Yes. You have to
say?
[21] A. Yes.
[22] Q. Okay.
[23] A. Sorry.
[24] Q. And what case is
t h a t ? W h a t is it
[25] about?
- Page 47 [1] A.
It's Pickering
versus Dow. [2] Probably
right up there at the
top. I put them [3] in
reverse order, I think,
with the most [4] recent.
It's Pickering versus
Dow. The firm [5] is
Hardin, Cook in Oakland,
California. I [6] support
the defense.
[ 7 ] Q . A n d is it a
2,4-D, a 2,4,5-T?
[8] A.
It's a 2,4-D
case.
[9] Q. Okay. And can you
g i v e me the bare
[10] essentials of it?
Was it somebody spraying
it [11] occupationally?
Worked in a factory?
[12] A. No. He worked in
the
Chevron
in
[13] Walnut Hills and got
cancer and is claiming
[14] it's from his occu­
pational exposure.
[15] Q. What type of
cancer?
Do
you
[16] recall?
[17] A. I think it's
also soft tissue
[18] sarcoma, but. . .
[19] Q. Is this a recent
case that was [20] filed
within the last year or
two?
[21] A.
Yes. And it's
not even
as f a r
[22] along as this one. I
haven't been deposed.
[23] Q. And the Hardin,
Cook Law Firm is [24] the
defense firm representing
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

^
^

,

Dow in that case?
[25] A. That's correct.
- Page 48 [1] Q. Who represents
the plaintiff?
[2] A. I don't know.
[3] Q. Gerson, Smoller,
does that name [4] sound
familiar to you?
[5] A. No. I really -- I
don't even think [6] I've
even seen it or heard it.
W e ' r e
v e r y
[7] preliminary into
that.
[8] Q. All right. Let me
take a look [9] here. Let
me try and do another
s u b s e t
on
a
[10] question.
[11] A. Okay.
[12] Q. Maybe to elimi­
n a t e , in t h e l i n g o
[13] that you probably
like to use. Do any of
these [14] cases on this
list that you gave me,
which we [15] will mark
as Plaintiff's 2, involve
allegations [16] of can­
cer being caused by the
substance [17] involved
in the case?
[18] A. I'd need to look
at the—
[19] Q. Sure.
[20] A.
-- cases. This
fourt~h c a s e , J o h n
[21] S o u b l i s , I am
plaintiff's expert there.
He has [22] skin cancer,
which we believe to be
related to [23] exposure
to c o a l t a r p i t c h
volatiles.
[24] Q. Okay. Occupational exposure?
[25] A. Occupational
exposure.______________
- Page 49 [1] Q. All right. Where
is that case [2] pending?
[3] A. In Atlanta, Geor­
gia.
[4] Q. Is that where the

firm
is,
Carr,
[5] Tabb-[6] A. Carr, Tabb & Pope
is in Atlanta. [7] Yes.
[8] Q. All right. Any
others
involve
[9] cancer?
[10] A. Boy, this is
hard. I'm rea l l y
[11] embarrassed, but
these things tend to
blend [12] together over
time. Okay. There are two
cases [13] here and I
can't
remember.
[14] Coffee versus Ten­
nessee Chemical,
[15] where I was defense
expert; and Blankenship
[16] versus AMP. Both of
these plaintiffs — I was
[17] plaintiff's expert
here. B o t h of t h e s e
[18] plaintiffs died. My
recollection is it was
[19] cancer; but for the
life of me, as I sit here
[20] today, I can't come
up with the exact details
[21] of either case.
[22] MR. SCHULER: Okay.
All right. [23] Let me go
a h e a d and m a r k this
Plaintiff's 2 for [24] a
moment here. [25] (PLF.
EXH. 2, Handwritten List
of*
0
9
8
7
6
5
4
3
2
1
- Page 50 [1] Cases, was marked for
[ 2 ]
identification.)
[3] BY MR. SCHULER:
[4] Q. We will get to
t h i s
c a s e ,
[5] eventually, I assure
you.
[6] A. Yes. I've done
this before.
[7] Q. Okay. Do you rec a l l
in
t h e
[8] Blankenship Case and
the — I think, you said
[9] it was the Fort Drum
Plaza Case?
[10] A. Yes. No. Coffee
versus Tennessee [11] was
the other.

J

A. WILLIAM ROBERTS & ASSOCIATES

14

SCHULZ, CARL O.
[12] Q. Okay. Coffee and
Blankenship?
[13] A. Yeah.
[14] Q. Do you recall
what kinds of cancer
[15] or what types of
products were involved in
[16] those cases?
[17] A. The chemicals
i n v o l v e d in C o f f e e
[18] versus Tennessee
were -- it was a very
[19] technical, legal
case. He was claiming
injury [20 ] from exposure
to chromated copper arsen a t e
w o o d
[21] preservative. Ten­
nessee Chemical manufac­
tured [2 2 ] the copper
component that was used
by the [23] company he
worked for in mixing up
to make [24] chromated
copper arsenate. [25] I
had very limited testimony in
- Page 51 [1] that case. That cop­
per was not responsible
[2 ] and, therefore, that
specific defendant should
[3] not be included in
the case. So I really
[4] didn't deal with cop­
per cancer, except to say
[5] that copper was not
— I don't remember what
[6 ] kind of cancer he
had.
[7] Q. All right. These
cases that you've
[8 ] listed on Plaintiff's
2 go back -- do these
[9] cover all the cases
where you've rendered
some [10 ] type of testi­
mony?
[11] A.
Only back
through '88 .
[12] Q. '88?
[13] A. I stopped.
[14] Q. Okay.
[15] A. Backwards to the
beginning of '88 .
[16] Q.
Okay. And so
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
f r o m '83, w h e n y o u r
[17] first involvement,
to '88, that five-year
[18] period-[19] A. There's probably
another dozen or [20] so
cases.
[21] Q. Okay. And would
y o u h a v e a n y of
[22] those listed some­
where?
[23] A. Well, I can re­
c o n s t r u c t -- a l l I
[24] have is business
records and files.
[25] Q. 'Okay. But you
have the records_______
- Page 52 [1] where you could re­
construct it?
[2] A. Yes, I could re­
construct it.
[3] Q. From '83 to '88,
d i d y o u t e s t i f y in
[4] any cases that in­
volved allegations of
cancer [5] causation for
particular chemicals?
[6] A.
The best I can
s a y is p r o b a b l y . I
[7] can think of -- I
can't think of any where
I [8] testified or gave a
deposition.
[9] Q. From '83 to '88?
[10] A. Yes.
[11] Q.*_ So those would
have all been review
[12] of cases, but it
never came to testimony?
[13] A. That's my recollection, without
[14] looking at the re­
cords .
[15] Q. Were there any
cases
that
you
[16] recall that involved
cancer allegations, of
[17] cancer being caused
by-[18] A. No.
[19] Q.
---specific
chemicals?
[20] A.
I'm quite cer­
tain that there was no
[21] cancer case where I

SCHULZ, CARL O.

was. . .
[1] A. Yes.
[22] Q. An expert?
[2] Q. Mr. McCracken?
[23] A. Yeah.
[3] A. Yes.
[24] Q. Okay.
[4] Q. And where's he
[25] A. The majority of out of?
these cases are________
[5] A. Augusta, Georgia.
[6 ] Q. Okay.
- Page 53 [7] A. Tucker versus
[I] really not personal
Wood
injury cases in the clas­ S o u t h e r n
[8 ] Piedmont is currently
sic [2] sense toxic tort,
they're more, you know. . one of these property
[9] cases, but I think
•
will become a personal
[3] Q. Pollution?
[10] injury case. And
[4] A. Yeah. Pollution,
there it's neurologic
nuisance, [5] property
value, trespass kind of damage, [1 1 ] dermatologic
changes, and possibly a
claims.
[6] Q. Okay. Other than genetic [1 2 ] mutation
involving, again, wood
the Pickering [7] Case
and the Coffee Case and preserving [13] chemicals
at S o u t h e r n W o o d
the Blankenship [8] Case,
Piedmont.
were there any other per­
[14] Q. Okay.
sonal injury [9] cases in
[15] A.
Brown versus
this group, in the list?
Chlorox
is
a personal
[10] A. Well, yes. This
[16]
injury
case. I'm
John Soublis that
defense
expert
in that
[II] I'm working on now.
case
[17]
for
Chlorox's
[12] Q. Soublis?
[13] A. Yes. Brown ver­ local attorney. Brown
claims [18] that she died
sus Chlorox is a-of
adult respiratory dis­
[14] Q. Let me stop you
tress
[19] syndrome. Her
one
second.
The
parents
claim she died of
[15] Soublis Case in­
adult
[
2 0 ] respiratory
volves what kind of inju­
distress
syndrome from —
ry?
Miller
[21]
versus-[16] A.
It's cancer,
[22] Q. Where is that
skin cancer.
[17] Q. That's a skin case pending trial?
[23] A. That case would
cancer case?
[18] A. With coal tar be in, I think, [24] Rock
Hill, South Carolina, is
pitch volatiles.
where her [25] residence
[19] Q. All right.
is. I don't know what
[20] A. Ruffin versus
court__________________
Beazer is a personal
- Page 55 [21] injury case. He's
got chloracne, neurologi­
[1 ] jurisdiction that
cal [22] deficits, which would be in.
I attribute to exposure
[2] Q. Okay.
[3] A. My local counsel
to wood [23] preserving
chemicals.
is here in [4] Columbia,
[24] Q. Okay. You're
Whaley, McCutchen.
r e t a i n e d
by
[5] Q. All right.
[25] plaintiff's counsel
[6 ] A. Miller versus
E x i d e is a p r o p e r t y
in that case?
[7] damage case involving
- Page 54 l e a d 1 p o l l u t i o n . I'm

A. WILLIAM ROBERTS & ASSOCIATES

15

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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

Ì37

[8] plaintiff's expert
there. [9] Anderson ver­
sus Muskegon County was
[1 0 ] purely a nuisance
kind of case. They didn't
[11] even need a toxicologist, but I was
plaintiff's [12] expert
there. Telling them that
sewage smelled [13] bad.
[14] Lyons versus Beazer
East,
again,
by
[15] Beazer, you know
it's wood preserving.
These [16] two are relat­
ed cases. They're primar­
ily [17] nuisance, prop­
erty damage, based on
potential [18] adverse
health effects including
cancer from [19] wood
preserving chemicals.
[20] B o g a r t v e r s u s
S t u r g i s Iron and
[21] Steel, I was defense
expert there. She claimed
[22] multiple chemical
sensitivity syndrome type
[23] reaction to her ex­
posure there. [24] Raven
versus Greenville County
is a [25] property damage
case with a leaking landfill.__________________
- Page 56 [1] F a r m e r v e r s u s
W e i s,s m a n
is
a
[2] silicone — not sili­
cone — teflon. Here I
was [3] defense expert.
Teflon injection in the
vocal [4] cord, medical
malpractice type case.
in
[5] Q* You mean a solid
teflon inplant?
^
[6] A. No. It's called
teflon paste.
[7] Q. Okay.
^
[8] A.
Injected.
?• V a n d e r l a a n v e r s u s
[9] Marathon is — here I
was plaintiff's expert.
[10] Again, it's nuisance
and property damage from
[11] an oil refinery.
[12] We talked about Cof­

V

SCHULZ, CARL O.

fee versus [13] Tennessee
[17] Laurinburg was an
Chemical. That's the cop­ underground [18] gasoline
per. [14] G o l d Cup
— leaking underground
Springs never got very gasoline [19] storage
[15] far. That's a jet tanks. That was a person­
f u e l o i l s p i l l in
al property [20 ] damage
[16] Charleston, South case. [21] Kelley versus
Carolina.
I was
P a r a - C h e m Southern,
plaintiff's [17] expert
[2 2 ] property damage
in
that
one.
case. I was plaintiff's
[18] Blankenship versus
[23] expert. That in­
AMP,
we
talked
volved just property val­
[19] about. That's a ue from [24] pollution by
worker compensation case,
a chemical plant adjacent
and [20] he died. And
to this [25] property.
boy, it just kills me. I
- Page 58 can't [21] remember — I
[1] M a r s h a l l versus
suspect it was cancer,
S o u t h e r n
Wood
but the [22] chemicals
[2] Piedmont is actually
were — no. I know what a precursor case of this
it was. [23] That can't
[3] Tucker versus South­
have been cancer.
ern Wood Piedmont, and
[24] It's coming back to this [4] went to a set­
me. I remember [25] now.
tlement for -- it was
He died of liver necrosis property [5] damage.
cirrhosis____________
[6 ] Q. Where was that
- Page 57 last case pending,
[1] fibrosis. Yeah. And
[7] the Marshall Case?
it was a glycol ether and
[8 ] A. That's settled.
[2] a chlorinated hydro­ This one is, [9] Tucker
versus Southern Wood
carbon exposure.
P i e d m o n t is p e n d i n g
[3] Diehl versus ASARCO,
I was defense [4] expert
[10] in Augusta, Georgia.
in that case. That's a
[11] Q. All right. And
property damage [5] case these are, as far [12 ] as
involving a lead smelter you know, a pretty ex­
haustive list of the
in Helena, [6] Montana.
[13] cases that you've
[7] Fort Drum Plaza was a
— oh, boy. [8] Now, I been involved in?
think about this one. I
[14] A. Since the begin­
think Billy Joe [9] Moss ning of 1988, yes.
[15] Q. All right. Other
died of cancer, leukemia,
and it was [10] gasoline than this case, [16] the
-- it was a gasoline
M o y e r Case, and the
spill at this—
Pickering Case, have
[17] you ever done any
[11] Q. Is that in Flor­
ida on the turnpike?
work for Dow Chemical
[12] A.
Yeah. On the
[18] Company?
turnpike
there.
[19] A. To my recollec­
t i o n , I ' v e d o n e no
[13] That's one of the
world's largest under­
[20] other work for Dow
ground [14] gasoline
Chemical Company, with
spills, that service area the [2 1 ] qualification,
on the [15] Florida turn­ Larry Rampy on that iso­
pike. I was plaintiff's
cyanide [2 2 ] case was a
e x p e r t [16] there.
Dow employee.

A. WILLIAM ROBERTS & ASSOCIATES

16

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March

5, 1993

MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

[23] Q. Okay. The per­ versity of South Carolina
centage of your time
[3] in 1985?
[24] over the last four
[4] A. Correct.
years, roughly since
[5] Q. And what was the
1988, [25] that's been background on [6 ] that?
involved in legal con­ Why did you do that?
sulting is
[7] A. My wife is an
h
i s t o r i a n a n d has
- Page 59 [
8
] always wanted to
[1] what?
teach
at the college lev­
[2] A. About 10 percent.
el
and
[9] had looked for
[3] Q. Okay. And how can
a teaching job for seven
you break down [4] the
years [10 ] when we lived
other 90 percent?
in the Washington metro­
[5] A. Well, for the
politan [1 1 ] area and was
last five years,
unable to find a perma­
[6] that's been about
two-thirds private cli­ nent [1 2 ] position, al­
though she had a one-year
ents [7] and one-third
government because, up teaching [13] appointment
every year for seven
until two [8] years ago,
years at [14] different
I had the VA contract
which was [9] about — on universities. [15] And so
phenoxy herbicides, which one of the reasons I
was about [10] a third of started [16] to sever my
my chargeable time each, ties with Clement was so
that she [17] could look
y e a r
on
t h a t
[11] project. [12] Since in a broader geographic
sense for [18] the type
that project's ended,
I've [13] done in — I've of position she was look­
ing for. So [19] in 1985,
done — so that's about
she got a job at the Uni­
the [14] last two years,
I've done almost no gov­ versity of [20] South
ernment [15] work. Been Carolina and, since they
almost exclusively pri­ had an airport, [21] I
vate work the [16] last came along and that's
w h e r e w e ' v e been.
two years.
[22] When I knew I was
[17] Q.._ Okay. Is there
c
oming
here,
I
one
particular
[23]
contacted
the
Uni­
[18] client that's your
versity, the Department
main client or. . .
of [24] Environmental
[19] A.
Well, at the
Health Science; and they
p r e s e n t time, as we
[20] look at a snapshot were [25] very gracious
today, I would say McGhan and said they would very
[21] Medical Corporation much__________________
is about a third of my
- Page 61 [22] chargeable time.
[1 ] like to have me af­
[23] Q. And how far back
f i l i a t e d w i t h the
would that go [24] where
[2] department. So it's
McGhan was your-worked out well, I hope,
[25] A. About two years.*
2 [3] for both of us since
then.
- Page 60 [4] Q. Well, how much
1] Q. And you became
time do you spend in
adjunct associate
[5] your teaching respon­
[2] professor at the Unisibilities?
A. WILLIAM ROBERTS & ASSOCIATES

17

[6 ] A. I teach about ten
l e c t u r e s
per
[7] semester. So as a
percentage of my time,
it's [8 ] quite minimal.
It's about 5 to 10 per­
cent of [9] my time on
teaching duties as a
whole. I do a [10 ] little
more than just come in
and lecture. [11] In
fact, the first five
years we [1 2 ] were here,
I maintained my office in
the [13] department, on
campus. So I do -- I
don't [14] direct re­
search, but students can
come to me [15] for as­
sistance and advice. I've
served on [16] committees
and, in general, partici­
pate.
[17] Q.
In conjunction
with your adjunct
[18] associate professor­
ship, do you teach regu­
lar [19] courses or just
come in and do spot lec­
tures?
[20] A. Well, I do both.
I have been — [2 1 ] the
bulk of my lecturing is
in one course that [22 ] I
share with another faculty m e m b e r . A n d , in
[23] fact, one year, when
we lost the faculty mem­
ber [24] late in the year
and couldn't replace her,
I [25] had responsibili­
ty, in f a c t , (f o r a
course.________________
- Page 62 [1] Hopefully, never
again. But I do have one
[2 ] course where the bulk
of my lectures are given,
[3] and then I give one
or two a semester as a
spot [4] lecturer in oth­
er courses.
[5] Q. What are the ti­
t l e s of s o m e of t h e
[6 ] courses that you've
taught on a continuing
MICROCopy

407

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
[7] basis?
[8] A. Well, they're
included on the very
[9] last page of the CV
that I've given you. And
[10] the one that I teach
in h e a v i l y is a b o u t
[11] two-thirds of the
way down, the 788, 789,
[12 ] Concepts of Hazard­
ous Materials Management
I [13] and II, two semes­
ters, basically, course.
[14] That's the one where
I do the bulk lecture.
[15] Q. Okay.
[16] A. And then I —
the first one on the
[17] list, Concepts of
Environmental Health
[18] Sciences, is our
introductory course for
[19] first-year graduate
students in the program,
[20] and I usually lec­
ture in there once a
[21] semester. The others
are come and go, now and
[22] then.
[23] Q. Okay. So Applied
Aquatic Sciences,
[24] Risk Assessment and
Interactions
of
[25] E n v i r o n m e n t a l
T o x i c a n t s are not
on-going_______________
- Page 63 [1] courses that you give
per se; correct?
[2] A. That's correct.
[3] Q. They're-[4] A. Taught by other
faculty members, [5] and
I typically give a guest
l e c t u r e , m a y b e not
[6] even every year. We
don't offer those courses
[7] every year. They come
when there's, you know,
[8] sufficient registra­
tion to offer them.
[9 ] Q . Do you use a
p a r t i c u l a r t e x t in
[10] your on-going cours­
es?
[11] A. We are getting
A. WILLIAM ROBERTS & AS

down
to
that,
[12] finally. We never
found one book that's
[13] satisfactory for
Concepts and Hazardous
Waste [14] Management I
and II. [15] We started
out almost exclusively
[16] with texts that we
created by coping por­
tions [17] out of other
books. The copy center
got a [18] little upset
with us on that, and we
now [19] purchase two
different texts, one for
each -- [20] have the
students purchase a text
for each [21] semester. I
don't know what those are
because [22] they're
heavy toward the engin e e r i n g
a n d
[23] regulatory aspects.
[24] Everything I do for
toxicology, I [25] hand
out detailed class notes,
plus I use a___________
- Page 64 [1] book called RISK AS­
SESSMENT IN THE FEDERAL
[2] GOVERNMENT. Yeah.
RISK ASSESSMENT IN THE
[3] FEDERAL GOVERNMENT
and that's-[4] Q. Who authored that
book?
[5] A.
Covello,
C-o-v-e-l-l-o, and I
t h i n k [6] he h a s a
co-author; and it's published
—
it's
[7] unusual. It's printed
by
the
federal
[8] government, Govern­
ment Printing Office; and
[9] it's very inexpen­
sive, but a very nice
[10] resource.
[11] Q. All right. Any
other texts that [12] you
use or is that the only
one?
[13] A. That's the only
one.
[14] Q. All right. Other
18

SCHULZ, CARL O.
than your work [15] with
McGhan and your legal
c o n s u l t i n g and y o u r
[16] teaching, that's —
actually the McGhan work
[17] and the legal con­
sulting and teaching com­
bined [18] is about 50
percent of your time?
[19] A. Sounds like it.
[20] Q. And the other 50
percent is what?
[21] A. A variety of
o t h e r clients. M a n y
[2 2 ] of them kind of
long-term things that go
on. [23] For example,
Chem Nuclear Systems,
[24] Incorporated, oper­
ates a low level, radio­
active [25] waste dispos­
al facility down here in
Barnwell,______________
- Page 65 [1] South Carolina.
[2] And in the years be­
fore they owned [3] that
facility, some of the
radioactive [4] materials
that they put in the
landfill down [5] there
had chemical, liquid
c h e
m i c a l
[6 ] constituents; and
some of those have es­
caped [7] the confines of
the specific trenches in
which [8 ] they were dis­
posed of and have gotten
into the [9] groundwater
immediately underlying
the site. [10] So they
asked me to develop a
[1 1 ] groundwater monitor­
ing strategy for that
site [1 2 ] and then they
follow that strategy and
I review [13] it, the
results, and make recomm e n d a t i o n s
[14] periodically for
adjustments in the pro­
gram and [15] so forth.
[16] And, now, they have
moved on. They [17] are
developing sites in sevMICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
eral o t h e r states,
[18] and I'm developing
and overseeing their
[19 ] groundwater monitor­
ing for non-radioactive
[20] materials at those
sites, also.
[21] Q. All right. And
that
t a k e s up a
[22] substantial portion
of your time?
[23] A. No. That's the
k i n d of t h i n g t h a t
[24] takes, at most, one
day a month, kind of
thing; [25] but it's an
on-going thing.________
- Page 66 [1]
Do you have a
c o n t r a c t w i t h these
[2] folks?
[3] A. I suppose.
[4] Q. All right.
[5] A.
I do. I'm being
flip. I'm sorry. [6] I do
have a contract with
t h e m , b u t it w a s
[7] signed five years ago
and it may or may not be
[8] expired by now.
[9] Q. Okay.
[10] A. But I've never
been a stickler [11] for
— I've never had a cli­
ent —
well, I had
[12] one client do me
wrong once, but much of
my [13] work is done on a
handshake and word of
mouth. [14] Right now,
I'm very busy with a num­
ber of other [15] clients
that manufacture medical
devices. [16] I suppose,
bec a u s e
of
my
[17] involvement in the
silicone and mammary im­
plant [18] issues, I had
some visibility; and now
[19] manufacturers of a
variety of medical devic­
es [20] are coming to me
to help them develop a
c21] strategy for testing
the materials in their
[22] devices, or the de­

vice as a whole, to meet
the [23] requirements for
the Food and Drug
[24] Administration and
to get approval for their
[25] products to be mar­
k e t e d in the U n i t e d
States________________
- Page 67 [ 1 ] and/or in the -abroad.
[2] Q. Other than the
silicone gel, [3] mammary
breast implant devices,
can you give me [4] some
examples of other devices
you're involved [5] with?
[6 ] A. Well, I've got to
be very cautious [7] here
because that's very much
confidential [8 ] business
information. But just in
general [9] terms, I'm
involved with denture
materials, [1 0 ] with
implantable devices for
treating [1 1 ] arthritis,
with external devices for
use in the [1 2 ] therapy
of cancer, and a couple
of others I [13] just
can't think of right now.
But those, I [14] can't
go into too much and it's
not relevant.
[15] Q.
I understand.
Are
those
all
[16] contracts with manu­
facturers?
[17] A. Yes.
[18] Q. All right. I
asked you about your
[19] testimony in legal
proceedings. Have you
ever [20 ] testified be­
fore governmental agen­
cies? When I [21] say
testified, I mean, given
any
type
of
—
[2 2 ] rendered any type of
opinions or provided
[23] information in an
open type forum?
[24] A. I have presented
to three [25] outside —
no. Four times, I've pre­

A. WILLIAM ROBERTS & ASSOCIATES

19

SCHULZ, CARL O.
sented to
- Page 68 [1] outside advisory
boards or committees to
the [2] Food and Drug
Administration.
[3] Q. Four times?
[4] A. Yes.
[5] Q. And was that all
in c o n n e c t i o n w i t h
[6] the silicone gel mam­
mary implant?
[7] A. No, no.
[8] Q.
Tell me what
those were.
[9] A. Well, the first
one was a c t u a l l y
[10] while I was an em­
ployee of the Food and
Drug [11] Administration,
when I was branch chief
in the [12] OTC drug di­
vision. [13] We initiat­
ed, from within FDA, an
[14] initiative to re­
classify paregoric from
the [15] list of con­
trolled substances. Basi­
cally, [16] reclassify it
from being a drug for
potential [17] abuse to
one that was not, so that
it could be [18] an ing r e d i e n t
in
over-the-counter drug
products [19] available
without prescription.
[20] And I presented that
argument to [21] the ad­
visory committee of the
— that would [22] have
been — oh, it's the Na­
t i o n a l I n s t i t u t e -[23] not National Insti­
tute of Drug Abuse, not
NIDA, [24] but a sister
agency. I can't think of
what the [25] name of it
is.
- Page 69 [1] Q. You provided tes­
timony on that [2] topic
in any event?
[3] A. Yes.
[4] Q. About what year
MICROCopy

408
399

•' ' 409
'V i i

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

___

was that?
[5] A. Well, it was
probably about 1980.
[6] Q. Okay. What are
the o t h e r
three
[7] occasions, then, that
you've testified?
[8] A. Then I testified
— the o t h e r three
[9] were before device
panels at the U. S. Food
and [10] Drug Administra­
tion. Two were silicone
mammary [11] implants.
[12] Q. Okay.
[13] A. In November of
'90 and February [14] of
— sorry. November of '91
and February [15] of '92.
And then I testified be­
fore a device [16] panel
for that teflon paste,
injectable teflon
[17] paste ior urinary
incontinence indication
and [18] that would have
been either late 1990 or
[19] early '91.
[20] Q. But those are
pan els set up by the
[21] FDA to investigate
these matters; correct?
[22] A. Yes.
[23] Q. And in your testimony
on
the
[24] silicone gel or be­
fore the silicone gel
special' [25] panel, were
you retained by McGhan or
someone________________
- Page 70 [1] else?
[2] A. By McGhan.
[3] Q. Were you testify­
ing specifically as [4] a
representative of McGhan
during that panel?
[5] A. As a paid consul­
tant to McGhan.
[6] Q. Okay.
[7] A.
Yes. Not an em­
p l o y e e or a d v o c a t e
[8] for McGhan.
[9] Q. Okay.
[10] A. Independent con­
sultant, paid for by

[16] your time in legal
consulting type work?
[17] A. $125 an hour for
preparation
and
[18] review of documents
and so forth. And $150 an
[19] hour for deposition
t i m e or t i m e on t h e
stand.
[20] Q. And can you give
m e an e s t i m a t e , or
[21] an exact number,
perhaps, if you have it,
of [22] how much time you
have involved in this
case up [23] to this
date?
[24] A. I can only esti­
m a t e th at and it's
[25] on the order — before today, prior to 8
- Page 72 [1] o'clock this morning
-- p r o b a b l y 16 to 24
[ 2 ]
hours.
[3] Q. Do you keep re­
cords of your time on
[4] a computer?
[5] A. Yes. I don't do
it in the [6] computer. I
do it in my daily calen­
dar.
[7] Q. Manually?
[8] A. Yes.
[9] Q. I asked you what
percentage of [10] time.
What percentage of your
i n c o m e
i s
[11] represented by re­
viewing and testifying in
[12] legal matters?
[13] A.
Would be the
same, 10 percent.
[14] Q. Okay.
[15] A.
I don't charge
higher rates.
[16] Q.
Okay. Do you
keep time sheets?
[17] A.
Well, yes. I
keep a time record in
[18] my daily calender. I
write — at the end of
[19] each day, I put down
the h o u r s I spent,
[20] chargeable hours.
[21] Q. All right. Now,

[11] them.
[12] Q. And do you have
r e t a i n e d c o p i e s of
[13] your testimony on
the silicone gel matter?
[14] A. No, I do not. In
that
k i n d
of
[15] situation, I speak
from notes; and there are
[16] transcripts of both
of those proceedings. I
[17] don't have a copy.
[18] Q. That's really
what I was asking,
[19] whether you had a
copy of the transcripts
of [20] the proceedings?
[21] A. No, I do not.
[22] Q. Other than yourself, did anyone
[23] else retained by
McGhan testify, to your
[24] knowledge, before
the subcommittee?
[25] A. Oh, yes. In my
mind, now, the two_____
- Page 71 [1] hearings have kind of
blended together. They
[2] had their own employ­
ees presented to one or
[3] both of those panels.
Outside experts included
[4] Gearheart Brand, sev­
eral others. I can't
[5] remember.
[6] Q. Okay. Have you
ever had any —
I
[7] know.I've kind of
piecemealed this ques­
tion, [8] but I want to
make sure I've covered
it. Have [9] you ever had
any consulting arrange­
ment with [10] any chemi­
cal , herbicide chemical
manufacturer [11] or
trade organization that
d e a l s
w i t h
[12] agricultural chemi­
cals?
[13] A. I think not. I'm
pretty
sure
I
[14] haven't.
[15] Q. Okay. How much
do y o u c h a r g e for

A. WILLIAM ROBERTS & ASSOCIATES

20

SCHULZ, CARL O.

MICROCopy

March

5, 1993

MOYER vs. DOW CHEMICAL COMPANY
there
was
some
[22] discussion off the
record, I think, when I
[23] first came in here
this morning about the
fact [24] that you have a
somewhat sizeable library
or, [25] at least, re­
search resources that you
keep. Is_______________
- Page 73 [1] that at home or in
your office?
[2] A. That's in my of­
fice.
[3] Q. Can you just kind
of describe for [4] me
generally what you have
and
how
it's
[5] organized?
[6] A. Well, I have a
copy of the [7] majority
— I hesitate to say exa c t l y
w h a t
[8] percentage, probably
roughly 75 percent of all
[9] the articles that are
included in Volumes 3
[10] through 18, is it? 3
t h r o u g h 18 of the VA
[11] review. [12] I prob­
a b l y h a v e c o p i e s of
[13] t w o - t h i r d s to
three-quarters of all the
[14] articles in there,
in file cabinets. Plus
[15] another 4- or 500
articles that are either
not [16] in that time
f r a m e or r e l a t e to
dioxins and [17] furans,
other than the ones that
we were [18] concerned
about for specifically
t h e
V i e t n a m
[19] herbicides. And so
those are all in a file
[20] cabinet. [21] And
then I have two book­
shelves. I [22] probably
have eight, ten, twelve
b o o k
b o o k s ,
r23] monographs, I guess,
_>n dioxin and Agent Or­
ange [24] and things. I
have, of course, a com­

SCHULZ, CARL O.

plete set [25] of the VA
reports and synopses. I
have__________________
- Page 74 [1] proceedings of all
the International Dixon
[2] Symposia that I at­
tended, chemosphere vol­
umes [3] covering those
conferences, and some I
didn't [4] goto. [5] Oh,
and miscellaneous docu­
ments, [6] like the World
Health associating crite­
ria on [7] 2,4-D and di­
oxin and the EPA drinking
water [8] criteria docu­
ments for dioxins and a
number of [9] those kind
of secondary references
in this [10] area.
[11] Q. Okay. And you
b r o u g h t
s o m e
[12] documents with you
today?
[13] A. Yes, I did.
[14] Q. What documents
did you b r ing with
[15] you today?
[16] A. Basically, what
I
b r o u g h t
is
[17] documents provided
to me by Mr. Wagner rele­
vant [18] to this case.
[19] Q. Before we get
started on that, let
[20] me just ask you a
few preliminary questions
[21] here. When were you
first contacted about
this [22] case?
[23] A. Forgot to look
t h a t up l a s t n ight.
[24] I think about last
summer or last fall. It
[25] would have been be­
tween July and November
of
- Page 75 [1] 1992, I think.
[2] Q. And who first
contacted you?
[3 ] A . W e l l , He id i
Garwood, who's in the
[4] office of Mr. Wagner.

A. WILLIAM ROBERTS & ASSOCIATES

21

[5] Q. And do you know
how they got your
[6] name?
[7] A. They got my name,
I understand, [8] from
Clement Associates. They
had become aware [9] of
the literature review and
called Clement; [10] and
Clement said, well, you
n e e d to t a l k to Dr.
[11] Schulz because he
was the key player there.
[12] And that's how they
got my name.
[13] Q.
The literature
s
e
a
r
c
h
,
[14] incidentally, that
we've discussed at length
at [15] the outset here.
When I looked at that,
and [16] maybe it's just
a copy that I got, I did­
n't see [17] your name on
it. Is there a reason for
that?
[18] A. Well, that's
s o m e t h i n g of t h e
[19] nature of contract
work to begin with. I'm
[20] really not the au­
thor. Although, if you
look [21] carefully, it's
— I don't know if it's
in the [22] preface or
the forward. I always get
those two [23] mixed up.
The responsible individu­
als are [24] identified.
[25] You have one of the
synopses. In
- Page 76 [1] the synopses, I was
not identified in that.
[2] It's in the actual
preface or forward of the
[3] two volumes.
[4] Q. Well, let me show
you
t h i s
for
[5] identification p u r - *
poses. We can mark it,
and [6] we don't have to
attach it necessarily.
Can [7] you take a look
at that? Is that the most
[8] recent synopsis of
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
the d i o x i n a r t i c l e s
that-[9] A. Yes. If it's all
here, that would [10] be
it. Yes.
[11] Q.
Can you just
l o o k a t it to s e e
[12] whether that's the
complete synopsis, the
best [13] you can tell? I
p r o b a b l y d o n ' t have
the-[14] A.
I think so. I
think so.
[15] Q. All right. We'll
m a r k
it
as
[16] Plaintiff's 3. I'll
just go ahead and put a 3
[17] on here. [18] This
is the one that does not
have [19] your name on
it; correct?
[20] A. That's correct.
[21] Q. And I have a
p a r t i a l , I b e l ieve,
[22] copy of what appears
to be-[23] A. That's the front
page of one. [24] Yeah.
[25] Q. There's an in­
troduction and then a
- Page 77 [1] list of all the arti­
cles. This is, obviously,
[2] far from complete.
[3] A. Yeah, it's part.
[4] Q.
But take a look
at t h i s a n d t e l l me
[5] which one of the as­
pects of the contract
that's [6] a partial rep­
resentative of.
[7] A. This would have
been that critical
[8] review portion.
[9] Q. Okay.
[10] A.
One of the two
^ volumes covering the
^
[11] year — the litera­
ture that was published
in [12] 1990. And there's
a cover page and a table
of [13] contents and
here's the forward and,
right [14] there, it
says, the project direc­

tor for [15] Clements was
me. The technical direc­
tor and [16] principal
author of the review was
me.
[17] Q. Okay.
[18] A. And then there
a r e
o t h e r
[19] contributors.
[20] Q.
Project direc­
tor, Wayne?
[21] A. Reichardt.
[22] Q. Reichardt?
[23] A. Uh-huh.
[24] Q. Was he your boss
on that?
[25] A. In an administrative sense, yes._____
- Page 78 [1] Q. Okay.
[2] A. He had no oversight
over
the
[3] technical completion.
He just had to make sure
[4] I didn't overrun my
budget.
[5] Q. And then Sharon
Segal an d S a n j i v a n i
[6] Diwan, they were both
employees?
[7] A. Of Clement. Yes.
[8] Q. Okay.
[9] A. And scientists
and drafted specific
[10] sections of the re­
view.
[11] MR. SCHULER: All
right. I guess [12] we'll
mark that for discussion
p u r p o s e s
as
[13] P l a i n t i f f 's 4.
[14] (PLF. EXH. 3, Fax
Transmittal with
[15] Synopsis of Scien­
tific Literature [16] on
Phenoxy Herbicides, was
marked [17] for identifi­
cation.) [18] (PLF. EXH.
4, Fax Transmittal with
[19] Review of Literature
on [20] Herbicides, was
m a r k e d
f o r
[21] identification.)
[22] BY MR. SCHULER:
[23] Q. Are Plaintiff's
3 and P l a i n t i f f ' s 4

A. WILLIAM ROBERTS & ASSOCIATES

22

SCHULZ, CARL O.
[24] the most recent ver­
sions of what you did?
[25] A. They're the most
recent versions of
- Page 79 [1] what I did. That con­
tract was re-awarded to
[2] another vendor in —
whenever that would have
[3] been. The year after
that.
[4] Q. Okay. This pur­
ports to be a [5] summary
of the literature from
1990.
[6] A. Uh-huh.
[7] Q. Was that the last
year that you [8] were
involved with it?
[9] A. That's correct.
[10] Q. And then do you
k n o w wh o has the
[11] present contract?
[12] A.
It's aij outfit
in Philadelphia, and
[13] I can't remember
their name.
[14] Q. All right. After
you were [15] contacted
about this case, what
were you asked [16] to do
initially?
[17] A.
Well, in the
i n i t i a l c o n t a c t , we
[18] just discussed the
very general aspects of
the [19] case and what my
experience was with phe­
noxy [20] herbicides and
dioxins, and then I was
sent a [21] number of
these documents at that
time to [22] review.
[23] MR. WAGNER: Before
you go on with [24] this
case, I need to take an­
other break.
[25] MR. SCHULER: Sure.
- Page 80 [1] MR. WAGNER: You might
want to just [2] glance
through those, give you a
head start on [3] what's
in there. [4] (A recess
transpired.)
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
[5] BY MR. SCHULER:
[6] Q.
I think my last
question to you, [7] Dr.
Schulz, was what you were
asked to do in [8] this
case. And I think you
told me that you [9] were
asked to review this case
and they were [10] going
to send some documents to
you with regard [11] to
the allegations that Mr.
M o y e r ' s c a n c e r was
[12] caused by his expo­
sure to the 2,4-D and
silvex [13] that was in­
volved in this matter;
correct?
[14] A. Correct.
[15] Q. And were you
asked to do anything
[16] else?
[17] A. No.
[18] Q. What specifical­
ly were you supplied
[19] with by the Defen­
dants Dow and Occidental
in [20] order to do your
review? And you can take
a [21] look at these doc­
uments here that I've
g o n e [22] t h r o u g h .
[23]-Let's kind of put
these documents [24] this
way because these are
the
[25] A. Yeah, they're
different.
- Page 81 [1] Q. -- documents that
y o u f u r n i s h e d , as
[2] opposed to the ones
that-[3] A. That's correct.
[4] Q. — were furnished
you.
[5] A. That's correct.
I n i t i a l l y , I was
[6] furnished with the
complaints and amended
[7] complaints.
[8] Q. Why don't you
iust go through.
9] A. Plaintiffs' Fifth
Amended [10] Complaint,
the proposed Sixth Amend­

ed [11] C o m p l a i n t ,
Moyer's answers to the
[12] interrogatories dat­
ed'January
3rd,
plaintiff's [13] answers
to interrogatories dated
January 5, [14] 1990,
t r a n s c r i p t s of Dr.
T e i t e l b a u m ' s
[15] deposition, selected
e x h i b i t s f r o m Dr.
[16] Teitelbaum's deposi­
tion. [17] Deposition
summaries for Moyer,
[18] Ellenbecker, Clapp,
and one other, Sassick,
[19] Nick Sassick, and. .
•

[20] MR. WAGNER: Sudderam
is in there.
[21] THE WITNESS: I think
so and I just [22] don't
find it initially. Oh,
here it is. No. [23] I'm
sorry. I thought I had a
deposition [24] summary
of Sudderam and it may be
in there. I [25] just
don't see it.__________
- Page 82 [1] BY MR. SCHULER:
[2] Q. Maybe we can do
it this way.
[3] A. That covers-[4] Q. Let me go through
that pile quickly
[5] with you and I can
kind of sort out-[6] A. Okay.
[7] Q.
-- just about
everything. I think,
[8] most of these things,
I have already. [9] Is
that part of it, too,
there, [10] Allen?
[11] MR. WAGNER: Yes.
[12] BY MR. SCHULER:
[13] Q. I'll just stick
t h i s on h e r e . Y o u
[14] received a copy of
the Fifth Amended Com­
plaint [15] which. . .
[16] A.
It's u n d e r
there.
[17] Q. A copy of the
Sixth
A m ended

A. WILLIAM ROBERTS £. ASSOCIATES

23

SCHULZ, CARL O.
[18] Complaint, Moyer's
a n s w e r s to e x p e r t
[19] interrogatories dat­
ed January 3rd.
[20] A. And the 5th of
January 1990.
[21] Q. Okay. I was go­
ing by the l e t t e r
[22]
here. Okay.
Plaintiff's answers to
[23] interrogatories dat­
ed January 5th. I guess
[24] that's what that is.
T h e
e x p e r t
[25] interrogatories may
be here. Yes. Okay._____
• - Page 83 [1] A transcript of Dr.
T e i t e l b a u m ' s
[2] deposition with ex­
hibits .
[3] A. These two are the
actual [4] deposition.
[5] Q. Okay.
[6] A. And the exhibits
are basically-[7] Q. Part of this?
[8] A. Basically almost
—
this
is
all
[9] exhibits.
[10] Q. Medical toxicol-

°gy.

[11] A. I think it goes
all t h e w a y d o w n to
[12] the bottom of that.
[13] Q. Yes. Okay. This
is it, too.
[14] A. Uh-huh.
[15] Q. Yes. Okay. And
this was w h a t you
[16] were furnished with
initially, along with
this [17] cover letter of
September 25, 1992?
[18] A. That's correct.
And that about [19] sets
the date. They probably
sent me that [20] within
a week or two of the ini­
tial contact.
[21] MR. SCHULER: Okay.
I'll go ahead [22] and
have the cover letter
m a r k e d as a s u m m a r y
[23] of what we have.
That will be Plaintiff's
MICROCopy

412
*/•*-■*

413

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
5, I [ 2 4 ]
think.
[25] (PLF. EXH. 5, Letter
to Dr. Carl O._________
- Page 84 [I] Schulz from Heidi E.
Garwood, [2] dated Sep­
tember 25, 1992, was
[3] marked for identifi­
cation. )
[4] THE WITNESS: I think
those are [5] exhibits to
Teitelbaum's.
[6] MR. WAGNER: Can I see
the letter? [7] When you
were going through — I
know we sent [8] him and
here's the letter enclosing
the
public
[9] record. The same
thing that Dr. Smith got.
[10] MR. SCHULER: Yes.
[II] THE WITNESS: That's
that.
[12] MR. WAGNER: Yes, but
the summary [13] sheets
aren't there.
[14] THE WITNESS: I think
they're in [15] there
somewhere.
[16] MR. WAGNER: They may
be buried in [17] there.
Okay. It's the same stuff
that we sent [18] to Dr.
Smith that was marked at
his [19] deposition.
[20] MR. SCHULER: You
mean Dr. Eaton?
[21] MR'. WAGNER: And Dr.
Eaton, as [22] well, yes.
[23] BY MR. SCHULER:
[24] Q. Okay. All right.
A n d s o m e of t h e
[25] public records from
Orange County. These are
- Page 85 [1] the records that you
were sent?
[2] A. Yes.
[3] Q. This goes with
this?
[4] A. Yes.
[5] Q.
Okay. Attach
this.
[6] MR. WAGNER: As I say,
I think [7] the — there

SCHULZ, CARL O.

was a typewritten summary
[15] A. This is Mr.
that I [8] don't see in Swanson's deposition.
there.
[16] Q. That's the one
[9] THE WITNESS: I don't t h a t
was
taken
see it, but I [10] don't
[17] recently. All right.
what you're talking
What else w ere you
about.
[18] furnished with?
[11] MR. SCHULER: Okay.
[19] A. That's all.
Let me go [12] ahead and
[20] Q. Okay.
h a v e this m a r k e d as
[21] A. I think. These
plaintiff's next
are all mine. [22] Yeah.
[13] number. [14] (PLF.
[23] Q. There are some
EXH. 6, Letter to Carl O.
other documents that
[15] Schulz from Heidi E.
[24] you brought with
Garwood, [16 ] dated Octo- you?
b e r 2 6 , 1 9 92 , w i t h
[25] A. Yes.
[17] attachments, was
- Page 87 m a r k e d
f o r
[1] Q. And these are
[18] identification.)
d o c u m e n t s that you
[19] BY MR. SCHULZ:
[2] furnished to the de­
[20] Q. Okay. Were you
fendants?
furnished
with
[3] A. No.
[21] anything else by the
[4] Q. Just notes?
defendants?
[5] A. The first one,
[22] A. Then at a later this clip is a [6] letter
date,
this
is
that I sent to Mr. Wagner
[23] described in the with the [7] articles
cover letter as — no.
that I cited in there.
I'm [24] sorry. This is
[8] Q. Okay.
Dr. H a r d e l l ' s m a n u ­
[9] A. These others are
scripts, I [25] guess,
just
things
I
that he supplied. And
[10] brought today. I
then I got, at a_______
consider them publica­
tions [11] containing
- Page 86 [1] later date, a tran­ relevant information for
this case.
script of his.
[2] Q. This is the tran[12] Q. Okay. The first
script
of
Dr.
letter and [13] articles
that you mention is a
[3] Hardell's deposition?
[4] A. Of his deposi­ letter of [14] October
22, 1992, from yourself
tion, yes.
to
Mr.
Wagner,
[5] MR. SCHULER: All
r i g h t . L e t me go
[15] attaching some ref­
[6] ahead and mark this
erences and some articles
as P l a i n t i f f ' s 7.
[16] regarding exposure
[7] (PLF. EXH. 7, Letter to TCDD?
to Carl 0. [8] Schulz
[17] A. Correct.
[18] MR. SCHULER: Okay.
from Alan F. Wagner, dat­
ed [9] November 19, 1992,
Have this [19] marked as
with [10] attachments,
Plaintiff's 8. [20] (PLF.
was
marked
for
EXH. 8, Letter to Alan
Wagner [21] from Carl O.
[11] identification.)
[12] BY MR. SCHULER:
Schulz, dated October
[13] Q. And what else
[22] 22, 1992, with attachments,
was
were you f u r n i s h e d
[14] with?
[23] marked for identifi­

A. WILLIAM ROBERTS & ASSOCIATES

24

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
cation.)
Let's mark [5] this as
[24] BY MR. SCHULER:
Plaintiff's 11. [6] (PLF.
[25] Q. And then what is EXH. 11, Series of Docu­
this next packet_______
ments , [7] were marked
for identification.)
- Page 88 [8] BY MR. SCHULER:
[1] here?
[9] Q. All right. Have
[2] A. That is a series
r e v i e w e d
of journal [3] articles y o u
[10] anything else or
describing studies of
l o o k e d at an y o t h e r
epidemiologic [4] studies
[11] documentation with
of cancer related to di­
r e g a r d to this c a s e
oxin exposure.
[5] MR. SCHULER: Okay. I that's [12] helped you in
the formulation of your
think we'll [6] mark this
opinions?
Plaintiff's 9. [7] (PLF.
[13] A. Well, my opin­
EXH. 9, Series of Journal
[8] Articles on Cancer ions are based on ten
[14] years or more of
Epidemiology, [9] was
marked for identifica­ experience and review of
all [15] the scientific
tion. )
literature available on
[10] BY MR. SCHULER:
it. But [16] other than
[11] Q. What's this next
that
and these documents
group?
and
so
[17] forth, no, I
[12] A. This is a series
have
not.
of t h r e e a r t i c l e s
[18] Q. Okay. You're
[13] from the published
t
estifying
as a
literature describing
[19]
toxicologist
in
this
[14] studies of exposure
case;
correct?
assessment to phenoxy
[20] A. That's correct.
[15] herbicides and diox­
[21] Q. And you're not a
in.
m
edical
doctor,
[16] MR. SCHULER: Mark
[
22
]
obviously?
this as [17] Plaintiff's
[23] A. That's correct.
10. [18] (PLF. EXH. 10,
[24] Q. You have neither
T h r e e A r t i c l e s on
[19] Exposure Assessment examined nor [25] treated
cancer patients or pa­
to
P h e n o x y
[20] Herbicides and Diox­ tients that have
in, were marked [21] for
- Page 90 identification.)
[1] been exposed to phe­
[22] BY MR. SCHULER:
noxy herbicides; correct?
[2] A. That's correct.
[23] Q. And then this
last packet with the
[3] Q. And if I under­
[24] rubber band around
stand, when you talk
it?
[4] about your experi­
[25] A. These are a se- ence, your experience is
ries of documents______
based [5] on your review
of the literature in this
- Page 89 field, [6] as opposed to
[1] that are relevant to
generating any indepen­
tissue levels of dioxins
dent [7] literature on
[2] and furans in the
general public and in your own or research on
*3] occupationally ex­ your own; [8] correct?
[9] A. Correct.
posed populations.
[10]
Q. All right. Have
[4] MR. SCHULER: Okay.
you
formulated,
A. WILLIAM ROBERTS & ASSOCIATES

25

SCHULZ, CARL O.
[11] then, some opinions
that you can state for me
[12] generally with re­
gard to this case and
then [13] we'll get to
the specifics of it?
[14] A. Yes, I have.
[15] Q. And what are
those opinions?
[16] A. Opinion is that,
to a r e a s o n a b l e
[17] degree of scientific
certainty, Mr. Moyer's
[18] c a n c e r was not
caused by an exposure
that he [19] experienced
while employed for Orange
County in [20] the sum­
mers of — in the years
1976, 1977.
[21] Q. Okay. And factua l l y -- a n d I k n o w
[22] these are broad
questions, but we'll get
to the [23] specifics.
Factually, generally,
what do you [24] base
that opinion on?
[25] A.
I base that
opinion on the fact____
- Page 91 [1] that there's no cred­
ible evidence that he was
[2] exposed to any mean­
ingful q u a n t i t y of a
[3] chemical or agent
hypothesized or known to
[4] cause human cancer,
including soft tissue
[5] sarcoma.
[6] Q. Okay. Let me ex­
plore that w i t h you
[7] for a few minutes
here.
[8] A. Okay.
[9] Q. When I hear words
like not exposed [10] to
any meaningful quantity,
t h a t s e e m s to be
[11] somewhat of a broad­
er or vague term. Let me
[12] start with this
question. Do you believe
that [13] TCDD is a human
carcinogen?
[14] A. Yes, I do.
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[15] Q. And so, at some
l e v e l of e x p o s u r e ,
[16] you believe that
that can cause cancer?
[17] A. Yes, I do.
[18] Q. Is your opinion
here today, that [19] Mr.
Moyer was not exposed to
a sufficient [20] amount
of TCDD in his time with
Orange County, [21] to
enable you to say, within
a reasonable [22] degree
of scientific certainty,
that that [23] exposure
causes cancer?
[24] A. That's correct.
[25] Q. Okay. And so are
you telling me_________
- Page 92 [1] that the exposure
that Mr. Moyer had at
Orange [2] County, you
have deduced from the
facts of this [3] case,
did not rise to that lev­
el that would [4] permit
you to say that that
caused
his
soft
[5] tissue sarcoma?
[6] A. That's correct.
[7] Q.
So if I under­
stand you correctly,
[8] again, to paraphrase,
your saying it's not
[9] probable that Mr.
Moyer's exposure at Or­
ange [TO] County caused
his cancer, but it might
be a [11] possibility?
[12] A. It's not likely.
Right.
[13] Q. Okay. But it's a
possibility?
[14] A.
Extremely re­
mote.
[15] Q. Okay. But a poss i b i l i t y
[16] nevertheless?
in [17] MR. WAGNER: Object
to form. Asked [18] and
^ answered. Vague.
[19] BY MR. SCHULER:
[20] Q. Correct?
[21] A. I answered. Not
likely.
a ” WILLIAM
\

[22] Q. As far as TCDD
being
a
human
[23] carcinogen is con­
cerned, would you agree
that [24] the scientific
literature supports the
fact [25] that TCDD is a
human carcinogen?_______
- Page 93 [1] A. Yes, I would.
[2] Q. When we say a
human carcinogen, we
[3] are referring to a
substance that causes
cancer [4] in human be­
ings; correct? I mean,
it's the [5] obvious, but
I need to ask that.
[6] A. Yes, that's cor­
rect.
[7] Q. Okay. Do you be­
l i e v e t h a t T C D D is
[8] associated with the
cause of certain types of
[9] cancer?
[10] A. Not — well, I
don't — I think [11] I
— well, I do not think
t h a t T C D D is t h e
[12] classic site specif­
ic carcinogen in that it
[13] causes only one kind
of cancer and no other
[14] kind. I think it
causes a broad variety of
[15] cancers.
[16] Q. And would soft
t i s s u e s a r c o m a be
[17] among those?
[18] A. There are stud­
ies that suggest that
[19] there's an elevated
incidence of soft tissue
[20] sarcoma among manu­
facturing workers heavily
[21] exposed to dioxin. I
hesitate to — I don't
[22] feel that there's
very solid evidence that
[23] dioxin causes soft
tissue sarcoma. [24] It's
a very poorly defined
category [25] of cancers.
It's not — soft tissue
sarcoma is

ROBERTS & ASSOCIATES

26

SCHULZ, CARL O.
- Page 94 [1] not a type of cancer
in the since that lung
[2] cancer is a type of
cancer or leukemia is a
[3] type of cancer.
[4] Q. What's different
about soft tissue
[5] sarcoma?
[6] A. Soft tissue sar­
c o m a a r e t y p e s of
[7] cancers of different
cell types that arise or
[8] occur in all differ­
ent tissues and organs of
[9] the body. The only
unifying theme of the
[10] category is that
t h e y a r i s e in t h e
so-called [11] soft tis­
sues. [12] But they es­
sentially have been
[13] lumped together be­
cause each and every
[14] individual type is
generally rare and a very
of [15] them is even
thought to be understood
and so [16] they're just
p u t in t h i s k i n d of
catch-all [17] category
for the purpose of clas­
sification, if [18] you
will.
[19] Q. The commonality
is t h a t t h e y a r i s e
[20] from the mesenchymal
type tissue; correct?
[21] A. That's correct.
[22] Q. And the same
tissues gives rise to
[23] the lymphomas; cor­
rect?
[24] A. Yes, there are
— yes.
[25] Q. Okay. Now, with
regard to Mr.__________
- Page 95 [1] Moyer's specific case
— well, let me strike
[2] that. [3] Do you be­
lieve that silvex is a
[4] human carcinogen?
[5] A. No, I do not.
[6] Q. Would you agree
that silvex [7] contains
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
. TCDD?
[8] A. Silvex, which we
have to talk about [9] in
the past tense, doesn't
exist
any more,
[10] probably was contam­
inated with TCDD in-[11] Q. I'm sorry. I
d i d n ' t m e a n to c u t
[12] you off. Is that-[13] A.
In the past.
Yes.
[14] Q. I understand
t h a t it's no l o n g e r
[15] available or hasn't
been available, I guess,
[16] since, what, '79 or
'80?
[17] A. About then. I
can't specifically
[18] say when.
[19] Q. And silvex was
first m a n u f a c t u r e d
[20] when, 1953, approxi­
mately?
[21] A. I don't know.
[22] Q. 2,4,5-T is that
the same as silvex?
[23] A. No.
[24] Q. Okay. What's the
difference?
[25] A. 2,4,5-T is
- Page 96 [1] 2,4,5-trichloropheno
xyacetic acid and various
[2] ester s thereof .
S i l v e x
i s
[3] 2,4',5-trichloropheno
xy propionic acid and
[4] various esters thereof.
So t h e y a r e
[5] structurally related
first cousins, perhaps,
[6] but they're different
compounds.
[7] Q. Structurally similar,
but
not
[8] identical?
[9] A. Correct.
[10] Q. And the applicat i o n s
a r e
[11] essentially the
same, are they not? Or
vere [12] when they were
being used?
[13] MR. WAGNER: Object

SCHULZ, CARL 0.

to the form.
[21] opinion as far as
[14] THE WITNESS: That's that's concerned?
beyond my area [15] of
[22] A. Well, other-expertise.
[23] Q. When I say car­
[16] BY MR. SCHULER:
c i n o g e n i c , by the
[17] Q. Does 2,4,5-T or
[24] way, I'm always re­
did 2 , 4 , 5 - T c o n t a i n
ferring to in humans un­
[18] TCDD?
less [25] we talk about
something else.
[19] A. Historically,
yes, it was probably
- Page 98 [20 ] contaminated.
[1] A. Okay. In my opin[21] Q. Other than TCDD,
i o n ,
o t h e r
h i s t o r ically, have
[2]
chlorinated
[2 2 ] other contaminants
dibenzo-p-dioxins and
been found in either
dibenzo [3] furans, in
silvex [23] or 2,4,5-T?
which the lateral ring
[24] MR. WAGNER: Object p o s i t i o n s
are
to form.
[4] occupied by — the
[25] THE WITNESS: I need
four lateral ring posi­
you to repeat__________
tions [5] are occupied by
chlorine atoms, contrib­
- Page 97 ute to [6] the carcino­
[1 ] the question.
genic activity. So that
[2] BY MR. SCHULER:
includes a [7] category
[3] Q. I'll repeat it.
of
tens of individual
[4] A. Okay.
compounds.
Not [8] all of
[5] Q. I'll repeat it. I
which, were likely to be
said, other than
[6 ] TCDD, have other con­ present in [9] 2,4,5-T,
taminants been found in but I'm not prepared to
[7] either silvex or
testify [10] exactly
which one were and were­
2.4.5- T?
[8 ] MR. WAGNER: Same ob­ n't present.
jection.
[11] Q.
You say that
[9] THE WITNESS: I think these are pr es ent in
[12] 2,4,5-T, but you
so.
don't have an opinion as
[10] BY MR. SCHULER:
[11] Q. Okay. Are you
to [13] silvex?
[14] A. I have not seen
familiar with what
[1 2 ] other contaminants
a n y i n f o r m a t i o n on
have been found in those
[15] contaminant levels.
[13] commercial grade
I've not seen factual
[16] information. I have
products over the years?
an o p i n i o n t h a t the
[14] A. I think small
[17] contamination pat­
q u a n t i t i e s of ot h e r
[15] chlorinated dioxins
tern of silvex, histori­
and furans have been
cally, [18] was probably
s i m i l a r to t h a t of
[16] i d e n t i f i e d in
2.4.5- T. I'm not familiar 2.4.5T.
with [17] what's been
[19] Q. All right. Have
found in silvex.
you,
from
your
[18] Q. Do you know
[20 ] review of the liter­
w h e t h e r a n y of t h e
a t u r e , n o t e d t h a t / |^ 0
[19] other contaminants
[2 1 ] heptacholorodibenzo
that have been found in dioxin is a contaminant
0
[20] 2,4,5-T are carcino­ of [22 ] either silvex or 40*3
genic, or do you have an 2.4.5T?

A. WILLIAM ROBERTS & ASSOCIATES

27

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Maren

MOYER vs. DOW CHEMICAL COMPANY
[23] A. I don't know.
- [24] Q. What about
hexacholorodibenzo
[25 ] dioxin?
- Page 99 [1] A. I don't know spe­
cifically.
[2] Q.
What about
octachlorodibenzo
[3] dioxin?
[4] A.
I think that's
very unlikely, but I
[5] don't — I say, I did
not — I'm not prepared
[6] to testify on which
specific ones were there
[7] and were not.
[8] Q. Okay.
[9] A. Other than TCDD,
2,3,7,8.
[10] Q. Would that an­
swer be the same if I
[11] asked you about
furans?
[12] A. Yes.
[13] Q. And would it be
t h e s a m e if I a s k e d
[14] you about xanthones?
[15] A. Yes.
[16] Q. Do you have an
o p i n i o n
as
to
[17] whether any of the
furans may be carcinogen­
ic?
[18] A.
I'd hoped my
earlier answer covered
[19] that, but the same
rule applies for furans
as [20] dioxins. That
those that are occupied
by [21] chlorine in the
four lateral positions
have the [22] potential
to cause a carcinogenic
response, [23] yes.
[24] Q. What about the
xanthones?
[25] A. I have no opin£«. ion on the xanthones.*
3
r-i
- Page 100 ^
[1] Q. Other than TCDD,
would Mr. Moyer [2] have
had any exposure to any
\ c a r c i n o g e n i c
[3] material, from your

ö ,

iyyj

SCHULZ, CARL O.

review of this case, in that. I said, I had no
any [4] of the other
opinion on [1 0 ] what a
chemicals he used? And I,
safe level would be.
also, [5] for the purpose
[11] BY MR. SCHULER:
of this question, want to
[12] Q. Okay. As far as
[6] exclude our discus­ Mr. Moyer's [13] exposure
s i o n of f u r a n s a n d
was concerned — I'm usxanthones [7] and the
ing
that
term
other dioxins.
[14] generically, expo­
[8 ] A. Uh-huh.
sure to. And, again, I'm
[9] Q. What I'm getting
[15] focusing, right now,
at,
to m a k e t h e
just completely on his
[10] question clearer, is
[16] time spraying chemi­
were there any other
cals for Orange County.
[11] chemicals or any
[17] Did you do any calother contaminants of any c u l a t i o n s
with
[12] other chemicals that
[18] regard to what you
you're aware of that he thought his exposure was
[13] used that, in your to [19] either any chemi­
opinion, were potentially cal or any contaminant of
[14] carcinogenic?
any [20 ] chemical?
[15] MR. WAGNER: You mean
[21] A. I have not made
a
quantitative
while [16] spraying in
Orange County?
[2 2 ] estimate of the
[17] MR. SCHULER: Right.
amount of any herbicide
or [23] c o n t a m i n a n t
[18] THE WITNESS: Right.
therein that he might
My review of [19] the
have been [24] exposed
list of those chemicals
indicate — [20] products to.
and chemicals indicates
[25] Q. Okay. How did
none that I am [21] aware you determine that_____
of that have been shown
- Page 102 to be [22] carcinogenic
[1 ] his exposure then was
in animals or humans.
not meaningful?
[23] BY MR. SCHULER:
[2] A. Well, it's based
[24] Q. Okay. Do you
on an overview of [3] all
have an opinion as to
the evidence and a number
[25] what the exposure
of [4] considerations;
level would have to be,
but, essentially, he han­
for___________________
dled [5] silvex very
rarely, at widely sepa­
- Page 101 [1] example, to something rated time [6 ] points,
like TCDD in order to perhaps, if at all. I
[2] make you suspect or think there's [7] some
opine that that would be question whether he ever
a [3] cause of human can­ handled silvex; [8 ] but,
even if he did, he hancer in an individual?
dled
it r a r e l y .
[4] A. No.
[5] Q. So there's no
[9] Widely separated in­
tervals with [1 0 ] very
minimum safe level of
little total use. When he
[6] exposure to TCDD; is
that correct?
was handling [1 1 ] it,
[7] MR. WAGNER: Object to exposure in any way in
form.
w h i c h he c o u l d h a v e
[12 ] experienced systemic
[8] THE WITNESS: I said
— no. I [9] didn't say absorption was minimal

A. WILLIAM ROBERTS & ASSOCIATES

28

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[13] because he wore pro­ review the diagnosis.
tective clothing, full
[18] Although there is
[14 ] protective clothing. some question in my mind,
[15] When he sprayed it, as [19] a biologist, with
the spray was [16] not in training in nisthology, I
a form that would have
[20] cannot understand
caused a [17] respirable this terminology, epithe­
mist or spray that he
lioid [21] sarcoma. It's
could have [18] inhaled like saying having a
and or ingested to any headache of [22] the toe.
great degree. [19] And
[23] BY MR. SCHULER:
his — any conceivable
[24] Q. Okay. Did you
e x p o s u r e to s i l v e x
see a n y t h i n g , other
[20] or contaminating
[25] than the fact that
inpurities was so small,
it was called epithelioid
[21] compared to his
- Page 104 background exposure, as
[1] sarcoma, which would
to be [22] negligible.
give you any reason to
[23] And the evidence,
[2] doubt that he had
the factual [24] evidence soft tissue sarcoma?
indicates that he did not
[3] A. No.
experience [25] any expo­
[4] Q. Was there any
sure because he has no
significance to you,
body burden__________
[5] in arriving at your
- Page 103 opinion, regarding the
[1] of — he had no body fact [6] that Bob Moyer's
burd en of the common
cancer was diagnosed in
[2] contaminating impuri­ 1985 [7] and his first
ty when it was checked.
exposure would have been
[3] Q. Okay. So you didin 1976?
n't
m a k e
any
[8] A. Yes.
[9] Q. In other words—
[4] calculations per se,
[10] MR. WAGNER: Object
b u t b a s e d on t h o s e
[5] observations, from to form. Wait [11] a min­
the information that you ute. Let me get an objec­
[6] were provided, that's tion. No [12] predicate
essentially what you're with respect to the expo­
[7] basing your opinion sure or to [13] what
you're referring.
on?
[14] BY MR. SCHULER:
[8] A. Correct.
[15] Q. In other words,
[9] Q. You don't dispute
w
as there a n y t h i n g
the fact, by the
[16]
about the latency
[10] way, that Bob Moyer
had soft tissue sarcoma;
period, from first expo­
[11] correct?
sure [17] to diagnosis,
[12] MR. WAGNER: Object that was signature to
you?
to
form
and
no
[13] predicate. As you
[18] MR. WAGNER: Same
said, he's not a medical objection.
[19] MR. LUTZ: I'd join
[14] doctor. I don't know
that if he could diagnose in the [20] objection.
[15] it or is qualified
[21] THE WITNESS: Yes. I
thought the [22] latency
o.
was very short, too short
L16] THE WITNESS: Yeah.
I ' m
n o t
a to link his [23] cancer
to the exposure.
[17] pathologist. I can't
A. WILLIAM ROBERTS & ASSOCIATES

29

SCHULZ, CARL O.
[24] BY MR. SCHULER:
[25] Q. What latency
period do you believe
- Page 105 [1 ] is sufficient or
would be a typical laten­
cy [2 ] period, assuming a
cause and effect
[3] relationship?
[4] A. Yes. I think that
l a t e n c y
like
[5] incidence is a func­
tion of the intensity and
[6 ] duration of the expo­
sure for a type cancer in
[7] g e n e r a l that is
caused by a chemical or
[8 ] physical agent. And
so, therefore, the vast
[9] majority of cancer
latencies range from 10
to [10] 30 years follow­
ing initial exposure. And
the [1 1 ] peak of these
are 15 to 25. Some types
of [12 ] tumors have even
longer peak latencies.
[13] But, you know, if
there's
a short
[14] latency tumor that
is quite clearly related
to [15] a given cause,
the literature suggests
that the [16] exposure,
the initial exposure was
very [17] intense.
[18] Q. Well, again,
assuming a cause and
[19] effect relationship
here for the purpose of
the [2 0 ] hypothetical
question and Bob Moyer's
latency [2 1 ] period would
have been approximately
nine [22 ] years; correct,
from initial exposure?
[23] A. No. Seven years.
[24] MR. WAGNER: Let me
object to the [25] form
of the question.
" Page 106 "
~
c
[1] MR. LUTZ: I join.
41o
[2] MR. WAGNER: Maybe we
can clear it [3] up.
You're asking him to 9tf)4

Zb

MICROCopy

Q'

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
sume exposure to [4] TCDD
in 1976?
[5] MR. SCHULER: Correct.
[6] MR. WAGNER: Okay.
That's
my —
no
[7] predicate objection.
[8] MR. LUTZ: I join.
[9] MR. WAGNER: And that
that exposure [10] caused
his cancer?
[11] MR. SCHULER: That's
correct.
[12] THE WITNESS: It's
hypothetical.
[13] MR. LUTZ: I join.
[14] THE WITNESS: Nine
years, yes. '76 [15] to
'85 is nine years. Yes.
[16] BY MR. SCHULER:
[17] Q. And if he was
e x p o s e d in 1977, it
[18] would have been
eight years; right?
[19] A. Correct. Seven
and a half.
[20] Q. Okay. I mean,
t h a t ' s not t h a t far
[21] out of the spectrum,
is it, the 10 to 30 years
[22] that you just gave
me?
[23] MR. WAGNER: Object
to form.
[24] MR. LUTZ: Object to
form.
[25] THE WITNESS: It's
very short.____________
- Page 107 [1] BY MR. SCHULER:
[2] Q. But within the
r e a s o n a b l e a r e a of
[3] argument; correct?
[4] MR. WAGNER: Object to
form. [5] Argumentative.
And it doesn't have the
[6] predicate that he
provided as to latency
being [7] a function of
^ duration and intensity.
Ij [8] MR. LUTZ: Join.
[9] THE WITNESS: I just
don't — you [10] know, I
feel that that, the short
latency in [11] this case
is a strong piece of evidence in my [12] argument
\

that it is not a cause
a n d
e f f e c t
[13] relationship.
[14] BY MR. SCHULER:
[15] Q. Okay. And the
s h o r t l a t e n c y is
[16] short by about a
year or two years?
[17] MR. WAGNER: Object
to form.
[18] MR. LUTZ: Join.
[19] THE WITNESS: No. You
know, I said [20 ] in the
range, 10 to 30 years,
with
the
peak
[2 1 ] latency occurring at
15
to
25.
It's
[2 2 ] exceptionally rare
to see. There are, I
think, [23] some laten­
cies under 10 years reported
in
the
[24] literature; but ex­
tremely rare incidences.
[25] I don't consider,
for example, any_______
- Page 108 [1 ] epidemiology study
that doesn't have a
[2 ] significant percent­
age of members of the
cohort [3] or cases far
in excess of 10 . I would
say a [4] minimum of 15
years of potential laten­
cy before [5] the study
can be considered to be a
valid [6 ] epidemiologic
study.
[7] BY MR. SCHULER:
[8 ] Q. So you disregard
studies as not [9] valid
that have latency periods
shorter
than
15
[10 ] years?
[11] MR. WAGNER: Object
to form.
[12] MR. LUTZ: Join.
[13] THE WITNESS: And to
answer the [14] question,
if a study is negative
and the [15] latency is
less than 15 years, then
I don't [16] consider it
to be a true negative
finding.

A. WILLIAM ROBERTS & ASSOCIATES

30

SCHULZ, CARL O.
[17] BY MR. SCHULER:
[18] Q. Let's talk about
the
i s s u e
of
[19] protective clothing
for a minute.
[20] A. Uh-huh.
[21] Q. That has to do
with Bob Mo yer's
[22] rate of absorption
of the chemical; correct,
[23] potentially?
[24] MR. WAGNER: Objec­
tion.
[25] THE WITNESS: No. It
has to do______________
- Page 109 [1] with the amount that
actually — that he was
[2] actually exposed to
getting and then, as a
[3] derivative of that,
the a m o u n t t h a t was
[4] absorbed. Yeah.
[5] BY MR. SCHULER:
[6] Q. Well, let's as­
s u m e for t h e m o m e n t
[7] hypothetically that,
in Bob Moyer's time at
[8] Orange County, he
never wore any protective
[9] clothing. In fact,
let's assume that he nev­
er [10] wore any clothing
at ali.
[11] A. Uh-huh.
[12] Q. Would he have
been -- if he was out
[13 ] there spraying with­
out any clothing on, from
[14] the air boat, would
he have been exposed to
[15] sufficient carcino­
g e n i c a g e n t s in the
2,4,5-T [16] silvex or
2,4-D to have been able
to cause his [17] cancer?
[18] MR. WAGNER: Object
to form. [19] Missing
predicates and missing
factual [20] information
from which he could give
an answer [21] that was
meaningful.
[22] MR. LUTZ: Join.
[23] BY MR. SCHULER:
[24] Q. The answer is
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
no?
[25] A. No.___________
- Page 110 [1] Q- So then protec­
tive clothing really
[2] is not an issue?
[3] A. Just gives me an
extra
degree
of
[4] confidence in my
opinion.
[5] Q. And so the same
m i g h t be s a i d a b o u t
[6] the issue of the
spray not being, for ex­
ample, [7] a mist as op­
posed to a steam; cor­
rect?
[8] MR. WAGNER: Object to
form. Loads.
[9] MR. LUTZ: Join.
[10] THE WITNESS: Cor­
rect.
[11] BY MR. SCHULER:
[12] Q. Irrespective of
w h e t h e r it w a s a
[13] mist or a stream, he
wasn't exposed to enough
[14] carcinogenic agents
at Orange County to cause
[15] his cancer; correct?
[16] A. That's correct.
[17] Q. I'm having trou­
bl e r e a d i n g my own
[18] writing here.
[19] MR. WAGNER: You're
as bad as I am [20] about
that. I've noticed that.
[21] BY MR. SCHULER:
[22] Q. Okay. I think
the thir d point that
[23] you made was that
the exposure that he re­
ceived [24] at Orange
County was small compared
to [25] background expo­
sure. That's a very gen­
eral___________________
- Page 111 [1] statement, but would
that be accurate for a
[2] general proposition?
[3] A. That's correct.
r 4 ] Q.
A n d are y o u
speaking specifically
[5] with regard to TCDD,

or are you speaking with
[6 ] regard to any carci­
nogenic agents which may
[7] have been present in
these chemicals?
[8 ] A. I'm talking specifically
about
[9] p o l y c h l o r i n a t e d
d i b e n z o d i o x i n s and
dibenzo [10 ] furans, with
heavy emphasis on 2 ,3,7,8
[1 1 ] tetrachlorodibenzo
dioxin.
[12] Q. Okay. By the
way, in f o r m u l a t i n g
[13] your opinion, are
you assuming total ab­
sence of [14] TCDD in the
2.4- D that he sprayed?
[15] A. Yes, I am.
[16] Q. And so, is it
f a i r to s a y t h e n ,
[17] that you don't be­
lieve that there was any
TCDD [18] in the 2,4-D
back in '76 and '77?
[19] A. That's correct.
[20] Q. And what do you
base that on?
[21] A.
I base that on
my own review of the
[2 2 ] literature and the
conclusion reached by the
[23] EPA independently in
1988 in their drinking
[24] water criteria docu­
ment that TCDD has not
been [25] detected in
2.4- D by modern, valid
chemical_______________
- Page 112 [1 ] analyses.
[2] Q. Do you have a
c o p y of t h a t E P A
[3] document?
[4] A. Yes, I do. At my
office.
[5] Q. That's in your
library?
[6 ] A. Yes.
[7] Q. Have you seen any
documentation [8 ] from
either Dow Chemical Comp a n y or a n y o t h e r
[9] defendant in this
case that indicated that

A. WILLIAM ROBERTS & ASSOCIATES

31

SCHULZ, CARL O.
the [10] TCDD contaminant
was found in 2,4-D?
[11] A. No, I haven't
seen any.
[12] Q. Have you seen
any
scientific
[13] articles that found
TCDD in 2,4-D?
[14] A. No, I haven't.
[15] Q. All right. As
f a r as 2 , 4 - D
is
[16] concerned, are there
any other carcinogenic
[17] contaminants that
you're aware of in 2,4-D?
[18] A. No.
[19] Q. Do you consider
2.4D i t s e l f to be
[20] carcinogenic?
[21] A. No, I do not.
[22] Q. And when I say
c a r c i n o g e n i c , now,
[23] I'm speaking of car­
cinogenesis in general,
as [24] opposed to-[25] A. Okay.
- Page 113 [1] Q.
-- a specific
type of cancer.
[2] A. Still stand by my
answer.
[3] Q.
Okay. You're
aware of the various
[4] studies that have
apparently seen a
[5] relationship between
2.4- D and other types of
[6] c a n c e r , s u c h as
non-Hodgkin's lymphoma;
[7] correct?
[8] A. Yes, I'm familiar
with those.
[9] Q. And the Sheila
Hoarizom and Company
[10 ] article dealing with
that?
[11] A. Yes.
[12] Q.
And I think
there are some others,
[13] as well; correct?
[14] A. Yeah, I suppose.
Some people say [15] some
other studies s u g g e s t 4 2 0
that.
[16] Q. So you're not
suggesting here that
<
MICROCop-

y

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
___
[8] instance, between
cigarette smoke and can­
cer [9] and other health
effects. [10] You can do
a state-of-the-art
[11] epidemiologic study
and perhaps miss a true
[12] causal association.
So there are inherent
[13] limitations in the
methodology of the sci­
ence, [14] but there are
also — it depends on the
nature [15] of the effect
and so forth, too.
[16] MR. WAGNER: Before
you ask your [17] next
question, I've been sayi n g o b j e c t to t h e
[18] form, frankly, to
a v o i d long s p e a k i n g
[19] objections. I assume
that's okay with you?
[20] MR. SCHULER: Sure.
That's a rule [21] of
civil procedure. All obj e c t i o n s
are
[22] reserved except as
to those as to form.
That's [23] fine. I un­
derstand.
[24] MR. LUTZ: You agree
that all I [25] need to
do is say, join, and I'm
okay, too? Or__________
- Page 118 [1] do you want me to-[2] MR. SCHULER: That's
fine.
[3] MR. LUTZ: Okay.
[4] MR. SCHULER: That's
fine. In [5] fact, you
can say amen, if you want
to.
[6] MR. LUTZ: Join. How
about if I [7] say noth­
ing?
^ [8] MR. SCHULER: Y'all
^ want to take a [9] break
^ for lunch or how do you
want to work [10] this?
[11] MR. WAGNER: Whatever
your pleasure [12] is.
[13] THE WITNESS: Yeah, I
think a [14] break.
[15] MR. SCHULER: We've

been
going
for
[16] probably two and
three-quarter hours.
[17] (A luncheon recess
transpired.)
[18] BY MR. SCHULER:
[19] Q. The summary of
a r t i c l e s that you
[20] did, Dr. Schulz, for
the
V e t e ran's
[21] Administration, in­
cluded, did it not, arti­
cles [22] that demon­
strated or concluded that
t h e r e
w a s
a
[23] relationship between
2.4- D and cancer?
[24] A. I don't believe
so.
[25] Q. Okay. Was Sheila
Hoarizom's_____________
- Page 119 [1] research included in
your group?
[2] A. I'm pretty sure,
yes. I t h i n k the
[3] timing is such that
we must have included it
in [4] the years I was
involved.
[5] Q. Okay. And in her
conclusions, as [6] we
discussed earlier — I
d on't want to beat a
[7] dead horse here —
were that there was a
[8] relationship between
2.4- D and cancer; cor­
rect?
[9] MR. WAGNER: Object to
the form.
[10] THE WITNESS: Yes.
[11] BY MR. SCHULER:
[12] Q. Were there any
o t h e r a r t i c l e s that
[13] you included in your
summary of the literature
[14] for the years that
we discussed earlier that
[15] concluded that there
was a relationship be­
tween [16] 2,4-D and can­
cer? And this is not a
memory [17] test. If you
need to look at this or.

A. WILLIAM ROBERTS & ASSOCIATES

33

SCHULZ, CARL O.
[18] A. Well, that's a
related
study,
[19] basically, by the
same group in Eastern
[20] Nebraska, I believe.
The first author of that
[21] was Weisberger or
Weisenberger or something
[22] like that. And I'm
talking, I think, now
from [23] faulty memory.
They also found an in­
creased [24] rate of
non-Hodgkin's lymphoma
with farming, [25] but
I'm not sure they were
able to establish______
- Page 120 [1 ] that it was related
to 2,4-D use. [2] Of
course, there-is a large
number [3] of epidemio­
logic studies of poten­
tial [4] association of
cancer of various forms
and [5] exposure to her­
bicides. The only other
study I [6 ] know where
the exposure was essen­
tially 2,4-D, [7] not
confounded by other phen o x y h e r b i c i d e s and
[8 ] stuff, was the occu­
pational study done by, I
[9] believe, Greg Bond at
Dow, who — they looked
[10] at their 2,4-D pro­
duction workers and found
no [1 1 ] excess risks of
any form of cancer in
that [1 2 ] cohort.
[13] Q. Was that study
published?
[14] A. Yes.
[15] Q. Is that part of
your summary?
[16] A.
It'd be in the
review.
[17] Q. Okay.
[18] A. Those are the
only ones where we're
[19] talking -- in my
recollection, where we're
[20] talking about 2,4-D
s p e c i f i c a l l y . It's
[2 1 ] essentially impossiMICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
[17] there is a total
lack of scientific eviience [18] linking 2,4-D
with cancer; correct?
[19] MR. WAGNER: Object
to
f o r m .
No
[20 ] predicate.
[21] THE WITNESS: Yes, I
am.
[22] BY MR. SCHULER:
[23] Q. You don't be­
lieve Sheila Hoarizom's
[24] results, then?
[25] A. That's correct.
Well, I don't.
- Page 114 [1] Now, that's — let me
qualify that. I believe
[2 ] her results, what she
observed. She's a good,
[3] competent researcher,
the people in her group.
[4] I don't agree with
the conclusion that she
and [5] most of the other
people have reached, that
her [6 ] work shows — is
e v i d e n c e of c a u s a l
[7] relationship between
exposure to 2,4-D and any
[8 ] form of cancer.
[9] Q. Okay. Let's go
b a c k to m y i n i t i a l
[1 0 ] question and make
sure we're on the same
page [11] here. There is
not a total lack of sci­
entific [1 2 ] support for
a cause and effect rela­
tionship [13] between
2,4-D and carcinogenesis;
correct?
[14] MR. WAGNER: Object
to form.
[15] BY MR. SCHULER:
[16] Q. I mean, her ar­
ticle exists; right?
[17] MR. WAGNER: Object
to form.
[18] THE WITNESS: Her
article exists, [19] yes.
[20] BY MR. SCHULER:
'21] Q. So I mean, there
^s evidence
out
[22 ] there, at least in
some observer's view, who

[23] have done actual
epidemiological studies
that [24] there is a re­
lationship between 2,4-D
and [25] cancer; correct?
- Page 115 [1] MR. WAGNER: Object to
the form.
[2] MR. LUTZ: Object to
the form.
[3] THE WITNESS: I really
don't think [4] there's
any evidence for an asso­
ciation. I [5] think you
can — it all crumbles
away, and that [6] a good
scientific reviewer would
not
come
to
a
[7] c o n c l u s i o n that
there's any evidence.
[8] BY MR. SCHULER:
[9] Q. Okay. Maybe we're
mincing words [10] here.
[11] A. Yes.
[12] Q. When I say that
there is no [13] evidence
and — when I say that,
I'm referring [14] to the
fact that there are arti­
cles out there, [15] by
qualified scientists,
well
qualified
[16] scientists that link
2,4-D with cancer;
[17] correct?
[18] MR. WAGNER: Object
to form.
[19] THE WITNESS: Where
t h e
a u t h o r s
[20] concluded that there
that was a link. Yes.
[21] BY MR. SCHULER:
[22] Q. You just don't
agree
with
the
[23] conclusions of those
articles?
[24] A. That's correct.
[25] Q. And you don't
agree with the
- Page 116 [1] conclusions of those
articles because you
[2] believe that certain
assumptions made within
[3] the studies are prob­

A. WILLIAM ROBERTS & ASSOCIATES

32

SCHULZ, CARL O.
ably not accurate; cor­
rect?
[4] MR. WAGNER: Object to
form.
[5] MR. LUTZ: Join.
[6] THE WITNESS: Correct.
[7] BY MR. SCHULER:
[8] Q. And you would
a g r e e w i t h me t h a t
[9] you can basically
take
nearly
any
[10] epidemiological
study and dissect its
[11] assumptions and dis­
pute its conclusions,
could [12] you not?
[13] MR. WAGNER: Object
to form.
[14] MR. LUTZ: Object to
form.
[ 15] THE W I T N E S S : I
wouldn't
make
a
[16 ] sweeping generaliza­
tion to that effect, no.
[17] BY MR. SCHULER:
[18] Q. Okay.
[19] A. There's a com­
p l e t e c o n t i n u u m of
[20] quality to epidemio­
logic studies, as there
is [21] to any other form
of s t u d i e s . I t h i n k
[22] epidemiology is an
imperfect tool, limited
in [23] what you can do
with it. And, in general,
I [24] think any epidemi­
ology study is probably
[25] subject to some
criticism; but whether or
not___________________
- Page 117 [1] the conclusions of
that study supports, are
[2] valid or not, is not
a function only of the
[3] quality of the study,
but is a function of the
[4] nature of the results
as well. So you can do a
[5] pretty — just as an
example, I think you can
[6] do a pretty sloppy
methodological epidemiol­
ogy [7] study and still
find an association, for
MICROCopy

9'

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
____________
ble to find cohorts or
cases [22] where people
were exposed to just one
phenoxy [23] herbicide or
where they have any rec­
ollection [24] that's of
any accuracy.
[25] Q. Well, that
brings up another point
- Page 121 [I] that you raised. I
mean, these chemicals,
the [2] phenoxy herbi­
cides are generally used
in [3] combination, ei­
ther with one another or
with [4] other chemicals,
are they not?
[5] MR. WAGNER: Object to
form.
[6] MR. LUTZ: Join.
[7] THE WITNESS: They're
often
used
in
[8] combination, yes.
[9] BY MR. SCHULER:
[10] Q.
I mean, I know
you're not a farmer,
[II] but you've reviewed
the literature and it's
[12] pretty easy to see
that — I mean, that's
been [13] the history of
the use of these chemi­
cals over [14] the last
30 or 40 years; correct?
[15] MR. WAGNER: Object
to form,
[16] MR. LUTZ: Join.
[17] THE WITNESS: Yes.
[18] BY MR. SCHULER:
[19] Q. And that would
be s o m e t h i n g that
[20] anyone that has even
a passing familiarity
with [21] agriculture or
the use of herbicides in
[22] agriculture, and
certainly a manufacturer
of [23] these chemicals,
^ should be familiar with;
vp [24] correct?
[25] MR. WAGNER: Object
to form.
- Page 122 [1] MR. LUTZ: Object to

the form.
[2] THE WITNESS: Proba­
bly, yes.
[3] BY MR. SCHULER:
[4] Q. Are there any
s t u d i e s th at y o u ' r e
[5] aware of that discuss
the issue of whether the
[6] use of these chemi­
cals — and when I say
these, [7] I'm referring
specifically to 2,4-D
silvex or [8] 2,4,5-T in
combination — potenti­
ates the [9] effect of
the carcinogenic elements
that may be [10] in, for
example, 2,4,5-T.
[11] MR. WAGNER: When you
say-[12] THE WITNESS: Can you
r e s t a t e
t h e
[13] question?
[14] MR. LUTZ: I'll ob­
ject to the form.
[15] BY MR. SCHULER:
[16] Q. Are there any
s t u d i e s th at y o u ' r e
[17] aware of that dis­
cuss the issue of whether
the [18] use of these
chemicals in combination,
m e a n i n g [19] 2,4-D,
2,4,5-T or silvex, enh a n c e s
t h e
[20] carcinogenic impact
of those elements that
may [21] be in 2,4,5-T or
silvex that are carcino­
genic?
[22] A. I'm not aware of
any.
[23] Q. Do you have any
opinions about [24] that,
one way or the other?
[25] A. I don't think
that 2,4-D, 2,4,5-T
- Page 123 [1] or anything else is
in — moderates or modi­
fies [2] the carcinogenic
activity of the dioxins
and [3] furans.
[4] Q. Is 2,4-D being
studied right now by
[5] the Environmental

SCHULZ, CARL O.

Protection Agency?
[6 ] A. Not that I'm
aware of.
[7] Q. Are you aware of
a n y a g e n c y of t h e
[8 ] government or any
private institution, for
that [9] matter, that is
-- other than what a
[1 0 ] manufacturer might
be doing for its own uses
— [1 1 ] that is conduct­
ing any intensive re­
search with [12] 2,4-D
with regard to its poten­
tial [13] carcinogenesis?
[14] A. I'm not aware of
any
o n - g o i n g
[15] studies, but I don't
— haven't made an effort
[16] recently to check
that. When I stopped do­
ing [17] the review two
years ago, nobody that I
know [18] nor my common
sources were doing any
s p e c i f i c
[19] toxicological inves­
tigation of 2,4-D.
[20] Q. Have you re­
viewed, at one time or
[2 1 ] another, any of the
testimony before the EPA
or [22] the Department of
Agriculture, for that
matter, [23] or any of
its subcommittees with
regard
to
the
[24] potential removal of
2,4,5-T or silvex from
the [25] market in the
1970s?_________________
- Page 124 [1] A-. I've seen very,
very little of [2 ] that.
I, of course, worked with
two people who [3] played
a key role in that hear­
ing in '78, '79, [4] Ian
Nisbet and Mary Paxton;
and t h e y —
I read
[5] the document that
they put together. I
think [6 ] they published
that actually. It was
[7] specifically related

Vo
A. WILLIAM ROBERTS & ASSOCIATES

34

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
to dioxins and 2,4,5-T
[8] specifically.
[9] Q.
W h o is I a n
Nisbet?
[10] A. Ian Nisbet is a
risk a s sessor, who
[11] is now an indepen­
dent consultant, was, at
that [12] time, employed
by Clement Associates.
[13] Q. What about Mary
Paxton?
[14] A. She's a toxicologist
with
the
[15] American Petroleum
Institute, who was at
[16] Clement Associates
at that time.
[17] Q. And this docu­
m e n t p r e p a r e d by
[18] Nisbet and Paxton,
was that done by Clement
[19] Associates when they
were there or not?
[20] A. Well, they were
-- y e a h . T h e y w e r e
[21] at Clements. It was
p r o b a b l y p a r t of a
[22] contract thing. It
was before I went to work
[23] there. They were
still working there when
I [24] came, and I knew
them then and I read this
[25]
document at some
point.
- Page 125 [I] Q. That was prepared
specifically for [2] the
hearings in '78, '79?
[3] A. Yes, it was.
[4] Q. And was it prep a r e d
f o r
a
[5] particular client?
[6] A. Well, I expect
t h a t t h e r e v i e w was
[7] probably requested by
EPA.
[8] Q.
You have a copy
of t h e d o c u m e n t , I
[9] assume?
[10] A. I don't know.
[II] Q.
You may or may
lot?
[12] A.
I may or may
not.

[13] Q. And where could
a copy
of
that
[14] document be o b ­
tained, if you don't have
one?
[15] A. I believe it was
p u b l i s h e d , and I
[16] don't have a refer­
ence to it. It would
[17] certainly be in the
docket of those hearings
at [18] EPA.
[19] Q. All right. We've
been discussing [20] kind
of studies in general
h e r e ,
t h e
[21] epidemiological
studies.
[22] A. Uh-huh.
[23] Q. Are there cer­
tain epidemiological
[24] studies with regard,
for example, to TCDD that
[25] you consider more
reliable than others?
- Page 126 [1] A.
I always take a
weight
of
the
[2] evidence approach,
which involves a review
of [3] all the studies;
and as I think I alluded
to [4] earlier, there's
very much a continuum of
[5] quality in these
studies. And no study is
[6 ] totally worthless and
no study is excellent.
[7] And I suppose I could
go
through
an
[8] exercise of ranking
the quality to some de­
gree; [9] but, basically,
I just feel quite strong­
ly that [10] the evidence
is that the only possible
[11] association shown by
all of these epidemiology
[12] studies is that
there may be an increased
risk [13] of cancer of
all sites associated with
v e r y [14] i n t e n s e ,
long-term exposure to the
chlorinated [15] dioxin
and furans.

A. WILLIAM ROBERTS & ASSOCIATES

35

SCHULZ, CARL O.
[16] Q. Okay. I guess my
question, though,
[17] was and maybe you
don't have an answer for
[18] this. My question
is, are there one or two
or [19] three studies
that come to mind as be­
ing the [20 ] best ones in
your opinion, that you
would rely [2 1 ] upon for
that type of opinion?
[22] A. No. I would hes­
i t a t e to s i n g l e out
[23] any specific studies
as being totally the
[24] reliable ones, to
the exclusion of the oth­
ers. [25] I think they're
all-- ----------------- Page 127 [1] Q.
I didn't say to
the exclusion of [2 ] the
others. I'm just talking
about — I mean, [3] if
you don't-[4] A. And, again, it
depends on what [5] the
— you know, there are
different end points
[6 ] we're looking at
here. Different exposure
[7] populations and all
that. There's a certain
[8 ] degree of comparing
apples and oranges, so we
[9] have studies that are
— we have case control
[10] studies. We have
cohort studies. [11] We
have people who are ex­
posed [1 2 ] primarily
through application in
agricultural [13] use. We
have people who are ex­
posed in [14] Vietnam. We
have people.who are ex­
posed [15] through the
manufacture and produc­
tion. [16] So it depends
on which one of those
[17] areas. I think that
I'm very much impressed
by [18] the methodology 4 2 4
and the care with which
the [19] studies were
MICROCopy
9

A

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
done In New Zealand by
Allen Smith [20] and Neal
Pierce and that group on
sprayers. I [2 1 ] consider
those studies to be very
d e f i n i t i v e ,
[22] upstanding. [23] The
manufacturing studies, I
think [24] that the
Fingerhut study is very
good. IOSH [25] study,
whatever you want to call
it. It's the
- Page 128 [1] same. Although I have
problems with it. The
[2] IARC, I-A-R-C, study
is good only in the size
[3] of the study. It's
got some very significant
[4] flaws. Again, these
are manufacturing exposed
[5] populations. [6 ] I
think in some ways the
NCI study, [7] Sheila
Hoarizom studies and aspects
of
those
[8 ] studies are very
good. I just think they
[9] really dropped the
ball on the whole expo­
sure [10] issue. Made a
terrible leap of faith
there [1 1 ] that isn't
justified.
[12] Q. Now, we've been
t a l k i n g in t e r m s of
[13] studies and the epi­
demiological studies, and
I [14] understand that
you are not an epidemiol­
ogist; [15] correct?
[16] A. Well, that's
correct. Yes.
[17] Q. And I guess what
I ' m t r y i n g to g e t
[18] at, I mean, I underLO stand that, apparently in
^
[19] this area of sci^
ence, there's a certain
overlap [20 ] between tox­
icology and epidemiology.
Would [21] that be a fair
statement?
^
[22] A.
I think that's
quite fair to say.
^

X

[23] Q. And from the
s t a n d p o i n t that a
[24] toxicologist, at
least to some extent —
and [25] correct me if
I'm wrong — rely on
- Page 129 [1] epidemiological stud­
ies as f a r as t h e i r
[2] opinions are con­
cerned, to some degree;
[3] correct?
[4] A. They should de­
pend very heavily on
[5] them, yes.
[6] Q. And that's why I
ask e d the q u e s t i o n
[7] about whether you
considered some studies
more [8] reliable than
others.
[9] A. Correct.
[10] Q. And I think
you've answered that.
[11] Now, you mentioned
that you believe that the
[12] exposure that Mr.
Moyer had, in terms of
his [13] spraying chemi­
cals for Orange County
and in [14] terms of his
exposure to TCDD, was
small [15] compared to
general background expo­
sure to [16] TCDD; cor­
rect?
[17] A. Correct.
[18] Q. And what do you
base that on?
[19] A. Well, I base
t h a t on the v e r y
[20] limited use that he
possibly or allegedly
made [21] of any herbi­
cide that might have been
[22] contaminated with
2,3,7,8-TCDD. [23] And
then, as I said earlier,
from [24] that — in ad­
dition, the fact that he
wore [25] protective
clothing, the methods
that they used
- Page 130 [1] to apply the herbi­

SCHULZ, CARL O.
cides and so forth. So
his [2] exposure was
small and, if there was
[3] contamination, the
contamination level was
[4] quite low. [5] And
then, of course, the oth­
er half [6] of that con­
clusion is the fact that
we're all [7] exposed to
dioxins, including
2,3,7,8-TCDD as [8] part
of our daily, day-to-day
existence.
[9] Q. What was the con­
t a m i n a t i o n lev el of
[10] the s i l v e x and
2.4.5- T and[11] A. I don't know.
[12] Q. Well, let me
finish my question.
[13] Otherwise, it would­
n't make any sense. Back
in [14] 1976 or '77 with
the materials that Mr.
Moyer [15] was spraying?
[16] A. I'm not qualif i e d to t o t a l l y
[17] address that issue.
I'm very confident it was
[18] less than 1 part per
million, and I'm quite
[19] confident that it
was significantly less
than i [20] part per mil­
lion. I have now rushed
to answer [21] your ques­
tion. This is silvex.
[22] Q. Right.
[23] A. Yes. Silvex.
[24] Q. Would you have
the same op inion for
[25] 2,4,5-T, 1 part per
million or less?_______
- Page 131 [1] A.
If there were
2.4.5- T involved,
[2] it'd be a similar
level.
[3] Q. And what about
2,4-D?
[4] A. No.
[5] Q. You don't believe
there was any [6] TCDD in
that?
[7] A.
Well, I would

_____________________________________________________________________________________________________________________________

A. WILLIAM ROBERTS & ASSOCIATES

__

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
say, unlikely to have
[8 ] been more than a part
per b i llion because
[9] that's all that has
been able to be reliably
[1 0 ] measured. I don't
think there'd be any,
from a [1 1 ] chemical
point of view. The only
way it could [1 2 ] get in
there
is
from
cross-contamination or
[13] something. But chem­
ically, it just doesn't
[14] form in the manufac­
ture of 2 , 4 - D or its
[15] precursors.
[16] Q. So because it
d o e s n ' t f o r m in the
[17] process of manufac­
turing 2,4-D, it would
h a v e [18] to be a
cross-contamination type
of situation?
[19] A. If there were
any. And, yes.

[ 2 0 ]

Q

.

Cross-contamination being
using the [2 1 ] same ship­
ping vessels to ship the
2,4-D as were [22] used
for 2,4,5-T?
[23] A. Anything. Any­
thing.
[24] Q. Okay. Do you
k n o w or d o y o u h a v e
[25] any information with
regard to the type of
- Page 132 [1 ] testing that was done
by manufacturers in 1976
[2] or 1977 to determine
what levels, if any, TCDD
[3] w e r e in s i lvex,
2,4,5-T or 2,4-D?
[4] A. There's very lit­
t l e i n f o r m a t i o n in
[5] publicly available
literature about such
[6 ] testing and whether
it was done and how often
[7] and what methods were
used. So, no, I don't
[8 ] really have much
first-hand information.
[9] Q.
Do you have any

information with
[10] regard to any test­
ing that was done by
[11] manufacturers on
their commercial grade
product [12] 2,4-D or
2 , 4 , 5 - T in t e r m s of
health
effects,
[13] either on animals or
man?
[14] A. What formula­
tions are we ta lking
[15] about now?
[16] Q. Commercial grade
2,4-D or 2,4,5-T [17] or
silvex.
[18] A. Gee, my recol­
lection is imperfect.
[19] I believe there are
studies in the published
[20] literature in the
'70s, '60s, perhaps, by
Dow [21] people on the
health effects of 2,4-D
or [22] 2,4,5-T; but I
really — without going
back and [23] looking
through my bibliogra­
phies, I can't say
[24] that for sure.
[25] Q. Let me be clear
that I'm being_________
- Page 133 [I] specific because I
don't want to mislead you
by [2] my question.
[3] A. Yeah.
[4] Q. There have been
or at l e a s t t h e r e ' s
[5] some indication that
we've found in the Dow
[6] Company records that
there was some testing
[7] w i t h r e g a r d to
trichlorophenol and then,
[8] ultimately, TCDD and,
initially, some of these
[9] tests were done on
rabbit ears.
[10] A. Uh-huh.
[II] Q. And at some
p o i n t in t h e 1 960s,
[12] there was some test­
ing on some prisoners at
the [13] Harrisburg Pris­
on with, I believe, TCDD.

SCHULZ, CARL O.
It [14] may have been
trichlorophenol. I can't
recall [15] at this point
in time. [16] My question
is specifically with
[17] regard to testing of
the commercial grade
[18] p r o d u c t 2,4-D,
silvex-[19] A. That's how I
u n d e r s t o o d it. I ' m
[20] familiar with the
dioxins studies, both
[21] published and unpub­
lished.
[22] Q. Okay.
[23] A.
I'm not — at
this point, can't
[24] drag up out of my
memory specifically
[25] commercial formula­
tions, which is, you
know,__________________
- Page 134 [I] how I interpreted
your question to be. I
can't [2] remember wheth­
er I saw some of those.
Whether [3] they pub­
lished any of that, I
don't know.
[4] Q. Okay. We took
this side road. [5] Let's
get back to main branch
here of my [6] initial
question that is that
your opinion that [7] the
exposure to Moyer was
small in '76 and '77
[8] compared to the gen­
eral background exposure
to [9] TCDD? [10] You
were, in that opinion,
[II] specifically focus­
ing on TCDD; correct?
[12] A. Well, no. All of
the c h l o r i n a t e d
[13] dioxins and furans.
B u t if s i l v e x is
[14] contaminated with
dioxins, it's almost
[15] e x c l u s i v e l y
2,3,7,8-TCDD.
[16] Q. All right. And.
how do you make [17] that
judgment? I mean, you've

426

______________________________________

A. WILLIAM ROBERTS & ASSOCIATES

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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

IN
C\j

TF

$

t o l d us t h a t y o u
[18] haven't calculated
any numbers; but how do
you [19] make the general
judgment? What is your
[20 ] knowledge, for exam­
ple, of background expo­
sure [21] to TCDD that
would permit you to ren­
der that [22 ] opinion?
[23] A. Well, I prepared
that report for [24] Mr.
Wagner. In the referenc­
es, I c i t e d s e v e r a l
[25] authors who have
compiled whatever able
data__________________
- Page 135 [ 1 ] t h e y c a n find.
[2] You can actually es­
timate daily [3] intakes
in two ways. You can put
together a [4] list of
all the ways we might be
exposed and [5] anything
you can find on the con­
centration of [6 ] those
things in what we're exp o s e d
to
and
[7] calculate from how
much food we eat, for
[8 ] instance, how much
dioxin we'll ingest every
[9] day. [10] You can
work back the other way
[11] now. If you know
what kind of levels,
[1 2 ] concentrations of
TCDD we carry around in
our [13] body, then you
back calculate to how
much we [14] have to in­
gest every day to achieve
that kind [15] of level
in our tissues. [16] And
so doing it both ways,
you come [17] out with
pretty similar estimates
from a [18] biological
sense. A thousand-fold
difference [19] is not
unusual.
[20] Q.
I think you've
completely befuddled
[2 1 ] me here.
[22] A. Okay.

[23] Q. But let me ap­
proach it this way.
[24] MR. WAGNER: Good
job.
[25] BY MR. SCHULER:
- Page 136 [1] Q. That's your job;
right? Got to [2] have
some humor about this.
[3] A. Just so you're
b e f u d d l e d and the
[4] jury isn't.
[5] Q. If I'm befuddled,
I guarantee you [6] the
jury is. Believe me.
Okay. [7] I'm looking at
your report here [8] that
we've
marked
as
Plaintiff's Number 8, and
[9] you talk about or
mention in this report
five [10] articles that
document daily exposure
of the [11] general popu­
lation to TCDD from envi­
ronmental [12] sources,
and it's primarily the
diet.
[13] A. Uh-huh.
[14] Q. That's based on
ot hers' work. But
[15] from your review of
others' work, you believe
[16] that that's the pri­
mary source of daily
[17] exposure to TCDD,
through the diet?
[18] A. Correct.
[19] Q. And why is that?
[20] A. Well, because
diet -- because TCDD
[21] and related dioxins
a n d f u r a n s t e n d to
[22] accumulate in the
food cycle. They
[23] bioaccumulate and
bioconcentrate.
[24] Q.
Is that from
herbicide use on the
[25] plants, the vegetables and things?_______
- Page 137 [1] A. We don't have a
good understanding [2] of
all the source of dioxin

A. WILLIAM ROBERTS & ASSOCIATES

38

SCHULZ, CARL O.
into the [3] environment.
In a talk given about well, [4] it's been about
three years ago now, by
Curt [5] Travis, who went
through all the identi­
fied [6 ] sources of TCDD
and related dioxins and
furans [7] in the envi­
ronment, he came to the
conclusion [8 ] that if we
— all the known sources
only [9] accounted for
about 5 to 15 percent of
our [10 ] daily known in­
take. [11] So it suggests
to me t h a t t h e r e ' s
[1 2 ] still important
sources of these com­
pounds in [13] the envi­
ronment that we haven't
identified [14] yet. And,
basically, when you go to
the [15] International
Dioxin Conference — I
like to [16] kid about
the source of the year.
Every year [17] you go,
they're discussing some
new
source
of
[18] dioxins and furans
in the environment as
being [19 ] the most im­
portant one. And it is
for a year [2 0 ] or so,
and then we move on to
something else. [21] So I
don't think — I think
[22 ] agricultural use of
pesticides is a very mi­
nor, [23] minor source of
dioxins in the environ­
ment. [24] Essentially,
any time you have chlo­
rine, [25] hydrocarbons
and heat, in almost any
- Page 138 [1 ] combination, the po­
tential exists to form
[2 ] dioxins and furans
and that's where they get
[3] into the environment.
But anyway. [4] So thei
once, t h e y ' r e in t h e
[5] environment, they
move up the food chain.
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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
If [6 ] they're in vegeta­
ble matter, cows graze on
them [7] and so forth. If
they're in plankton and
[8 ] algae, the fish and
aquatic organisms eat
them [9] and so forth.
[10 ] So that the highest
levels
in
the
[1 1 ] environment tend to
concentrate in animal
fat, [1 2 ] which we eat a
lot of. So that part of
our [13] diet, meat,
dairy products. Meat,
especially [14] fish, for
reasons that aren't to­
tally clear to [15] me,
dioxins and furans conc e n t r a t e in f i s h
[16] about three times
the level they do in
[17] terrestrial animal
tissues. [18] So if some­
body has a diet that's
[19] high in fish, they
tend to get even a higher
[ 2 0 ] d a i l y d o s e of
dioxins and furans.
[21] Q.
It's probably
from all those paper
[22 ] mills; right?
[23] A.
A lot of it's
paper mills. That's
[24] a major source.
[25] Q. The-- -------- Page 139 [1] A. Was. Was a major
source.
[2] Q. Okay. The diet
then, what you're
[3] describing, you just
gave me an example of how
[4] TCDD can get in cer­
tain types of-[5] A. Uh-huh.
[6 ] Q.
-- animal life
that we eat; [7] correct?
[8 ] A. Right.
[9] Q.
Okay. The
non-occupational
[10 ] exposures you men­
tion in Paragraph 2 of
your [1 1 ] letter, you say
range from 40 to 240, I
just [1 2 ] want to make

sure I understand this,
pg per [13] day. What is
that?
[14] A. Picograms per
day.
[15] Q . W h a t is a
picogram?
[16] A. Picogram is —
well, it's 10 to the
[17] minus 12th grams.
[18] Q. Okay.
[19] A. It's one trillionth of a gram.
[20] Q. Okay. In any
event,
the diet
[21] source that you're
referring to — well, let
me [ 2 2] strike that.
[23] In Paragraph 2 here,
these 40 to [24] 240
picograms per day, you're
r e f e r r i n g o n l y to
[25] diet or is that from
all sources?___________
- Page 140 [1] A. That's all sourc­
es.
[2] Q. Okay. And of that
all source [3] exposure,
you're saying diet may
be, what, 5 to [4] 15
percent? Is that what
you're saying?
[5] A. No. More like 75
to 80 percent.
[6] Q. So diet is 75 to
80 p e r c e n t of t h e
[7] t o t a l i n t a k e in
general-[8] A. Yes.
[9] Q. -- of TCDD? And
the diet, [10] obviously,
if you're exposed to TCDD
through [11] diet, you're
being exposed after the
[12] consumption of the
food that's going through
[13] y o u r d i g e s t i v e
tract; correct? I mean,
it gets [14] into your
system, I would assume,
t h r o u g h
t h e
[15] digestive tract in
some form; correct?
[16] A. Yes.
[17] Q. Okay. And those

A. WILLIAM ROBERTS & ASSOCIATES

O O

SCHULZ, CARL O.
are e s t i m a t e s t h a t
[18] you're making; cor­
rect? You mention here
from [19] background con­
centrations ; right?
[20] A. These are not
e s t i m a t e s
I'm
[21] making.
[22] Q. Someone else is
making?
[23] A. Yes.
[24] Q. And you're re­
citing here; right?
[25] A. Yes.
- Page 141 [I] Q. Okay. And the 40
to 240 picograms [2] per
day, you state from your
review
of
the
[3] literature, represent
t h e a m o u n t of t h e
[4] compound that is ac­
tually absorbed, as op­
posed [5] to what's taken
in?
[6] A. Correct.
[7 ] Q . A 1 1 r i g h t .
There's
great
[8] variability in that,
isn't there? I mean, the
[9] amount that's ab­
sorbed through diet, for
[10] example, from indi­
vidual to individual?
[II] A. I don't believe
a great [12] variability.
Every biological process
has a [13] lot of vari­
ability; but I don't
think
there
are
[14] distinct classes of
people, some who absorb
and [15] some don't, in
this case. No. I'd say
it's [16] relatively not
variable, based on from
[17] individual to indi­
vidual .
[18] Q. The reason, I
w a s l o o k i n g at y o u r
[19] summary here and
I'll show this to you. In
the [20] s e c t i o n orw
dioxins in tissues, r
think this is [21] in the
— right before the conMICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

V -}W

^
^

elusion section. [22] It
states, there is clearly
a great deal
of
[23] variability among
individuals in how much
[24] dioxin they tend to
absorb and how quickly it
[25] is eliminated from
the body.______________
- Page 142 [I] Would you agree with
that [2] statement?
[3] A. Yes, if-[4] Q. I'm reading from
Plaintiff's 3.
[5] A. Yes. In context,
I agree. I don't [6] feel
that's inconsistent with
what I just said.
[7] Q. Okay. Some people
w h o
a r e
[8 ] unquestionably heavi­
ly exposed to dioxins in
[9] the past have blood
concentrations in the
[10] normal range, where­
as other individuals with
[II] little or no known
exposure have elevated
[12] concentrations.
[13] Do you agree with
that statement?
[14] A. That's correct.
[15] Q. And so my question
is,
it's
[16] difficult to make a
statement as to what a
[17 ] particular individu­
al will retain or absorb
[18] from a given expo­
sure. Is that what you're
[19 ] saying?
[20] A. Yes. I've used
t h e t e r m a b s o r b in
[21] two different things
there. In the latter, I
[22] am describing specifically absorption from
the [23] stomach, for
example, the GI tract;
whereas, in [24] there,
I'm talking in broader
terms
about
the
[25 ] relationship between
environmental

- Page 143 [1 ] concentration and the
amount that gets into the
[2 ] actual system, the
body.
[3] Q. So are you saying
it's
easier
to
[4] predict what's ab­
sorbed from-[5] A. The stomach.
[6 ] Q. -- consumption of
the stomach?
[7] A. Food. Yes.
[8 ] Q.
-- than it is
from e n v i r o n m e n t a l
[9] exposure?
[10] A. Yes.
[11] Q. And what are the
factors that you
[1 2 ] need to look at to
determine absorption from
an [13] environmental
source?
[14] A. Okay.
[15] Q. And we've proba­
bly m e n t i o n e d some
[16] of those already,
but. . .
[17] A. Well, first, of
course, the [18] chemical
and physical form of the
dioxin or [19] furan in
the environmental media
and
even,
for
[2 0 ] example, in the
soil. Mike Gallo and his
group [21] up at Rutgers
did same really interest­
ing [2 2 ] studies, where
different soil types,
when [23] ingested by
rats, you'd absorb more
o r
l e s s
[24] percentage-wise of
the dioxin. [25] I think
the same happens. Dioxin
- Page 144 [1 ] that's inhaled, if
it's absorbed on particu­
late [2 ] matter in the
air, which is the most
common [3] source, would
be less likely to be ab­
sorbed [4] into the body
than if it's free, vola­
tile [5] dioxin in the

A. WILLIAM ROBERTS & ASSOCIATES

40

SCHULZ, CARL O.
air. So the form that
it's in [6] before i
goes into body is impor­
tant. [7] And then in my
conclusion
over
[8] there, that involved
not just absorption, but
[9] also elimination. And
I do think that there's
[10] q u i t e a b i t of
inter-individual vari­
ability in [11] the rate
at which dioxins and
f u r a n s
a r e
[12] eliminated through
the body, where they're
[13] stored.
[14] A fat person, like
me, is going to [15] be
able to pick it up a little b e t t e r than a
[16] skinny guy because
we have more place to put
[17] it.
[18] MR. WAGNER: Skinny
guy, like none [19] of us
here.
[20] BY MR. SCHULER:
[21] Q. Okay. What other
factors involve [22] or
affect absorption, if any
others?
[23] A. Those are the
important ones.
[24] Q. And now getting
b a c k to B o b M o y e r ' s
[25] situation and the
spraying of these chemi­
cals^__________________
- Page 145 [1] A. Uh-huh.
[2] Q. Would it affect
a b s o r p t i o n if h e
[3] wasn't wearing pro­
tective clothing?
[ 4 ] A . Oh , yes , of
course.
[5] Q. Okay.
[6] A.
Well, again,
w e ' r e m i s u s i n g the
[7] word absorption here.
Would that affect, say,
[8] internal dose, is the
word I think we want to
[9] use, the term we want
to use. And, clearly,
MICROCopy

March 5, 1993
MOYER VS . DOW CHEMICAL COMPANY
[10] the internal dose
would be higher if he
wasn't [11] wearing pro­
tective clothing, than it
would be [12] if he was
wearing protective cloth­
ing. Yes.
[13] Q. Maybe we can
look at it this way.
[14] There's the exposure
initially; correct, to a
[15 ] particular chemical?
[16] A. Yes.
[17] Q. And that, in
order to be converted
[18] to what the internal
d o s e is, o n e of t h e
[19] factors is the rate
of absorption, is it not?
[20] A. Yes.
[21] Q. Okay. And that
r a t e of a b s o r p t i o n
[22] can be affected by
the barrier, for example,
[23] whether there's
clothing there or not?
[24] A. Well, okay. To
me, t h e c l o t h i n g is
[25] affecting the expo­
sure.
- Page 146 [1] Q. Okay.
[2] A. The absorption is
o n l y t h e r a t e at
[3] which it goes through
the skin or through the
[4] stomach lining or
through the lung.
[5] Q. All right. I un­
derstand you. So [6] the
absorption is affected,
the
way
you're
[7] interpreting absorption, is the rate at
which [8] it goes through
the skin, the medium that
it's [9] in, as you've
described, the chemical
form that [10] it's in;
correct?
[11] A. Correct.
[12] Q. The condition of
the skin would [13] also
affect that, too, would
it not?
[14] A. Yes, it would.

[15] Q. I mean, if there
was an o p e n w o u n d ,
[16] for example, that
the chemical was exposed
to, [17] as opposed to a
clean skin and healthy
[18] condition, that
would affect absorption
and, [19] subsequently,
dose?
[20] A. Correct.
[21] Q. Do you know
whether Bob Moyer, in
[22] the course of his
spraying either 2,4,5-T,
[23] silvex or 2,4-D, had
any open wounds or sores?
[24] A.
I don't know
whether he did or not.
[25] Q. Would that make
any difference to______
- Page 147 [1] you in your opinion?
[2] A. Not really.
[3] Q. Why not?
[4] A.
Because, as I
said earlier, whether
[5 ] or not he wore pro­
tective clothing is not
[6] important. This expo­
sure was so short term
and [7] so small a quan­
tity that, you know,
we're [8] quibbling over
nets in this little exer­
cise. I [9] feel rela­
tively confident that if
he was bare [10] naked
and had sores all over
h i m a n d d u n k e d his
[11] hand down in the
tank each day he used it
and [12] all, he still -his exposure for the few
days [13] that he used it
over a widely scattered
point, [14] would have
been extremely minimal.
[15] Q. Okay. I just
need to understand.
[16] A. Yeah.
[17] Q. Some of my questions
may
seem
[18] basic.
[19] A. Yeah.
[20] Q.
So now we can

A. WILLIAM ROBERTS & ASSOCIATES

A1

SCHULZ, CARL O.
not only do away with
[2 1 ] the clothing, but
even if we do away with
part [22 ] of the skin, it
still wouldn't affect
your [23] opinion because
the overall amount-[24] A. Amount. Yeah.
[25] Q. -- of the TCDD
was too small, in
- Page 148 [1 ] your opinion, to rise
t o t h e l e v e l of a
[2 ] probable carcinogen
in his case?
[3] A. Correct.
[4] Q. Okay. While we're
at it, I w a n t to
[5] finish this topic.
Are there any other fac­
tors [6 ] that you didn't
mention that may affect
the [7] rate of absorp­
tion and, ultimately, the
dose [8 ] for an individu­
al?
[9] A. Well, as soon as
I say
no,
I'll
[1 0 ] probably think of
one; but I don't think
there [1 1 ] are any others
that are important.
[12] Q.
I know we went
t h r o u g h
this
[13] initially, as far as
the gear that Bob Moyer
[14] had; but did you
make any other assump­
tions? [15] And in talk­
ing about it, you also
talked about [16] the
spray, the form of the
spray. Did you make
[17] any other assump­
tions with regard to con­
ditions [18] under which
Bob Moyer applied either
silvex, [19] 2,4,5-T or
2,4-D?
[20] A. Well, I assumed
t h a t Mr. S w a n s o n ' s ,
[21] Mr. Sassick's recall.
was pretty accurate. ThattDvJ
[2 2 ] the records the
county kept of what was
sprayed [23] when and
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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
what quantities were
used, I assumed [24] they
were pretty accurate.
[25] S o l r e l i e d , I
think, on the__________
- Page 149 [1 ] testimony of a lot of
people, including Mr.
[2] Moyer himself, which
he, you know, admitted
[3] that he wore protec­
tive clothing. He seemed
to [4] have pretty faulty
recall about what he
sprayed [5] when, but
that's not unusual. I
think, at this [6 ] point,
15-year recall would be
-- I w o u l d
find
[7] pretty unreliable for
anybody; but the records,
[8 ] I assumed, were pret­
ty accurate.
[9] Q. Any other assump­
t i o n s or d o e s t h a t
[10 ] pretty much cover
it?
[11] A. That pretty much
covers it.
[12] Q.
Did you have
o c c a s i o n to r e a d ,
[13] other than — and,
incidentally, did you
[14] actually read Bob
Moyer's depositions?
[15] A. No. A summary of
it. I'm sorry.
[16] Q. And did you read
the summaries of [17] all
of the depositions or-[18] A. At one point or
other,
I think I
[19] covered it all.
Ellenburger's and the
other [20 ] ones. I didn't
in preparation for today.
1 [2 1 ] haven't looked at
any of those probably
since I [2 2 ] first re­
ceived them.
[23] Q. The depositions
o f
D r .
[24] Ellenbecker-[25] A. Ellenbecker.
- Page 150 -

[1] Q. -- Dr. Clapp, I
mean,
you
read
[2 ] summaries of those or
not?
[3] A. I can't remember
w h e t h e r -- I t h i n k
[4] they're summaries,
yes.
[5] Q. Did you read the
d e p o s i t i o n s of a n y
[6 ] other people that we
haven't discussed? For
[7] example, the deposi­
t i o n of a n y of t h e
[8 ] defendants' experts
that have been taken to
[9] date? I think it's
Dr. Smith.
[10] A. No.
[11] Q. And Dr. Eaton?
[12] A. No.
[13] Q. And Mr. Nigg?
[14] A. No.
[15] Q. Have you dis­
cussed this case with
[16] any of those people,
any of the other experts?
[17] A. No. No. I have
sent — I have [18] sent
some papers to Kenny
Crump's office.
[19] Q. What papers are
you referring to?
[20] A.
I think I sent
him a copy of this.
[21] Q. Referring to
Plaintiff's 8 , the-[22] A. Yes.
[23] Q.
-- letter of
October 22, 1992-[24] A. Yes. And the
papers.
[25] Q. Hold on a second. We can't talk at
- Page 151 [1 ] the same time.
[2] A. Yes.
[3] Q. The letter of
October 22, 1992?
[4] A. Yes. And the references
cited
[5] therein. I-[6 ] Q. The — I'm sorry.
[7] A. I also sent Kenny
c o p i e s of t h e t w o
[8 ] most recent epidemi­

A. WILLIAM ROBERTS & ASSOCIATES

42

SCHULZ, CARL O.
ology studies done by
Argali [9] and Eriksson
I think Eriksson is the (
first [1 0 ] author on
those, but I don't remem­
ber how it [1 1 ] works.
[12] Q. Anything else?
[13] A. That's all.
[14] Q. To get back to
the
background
[15] exposure to TCDD,
what is the background,
[16] quote/unquote, nor­
mal b a c k g r o u n d T C D D
[17] absorption, I guess,
or r e t e n t i o n in the
[18] average individual?
[19] A. I'd have to look
at that. Well, [20] like
I say here, the range
reported is [21] from .04
— well, I've only fig­
ured it for an [2 2 ] 80
kilogram adult, which was
Moyer's size at [23] that
time. 40 to 240 picograms
per day.
[24] Q. Okay. Is that
intake or what?
[25] A. No. That's the
amount that____________
- Page 152 [1 ] actually gets into
the body.
[2] Q. Into the body?
[3] A. Yeah.
[4] Q. Is that retained
in the body or is [5] it
ultimately eliminated?
[6 ] A. Well, it's elimi­
nated; but so [7] slowly
as to be -- I m e a n ,
that's the daily
[ 8 ] intake; and the
amount that goes out is a
[9] function of how much
is already in the body.
[10] But, generally, we
— even from environmen­
tal [1 1 ] sources, we tend
to intake a little more
than [12 ] we excrete on a
daily basis. So that the
[13] general population's i
concentrations increase
[14] with age. [15] Now,
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March 5/ 1993
MOYER vs. DOW CHEMICAL COMPANY
we seem to be reversing
that [16] in the last
five or ten years, but
that's-[17] Q. Since silvex was
taken
off
the
[18] market? I'm just
kidding.
[19] A. Gosh.
[20] MR. WAGNER: Got to
watch him.
[21] BY MR. SCHULER:
[22] Q. Go ahead.
[23] A.
In a more -y e a h . It's a f a i r l y
[24 ] complex relationship
between what comes in and
[25] what goes out. But,
again, the key important
- Page 153 [1 ] thing here is that
it's very well retained
and [2 ] that the half
life for elimination is
on the [3] order of seven
years or more to clear,
what, [4] half of what is
in us, if we had no more
[5] exposure.
[6 ] Q. Okay. Let me see
if I can get it [7] maybe
into its simplest form
without confusing [8 ] the
issue here myself. [9] If
you take an individual of
a [1 0 ] given age and a
given weight and assuming
that [1 1 ] they live a
normal, American life
style, [1 2 ] without any
undue vices and they
don't work in [13] a-[14] MR. WAGNER: That's
not
a
n o r m a l
[15] A m e r i c a n life.
You've screwed up the
question.
[16] BY MR. SCHULER:
[17] Q. That's right.
T h e y d o n ' t w o r k in
[18] Dow Chemical Plant
or spraying this stuff in
[19] one form of another.
Is there a number that
[20 ] you say that an in­
dividual can be expected

to [2 1 ] test positive to
if you're looking for
retained [22 ] dioxin?
[23] A. Well, I do have
a l o t of d a t a on
[24] what levels are in
people in the normal
[25] population. And people do tend to carry a —
- Page 154 [1 ] even people with no
known e x t r a o r d i n a r y
[2 ] exposure do have mea­
surable body burdens of
all [3] the dioxins and
furans including
2,3,7,8-TCDD. [4] Yes.
[5] Q. Well, I guess
what I'm looking for
[6 ] is, is there a num­
ber, a range of a number?
[7] A. Well, the number,
i t ' s
r e a l l y
[8 ] difficult; but I be­
lieve that NHATS, 1982,
[9] concluded, I think-[10] Q. That N-H-A-T-S?
[11] A. N-H-A-T-S, all
capitals, National
[12] Human Adipose Tissue
Survey, 1982. I think
[13] their geometric mean
TCDD concentration was 7
[14] parts per trillion
in body fat. And I'm do­
ing [15] this from strict
memory. It's setting in
your [16] pile of docu­
ments there somewhere.
[17] Q. And that's with­
o u t r e g a r d to a g e
[18] or. . .
[19] A. As I said, the
relationship with
[2 0 ] age is changing.
Those were all adult or
— I [2 1 ] don't know if
they broke — I'm sorry.
I don't [22 ] know if they
broke those down by age.
Those [23] samples were
more likely heavily
skewed toward [24] the
adult population because
they're
taken
[25] randomly when people

A. WILLIAM ROBERTS & ASSOCIATES

A •?

SCHULZ, CARL O.
have surgery. And I would
- Page 155 [1 ] say a lot more adults
are undergoing surgery
[2 ] than children.
[3] Q. There were stud­
ies d o n e of c e r t a i n
[4] populations, some
Vietnam veterans that
[5] supposedly had been
exposed to Agent Orange
[6 ] with regard to the
TCDD and their body fat;
[7] correct?
[8 ] A. Correct.
[9] Q. And the results
of t h o s e w e r e t h a t
[10] the TCDD was not
found to be elevated be­
yond [1 1 ] the normal
background in that group
as well; [1 2 ] correct?
[13] A. That's correct.
[14] Q. You think that
was
an a c c u r a t e
[15 ] assessment frcro your
review
of
that
[16] information?
[17] A. Yes. Because I
feel th a t the va s t
[18] majority of Vietnam
veterans were not heavily
[19] exposed to phenoxy
herbicides or their diox­
in [20] contaminants. So
if you take one guy,
three [2 1 ] guys, six
guys, who were heavily,
ver. y
h e a v i l y
[22 ] exposed, put them in
a group of people of
[23] hundreds or thou­
sands of people who were­
n't [24] exposed at all,
the average is going to
not [25] look different
than the total popula­
tion.
- Page 156 [1] Q. Wasn't there,
though, a study don«i[32
[2 ] specifically on those
involved in Operation
[3 ] Ranch Hand that sup­
posedly were involved in
i
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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
the [4] distribution of
Agent Orange and still a
normal [5] result?
[6 ] A. No. It's not nor­
mal. There are [7] ranch
handers that do have very
elevated levels [8 ] of
d i o x i n and —
but,
again-[9] Q.
I don't mean to
i n t e r r u p t , b u t I'm
[10 ] not talking about a
couple. I'm talking about
[1 1 ] the overall study.
[12] A.
The overall
study, I think if you
[13] compare all ranch
handers with the compari­
son [14] group, the mean
levels are not statisti­
cally [15] significantly
different, although the
ranch [16] handers do
have higher body burdens
because of [17] these few
guys that are in the —
do have the [18] high
levels. And they're just
a smaller case [19] of
Vietnam veterans in gen­
eral. [20] The population
of t h a t R a n c h H a n d
[21] Study includes, you
know, the pilots and
[2 2 ] co-pilots that came
out of their cushy offi­
cers [23] quarters when
the plane was all loaded
up, [24] climbed up into
cockpit and flew, and all
the [25] herbicide was
behind them. You know,
came__________________
- Page 157 [ 1 ] back, parked the
plane, walked back in.
[2] You know, it includes
a fair number [3] of ad­
ministrative personnel.
It includes [4] people
who were assigned to
R a n c h H a n d for two
[5] years and people who
were assigned for three
[6 ] months. So you have
t h e s a m e k i n d of

[7] distribution of expo­
sure in Ranch Hand cohort
[8 ] as you've got — but,
in general, they had
[9] higher exposure. But
I emphasis, again, that a
[10 ] few of them did have
high levels — do have,
do [1 1 ] have high levels
of dioxin.
[12] Q. In this case, do
you know what the
[13] measurement was for
Bob Moyer's body fat for
[14] retained TCDD?
[15] A. Yeah. It was
less than 5 parts per
[16] trillion.
[17] Q. Of what signifi­
c a n c e is t h a t t o
[18] you, if any?
[19] A. That means that
he's very normal,
[20 ] perhaps below aver­
age.
[21] Q. And where did
you
get
that
[22 ] information from?
[23] A. From the attachm e n t , an e x h i b i t
[24]
with
Dr.
Teitelbaum's deposition.
[25] Q. The Triangle
Lab-- ----------------- Page 158 [1] A. Research or Tri­
angle Labs. Yes.
[2] Q. And do you have
that with you here
[3 ] today?
[4] A. Yes, I do.
[5] Q. Why don't you
p u l l t h a t o u t of
[6 ] there for a second?
[7] A. You've messed up
my wonderful [8 ] order.
There we go.
[9] Q. Do you have it
t h e r e in f r o n t of
[10 ] you?
[11] A. Yes, I do.
[12] Q. Okay. Before I
get into that w i t h
[13] you, I just want to
know that you have that
[14] there. And I also

A. WILLIAM ROBERTS & ASSOCIATES

44

SCHULZ, CARL O.
see that Krumel report
[15] there.
[16] A. Yeah.
[17] Q. I'm going to ask
y o u to k e e p t h a t ,
[18] because I'm going to
ask you some questions
[19] about that, too. I
think you told us about
the [20 ] measurements —
I'm trying to relate your
[21] measurements of 40
to 240 picograms per day
to [22] what — well, I'm
talking about apples and
[23] oranges here.
[24] A. Yeah, you are.
[25] Q. Let me, before
we get into that_______
- Page 159 [1] analysis and the Re­
search Triangle Lab, ask
[2 ] you, do you know or
have an estimate for what
[3] amount of TCDD that
Bob Moyer was exposed to
[4] when he was spraying
chemicals for Orange
[5] County?
[6 ] A.
I have not made
that calculation.
[7] I'll leave that to
Dr. Nick and Dr. Crum.
[8 ] Q. Okay. All right.
That's fair [9] enough.
Have you seen any calcu­
lations that [1 0 ] they
have done?
[11] A. No.
[12] Q. All right. Let's
go to that [13] study.
Where did you see the
measurement,
I
[14] think, of less than,
you said, five parts per
[15] trillion?
[16] A. Okay. It's on
this page here.
[17] Q.
Do you have a
page number there?
[18] A. Page 1 of 2.
[19] Q. Okay. Let me
just-- why don't you
[20 ] take a-[21] A. Got a yellow
sticky?
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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY_________
[22] Q. Yes. Here.
[23] MR. WAGNER: It's
Exh i b i t
10
to
[24] Teitelbaum's Deposi­
tion.
[25] BY MR. SCHULER:
- Page 160 [1] Q.
Why don't you
just tag it?
[2] A. And it says here,
2 , 3 , 7 , 8 - T C D D not
[3] detected. Detection
5.1.
[4] Q.
Okay. Is it un­
u s u a l n o t to d e t e c t
[5] TCDD in an individual
of that age?
[6 ] A. Not unusual.
[7] Q. Okay.
[8 ] A. I'm a little surprised
at
that
[9] detection limit in
this day and age. This is
[10] 1990. It's routine
to have detection limits
of [1 1 ] 1 part per tril­
lion or less. And I'm not
[1 2 ] enough of analytical
chemist to understand
what [13] the problem
with Moyer's sample was,
but five [14] is a fairly
high detection limit to
see on [15] these kinds
of studies now. [16] But
all you can say is that
it's [17] possible he had
a level of five, you
know. [18] Although, typ­
ically, that might show
up as what [19] they call
a trace or a que.
[20] Q. The exposure of
a n i n d i v i d u a l to
[21] TCDD would result —
I mean, if an individual
[22 ] had — let me strike
that. [23] What would you
call a r el a ti v el y
[24] intense exposure?
[25] MR. WAGNER: Object
to form.
- Page 161 [1] MR. LUTZ: Join.
[2] BY MR. SCHULER:

[3] Q. Is it possible
for you to say?
[4] A. What?
[5] Q. Is it possible
for you to say?
[6 ] A. Well, I'm not
sure. The relatively
[7] intense exposures are
those experienced by the
[8 ] people who worked in
the m a n u f a c t u r e and
[9] p r o d u c t i o n of
trichlorophenol, phenoxy
[10 ] herbicides and re­
lated compounds in the
'50s [ 1 1 ] and ' 60s.
That's my definition of
intense [12 ] exposure. I
can't put a number on
that.
[13] Q. Okay.
[14] A. Nobody measured
those levels then.
[15] Q. You can't give
me a n y n u m b e r s on
[16] that, so I'll just
move along. What about
the [17] retained TCDD in
the body fat of some­
thing, [18] let's say,
higher than 5 percent per
trillion. [19] Say 5.5.
What would that signify
to you?
[20] A.
That's still
w i t h i n the r a n g e of
[2 1 ] normal.
[22] Q. What is the
range of normal?
[23] A. I don't really
have a good o p i n i o n
[24] on that. Certainly
up to 10 and maybe rough­
ly [25] as high as 15
parts per trillion would
not be_________________
- Page 162 [1 ] terribly surprising
in an individual with no
[2 ] known occupational or
accidental exposure.
[3] Q. All right. You
a l s o n o t e on t h a t
[4] laboratory result the
fact that there were
[5] other dioxins found;

A. WILLIAM ROBERTS & ASSOCIATES

AC

SCHULZ, CARL O.
correct?
[6 ] A. That's correct.
[7] Q. Or at least mea­
sures taken of other
[8 ] dioxins?
[9] A. Correct.
[10] Q. One was the
heptacholorodibenzo
[1 1 ] dioxin; correct?
[12] A. Correct.
[13] Q. And 41.7 was the
number on that?
[14] A. Correct.
[15] Q. That have any
significance to you?
[ 16 ] A. Not at a l l .
Just, a g a i n , a v e r y
[17] normal guy.
[ 1 8 ]
Q .
Hexacholorodibenzo diox­
in, 20.9, I [19] believe?
[20] A. Well, 20.9 for
1 , 2 , 3 , 6 , 7 ,8 isomer,
[2 1 ] but total hexa was
20.4, other ball park.
[22] Q. Okay. Any sig­
nificance to that?
[23] A. No. Very normal.
[24]
Q .
The
octachlorodibenzo dioxin,
233?
[25]
A. Yeah. That's an
estimated______________
- Page 163 [1] concentration. Actu­
ally, it's a little bit
[2 ] low.
[3] Q. Any significance
to that?
[4] A. No. We all have
—
again, a very,
[5] American profile.
[6 ] Q. So those are not
uncommon [7] measurements
in your view?
[8 ] A.
Not at all. If
anything, he's [9] below
average in total.
[10] Q. And there's no
significance
to
[1 1 ] those measurements
as far as you are con-*
cerned, [1 2 ] other than*
the fact that they're
normal?
[13] A. Yeah, they're
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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
significant -- yeah,
[14] that's all. He's
just — they don't re­
flect [15] any unusual
exposure.
[16] Q. Okay. None of
t h o s e are a m a r k e r
[17] of any particular
exposure?
[18] MR. WAGNER: None of
these levels?
[19] MR. SCHULER: Right.
[20] THE WITNESS: No.
Other than [21] normal
background exposure.
[22] BY MR. SCHULER:
[23] Q. Do you have an
o p i n i o n as to t h e
[24] probable source of
any of those dioxins?
[25] A. Well, I've already addressed________
- Page 164 [1] sources. Many differ­
ent sources, ultimate
[2] sources. His direct
exposure and yours and
[3] mine is mostly in the
diet. How it gets into
[4] the food chain to
begin with, we don't ful­
ly [5] understand.
[6] Q. Do you have any
opinions with [7] regard
to the relative health
e f f e c t s of a n y of
[8] those dioxins in Mr.
Moyer?
[9] A.
I don't think
that these -- I think
[10] that these levels do
not reflect any levels
[11] that suggest concern
for
any particular health
LO
[12]
effect.
CO
[13] Q. Other than your
o p i n i o n that the
[14] chemicals Mr. Moyer
used at Orange County did
[15] not cause his can­
cer, do you have any
opinion [16] as to what
did cause his cancer?
[17] A.
No. We don't
know the ideolog y of
[18] most human cancer

and this odd class of
[19] cancers, referred to
as soft tissue sarcomas,
[20 ] are probably more
poorly understood than
any — [2 1 ] than other
g r o u p s of c a n c e r .
[22] Within this group,
Kaposi sarcoma [23] is a
soft tissue sarcoma and
we
know
it's
[24] associated with
AIDS; but it's not only
caused [25] by AIDS be­
cause it's been around.
Dr. Kaposi_____________
- Page 165 [I ] discovered it long
before we knew about
AIDS. [2] Mesothelioma is
another soft tissue sar­
coma. [3] That's caused
by asbestos. [4] But by
and large, the rest of
the [5] soft tissue sar­
comas, we have not iden­
tified [6 ] specific caus­
es for. Which is true of
most [7] cancers. I mean,
if we understood what
caused [8 ] them and un­
derstood how they hap­
pened, the [9] mechanism,
then we'd probably be
able to cure [10 ] them.
[II] Q. Well, in terms
of causes of cancer,
[1 2 ] I mean, you don't
have to understand abso­
lutely [13] the mechanism
in order to determine
that [14] something caus­
es cancer, do you?
[15] MR. WAGNER: Object
to form.
[16] MR. LUTZ: Join.
[17] THE WITNESS: Well,
I'm going to [18] get up
on my soapbox here a lit­
tle bit. I [19] think
there's too much speculation
about
the
[20 ] mechanism of cancer
induction, with too lit­
tle [2 1 ] scientific, fac­
t u a l b a s i s f o r it.

A. WILLIAM ROBERTS & ASSOCIATES

46

SCHULZ, CARL O.
[22] In answer to your
question, [23] directly,
no, you don't have to
understand
the
[24] mechanism to know
whether something causes
[25] cancer or not.
- Page 166 [1] BY MR. SCHULER:
[2 ] Q. I mean, I understand —
to t a l k
[3] about a different
issue. I mean, the tobac­
co [4] companies still
deny that their product
causes [5] lung cancer.
[6 ] A. Uh-huh.
[7] Q. But you wouldn't
agree with that,
[8 ] would you?
[9] A. I would not agree
with that.
[10] Q. Okay.
[11] A. I would agree
w i t h the s t a t e m e n t
[1 2 ] that tobacco smoke
doesn't cause all lung
[13] cancer and that
there is lung cancer out
there [14] of unknown
ideology. And even some­
thing that [15] we know
so well as that, there
are cases of [16] lung
cancer. [17] I had a very
good
f r i e n d die
[18] recently of lung
cancer. She never smoked,
[19] wasn't the type that
could, smoke. Never lived
[2 0 ] with anybody that
could smoke, that would
[21] smoke. It's a com­
plete mystery.
[22] Q. Just lived next
to a D o w C h e m i c a l
[23] Plant.
[24] MR. WAGNER: Now,
now.
Don't
get
[25] tired. Keep your
guard up.
- Page 167 [1] THE WITNESS: That's
right.
[2] BY MR. SCHULER:
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March 5, 1993
MOYER V S . DOW CHEMICAL COMPANY
[3] Q.
You mentioned
mesothelioma
on
[4] another issue. Have
you ever testified in any
[5] asbestos cases?
[6 ] A . N o . But I 've
w r i t t e n the b o o k on
[7] it.
[8] Q. Okay. What is the
name of that [9] book?
[10] A.
It's SILICONE
AND
SILICATES,
[11] INCLUDING ASBESTOS;
and
it's
in t h e
[12] not-yet-published
f o u r t h e d i t i o n of
Patties' [13] Industrial
Hygiene and Toxicology.
[14] Q. And when is that
g o i n g
to
be
[15] published?
[16] A.
Probably later
this year. I've [17] just
r e c e i v e d the g a l l e y
proofs this week.
[18] Q. Is that another
area w h e r e you have
[19] expertise, the as­
bestos area, in terms of
its [20] relationship to
causing mesothelioma?
[21] A. Yes. I'd say the
area
of
fiber
[22] toxicology, of which
asbestos is a subcatego­
ry.
[23] Q. But you haven't
testified-[24] A. No.
[25] Q.
-- before any
committees or__________
- Page 168 [1] anything of that
nature-[2] A. There is no sci­
ence in that.
[3] Q.
No science in
t e s t i f y i n g or no
[4] science in-[5] A. Well, that too;
but there's. . .
[6] Q. Does TCDD have an
effect on the [7] immune
system, in your view?
[8] A.
In experimental
a n i m a l s , T C D D has

[9] quite potent effect
on the immune system,
yes.
[10] Q. What about in
humans?
[11] A. There is no evi­
d e n c e , no c r e d i b l e
[1 2 ] evidence that I've
seen that TCDD exposure
[13] alters immune func­
tion or status in humans.
[14] Q. Can you extrapolate
the animal
[15] studies to humans in
this instance?
[16] A. Well, I think
you can. I mean, I'm
[17] basically an animal
toxicologist, and I have
a [18] certain degree of
faith in the predictabil­
ity [19] of data we get
in certain animal stud­
ies. And [20] I believe
that 2,3,7, 8 -TCDD and
related dioxins [2 1 ] and
furans probably can somehow
affect
the
[2 2 ] immune system in
humans, but I've seen no
[23] verifying evidence
of that in studies of
[24] humans.
[25] Q.
I'm sorry. I
didn't hear the last
- Page 169 [1 ] part of your answer.
[2] A. I've seen no veri f y i n g e v i d e n c e of
[3] that in studies of
exposed humans.
[4] Q. Let me ask you to
refer to that [5] Krumel,
Krommel, I'm not sure how
it's [6 ] pronounced at
this point, memo.
[7] A. I don't either.
[8 ] Q. Okay.
[9] A. I've got it here.
[10] Q.
Okay. We've
marked that an exhibit
[1 1 ] to other deposi­
tions. I don't think
there's [1 2 ] any tag on
that one, but I don't
think there's [13] any

A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
n e e d t o m a r k it.
[14] Have you reviewed
the memorandum?
[15] A.
I've gone
through it superficially,
[16] yes.
[17] Q. Does that memo­
randum indicate that
[18] with respect to
2.4- D that there were any
[19] chloracnegenic ele­
ments discovered in 2,4-D
in [20 ] your opinion?
[21] A. In my opinion,
there's a reference
[2 2 ] to the fact that
there are chloracnegenic
[23] materials in process
materials, and I think
[24] that's waste, of the
2.4- D manufacture
[25] process. There's
nothing in here that di­
rectly________________
- Page 170 [1 ] tells me there are
chloracnegens in the
2.4- D [2] produced by
this process.
[ 3 ]
Q .
What
chloracnegens are re­
ferred to [4] in that
memorandum that you con­
sidered?
[5] A. Well, he doesn't
— he identifies [6 ] two
component -- or they
i d e n t i f y
two
[7] components of the
mix, which I think they
[ 8 ]
a t t r i b u t e
chloracnegenic potential
to; and I [9] don't agree
with that.
[10] Q. What are the
elements?
[11] A.
Th e y are
1 ,3, 6 , 8 -tet r a c h l o r o
[1 2 ] xanthone and 1 , 1
primed 3, 3 prime, 6 , 6
[13] prime, 8 , 8 prime,
octachloro, 9, 9 prime,, q p
[14 ] spirobixanthene. 4 o b
[15] Q. Okay. You don't,
agree
with
his
[16] assessment that
J
_______________________________________

47

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
those by-products are
acne is a marker [23] of
[17] chloracnegenic?
heavy dioxin exposure,
[18] A. That's correct.
but's it not entirely
[19] Q. Why not?
[24] reliable.
[20] A. Well, they're
[25] BY MR. SCHULER:
not of the structural
- Page 172 [2 1 ] type, the geometric
[1 ] Q- Is there any sigshape to be in the group n i f i c a n c e to y o u ,
of [22 ] compounds that we
[2 ] from your review of
know from structure ac­ the literature — well,
tivity [23] relationships let [3] me strike that.
cause chloracne.
[4] Is there any pattern
[24] Q. Are there any that you've [5] noticed,
other by-products
in your review of the
[25] identified in that
literature, with
report as chloracnegenic?
[6 ] regard to cancer cau­
- Page 171 sation as to whether it's
[1] A. I don't think so. [7] related to evidence
I found this [2 ] report of chloracne? [8 ] Let me
extremely difficult to j u s t c a n t h e w h o l e
understand.
[9] question. Let me ask
[3]
Q.
The two
it this way. [10] Is
by-products that you
chloracne a marker, a
[4] mentioned just now,
potential [1 1 ] marker of
do you believe those
an exposure sufficient
[5] b y - p r o d u c t s are
enough to [12 ] cause can­
immunotoxic?
cer?
[6 ] A.
I have no basis
[13] MR. WAGNER: Object
to say yes or no. [7] I to form.
believe they're not,
[14] THE WITNESS: I have
again,
b a s e d on
to give [15] probably a
[8 ] structure activity pretty long-winded answer
principles.
to that. [16] Chloracne
[9] Q. Do you believe
is a pretty good indica­
that by-products are
tor that a [17] person is
[10 ] carcinogenic?
at an increased risk of
[11] A._ I have no factu- cancer. The [18] absence
al b a s i s ,
other
of chloracne provides no
[1 2 ] than, again, from assurance that [19] the
structure activity
person won't get cancer.
[13] relationship consid­ Is that clear?
erations. I think not.
[20] BY MR. SCHULER:
[14] Q. May I see that
[21] Q. I understand.
m e m o r a n d u m just for
[22] A. That helps you.
[15] one second?
[23] Q. Any answer you
[16] A. Uh-huh.
h a v e to t h i n k a b o u t
[17] Q. Is chloracne, in
[24] doesn't help me.
your
opinion,
a Okay.
[25] THE COURT REPORTER:
TO [18] marker of relatively
intense exposure to TCDD?
Is this a good
[19] MR. WAGNER: Object
- Page 173 to form. Marker [20] is
[1 ] place for a break?
unclear and relatively
[2] MR. SCHULER: Yes.
intense is unclear.
We've been [3] going for
[21] MR. LUTZ: Join.
about an hour and a half.
<\ [22] THE WITNESS: Chlor­
A. WILLIAM ROBERTS & ASSOCIATES

48

SCHULZ, CARL O.
[4] (A r ecess t r a n ­
spired. )
[5] BY MR. SCHULER:
[6 ] Q . Was there any­
thing in the medical
[7] history of Bob Moyer
that you saw that was
[8 ] significant to you
from exposure point of
view?
[9] A. No. Well, in med­
ical history, [10 ] there
was one thing that raised
questions and [1 1 ] that
was the fact that he
w o r k e d with the
[12 ] cutting oil at the
aircraft factory. I think
[13] that was subsequent
to — I can't remember.
[14] Whenever he worked
there.
[15] Q. Do you know what
kind of cutting [16] oil
he worked with?
[17] A. No.
[18] Q. It would make a
difference, [19] wouldn't
it?
[20] A. To some degree.
Although, I [21] disagree
with Teitelbaum that it's
only certain [22 ] kinds.
Almost all cutting oils
are [23] carcinogenic in
experimental animals,
except [24] the newer
ones that have been spe­
cifically [25] designed
to make them not.
- Page 174 [1] Q. And so the only
significance would
[2 ] be, potentially, he
was w o r k i n g with a
[3] substance that could
be carcinogenic in hu­
mans, [4] in your view?
[5] A. Yes. But I don't
—
I think that
[6 ] probability is low,
also. Certainly the type
[7] of cancer he had
would probably not be
[8 ] associated with that
exposure either.
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[9] Q. That was going to
be my next [10] question.
Has cutting oil been
linked to a [11] soft
tissue sarcoma?
[12] A. Not to my knowl­
edge, no.
[13] Q. Anything else in
his medical [14 ] history
that was significant from
an
e x p o s u r e
[15] standpoint, in your
view?
[16] A. No. He generally
seemed
to
be
a
[17] healthy, moderately
clean living individual.
[18] Q. Did you have an
o p p o r t u n i t y to see
[19] any of the videotape
deposition that was taken
[20] of Mr. Moyer?
[21] A. No, I did not.
[22] Q. Anything else
a b o u t his m e d i c a l
[23] history that was
significant to you in any
way?
[24] A. No.
[25] Q. What about his
living history?________
- Page 175 [1] Anything in his liv­
ing his tory that was
[2] significant to you,
other than the fact that
he [3] sprayed the chemi­
cals for Orange County?
When [4] I say living
history, I'm talking
about [5] locations,
where he was born and
raised, that [6] type of
thing.
[7] A.
No, no. I don't
think anything [8] there
was particularly notewor­
thy. He smoked, [9] but I
think briefly.
[10] Q. Well, I was go­
i n g to g e t to t h a t
[11] under personal hy­
giene .
[12] A. Okay.
[13] Q.
I'm just now
talking about--

[14] A. No. His living
h i s t o r y ,
his
[15] parents, there was
familia cancer; but it
was [16] not — that's
not the kind that would
[17] genetically predis­
pose him to cancer.
[18] Q. Okay. Other than
the cutting oil [19] that
you mentioned, anything
else
about
his
[20 ] employment history
that would be significant
to [2 1 ] you?
[22] A. Not that I saw.
[23] Q. Anything about
his personal habits,
[24] hygiene history, I
c a l l it, t h a t w a s
[25] significant to you?
- Page 176 [I] A. Well, he smoked;
but I think [2 ] briefly
and at a fairly low lev­
el. And, again, [3] I
don't think soft tissue
sarcoma is one of the
[4] smoking cancers.
Again, it's hard to say
since [5] soft tissue
sarcoma is a poorly de­
fined [6 ] category.
[7] Q. You mentioned,
j u s t a m o m e n t ago,
[8 ] that you had dis­
a g r e e d w i t h Dr.
Teitelbaum and [9] one of
the statements he made, I
guess, about [1 0 ] the
cutting oil.
[II] A. Uh-huh.
[12] Q. One of the areas
that I have been
[13] told that you are
going to testify about is
[14] potential rebuttal
t e s t i m o n y to Dr.
[15] Teitelbaum. Based on
y o u r r e v i e w of h i s
[16] deposition or -well, I guess you had the
full [17] deposition for
him. [18] Based on your
review
of
his
[19] deposition, what

A. WILLIAM ROBERTS & ASSOCIATES

AQ

SCHULZ, CARL O.
comments or criticisms do
you [20 ] intend to offer
in this case with regard
to his [2 1 ] testimony?
[22] MR. WAGNER: And I
told
you,
it's
[23] purely preliminary
at this point since we
[24] haven't finished Dr.
Teitelbaum.
[25] MR. SCHULER: I un­
derstand.
- Page 177 [1] THE WITNESS: That's a
p r e t t y
b r o a d
[2 ] question.
[3] BY MR. SCHULER:
[4] Q. I understand. But
I mean, I'm [5] trying to
-- you know, I mean,
there's 300 and [6 ] some
odd pages of testimony.
And the [7] alternative
is to go through it line
by line. [8 ] I thought we
might focus—
[9] A. All right. Well,
m y
o v e r a l l
[ 1 0 ] i m p r e s s i o n is
that-[11] MR. WAGNER: Before
you start [ 1 2 ] that.
Frankly, I told him —
and I don't mind [13] him
answering. He can take
care of himself. [14] But
I told him to focus on
h i s o t h e r a r e a s in
[15] preparing for this
deposition, as opposed to
[16] doing a line-by-line
a n a l y s i s t h a t I do
[17] contemplate at some
future point, once it's
[18] finished. [19] But
with that in mind, go
ahead [20 ] and — he has
reviewed Teitelbaum, and
he has [2 1 ] told me, at
least, what his general
criticisms [22] are. And
feel free to respond to
the question.
[23] THE WITNESS: My.
overall impression
[24] w a s t h a t Dr.
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

Cî
CO
^

^

Teitelbaum did not have a
good [25] grasp of the
entire body of the avail­
able
- Page 178 [1] information. He used
information available to
[2] him very selectively
to pull documents and
even [3] statements in
documents out of context
that [4] supported his
performed opinion.
[5] BY MR. SCHULER:
[6] Q. And what, specifically,
are you
[7] referring to there?
[8] A. Well, I'm refer­
r i n g to his h e a v y
[9] reliance, for exam­
ple, on the studies of
[10] H a r d e l l and
Eriksson, to the exclu­
sion of [11] others. And
his — oh, I can't even
come up [12] with specif­
ic examples, but — well,
I'm having [13] trouble
recalling specific exam­
ples. [14] Again, I'm
talking about general
[15] impressions; and
I'll be prepared at some
later [16] date to ad­
dress specific issues.
[17] So then he — I felt
he was__[18] careless in
referring to evidence
relevant only [19] to
non-Hodgkin's lymphoma,
as r e l e v a n t t o a
[20] possible causal as­
sociation between com­
pounds [21] and soft tis­
sue s a r c o m a . [22] I
thought he was careless
a
b
o
u
t
[23] differentiating be­
tween phenoxy herbicides
[24] likely to be contami n a t e d
w i t h
tetrachlorinated [25] and
higher dioxins from those
that were
- Page 179 -

[1] unlikely to be. And
just in balance, not a
[2 ] very credible or ex­
pert witness.
[3] Q. Okay. I mean, I
understand
that
[4] you're probably not
fully prepared on this;
but [5] the credibility
and the grasp and so
forth are [6 ] opinions.
What I'm looking for is
specifics [7] and you
gave me the issue of re­
lying on the [8 ] Hardell
studies. I assume, from
your statement [9] there,
that you don't think the
Hardell studies [10] are
very credible either?
[11] A.
I just think
that they have some
[12 ] severe limitations,
that are p o t e n t i a l
[13] explanation for why
these few studies appear
to [14] be inconsistent.
And I emphasis the word
[15] appear. Appear to be
inconsistent with the
[16] overall body of evi­
dence.
[17] Q. Are you familiar
with the —
and I
[18] brought a copy with
me here today, and I
[19] discussed this with
Dr. S m i t h in h i s
[20] deposition. Are you
familiar with this EPA —
[21] and I have September
of 1992. I don't even
[2 2 ] know whether it's
been revised since then
or [23] not, but this
preliminary review draft
of [24] epidemiology in
human data on dioxin?
[25] A. No, I haven't
gotten a copy of that
- Page 180 [1 ] yet. I know the pro­
cess is going on.
[2] Q. Did you have any
input
into this
[3] process?

A. WILLIAM ROBERTS & ASSOCIATES

50

SCHULZ, CARL O.
[4] A. Extremely little.
We talked about [5] it at
the dioxin conference a j
year and a half [6 ] ago
in Raleigh, but I had no
formal involvement
[7] whatsoever.
[ 8 ] Q.
Do you k n o w
Charles Pool or David
[9] Balitz of Stephen
Baird, who they cite here
as [10 ] people that put
this together?
[11] A. Yes.
[12] Q. And what is your
k n o w l e d g e of th e m ,
[13] as far as-[14] A. Well, they're
all r i s k a s s e s s o r s
[15] that have worked in
the Office of Health
[16] Effects at EPA for a
number of years. They, in
[17] this particular ex­
ercise, are primarily
[18] reporters or compil­
ers of data. The key
[19] decisions on what's
going on, they're being
[2 0 ] made by people on
the committee.
[21] Q. Well, let me ask
you
about
the
[22] process then. And if
you don't know, tell me.
[23] A. Uh-huh.
[24] Q. I don't want you
to s p e c u l a t e .
I
[25] mean, are these peo­
ple that put together
this
- Page 181 [1 ] report reporting to a
committee who is going to
[2 ] make the final adop­
tion or take the final
[3] stance with regard to
d i o x i n ? Is that the
[4] function of this re­
port?
[5] A. Yes. And that is
a draft. The [6 ] history
of the situation is that
the pulp and [7] paper
industry in the United
S t a t e s has t a k e n
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
[8] every possible avenue
or recourse possible to
[9 ] atte mpt to get a
stamp of authoritative
[10] approval on their
position that dioxin is­
n't as [11] bad for you
as everybody says it is.
[12] And their lobbying
paid off with [13] the
EPA about four years ago,
t h r e e y e a r s ago,
[14] when EPA said, we
will re-review the risk
[15] assessment and evi­
dence for dioxin in hu­
mans. [16] And this is an
interim product of that
process.
[17] Q. So the pulp and
p a p e r m a k e r s , is
[18] that what you're
saying, initiated a pro­
cess [19 ] to:—
[20] A.
Get EPA to re­
co n s i d e r their risk
[21] assessment for diox­
in. And so this whole
[22] process is taking
p l a c e v e r y m u c h in a
[23] fishbowl.
[24] Q. You haven't seen
this report yet?
[25] A. No, I haven't.
- Page 182 [1] Q. So it wouldn't do
me any,good to [2] ask
you if you agree or disagree
with
the
[3] conclusions; is that
correct?
[4] A. That's correct.
[5] Q.
And if this re­
port also placed
[6] r e l i a n c e on Dr.
Hardell's studies, would
you [7] feel that these
people were also careless
in [8] their analysis?
[9] A. I didn't say you
c a n ' t r e l y o n Dr.
[10] Hardell's data. I
say you can't take them
[11] exclusively and, in
the w h o l e w e i g h t of
[12] evidence, they just

don't carry much weight.
[13] Q. Are you familiar
w i t h t h e s t u d y by
[14] Ling in Denmark?
[15] A. Yes, I am.
[16] Q. And do you con­
s i d e r t h a t to be a
[17] credible study?
[18] A. Not very. It's
what's
called
a
[19] r e c o r d linkage
study, which is one of
the [20 ] weakest types of
epidemiologic studies you
can [2 1 ] do.
[22] Q. Are you familiar
w i t h t h e s t u d y by
[23] Manz, M-a-n-z, from
Germany?
[24] A. Yes. That's in
my pile.
[25] Q.
Okay. Do you
think that's a_________
- Page 183 [1 ] credible study?
[2] A. Yes. Fairly. I
mean, again, these
[3] are all degrees. It
has flaws. It's a pretty
[4] good study.
[5] Q. And I think you
mentioned before [6 ] the
Fingerhut, IOSH as it's
called,
study;
[7] correct?
[8 ] A. Yes.
[9] Q. And you do you
c o n s i d e r t h a t to be
[10 ] credible, also?
[11] MR. WAGNER: Object
to form.
[12] THE WITNESS: I cons i d e r it t o . b e a
[13] pretty good study. I
have some problems with
[14] it. They cut the
cohort in size after the
[15] study was underway.
That's never been
[16] satisfactorily ex­
plained.
[17] BY MR. SCHULER:
[18] Q. One of conclu­
sions that they make
[19] in this study is
that of all the cancers

A. WILLIAM ROBERTS & ASSOCIATES

ei

SCHULZ, CARL O.
[2 0 ] examined in both
case c o n t r o l and
follow-up [2 1 ] studies,
soft tissue sarcoma pro­
vides the [22 ] strongest
evidence of an associa­
tion with [23] T C D D .
[24] Do you disagree with
that?
[25] MR. WAGNER: Object
to form.
- Page 184 [1] MR. LUTZ: Object to
the form.
[2] THE WITNESS: I don't
fully [3] subscribe to
that statement. As I said
[4] earlier, I think that
TCDD — the evidence is
[5] that TCDD causes can­
cer at many different
[6 ] sites. And to say
that the evidence is
[7] stronger for one or
another is playing a lit­
tle [8 ] fast and loose
with the data. But I've
never [9] said, today,
that I don't think that
TCDD [10] doesn't cause
or isn't associated with
soft [1 1 ] tissue sarcoma.
That's a given.
[12] BY MR. SCHULER:
[13] Q. They state, in
their conclusions in
[14] this report, that
the original report by
[15] Hardell and col­
leagues of an association
[16] between soft tissue
sarcoma and exposures
[17] involving TCDD con­
taminated phenoxy herbi­
cides [18] have stood up .
to extensive criticism y ,"
and a [19] great deal of subsequent research.
[20] Do you agree with
t h a t or d i s a g r e e
[21] with that?
AA
[22] MR. WAGNER: O b j e c t U
to form. Would [23] you
identify the page, so we
can
-you're
[24] reading a sentence

i>r

MICROCopy ■s

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

*3*

out of a lengthy text.
And [25] since he's never
seen the text, it's dif­
ficult________________
- Page 185 [1] for him to even say
whether it's in context
or [2] out of context.
That's the basis of my
[3] objection.
[4] MR. LUTZ: I join.
[5] BY MR. SCHULER:
[6] Q. This is page 7-39
o f t h e r e p o r t of
[7] September 10, 1992,
review draft, United
States [8 ] Environmental
Protection Agency, Chapt
e
r
7
,
[9] epidemiology/human
data. And I'm reading
from [10] that page vir­
tually the entire first
paragraph [11] of the
c o n c l u s i o n section.
[12] Want me to read back
that sentence [13] that
I-[14] A. Yes, please.
[15] Q. Okay. What I
read
from here,
[16] referred to here is
that the conclusion of
the [17 ] folks that put
this draft together were
that [18] the original
report, by Hardell and
colleagues [19] of an
association between STS
and
expos u r e s
[20] involving TCDD con­
taminated phenoxy herbi­
cides [21] have stood up
to extensive criticism
and a [22] great deal of
subsequent research.
[23] And my question was,
would you [24] agree with
that conclusion?
[25] MR. WAGNER: Object
to form. Same
- Page 186 [1] problem.
[2] MR. LUTZ: Same objec­
tion.

[3] THE WITNESS: I can't
agree to that [4] in toto. I would not word it
that way.
[5] BY MR. SCHULER:
[6] Q. Would you think
that conclusion [7] would
be careless or not very
credible?
[8] MR. WAGNER: Object to
the form. [9] Compound
and vague.
[10] MR. LUTZ: I object
to the form; [11] but,
also, no predicate.
[12] THE WITNESS: As
worded,
I don't
[13] think that conclu­
sion is supported by the
[14] evidence.
[15] BY MR. SCHULER:
[16] Q. And they go on
to say, in the n e x t
[17] sentence in the same
first paragraph on the
[18] same page, the de­
gree of increased risk,
as [19] estimated in lat­
er studies by Hardell's
[20] research group and
several others, does not
[21] appear to be as
great as originally indi­
cated, [22.] but the asso­
ciation with TCDD expo­
sure appears [23] more
certain. [24] Would you
agree with that
[25] conclusion?_______
- Page 187 [1] MR. WAGNER: Object to
the form. [2] And, also,
that seems to be directly
contrary [3] to the sen­
tence you read two sec­
onds ago that [4] says
that their work had with­
stood scrutiny. [5] But
my same problem, reading
from this review
[6] draft, not even fi­
nal, and a document that
he [7] hasn't reviewed.
[8] MR. LUTZ: Join.
[9] THE WITNESS: That
particular [10 ] sentence

A. WILLIAM ROBERTS & ASSOCIATES

52

SCHULZ, CARL O.
doesn't make any sense.
[11] BY MR. SCHULER:
[12] Q. Finally, they
say that moreover no
[13] persuasive case has
been made that the en­
tirety [14] of the asso­
ciation in these studies,
referring [15] to the
Hardell studies, is due
to selection [16] bias,
differential exposure,
misclassification,
[17] confounding, or
change. [18] Would you
agree with that
[19] conclusion?
[20] MR. WAGNER: Same
objection. Also,
[2 1 ] that is a conclusion
t h a t is v a g u e a n d
[22 ] ambiguous as to its
meaning.
[23] MR. LUTZ: Join.
[24] THE WITNESS: That's
really a [25] funnily
worked statement. They're
essentially____________
- Page 188 [1 ] admitting the recall
bias, which is one of the
[2 ] serious flaws of the
Hardell studies is -[3] they're saying, it's
there, it's just not bad
[4] enough to account
for. Which is the weakest
[5] d e f e n s e of t h e
Hardell study I've heard.
[6 ] BY MR. SCHULER:
[7] Q.
So you don't
agree
with
that
[8 ] statement, I take it?
[9] A. Well, actually-[10] MR. WAGNER: Same
objection.
[11] THE WITNESS: -- I
agree with [1 2 ] elements
of it, but I wouldn't —
it's really [13] twisted
logic.
[14] BY MR. SCHULER:
[15] Q. Not careless or
very credible?
[16] MR. WAGNER: Object
to the form.
MICROCopy

[17] THE WITNESS: I'll
reserve. Won't [18] use
those words.
[19] BY MR. SCHULER:
[20] Q. The other stud­
ies t h a t w e r e c i t e d
[21] in this report I
mentioned. We have dis­
cussed [22] the Fingerhut
study.
[23] A. Uh-huh.
[24] Q. And they mention
the Sevaso study,
[25] and we discussed —
which I don't think we
- Page 189 [1 ] discussed here today.
The IARC Registry cohort
[2] study and the New
Zealand sarcoma study.
[3] A. Uh-huh.
[4] Q.
Those are all
s t u d i e s that y o u ' r e
[5 ] familiar with; cor­
rect?
[6 ] A. Yes.
[7] Q. Were any outside
consultants [8 ] involved
in the preparation of
this, if you [9] know?
[10] A.
I don't know
a b o u t
outside
[1 1 ] consultants.
[12] MR. WAGNER: You
mean,
non-EPA
[13] employed people?
From outside?
[14] MR. SCHULER: Yes.
[15] THE WITNESS: I think
— it's a [16] committee
headed by Linda Bumbaum,
and I think [17] the mem­
bers are from — they're
all from [18] government
a g e n cies. Although,
whether they're [19] all
just from EPA or not, I
can't recall. [20] Isn't
there, up at the front —
of [2 1 ] course, that's a
volume of other volumes.
[22] Isn't there a list
of the committee members
in [23] the first few
pages?
[24] BY MR. SCHULER:

[25] Q. Not that I see.
But the three__________
- Page 190 [1] people that are list­
ed are the ones-[2] A.
It's because
that's Chapter 7. I'm
[3] sure that if there's
a Chapter 1, it'll be in
[4] there. My recollec­
tion is that it's people
[5] from several differ­
ent offices of EPA and,
[6] possibly, people from
NIEHS, the N a t i o n a l
[7] Institutes of Envi­
ronmental Health Sciences
are [8] involved in that
overall.
[9] MR. WAGNER: Since
we've read from [10] that
so much and referred to
it, let's — you [11] can
keep your hard copy, but
I'd like a copy
[12] sooner or later.
[13] MR. SCHULER: Sure.
[14] MR. WAGNER: And
let's make it a [15] part
of this. I just note,
specifically on the
[16] front, it says: Do
not quote or something.
[17] What does it say?
[18] MR. SCHULER: Do not
cite or quote.
[19] MR. WAGNER: Do not
cite or quote. [20] Since
we're citing and quoting
that, let's get [21] a
copy of it for the re­
cord.
[22] MR. LUTZ: Join. That
may be a [23] felony or
something.
[24] MR. SCHULER: Proba­
bly wouldn't be [25] the
first one I've committed.
We'll go ahead
- Page 191 [1] and mark it as the
next exhibit. Go ahead
and [2] put a sticker on
it. I'll furnish every­
body a [3] copy of it.

A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
[4] (DFT. EXH. 12, EPA
Draft
Document,
[5] Chapter 7, September
1992, was [6 ] marked for
identification.)
[7] BY MR. SCHULER:
[8 ] Q. Have you heard of
the Syracuse [9] Research
C o r p o r a t i o n because
t h e y ' r e l i s t e d in
[10 ] here?
[11] A. Yes, I have.
[12] Q. What do you know
abo u t the S y r a c u s e
[13] Research Corpora­
tion?
[14] A. They're a con­
sulting firm.
[15] Q. Similar to the
one that you w e r e a
[16] member of?
[17] A. Yes.
[18] Q. Do you know any
p a r t i c u l a r
[19] individuals at that
firm?
[20] A.
I doubt if I
know anybody who's
[2 1 ] there now. I can't
even remember who I used
to [22] know there. I'm
not even going to say his
name [23] because I don't
know how to spell, but I
used [24] to know some
people there. I don't
know if [25] they still
work there. I've not done
any work
- Page 192 [1 ] with them ever.
[2] Q. Are they in Wash­
ington or are they [3] in
Syracuse, New York?
[4] A. Well, they have
offices
in b o t h
[5] places. Their head­
quarters is Syracuse, New
[6 ] York.
[7] Q. Are they associated
with
the
[8 ] university there? Do
you know?
[9] A.
I supposed that ,
in t h e i r o r i g i n a l
[10] history, like Stan-

442

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

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MOYER vs. DOW CHEMICAL COMPANY

'7 75

CO

k

cV

ford Research Institute,
they [11] were probably
founded by university
faculty; [12] but to the
best of my knowledge,
they're not [13] now af­
filiated.
[14] Q. Do you know-[15] A. It's a private
company.
[16] Q. Do you know Carol
H a y n e s ,
[17] environmental crite­
ria and assessment offi­
cer, [18] apparently?
[19] A. No.
[20] Q. Who worked on
this
as p r o j e c t
[21] officer?
[22] A. No.
[23] Q. And it's an ac­
curate statement that
[24] you have never read
or seen this report be­
fore?
[25] A. I've never seen
that.__________________
- Page 193 [I] Q. Have you seen any
other sections of [2] the
dioxin report that -it's a b o u t e i g h t or
[3] nine volumes, I think
with that?
[4] A.
No, I haven't
seen any of them that
[5] have been -- the
whole process has been
[6] somewhat contained
because of the political
[7] sensitivity.
[8] Q.
Do you know how
long these volumes
[9] have been available?
I assume they've been
[10] available since Sep­
tember of '92.
[II] A.
That's not a
good assumption. The
[12] date on there does­
n't typically reflect —
[13] there's typically
about a three to six
month [14] lag. So it's
probably been available
since the [15] end of

last year, three months
ago or four [16] months
ago.
[17] Q. I assume you're
g o i n g to get it and
[18] review it?
[19] A. Going to try.
[20] Q.
It is in your
area of expertise?
[21] A. Right.
[22] Q. One of your ar­
e a s of e x p e r t i s e ;
[23] right?
[24] A. Right.
[25] MR. WAGNER: I'm going to hold you________
- Page 194 [1 ] to that admission.
[2] BY MR. SCHULER:
[3] Q. I'm looking now
at your synopsis [4] that
we've marked
as
Plaintiff's 3.
[5] A. Uh-huh.
[6 ] Q. And I want to ask
you some [7] questions
about some s p e c i f i c
statements in [8 ] there.
[9] A. Okay.
[10] Q. It's your understanding
that
[11] 2,4,5-T has not been
used in the United States
[12] since 1979 or '80;
correct?
[13] A. Correct.
[14] Q. And in terms of
t h e
d i o x i n
[15] compounds, there's a
s t a t e m e n t , a n d I'm
[16] referring to page 1
now of Plaintiff's 3—
[17] A. Uh-huh.
[18] Q.
-- third para­
graph. The diox in
[19] compounds, it says
here, and the amounts of
[20 ] them that were pres­
ent in phenoxy herbicide
[2 1 ] preparations varied
from p r e p a r a t i o n to
[22 ] preparation and per­
haps even from batch to
[23] batch. [24] Do you
agree with that state­
ment?

A. WILLIAM ROBERTS & ASSOCIATES

54

SCHULZ, CARL O.
[25] A. In the Vietnam
era, yes.
- Page 195 [1] Q. What about in the
1970s?
[2] A. No.
[3] Q. Okay. What is
your understanding
[4] when the change took
place?
[5] A.
It wasn't over­
night and that's
[6 ] important to remem­
ber. I think the first
real [7] sensitivity to a
need to reduce the amount
of [8 ] dioxin occurred
around 1968, '67, '68 ;
and was [9] probably —
everybody was probably on
board by [10] about 1970.
[11] Q. So after 1970,
t h e r e w a s no m o r e
[1 2 ] variability in the
amount of dioxin com­
pounds?
[13] A. Well, there was
variability, but [14] not
in the sense that I was
talking about [15] there,
and very little variabil­
ity because [16] there
was much more control on
the raw m a t e r i a l
[17] manufacture.
[18] Q. And what infor­
m a t i o n do y o u p o i n t
[19] to to support that
conclusion?
[20] A. Well, it's mostly
second-hand
[2 1 ] information included
in books. Oh, Warren
[22] Krumet writing in
the history of this issue
[23] for — he was a for­
m e r e m p l o y e e of D o w
[24] Chemical, and I
think A1 Young has writ­
ten some [25] information
about this, though, I
can't
- Page 196 [1 ] remember.
[2] Q.
K r u m e t is
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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
K-r-u-m-e-t or how do you
[3] spell it?
[4] A.
I think that's
correct.
[5] Q. And do you remem­
b e r the p a r t i c u l a r
[6 ] article or book?
[7] A. It would probably
be a chapter, and [8 ] I
don't remember what book
it would be in.
[9] Q- Is TCDD a potent
c a r c i n o g e n in y o u r
[1 0 ] opinion?
[11] MR. WAGNER: Object
to form.
[12] THE WITNESS: Well, I
have
a
little
[13] trouble with the
term potent; but to try
and [14] help you and to
answer it, the amounts
required [15] to cause
cancer in experimental
a n i m a l s
a r e
[16] extremely low. And
by that definition, it is
a [17] potent carcinogen.
[18] BY MR. SCHULER:
[19] Q.
Of all the
d i o x i n s is it t h e
[20 ] strongest carcinogen
that you're aware of?
[21] A. Well, it is a —
o f
a l l
t h e
[2 2 ] carcinogens, is it?
[23] Q.
I said, of all
the dioxins.
[24] A. 2,3,7,8 is the
strongest, yes.
[25] Q. In terms of car­
cinogenic______________
- Page 197 [1 ] capability?
[2] A.
Correct. A l ­
though, possibly very
[3] closely followed by
1 ,2 ,3,7,8-pentachlorofur
an, [4] dibenzofuran.
[ 5] Q .
T h a t 's in
pentachloro phenol? Is
[6 ] that contained in
pentachloro phenol?
[7] A. Ah—
[8 ] Q. Well, let me. The
furan that you [9] just

referred to-[10] A. There would be
very little of it in
[1 1 ] pentachloro phenol.
[12] Q.
Is that con­
tained in any of the
[13] phenoxy herbicides?
[14] A.
If at all, at
extremely low levels.
[15] Q. Would 2,4-D in
1976
and
1977
[16] contain small quan­
tities of dioxins?
[17] A. Not tetra and
higher.
[18] Q. Which ones would
it c o n t a i n in y o u r
[19] opinion?
[20]
A.
Di a n d
trichlorodibenzo dioxin.
[21] Q. Are these car­
c i n o g e n s in y o u r
[22 ] opinion?
[23] A. No.
[24] Q. When you say
that
TCDD
is
a
[25] carcinogen, and you
do discuss this in your
- Page 198 [I ] synopsis here, you
talk about it as a pro­
moter; [2 ] correct?
[3] A. Well, I don't
k n o w if I u s e d t h a t
[4] term. That is a term
that comes up in the
[5] discussion. I don't
consider it to be purely
a [6 ] promoter.
[7] Q. You also consider
it
to
be
an
[8 ] initiator, as well?
[9] A. Well, I'll need
to talk about that [10 ] a
little bit. I believe
promoter
is
an
[I I ] operational term,
rather than a precise,
[1 2 ] mechanistic term
because I don't under­
stand the [13] mechanism
by which dioxin causes
cancer. I [14] think if
we did, again, we'd cure
cancer. [15] But anyway,
promoter is simply a

A. WILLIAM ROBERTS & ASSOCIATES

g5

SCHULZ, CARL O.
[16] definition of how it
behaves in a certain as­
say [17] that's designed
to identify or separate
this [18] one form of
cancer induction from
another. And [19] in
those types of assays,
TCDD very clearly
[20] operates as a prom
d
t
e
r
[21] Interestingly, it
isn't very [22] effective
as an initiator in those
assays; but [23] it does
cause cancer by itself in
e x p e r i m e n t a l
[24] animals, so there
will be some initiating
[25] aspect to its activ­
ity. But it is not what
we____________________
- Page 199 [1] call a genotoxic car­
cinogen. It d o e s n ' t
[2] initiate the carcino­
genic process by causing
a [3] gene mutation or
chr o m o s o m a l damage.
[4] It has this effect,
this [5] carcinogenic
effect through its inter­
action [6] with the AH
receptor. But what hap­
pens from [7] that step
on, to the development of
a tumor, I [8] don't
think is known. And any­
body who thinks [9] they
know what happens is presumptuous
and a
[10] little foolish.
[11] Q. Well, do you
have your own theory
[12] as to what happens?
[13] MR. WAGNER: Object
to form.
[14] BY MR. SCHULER:
[15] Q.
I know you're
not a medical doctor,. . .
[16] but -444
[17] A. Well, you don't
need to be a [18] medical
doctor. That's not an
^
aspect of a [19] medical
doctor's understanding or \N
______________________ Q
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445

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
training. [20] But I have
my current theory, which
changes at [21] every
month or each paper I
r e a d o r so f o r t h ,
[22] but I think that its
carcinogenic effect is
the [23] result of the
way it regulates or de­
regulates [24] the gene
in the genetic material
of the cell. [25] And
that it is simply altering the way the cell
- Page 200 [1] responds to endoge­
nous growth factors,
which [2] essentially the
cell loses its ability to
[3] control growth and
becomes a cancer cell.
[4] Q. That's what your
present opinion [5] is?
[6] A. Yeah. That's this
week's theory.
[7] Q. This week's theo­
ry?
[8] A. Yes.
[9] Q. Okay. I touched
o n t h i s at a v e r y
[10] early stage in your
deposition, but do you
feel [11] that even one
molecule of TCDD could
initiate [12] this type
of reaction?
[13] A. That's not — I
think" t h a t t h a t ' s
[14] extremely unlikely
in that the one hit mod­
el, [15] which that is a
verbal expression of, is
[16] probably not the
most appropriate model;
but it [17] can't be
ruled out by — on the
b a s i s
of
the
[18] evidence that we
have now. So I guess a
very [19] honest and easy
answer is I can't reject
that [20] hypothesis.
[21] Q. Do you feel that
T C D D or m a t e r i a l
[22] such as silvex or
2,4,5-T that might con­

tain [23] TCDD — and I
want to be careful the
way I [24] choose my
words here because I know
that [25] there's some
terms of art that you
use. Let me____________
- Page 201 [1 ] start over again.
[2] Do you feel that the
chemical [3] exposure and
ultimate cancer in those
that have [4] had suffi­
cient exposure to TCDD
through the [5] medium of
these phenoxy herbicides
can be site [6 ] specific?
And what I mean by that
is, if an [7] individual
— I think there's some
mention in [8 ] one of the
studies about some spray­
ers that [9] carried
backpacks that leaked and
there's some [10 ] comment
about tumors occurring or
t h e
d i s e a s e
[1 1 ] occurring in proxim­
ity to where the leakage
[12] w a s . [13] And
Moyer's testimony in this
[14] case-[15] A.
On his right
arm.
[16] Q. -- about the-[17] A.
with the gun
and all that.
[18] Q.
I think it was
the left arm.
[19] A. Oh.
[20] Q. But discussed
t h e i s s u e of t h e
[2 1 ] leaking of the gun
onto the arm area. What's
[2 2 ] your' opinion as to
whether or not this can
[23] be — there's a re­
lationship between the
[24] exposure site for
example on a human's body
and [25] the cancer?
- Page 202 [1] MR. WAGNER: Object to
form.
And
no
[2] predicate.

A. WILLIAM ROBERTS & ASSOCIATES

56

SCHULZ, CARL O.
[3] MR. LUTZ: Join.
[4] THE WITNESS: My opin­
ion is that, [5] if it
were, in fact, a skin
cancer, that might [6] be
a little more credible. I
do believe that, [7] to
some extent, d i o x i n
2,3,7,8-TCDD is a point
[8] of contact carcino­
gen. That explains why
the [9] animals in — and
I may reverse the studies
— [10] but the animals
in the NTP study got na­
sal [11] cancers, whereas
the animals in Cosiba
study [12] did not. In
Cosiba, they were intu­
bated. [13] In the NTP
study, they.ate it in
[14] the diet, so the
dust got into their nasal
[15] passages and so
forth. And since there
has [16] been an associa­
tion Of dioxin with stom­
ach [17] cancer in some
cases, lung cancer in
other [18] cases, I feel
that there is some evi­
dence that [19] 2,3,7,8
may be a point of contact
carcinogen, [20] as well
as a s y s t e m i c one.
[21] But I don't believe
that's relevant [22] to
Moyer's case because that
soft
tissue
is
[23] underneath and in­
side and it's not an area
[24] where the dioxin
would go. If the dioxin
got [25] into the skin,
it would stay in the skin
or be_________________
- Page 203 [1] taken by the vascula­
ture, which overlies the
[2] soft tissue, to the
systemic circulation. So
[3] it's not a credible
hypothesis to me.
[4] BY MR. SCHULER:
[5] Q. And that hypothe­
sis that you've [6] just
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MOYER VS. DOW CHEMICAL COMPANY
enunciated would not
change, even assuming
[7] that there was some
type of breakage in the
[8 ] skin area where Moyer
was exposed?
[9] A. No. It would have
to be, you know, [10 ] a
deep puncture wound going
into
the
soft
[1 1 ] tissue, which is —
and, a g a i n — well,
that's [1 2 ] it.
[13] Q. Okay. I didn't
m e a n to c u t y o u off
[14] earlier, unless you
were finished at this
point [15] with your
c r i t i c i s m s of Dr.
T e i t e l b a u m . We got
[16] k i n d of s i d e
tracked.
[17] A. I'd rather not
—
I did not make
[18] marks in his tran­
script. I haven't read it
all [19] in the last 24
hours. I just went back
last [2 0 ] n i g h t and
re-reviewed it. I was
only prepared [2 1 ] today
to give general impress i o n s . If I c o u l d
[2 2 ] take some time and
go through it and find
[23] specific examples of
what I'm talking about,
[24] bat I'd prefer to
save that for a later
date, [25] when I have
all his material before
me.____________________
- Page 204 [1] Q. Let me ask you
the same q u e s t i o n
[2 ] then with respect to
Dr. Hardell's deposition,
[3] since you also had
that-[4] A. Uh-huh.
[5] Q.
-- and you've
b e e n o f f e r e d as a
[6 ] critiquer, if you
will, of his testimony as
[7] well.
[8 ] A. Uh-huh.

SCHULZ, CARL O.

[9] Q. What about his
t e s t i m o n y do y o u
[10] wish to criticize at
this point?
[11] A. Well, maybe I
s h o u l d be c a r e f u l
[12] since he's careful
to always say he's not a
[13] toxicologist. But,
generally, I had very
[14] little problem with
his deposition. I thought
[15] he was open and hon­
est and careful. I can't
[16] think of a single
specific statement of his
[17] that I would say is
absolutely wrong. Again,
I [18] think he carries a
bias. It's understand­
able. [19] We're all bi­
ased.
[20] Q. All right. Let
me a s k y o u a b o u t
[21] effects on the im­
mune system, which I
touched [22] on before.
[23] A. Uh-huh.
[24] Q. Do you feel that
TCDD is [25] immunotoxic?
- Page 205 [I] A.
In experimental
animals, it's [2] clearly
immunotoxic. Yes.
[3] Q. And can that be
extrapolated to [4] man?
[5] A. Well, to some
degree and -- but the
[6] few studies that have
been done to look for it
[7] in h u m a n s , have
failed to confirm a real
[8] effect.
[9] Q. So your opinion
is t h a t it c a n or
[10] you're uncertain at
this time or it can't?
[II] A. I would say that
we ought tb [12] regulate
it or treat it as if it
can cause [13] immune
effects in humans. One of
the [14] interesting
things that's not clear
to me is [15] whether
those effect might be

A. WILLIAM ROBERTS & ASSOCIATES

57

immunosuppressive [16] or
immunostimulatory.
[17]

If

i t ' s

immunostimulatory, it
[18]
might, in fact, be
anti-carcinogenic in that
[19] sense. Some of the
animal evidence indicates
[2 0 ] that that is the
nature of the immuno ef­
fect. [21] But, in gener­
al, in experimental anim a l s ,
i t ' s
[22 ] immunosuppressive.
[23] Q. Or it could be
both, couldn't it?
[24] A. It could be both
at d i f f e r e n t d o s e s
[25] and that's a very
important and potential
- Page 206 [1 ] issue.
[2] Q. Have you spoken
w i t h a n y o n e at D o w
[3] Chemical Company re­
garding this case, any
[4] aspect of it?
[5] A. No.
[6 ] Q. Are you familiar
w i t h a n y o n e at D o w
[7] Chemical Company,
other than, I think we've
[8 ] mentioned a few names
on and off here, that was
[9 ] actively involved in
the research regarding
[10] 2,4-D and 2,4,5-T as
f a r as t o x i c i t y is
[1 1 ] concerned?
[12] MR. WAGNER: When you
say familiar, [13] do you
mean does he know them
personally?
[14] MR. SCHULER: Does he
k n o w
t h e m
[15] personally. Yes.
[16] THE WITNESS: Sure.
[17] BY MR. SCHULER:
[18] Q. Who are you fa­
miliar with?
a t r*
[19] A.
Well, D i c K ^ °
Cosiba, Bemie Schwetz.
[20] Q. How do you spell
that last name?
\
[21] A.
Schwetz,
^
S-c-h-w-e-t-z.
^
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MOYER vs. DOW CHEMICAL COMPANY

V 't f f

[22] Q. Are they both
toxicologists ?
[23] A. Yes. Bernie is
no longer with [24] Dow.
He's now, I believe, at
CUT, which is [25] the
Chemical Industry Insti­
tute of Toxicology.
- Page 207 [1] Oh, gee. I know oth­
ers. I've known other
[2] people at Dow. Wheth­
er they participated in
[3] the dioxin studies, I
can't remember for sure.
[4] Perry Gehring and
Phil
Watanabe,
[5] W-a-t-a-n-a-b-e.
Gehring is G-e-h-r-i-n-g.
[6] Q.
Have you dis­
cussed, at one time or
[7] another, any of the
issues with them that
we're [8] involved with
in this case?
[9] A. No, no. I don't
talk to any of [10] those
guys very frequently or
p a r t i c u l a r l y
[11] recently, except
Dick Cosiba, who goes to
all [12] the internation­
al dioxin meetings. But
we just [13] talk in gen­
eral terms.
[14] Q. Are you familiar
w i t h the p r o c e s s
[15] that a company like
Dow Chemical goes through
[16] in order to comply
with registration
[17] requirements for
these chemicals?
[18] MR. WAGNER: Object
to
form.
Time
[19] period.
t> [20] THE WITNESS: I have
assisted [21] pesticide
'"S* manufacturers in assemb l i n g
t h e
[22] information for a
registration petition to
EPA, [23] if that's what
you're seeking, yes.
[24] BY MR. SCHULER:
[25] Q. That's what I'm

seeking.
- Page 208 [1] A. Yes.
[2] Q. And since you've
participated in [3] the
registration process,
then I assume you are
[4] familiar with the
types of information that
[5] needs to be supplied
to the EPA in order to
get [6 ] a pesticide reg­
istered; correct?
[7] A. Yes, I am.
[8 ] MR. WAGNER: Same ob­
jection.
[9] BY MR. SCHULER:
[10] Q. And can you tell
m e w h a t t y p e s of
[1 1 ] information are re­
quired to be provided?
[12] MR. WAGNER: Same
objection.
[13] THE WITNESS: Oh,
boy. [14] Manufacturing
information, toxicity
information [15] to the
target species and to
non-target [16 ] species.
Non-target species include
humans,
[17] terrestrial organ­
isms and aquatic organ­
isms. [18] All of these
depending on the intended
use of [19] the product.
So if the intended use
would not [20 ] result in
any exposure of humans or
t e r r e s t r i a l
[2 1 ] organisms, whatever,
you don't have to do that
[22 ] kind of data.
[23] BY MR. SCHULER:
[24] Q. Let me stop you
for
one
second
[25] before you go on.
- Page 209 [1] A. Okay.
[2] Q. Because I want to
make one point [3] clear.
The type of information
that you're [4] talking
about the manufacturer
needs to supply, [5] is

A. WILLIAM ROBERTS & ASSOCIATES

58

SCHULZ, CARL O.
this pursuant to rules
and regulations under
[6 ] the FEFRA or FIFRA
Act?
[7] A. FIFRA. Right.
Yes.
[8 ] Q. And have essentially
the
same
[9 ] requirements been in
e f f e c t s i n c e the
[10] early '70s?
[11] MR. WAGNER: Object
to
f o r m .
No
[1 2 ] predicate.
[13] THE WITNESS: Yeah,
I'd say the [14] general
requirements. Well, let's
see. [15] Early '70s. The
general broad areas that
I'm [16] talking about,
yes. The guidelines for
what [17] studies to do
when and that kind of
thing have [18] evolved
quite a bit since the
early '70s. [19] I'm tryi n g to t h i n k w h e n
sub-part [20] G. The tox
guidelines, I think, were
published [2 1 ] in about
1978 or — oh, even later
than that. [22] When I
was — well, maybe not.
'78
to
'82,
[23] somewhere in there.
And that represented, you
[24] know, quite a bit of
change in how much safety
[25] data and so forth
was needed.____________
- Page 210 [1] BY MR. SCHULER:
[2] Q.
Prior to that
publication
of
[3] sub-part G, those are
the
toxicology
[4] guidelines?
[5] A. Uh-huh.
[6 ] Q. Yes?
[7] A. Yes.
[8 ] Q. Were there still
r e q u i r e m e n t s for
[9] toxicological data to
be supplied, it's just
[10 ] that they were less
stringent? Is that what
MICROCopy

March

5, 1993

MOYER vs. DOW CHEMICAL COMPANY
[11] you're saying?
[12] MR. WAGNER: Object
to form.
[13] THE WITNESS: There
were — yeah, [14] less
stringent is a possible
w o r d .
L e s s
[15] formalized more than
anything else. There was
[16] more give and take.
[17] In the old days, the
manufacturer [18] used to
come into EPA and sit
down with the [19] guys
and say, if we do this
s t u d y and that and
[20] this, will that be
okay? And they'd say yes
or [21] no. Then they'd
go back. And you look at
some [22] of those old
registration packages,
and there's [23] a tre­
mendous difference in the
amount of data. [24] So
the promulgation of stan­
dards or [25] guidelines
like those in sub-part G
was an__________ ______
- Page 211 [I] attempt to get a han­
d l e on t h i s so t h a t
[2 ] everybody was playing
on a level playing field,
[3] is the expression
they use. [4] It was a
very informal process in
[5] the early days when
-- even when I was at
Food [6] and Administra­
tion. There was very lit­
tle in [7] the way of
written guidance to a
sponsor [8] wanting to
submit something for ap­
proval .
[9] BY MR. SCHULER:
[10] Q. Was there any
type,
to
your
[II] knowledge, and I
understand you're a
[12] toxicologist and
haven't been involved in
the [13] process, is
there any type of contin­
uing [14] obligation to
A. WILLIAM ROBERTS

fit

SCHULZ, CARL O.

provide information if a
[15] manufacturer comes
across some information
in [16] the course of
manufacturing a particu­
lar [17] chemical that
might be relevant to its
[18] toxicological prop­
erties?
[19] MR. WAGNER: Object
to form. Over [20] broad
as to time. Also, no
p r e d i c a t e a n d it
[2 1 ] suggests itself to
ask for a legal opinion.
[22] THE WITNESS: Yeah.
I'm not [23] qualified to
talk about the regulatory
[24] requirements for —
across the broad for a
[25] manufacturer of ag­
ricultural chemical. I'm
not___________________
- Page 212 [1 ] familiar with all
parts of the FIFRA regs.
[2] BY MR. SCHULER:
[3] Q.
T h a t ' s fair
enough.
I'm just
[4] asking within your
expertise, having
[5] participated in the
process.
[6 ] A. I think there now
is-[7] MR. WAGNER: Same ob­
jection.
[8 ] THE WITNESS: I think
now that [9] there are
requirements to submit
and it may [10 ] even be
under TSCA, rather than
under FIFRA; [11] but I
don't know what the re­
q u i r e m e n t s w e r e in
[12] the '70s.
[13] BY MR. SCHULER:
[14] Q. Do you know Lar­
r y S i l v e r s t e i n at
[15] Dow Chemical Compa­
ny?
[16] A. No.
[17] Q. V. K. Row?
[18] A. Well, I know of
V.
K.
He's
the
[19] grandfather of the

ASSOCIATES

59

whole group.
[20] Q. Have you ever
b e e n to M i d l a n d ,
[21] Michigan, and-[22] A. Yes, I have.
[23] Q. -- and seen the
Dow Plant?
[24] A. Yes.
[25] Q. When did you go
there?
- Page 213 [1] A.
In 19 — well,
probably
a year
[2 ] after, two years af­
ter I went to work for
FDA. [3] I inspected it
as part of the biore­
search [4] monitoring
project. I sent a week
there with [5] an FDA
inspector, and we in­
s p e c t e d their old
[6 ] toxicology laborato­
ry.
[7] Q. And that was in
connection with [8 ] your
FDA employment?
[9] A. Yes.
[10] Q. Were there drugs
being
made
or
[1 1 ] something that you
were interested in look­
ing [1 2 ] at at the labo­
ratory?
[13] A. Data that Dow
submitted to the Food
[14] and Drug Administra­
tion. Yes, they had FDA
[15] regulated products
that were tested there.
[16] Q. Any other time
t h a t y o u ' v e b e e n to
[17] Midland, Michigan,
to Dow?
[18]
A .
No.
[19]
(Off-the-record con­
ference.)
[20] BY MR. SCHULER:
[21] Q. Do you know how
long,
f r o m y o u4 f4 8
[22 ] review of the liter­
ature, Dow was aware that
[23] certain of the chlo­
rinated organic compounds
it [24] manufactured ^
could cause chloracne?

(

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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY_______________

J7-fs?

&Ì

[25] MR. WAGNER: Object
to form._______________
- Page 214 [1] MR. LUTZ: Join.
[2] MR. WAGNER: No predi­
cate.
[3] THE WITNESS: And I-[4] MR. WAGNER: Asking
knowledge of [5] another
person.
[6 ] THE WITNESS: I'm not
aware, no.
[7] BY MR. SCHULER:
[8 ] Q. Well, I'm asking
— I mean, all [9] your
knowledge is from other
people
because
[10 ] you're quoting-[11] A. Right. I just-[12] Q. My question was
carefully worded,
[13] from your review of
the literature. Your
[14] answer would be the
same?
[15] A. I don't know.
[16] Q. Okay.
[17] A. They had an ac­
cident there and the
[18] workers got chloracne, and I can't remember
[19] what year that was;
but they must have made a
[20 ] connection then, if
not later.
[21] Q. Do you remember
what
decade
the
[22 ] accident-[23] A. '60s, I think.
[24] Q. Do you know when
Dow C h e m i ca l first
[25] may have started
testing compounds to de­
termine________________
- Page 215 [1 ] what the source of
the chloracne was in its
[2 ] manufacturing pro­
cess?
[3] MR. WAGNER: Same ob­
jection.
[4] THE WITNESS: No, I
don't.
[5] BY MR. SCHULER:
[6 ] Q. Have you seen any

SCHULZ, CARL O.

i n t e r n a l
Dow
gone through most of the
[7] documentation with bases [14] of your opin­
regard to any testing
ion here, at least the
that [8 ] was done on TCDD ones that [15] I've writ­
within the company prior ten down. [16] Are there
any other bases for your
to [9] 1977?
[10] A. No.
[17] ,opinion that we
[11] Q. Are you familiar haven't discussed here
with the G e r m a n
today?
[12] company, Boehringer?
[18] A. Not that I know
[13] A. There are sever­ of. I t h i n k I l a i d
al G e r m a n c o m p a n i e s
[19] them out carefully.
[14] that have Boehringer
[20] MR. SCHULER: This
in their name.
might
be a g o o d
[15] Q. Okay. I'm refer­
[21] place to stop. Let
ring specifically [16] to me just check my notes
the chemical manufactur­ for [22 ] a few minutes.
ing company.
[23] (A recess tran­
[17] A. Well, I think spired. )
what y o u ' r e l o o k i n g
[24] BY MR. SCHULER:
[25] Q. Let me just ask
[ 1 8 ]
for
is
you a couple of________
Boehringer-Ingelheim.
T h e r e
' s
- Page 217 [19]
Boehringer-Mannheim, [1 ] questions to clear up
also.
a couple of things, at
[20] Q. Okay.
[2 ] least in my mind,
[21] A. And they're both about your opinion. You
c h e m i c a l
make [3] the statement in
[22 ] manufacturers.
Plaintiff's 8 , your let­
[23] Q. Have you seen ter of [4] October 22,
any r e s e a r c h that
1992, that the estimated
[24] Boehringer-Ingelheim daily [5] intake of TCDD
has done with respect to
from non-occupational
[25] TCDD?_____________
exposures [6 ] ranges from
- Page 216 40 to 240 picograms per
[I] A. Yeah. It's one of day for a [7] 176 pound
those papers in [2 ] the man; correct?
[8 ] A. Yes.
cancer epidemiology. It's
called the [3] Hamberg
[9] Q. And that's an
study. Let me. That's the average that you get
[10 ] from your review of
Manz [4] study. This is
the literature? Is that
Boehringer-Ingelheim.
[1 1 ] what you're saying?
[5] Q. That's the study
[12] A. Correct.
t h a t we d i s c u s s e d
[6 ] earlier-[13] Q. Okay.
[14] A.
It's a range I
[7] A. Yes.
[8 ] Q. -- that you felt g e t f r o m m y r e v i e w
was a credible [9] study
[15] of the literature.
with regard to cancer
[16] Q. That's not done
mortality?
from i n d e pendent
[10] A. Yes.
[17] research and it's
[II] Q. Okay. To get
not-back to the specifics
[18] A. No.
[1 2 ] of this case for a
[19] Q.
-- something
moment. I've asked you,
t h a t y o u a r r i v e d at
and [13] I think you've
[20 ] independent of what

A. WILLIAM ROBERTS & ASSOCIATES

60

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
someone else has put
[2 1 ] together; correct?
[22] A. Right.
[23] Q. All right. And
y o u s t a t e t h a t this
[24] measurement is ob­
tained from background
[25] concentrations of
this compound in the
blood
- Page 218 [1 ] and adipose tissues
and, therefore, represent
[2 ] the amount of this
compound that is actually
[3 ] absorbed each day.
[4] A. Uh-huh.
[5] Q. Correct?
[6 ] A. Correct.
[7] Q. So that you're
saying, because I
[8 ] want to be clear I
understand it, that 40 to
[9] 240 picograms on the
average, per day, are
[10] absorbed in a 176
pound man?
[1 1 ] A. Correct.
[12] Q. And we d i s ­
cussed, I think, earlier,
[13] the sources of that
a n d I w o n ' t get into
that. [14] Then you go on
to say, it's my opinion
that if [15] Mr. Moyer
were exposed to TCDD as a
r e s u l t
o f
[16] application of her­
bicides during his em­
ployment [17] by Orange
County in 1976 and 1977,
the minute [18] amount of
that compound that he
would have [19 ] absorbed
and retained would be
negligible [20 ] compared
to the total amount that
he absorbed [2 1 ] from the
general environmental
sources in the [22 ] same
two year period. [23] And
my question is, how do
you make [24] the compar­
ison? I mean, you made
s o m e
g e n e r a l
[25] statements before

about that he used the
- Page 219 [1 ] chemical sporadical­
ly, and used very small
[2 ] amounts of it over
the time that he was with
[3] O r a n g e C o u n t y .
[4] What I'm getting at
is what [5] specifically
— what type of compari­
son are you [6 ] making
here? I mean, are you
just making a [7] general
statement based upon the
general [8 ] statements in
the depositions or do you
have [9] some type of
number or measurement
that you can [10 ] point
us to? [11] And I understand you didn't
[1 2 ] calculate numbers
for this and that's—
[13] A. Yeah.
[14] Q. -- probably go­
i n g to be s o m e b o d y
[15] else doing that.
[16] MR. WAGNER: Object
to form.
[17] MR. LUTZ: Join.
[18] THE WITNESS: What
i t ' s b a s e d o n is
[19] that if — the docu­
ments show that if Mr.
Moyer [20] used a dioxin
contaminated preparation
at all, [2 1 ] it would
have been silvex on any­
where from one [2 2 ] to
three days, very small
a m o u n t s .
The
[23] contamination of
that silvex, because it
was in [24] the late
'70s, would have been
well, well, well
[25] under one part per
million dioxin._________
- Page 220 [1] BY MR. SCHULER:
[2] Q. Let me just stop
you for a s e c o n d ,
[3] then we'll piece this
together. When you say
[4] small amounts, what

A. WILLIAM ROBERTS & ASSOCIATES

61

SCHULZ, CARL O.
are you referring -what's [5] your under­
standing of the evidence
in the case [6 ] with re­
gard to that?
[7] A. My understanding
of t h e e v i d e n c e in
[8 ] the case is that
probably the maximum
amount of [9] silvex
preparation used of the
concentrate was [10 ] zero
to ten gallons.
[11] Q. Okay.
[12] A. And if Moyer was
exposed to that, [13] his
exposure could have been
none or three or [14] six
or nine, basically in
that range. And that
[15]-it was contaminated
with 2 ,3,7,8 dioxin or
its [16] equivalence at a
level of probably a tenth
of a [17] part per mil­
lion or less. And that's
just -- [18] then it
wouldn't get onto his
skin. What [19] little
bit did get onto his
skin, there's not
[2 0 ]-100 percent a b ­
sorbed, not even 50 per­
c e n t [2 1 ] a b s o r b e d
through the intact skin.
So-- .
[22] Q. You're assuming
the skin was [23] intact?
[24] A.
I don't even
think I have to do the
[25] calculation, you
know.
- Page 221 [1] Q. All right.
[2] A.
It's one ciga­
r e t t e c o m p a r e d to a :
[3] two-a-day smoker, you
know.
[4] Q. Okay.
[5] A. It's that kind of
c o m p a r i s o n in
"150
[6 ] mind.
[7] Q. All right. I un­
derstand what [8 ] you're
saying. So without doing
the [9] calculation, I
MICROCopy

o!

March 5# 1993
MOYER vs. DOW CHEMICAL COMPANY
you're just saying that
— making [1 0 ] the as­
sumption that his skin
was intact, m a k i n g
[1 1 ] the assumption that
he used zero to ten galls
[1 2 ] of the concentrated
form, using the assump­
tion [13] that there was
.1 part per million or
l e s s in [1 4 ]
the
concentrate—
[15] A. Uh-huh.
[16] Q. -- and the other
things that you've
[17] discussed already
with me earlier in the
[18] deposition, you just
don't think that his
[19] exposure to TCDD at
Orange County would have
[20 ] materially elevated
or materially been great­
er [2 1 ] than the back­
ground exposure?
[22] A. That's right.
[23] MR. LUTZ: I object
to the form of [24] the
question.
[25] BY MR. SCHULER:
- Page 222 [1] Q. To TCDD; correct?
[2] MR. WAGONER: So do I.
[3] THE WITNESS: Correct.
[4] MR. SCHULER: Okay.
That's
all
the
[5] questions I have to­
day. [6j (The deposition
was adjourned at
[7] 3:53 PM •) [8 ] [9]
[1 0 ] [1 1 ] [1 2 ] [13]
[14]
[15]
[16]
[17]
[18]
[19]
[2 0 ] [2 1 ]
[22 ] [23] [24] [25]
- Page 223 [1] SIGNATURE OF DEPONENT
[2 ] [3] I/ the underm signed,
Carl 0. Schulz,
Tf<
[4] do hereby certify
that I have read the
[5] foregoing deposition
and find it to be a true
[6 ] and accurate tran­
scription of my testimo­
ny,

SCHULZ, CARL O.

[7] with the following
corrections, if any: [8 ]
[9] PAGE LINE CHANGE
REASON [10] [11] [12]
[13]
[14]
[15]
[16]
[ 17 ]
[ 18 ]
[ 19 ]

[1] Witness my hand, I
have hereunto affixed
[2 ] my official seal this
25th day of March, 1993,
[3] a t C o l u m b i a ,
Lexington County, South
Carolina. [4] [5] [6 ]
___ [20] CARL O. SCHULZ
[7] __________________
Date [21]
[22]
[23]
______ Wanda K. Cecil
[8 ] Notary Public My Com­
[24] [25]_____________
mission expires [9] March
- Page 224 [I] CERTIFICATE OF RE­ 27 , 1997 [ 10 ] [ 11 ]
[12] [13]
[14] [15]
PORTER [2] [3] I, Wanda
[16] [17]
[18] [19]
K. Cecil, Court Reporter
[20] [21]
[22] [23]
and [4] Notary Public for
[24] [25]_____________
the State of South Caro­
lina
- Page 226 [5] at Large, do hereby [ 1 ] I N D E X [ 2 ]
certify: [6 ] That the
[3] Page [4] STIPULATION
foregoing deposition was
3 [5] CARL O. SCHULZ,
taken [7] before me on Ph.D. [6 ] EXAMINATION
[7] BY MR. SCHULER 3
the date and at the time
[8 ] SIGNATURE OF DEPONENT
and [8 ] location stated
on page 1 of this tran­ 223 [9] CERTIFICATE OF
script; [9] that the wit­ REPORTER 224 [10] [11]
[12] REQUESTED INFORMA­
ness was duly sworn to
t e s t i f y to [ 1 0 ] the
TION INDEX [13] [14] (No
Information Requested)
truth, the whole truth,
a n d n o t h i n g but the
[15] [16] [17] E X H I
[I I ] truth; that the tes­ B I T S [18] P a g e
timony of the witness and
[19] PLF. EXH. 1, Resume
[1 2 ] all objections made
for Carl O. [20] Schulz
at t h e t i m e of the
5 [21] PLF. EXH. 2, Hand[13] examination were w r i t t e n
List
of
recorded stenographically
[22] Cases 50 [23] PLF.
by [14] me and w e r e
EXH. 3, Fax Transmittal
thereafter transcribed by with Synopsis [24] of
[15 ] computer-aided tranScientific Literature on
s c r i p t i o n ; that the
[25] Phenoxy Herbicides
[16 ] foregoing deposition 78_____________
as t y p e d is a true,
- Page 227 [17] accurate, and com­
[1] E X H I B I T S
plete record of the tes­
[2] Page [3] PLF. EXH. 4,
timony [18] of the wit­ Fax Transmittal with Re­
ness and .of all objec­ view [4] of Literature on
tions made at [19] the Herbicides 78 [5] PLF.
time of the examination.
EXH. 5, Letter to Dr.
[2 0 ] I further certify Carl 0. Schulz [6 ] from
tha t I am n e i t h e r
H e i d i E. G a r w o o d ,
[2 1 ] related to nor coun­
[7] dated September 25,
sel for any party to the
1992 84 [8 ] PLF. EXH. 6 ,
[2 2 ] cause pending or Letter to Carl O. Schulz
interested in the events
f r o m [9] H e i d i E.
[23] thereof. [24] [25]
Garwood, dated October
- Page 225 [10] 26, 1992, with at-.

A. WILLIAM ROBERTS & ASSOCIATES

62

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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

tachments
85 [11] PLF.
EXH. 7, Letter to Carl O.
Schulz [12] from Alan F.
Wagner,
dated
[13] November 19, 1992,
Attachments 86 [14] PLF.
EXH. 8 , Letter to Alan
Wagner [15] from Carl 0.
Schulz, [16] dated Octo­
ber 22, 1992, [17] with
attachments 87 [18] PLF.
EXH. 9, Series of Journal
Articles [19] on Cancer
Epidemiology
88
[20] PLF. EXH. 10, Three
Articles on [21] Exposure
Assessment to Phenoxy
[22] Herbicides and Diox­
in 88 [23] PLF. EXH. 11,
Series of Documents 89
[24] DFT. EXH. 12, EPA
Draft
Document,
[25] Chapter 7, September
1992 191

452

A. WILLIAM ROBERTS & ASSOCIATES

63

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
$

$125 71-17
$150 71-18
/

'50s 161-10
'57 27-15; 28-22
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214-23; 27-13; 28-23;
28-24
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209 -15; 209-18; 212- 1 2 ;
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'81 17-3; 19-1; 27 - 2 ;
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'82 15-17; 19-1; 20 -13;
209--22
'83 20-2 1 ; 37-24; 43--18;
51-16; 52-3 ; 52-9
'84 21-8
'85 106-15; 35-14; 43-18
'88 51-11; 51-12; 51-■15;
51-17; 52-3 ; 52-9
'90 69-13
'91 69-14; 69-19
'92 193-10; 69-15
*
* 3--11
— a 113-1
— about 201-16
— and 204-5; 212-23;
221-16
— animal 139-6
— before 167-25
— cases 48-20
— consumption 143-6
— documents 81-1
— Dr 150-1
— during 35-13
— I 188-11
— involved 35-9
— just 82-7
— letter 150-23
— of 140-9; 147-25
— oral 16-13
— Ponce 27-24
— probably 219-14
— quickly 46-7
ä _ w t t .t .t a m

— something 217-19
— specific 52-19
— than 143-8
— that 216-8; 39-9
— third 194-18
— were 81-4
— where 42-18
— while 38-6
— with 201-17

SCHULZ, CARL O.

1972 10-19; 24-15
1976 104-7; 1 0 6 - 4 ;
130-14; 132-1; 197-15;
218-17; 37-2; 90-20
1977 106-17 ; 132-2 ;
197-15; 215-9; 218-17;
90-20
1978 15-17; 209-21
1979 194-12; 32-21
0
1980 69-5
04 151-21
1981 16-22; 17-11; 20-12;
1
25- 2; 34-4
I 130-18; 130-19; 130-25;
1982 154-12 ; 154-8 ;
159-18; 160-11; 170-12;
19-10; 19-22; 20-16;
190-3; 194-16; 21-5;
24-12; 24-15; 26-16;
37-24
221-13; 224-8; 226-19;
24-23; 25-21; 26-13;
1983 42-8; 43-25; 43-4;
26-14; 26-25; 26-6; 29-1;
45-3; 45-6
29-18; 29-5; 5-21; 5-23;
1984 20-19; 20-24; 21-3
6-8
1985 104-6; 19-23; 20-5;
1,2,3,6 ,7,8 162-20
34-4; 42-10; 43-1; 60-19;
1 .2 .3.7.8- pentachlorofur 60-3
an 197-3
1988 111-23; 58-14; 58-24
1 . 3 . 6 . 8 - t e t r a c h l o r o 1990 160-10; 69-18;
170-11
77-12; 79-5; 81-14; 82-20
1/2 21-16
1992 151-3; 179-21;
10 105-9; 106-21; 107-20; 185-7; 191-5; 217-4;
107- 23; 108-3; 139-16; 227-10; 227-13; 227-16;
159-23; 161-24; 185-7;
227-25; 227-7; 75-1;
2 2 7 - 2 0 ; 59-2 ; 6 1-8;
83-17; 84-2; 85-16; 86-9;
87-14; 87-22
72-13; 88-17; 88-18
100 220-20
1992— 150-23
II 21-16; 227-23; 89-5;
1993 1-15; 225-2; 7-19;
89-6
7-24; 7-6
12 16-7; 191-4; 227-24
1997 225-9
12th 139-17
2
1441 1
2 139-10; 139-23; 159-18;
15 1 0 5 - 1 1 ; 1 0 7 - 2 1;
226-21; 24-23; 25-22;
108- 15; 108-4; 108-9; 2 6 - 13; 26-14; 26-25;
137-9; 140-4; 161-25
26-6; 29-1; 29-5; 48-15;
15-year 149-6
49-23; 49-25; 51-8
16 72-1
2,3,7,8 111-10; 196-24;
1615 2-6
202-19; 220-15; 99-9
176 217-7; 218-10
2,3,7, 8 -TCDD 129-22;
18 7-24; 73-10
130-7; 134-15; 154-3;
19 213-1; 227-13; 86-9
160-2; 168-20; 202-7
190 2
2,4,5-T 109-15; 122 - 1 0 ;
191 227-25
122-19; 122 -2 1 ; 122-25;
1950s 28-12; 30-2
1 2 2 - 8 ; 123-24; 1 2 4 - 7 m ^ 4
1953 95-20
130-10; 130-25; 131-1;4
1957 27-11
131-22; 132-12; 132-16;
1960s 133-11; 30-6
132-22; 132-3; 146-22;
1968 195-8
148-19; 194-11; 200 -2 2 ;
\fl
1970 11-3; 195-10; 195-11
206-10; 47-7 ; 95-22;
1970s 123-25; 195-1
95-25; 96-17; 96-23;
1971 10-19; 11-4
97- 16 ; 97-20 ; 9 7 - 7 ; A<

prmTTDfrc £ iQcnfTiirrc

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
98-12; 98-18; 98-22; 98-9
32nd 7-23
2.4.5trichlorophenoxy
33401 2
96-3
34236 2-18
2.4.5- trichlorophenoxyac 3:53 222-7
etic 96-1
3rd 81-12; 82-19
2/4 -D L09-16; 111- 14;
4
111--18; 111-•25; 112- 10;
4 21-5; 21-9; 227-3;
112--13; 112-■15; 112- 17;
24-23; 26-3; 26-7; 29-18;
112--19; 113 -18; 113-5;
73-15; 78-13; 78-18;
114--13; 114 -24; 114 -7;
78-23
115--16; 118- 23; 119- 16;
40 1 2 1 - 1 4 ; 1 3 9 - 1 1 ;
119 -8; 120- 1; 120- 10;
139-23; 141-1; 151-23;
120--20; 120 -6; 122- 19;
158-21; 217-6; 218-8
122--25; 122 -7; 123- 12;
400 29-10
407 2-7
123--19; 123 "4; 131- 14;
131--17; 131 -21; 131-3;
41.7 162-13
132--12; 132- 16; 132- 21;
5
132--3; 133- 18; 146-23;
5 1-15; 137-9; 140-3;
157-15; 161-18; 18-24;
148-•19; 169- 18; 169-19;
226-20; 227-5; 61-8;
169--24; 170--1; 197- 15;
81-13; 83-23; 83-25
206-10; 47-7; 47-8; 74-7;
80-12
5.1 160-3
20.4 162-21
5.5 161-19
50 220-20; 226-22; 64-18;
20.9 162-18; 162-20
22 150-23; 151-3; 217-4;
64-20
227-16; 87-14; 87-22
500 27-3; 27-5; 73-15
5th 82-20; 82-23
223 226-8
6
2231 4-25
6 170-12; 227-8; 85-14
224 226-9
224-1585 2
60 17-18
233 162-24
689-8180 2-7
7
24 203-19; 72-1
240 139-11 ; 139-24 ; 7 154-13; 185-8; 190-2;
191-5; 227-11; 227-25;
141-1; 151-23; 158-21;
86-6; 86-7
217-6; 218-9
25 105-11; 107-21; 227-7;
7-39 185-6
722-8414 1-25
83-17; 84-2
731-5224 1-25
2500 3-19
25th 225-2
75 140-5; 140-6; 73-8
78 226-25; 227-4
26 227-10; 85-16
788 62-11
27 225-9
789 62-11
29 7-19
8
29205 3-20
8 136-8; 150-21; 170-13;
3
3 142-4; 170-12; 194-4;
21-16; 217-3; 227-14;
21-10; 21-9; 226-23;
71-25; 87-19; 87-20
80 140-5; 140-6; 151-22;
226-4; 226-7; 24-23;
26-3; 26-7; 6-10; 73-10;
43-20
73-9; 76-16; 78-14; 78-23
803 1-25
3— 194-16
813 2
84 227-7
30 1 0 5 - 1 0 ; 1 0 6 - 2 1;
107-20; 121-14
85 227-10
300 177-5; 22-19; 23-16;
86 227-13
23-23; 23-7; 24-1; 29-10
87 227-17
3200 6-25; 7-22; 7-9
88 227-19; 227-22
32302 2-13
89 227-23
A. WILLIAM ROBERTS & ASSOCIATES

2

SCHULZ, CARL O.
89-8657 1
9
9 170-13; 227-18; 88-6;(
88-7
90 59-4
904 2
95 18-23
951-1800 2
9:32 1-16
A
a-- 153-13; 159-20;
25-20; 29-13; 53-13
A.M 1-16
ability 200-2
able 109-16; 119-25;
131- 9; 134-25; 144-15;
165-9; 39-17
about 104-16; 107-16;
108-18; 110-20; 110-5;
111-8; 118-6; 12-25;
120-20; 122-23; 124-13;
127-2; 129-7; 131-3;
132- 15; 132-5; 136-2;
136- 9; 137-16; 137-3;
137- 4; 137-9; 138-16;
142-24; 148-15; 149-4;
156-10; 158-19; 158-22;
16-24; 16-7; 161-16;
165-1; 165-19; 166-3;.:
168-10; 17-18; 172-23;
173-3; 174-22; 174-25;
175- 19; 175-23; 175-4;
176- 13; 176-9; 178-14;
178-22; 18-16; 18-24;
180-21; 180-4; 181-13;
189-10; 19-10; 191-12;
193-13; 193-2; 194-7;
195-1; 195-10; 195-14;
195-25; 198-1; 198-9;
201-10; 201-8; 203-23;
204-20; 204-9; 209-16;
209-21; 209-4; 211-23;
217-2; 218-25; 27-18;
28-19; 29-2; 29-8; 30-6;
32-21; 33-13; 37-24;
42-10; 42-8; 43-20; 43-3;
44-20; 46-2; 46-25;
56-12; 56-19; 57-8;
59-13; 59-2; 59-21;
59-25; 59-6; 59-9; 61-6;
61-8; 62-10; 64-18;
67-18; 69-4; 69-5; 72-23;
73-18; 74-21; 74-24;
79-15; 82-7; 83-18; ¡
85-10; 90-4; 94-4; 95-17;
95-8; 97-25; 98-24;
MICROCopy

March 5, 1993
MOYER V S . DOW CHEMICAL COMPANY
99-11; 99-14; 99-2; 99-24
about— 175-13
above 21-6
abroad 67-1
absence 111-13; 172-18
absolutely 165-12; 204-17
absorb 141-14; 141-24;
142-17; 142-20; 143-23
absorbed 109-4; 141-4;
141-9; 143-4; 144-1;
144-3; 17-19; 218-10;
218-19; 218-20; 218-3;
220-20; 220-21; 41-25;
42-3
a b s o r p t i o n 102-12;
108-22; 142-22; 143-12;
144- 22; 144-8; 145-19;
145- 2; 145-21; 145-7;
146- 18; 146-2; 146-6;
146-7; 148-7; 151-17;
6-24; 7-20
abstracts 32-10; 32-7;
32-8
abuse 68-17; 68-23
accident 214-17
accident— 214-22
accidental 162-2
accordance 3-4
account 188-4
accounted 137-9
accumulate 136-22
accuracy 120-24; 25-24
accurate 111-1; 116-3;
148-21; 148-24; 149-8;
155-14; 192-23; 223-6;
224-17; 23-25
achieve 135-14
acid 96-1; 96-3
acronym 4-5
across 211-15; 211-24
Act 209-6
active 23-17; 46-16
actively 206-9
activities 18-18; 5-7
activity 123-2; 170-22;
171-12; 171-8; 198-25;
24-16; 26-17; 98-6
actual 114-23; 143-2;
36-9; 43-7; 76-2; 83-3
actually 109-1; 109-2;
11-4; 124-6; 135-2;
141-4; 149-14; 152-1;
163-1; 218-2; 26-2; 38-8;
5-12; 58-2; 64-16; 68-9
actually— 188-9
add 40-8

SCHULZ, CARL O.

added 6-21; 6-9; 7-14;
again— 156-8
7-5; 8-4
age 152-14; 153-10;
addition 129-24
154-17; 154-20; 154-22;
additives 15-10
160-5; 160-9
address 130-17; 178-16;
agencies 189-18; 67-20
3-18; 4-22; 4-23; 4-24
Agency 123-5; 123-7;
addressed 163-25
185- 8; 68-24
Adipose 154-12; 218-1
a g e n t 105-8; 155-5;
adjacent 57-24
156-4; 33-14; 73-23; 91-3
adjourned 222-6
agents 109-15; 110-14;
adjunct 5-9; 60-1; 61-17
111-6
adjustments 65-14
ago 123-17; 137-4; 176-7;
administering 16-2
180-6; 181-13; 187-3;
Administration 118-21;
193-15; 193-16; 59-8;
13- 10; 13-17; 14-18; 66-7
14- 23; 14-5; 15-18; 18-8; agree 114-4; 115-22;
19-15; 21-2; 21-25;
115-25; 116-8; 117-24;
211-6; 213-14; 24-25;
142-1; 142-13; 142-5;
32-18; 32-23; 35-16;
166-11; 166-7; 166-9;
37-5; 66-24; 68-11; 68-2;
170-15; 170-9; 182-2;
69-10
184-20; 185-24; 186-24;
administrative 157-3;
186- 3; 187-18; 188-11;
43-5; 77-25
188-7; 194-24; 92-23;
admission 194-1
95-6
admitted 149-2
AGRICULTURAL 1; 127-12;
admitting 188-1
137-22; 211-25; 71-12
adoption 181-2
a g r i c u l t u r e 121-21;
adult 151-22; 154-20;
121-22; 123-22
154-24; 54-18; 54-19
AH 199-6
adults 155-1
Ah— 197-7
advance 16-4
ahead 152-22; 177-19;
adverse 55-18
190-25; 191-1; 49-23;
advice 61-15
5-20; 76-16; 83-21;
adviser 43-19
85-12; 86-6
advisory 68-1; 68-21
AIDS 164-24; 164-25;
advocate 70-7
165-1
affect 144-22; 145-2;
air 109-14; 144-2; 144-5
aircraft 173-12
145-7; 146-13; 146-18;
147-22; 148-6; 168-21
airport 60-20
affected 145-22; 146-6
Al 195-24
affecting 145-25
Alabama 45-12
affiliated 192-13; 61-1
ALAN 2; 227-12; 227-14;
affixed 225-1
86-8; 87-20
a f t e r 11-5; 140-11;
alcohol 13-3
183-14; 195-11; 213-2;
algae 138-8
30-17; 37-23; 41-8;
All 10-5; 102-3 ; 102-6;
79-14; 79-3
109-10;r 11-3 ; 112-15;
again 101-14; 105-18;
115-5; 117-21; 117-24;
127-4; 128-4; 145-6;
125-19; 126-11; 126-13;*
152-25; 157-9; 162-16;
126-3; 127-7 ; 130-6,4
163-4; 171-12; 171-7;
131-9; 134-12; 134-16;
176-2; 176-4; 178-14;
135-4 ; 137-2; 137-5 ;
183-2; 19-22; 198-14;
137-8; 138-21; 139-25;
201-1; 203-11; 204-17;
140-1; 140-2; 141-7;
24-3; 46-7; 54-12; 55-14;
146-5; 147-10; 147-12;
149-17; 149-19;: 15-17;
56-10; 62-1; 92-8

A. WILLIAM ROBERTS & ASSOCIATES

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
151-13; 154-11; 154 -2;
154-20; 155-24; 156--13;
156-23; 156-24; 159- 12;
159-8; 160-16; 162- 16;
162-3; 163-14; 163 -4;
163-8; 166-12 ; 17 -3;
173-22; 177-9; 180- 14;
183-19; 183-3; 189- 17;
189-19; 189-4; 196- 19;
196-21; 196-23; 197- 14;
20-18; 201-17; 203- 18;
203-25; 204-19; 204- 20;
207-11; 208-18; 212 -l;
214-8; 217-23; 219-20;
221-1; 221-7; 222 -4 ;
224-12; 224-18 ; 24 -7;
25-1; 27-7; 29- l; 3-5;
3-6; 31-23; 33-'f} 35 -4;
36-9; 37-5; 39-15; 40--20;
42-25; 48-8; 49-1 ; 49-•22;
49-8; 51-23; 51- 7; 51-9;
52-11; 53-19 ; 55--5;
58-11; 58-15; 64- 11;
64-14; 65-21; 66--4;
67-15; 67-18; 68-5; 7-25;
7-4; 72-21; 73-13; 73-19;
73-8; 74-1; 76-15; 76-9;
77-1; 78-11; 79-14 ;
83-11; 83-8; 84-24 ;
86-17; 86-19; 86-:21;
86-5; 89-14; 89-9 ; 90-10;
94-8; 98-19; 98-8
all— 126-25
allegations 48-15; 52- 16;
52-4; 80-11
allegedly 129-20
Allen 127-19; 82-10
allowed 40-22
alluded 126-3
almost 134-14; 137- 25;
173-22; 42-24; 46- li;
59-14; 59-15; 63-15; 83-8
along 161-16; 47-22;
60-21; 83-16
already 143-16; 152 -9;
163-25; 221-17; 82-8
r- altering 199-25
\n alternative 177-7
alters 168-13
Although 103-18; 128 -l;
156-15; 160-18; 173- 20;
189-18; 197-2; 31--9;
41-16;
60-12; 75-20
Ok
always 126-1; 204-12;
60-8; 75-22; 97-24
l
ambiguous 187-22

amen 118-5
Amended 81-10 ; 81 -6;
81-9; 82-14; 82-17
amendments 37-3
American 124-15; 153 -li;
153-15; 163-5
among 141-23; 3-2; 93 -17;
93-20
amount 101-22; 109 -l;
109-3; 141-3; 141 -9;
143-1; 147-24; 151- 25;
152-8; 159-3; 195- 12;
195-7; 210-23; 218- 18;
218-2; 218-20; 220 -8;
91-20
amount— 147-23
amounts 194-19; 196--14;
219-2; 219-22; 220-4
AMP 49-16; 56-18
analyses 112-1
analysis 159-1; 177--16;
182-8; 40-15
analytical 160-12
and— 130-10; 16- ii;
212-21; 25-5
and/or 67-1
Anderson 55-9
animal 13-17; 138- 11;
138-17; 15-10; 168- 14;
168-17; 168-19; 205-19
animals 100-22; 13- 19;
13-23; 132-13; 15- 10;
15-4; ].68-8; 173- 23;
196-15; 198-24; 202- 10;
202-11; 202-9; 205 -l;
205-21
annotated 21-17 ; 21-9;
22-2
annotation 29-12
Annual 7-23
another 120-25; 121-3;
123-21; 13-4; 15- 21;
153-19; 165-2; 167- 18;
167-4; 184-7; 198- 18;
207-7; 214-5; 24- 24;
36-2 ; 41-20; 41-24 ;
4 1-25 ; 4 8 - 9 ; 51-:L9;
61-22; 73-15; 79-2; IS -24
answer 108-13; 109-20;
109-24; 113-2; 126- 17;
130-20; 165-22; 169 -l;
172-15; 172-23; 196- 14;
200-19; 214-14 ; 40 -8;
99-10; 99-18
answered 129-10 ; 40 -6;
92-18; 92-21

A. WILLIAM ROBERTS & ASSOCIATES

4

SCHULZ, CARL O.
answering 177-13
answers 81-11; 81-13
82-18; 82-22
,
anti-carcinogenic 205-18'
antiacid 16-11
Antiacids 16-12
anybody 149-7; 166-20;
191- 20; 199-8; 27-25
anyone 121-20; 206-2;
206-6; 25-17; 70-22
anything 103-24; 104-15;
123-1; 131-23; 135-5;
151-12; 163-8; 168-1;
173-6; 174-13; 174-22;
175-1; 175-19; 175-23;
175-7; 210-15; 25-5;
35-2; 35-25; 4-4; 4-8;
40-7; 8-5; 80-15; 85-21;
89-10
anyway 138-3; 198-15
anywhere 219-21
apparently 113-4; 128-18;
192- 18
appear 179-13; 179-15;
186-21; 28-18
APPEARANCES 2-1
appears 186-22; 5-14;
76-22
apples 127-8; 158-22
a p p l i c a t i o n 127-12;
218-16
applications 13-16;
13-18; 96-10
applied 148-18; 62-23
applies 99-19
apply 130-1
appointment 60-13
approach 126-2; 135-23;
31-10
approached 43-9
appropriate 200-16
approval 181-10; 211-8;
66-24
approximately 105-21;
16-19; 22-19; 23-7; 27-3;
95- 20
April 7-19
aquatic 138-8; 208-17;
62-23
a r e a 10-24; 10 7 - 2 ;
128-19; 167-18; 167-19;
167-21; 193-20; 201-21;
202-23; 203-8; 26-23;
30-11; 32-11; 4 0 - 2 ; (
57-14; 60-11; 74-10;
96- 14
MICROCopy

March 5, 1993
MOYER V S . DOW CHEMICAL COMPANY
areas 127-17; 176-12;
177-14; 193-22; 209-15
aren't 138-14; 84-13
Argali 151-8
argument 107-12; 107-3;
68-20

Argumentative 107-5
arise 94-10; 94-19; 94-7
arising 33-13
a r m 201-15; 201-18;
201-21
around 135-12; 164-25;
195-8 ; 20-16 ; 20-5;
23-22; 45-3; 88-24
arrangement 71-9
arrived 217-19
arriving 104-5
arsenate 50-20; 50-24
art 200-25
arthritis 67-11
article 113-10; 114--16
114-18; 196-6; 27--14
28-12; 28-23
articles 112.-13; 115-14
115-23; 116-1; 118--19
118-21; 119-12; 136--10
22-20; 227-18; 227--20
23-14; 23-16 ; 23- 18
23-3; 23-7; 24-6 ; 26-18
27-4; 27--5; 28-17 ; 28-22
30-11; 31-14; 31- 17
32-13; 73-14; 73- 15
73-9; 76-8; 77-1; 87-13
87-15 ; 87-7 ; 88- 12
88-18; 88-3; 88-8
as— 180-13
ASARCO 57-3
asbestos 165-3; 167-11;
167-19; 167-22; 167-5
a s k 117-16 ; 158-17 ;
158-18; 159-1; 169-4;
172-9; 180-21; 182-2;
194-6; 204-1; 204-20;
211-21; 216-25; 27-18;
39-2; 40-3; 5-18; 6-5;
74-20; 93-5
a s k e d 129-6; 14-25;
216-12; 65-10; 67-18;
72-9; 79-15; 80-15; 80-7;
80-9; 92-17; 99-11; 99-13
asking 106-3; 212-4;
214-4; 214-8; 70-18
aspect 198-25; 199-18;
206-4
aspects 128-7; 63-23;
77-5; 79-18

aspirin 36-17; 36-18
assay 198-16
assays 198-19; 198-22
assembling 207-21
assessment 155-15; 17-8;
170-16; 181-15; 181-21;
192-17; 227-21; 36-7;
62-24; 64-1; 64-2; 88-14;
88-19
assessor 124-10
assessors 180-14
assigned 157-4; 157-5
assistance 61-15
assistant 18-17; 4-13
assisted 207-20
associate 11-25; 18-13;
19-1; 5-9; 60-1; 61-18
a s s o c i a t e d 126-13;
164-24; 174-8; 184-10;
192- 7; 20-23; 21-4; 93-8
ASSOCIATES 1; 124-12;
124-16; 124-19; 16-23;
17-12; 17-16; 17-23;
17-4; 17-5; 17-6; 18-20;
25-10; 25-13; 26-15;
30-23; 33-17; 40-13;
40-25; 40-4; 41-24; 43-1;
45-5; 75-8
associating 74-6
a s s o c i a t i o n 115-4;
117-12; 117-7; 120-4;
126-11; 178-20; 183-22;
184-15; 185-19; 186-22;
187-14; 202-16; 30-22
assume 106-3; 109-6;
109-9; 117-19; 125-9;
140-14; 179-8; 193-17;
193- 9; 208-3
assumed 148-20; 148-23;
149-8
assuming 105-18; 105-2;
111-13; 153-10; 203-6;
220-22

assumption

193-11;

2 2 1 - 1 0 ; 2 2 1 - 1 1 ; 2 2 1 -1 2

a s s u m p t i o n s 116-11;
116-2; 148-14; 148-17;
149-9
assurance 172-18
assure 50-5
ate 202-13
Atlanta 49-3; 49-6
atoms 98-5
attach 76-6; 85-5
attaching 87-15
attachment 157-23

A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
att a c h m e n t s 227-10;
227-13; 227-17; 85-17;
86-10; 87-22
attempt 181-9; 211-1
attended 74-2
attorney 54-17
ATTORNEYS 2; 2-15; 2-2;
44-9; 9-10; 9-6
attribute 170-8; 53-22
Augusta 54-5; 58-10
author H9-20; 151-10;
75-20; 77-16
authored 64-4
authoritative 181-9
authors 115-19; 134-25
available 132-5; 177-25 /
178-1; 193-10; 193-14
193-9; 30-15; 68-19
89-15; 95-15
avenue 181-8
average 151-18; 155-24
157-20; 163-9; 217-9 /
218-9; 23-22
avoid 117-18
awarded 19-21
aware 100-12; 100-21
112-17; 113-3; 122-17 t
122- 22; 122-5; 123-14
123- 6; 123-7; 196-20
213-22; 214-6; 37-13
6-16; 75-8
a w a y 115-5 ; 147-20
147-21; 43-23
B
B 226-17; 227-1
b a c k 11-23; 111-18
114-9; 130-13; 132-22
134-5; 135-10; 135-13
144-24; 151-14; 157-1
17-11; 185-12; 20-17
203-19; 210-21; 216-11 Í
22-24; 24-11; 24-13
24-3; 25-4; 26-12; 26-17
27-14 ; 27-7 ; 28-16
29-19 ; 51-11 ; 51-8
56-24; 59-23
background 10-6; 102-21
110-25; 129-15; 134-20
134-8; 140-19; 151-14
151-15; 151-16; 155-11
163-21; 217-24; 221-21
39-21; 40-11; 60-5
backpacks 201-9
backward 26-16
Backwards 51-15
bad 110-19 ; 181-11 f
MICROCo d v

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
188-3; 55-13
B a ir d 180-9
B A IT T Y 2
b a la n c e 179-1
B a lit z 180-9
b a ll 128-9; 162-21
b and 88-24
B a n k 2-12
B a rb a ra 8-24
b a re 147-9; 47-9
B a rn w e ll 64-25
b a r r ie r 145-22

05
LO

base 1 1 1 - 2 0 ; 1 1 1 - 2 1 ;
129-18; 129-19; 31-11;
90-24; 90-25
b a s e d 102-2; 103-4;
136-14; 141-16; 171-7;
176-15; 176-18; 219-18;
219-7; 23-18; 55-17;
89-13; 90-4
bases 12-13; 216-13;
216-16; 31-11
basic 147-18
basically 116-9; 119-19;
126-9; 137-14; 168-17;
21-14; 220-14; 37-2;
40-10; 41-22; 62-13;
68-15; 74-16; 83-8
basically— 83-6
basing 103-7
basis 152-12; 165-21;
171-11; 171-6; 185-2;
200-17; 43-12; 62-7
bat 46-10
batch 194-22; 194-23
Bates 7-6
be— 76-22
Beach 2
beat 119-6
Beazer 53-20; 55-14;
55-15
b e c a m e 10-17; 25-3;
30-21; 60-1
because 102-13; 102-25;
116-1; 131-16; 131-8;
133-1; 136-20; 144-16;
147-23; 147-4; 154-24;
155-17; 156-16; 158-18;
16-14; 16-22; 164-25;
190-2; 191-23; 191-9;
193-6; 195-15; 198-12;
200-24; 202-22; 209-2;
214-9; 218-7; 219-23;
27-19; 59-7; 63-21;
66-16 ; 67-7; 75-11;
80-24; 94-13

become 11-13; 16-4; 54-9;
75-8
becomes 200-3
befuddled 135-20; 136-3;
136-5
began 11-6; 17-24; 19-10;
19-7; 20-11
begin 164-4; 44-7; 75-19
beginning 44-21; 51-15;
58-14
behaves 198-16
behind 156-25
b e i n g 107-6 ; 110-6 ;
123-4; 126-19; 126-23;
131-20; 132-25; 137-18;
140-11; 180-19; 21-10;
21-16; 21-9; 213-10;
3-13; 3-3; 48-16; 52-17;
66-5; 68-16; 92-22; 96-12
beings 93-4
believe 104-25; 111-17;
113-23; 114-1; 116-2;
118-24; 119-20; 120-9;
125-15; 129-11; 131-5;
132-19; 133-13; 136-15;
136-6; 141-11; 154-8;
162-19; 168-20; 171-4;
171-7 ; 171-9 ; 19-25;
198-10; 202 -2 1 ; 202 -6 ;
206-24; 36-19; 48-22;
76-21; 8-2; 9-16; 91-12;
91-16; 93-7; 95-3
below 157-20; 163-9
Bemie 206-19; 206-23
best 126-20; 192-12;
52-6; 76-12
better 144-15; 22-4
between 113-5; 114-13;
114-24; 114-7; 117-8;
118-23; 119-15; 119-8;
128-20; 142-25; 152-24;
178-20; 178-23; 184-16;
185-19; 201-23; 32-24;
36-17; 6-6 ; 74-25
beyond 155-10; 24-12;
96-14
bias 187-16 ; 188-1;
204-18
biased 204-19
bibliographies 132-23;
31-16
bibliography 2 1 - 1 0 ;
21-17; 22-2; 23-13; 27-1;
27-4; 29-11; 29-12
big 17-15; 29-7
billion 131-8

A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
Billy 57-8
bioaccumulate 136-23
bioassay 38-14
s
bioconcentrate 136-23
biological 135-18; 14-9;
141-12
biologist 103-19
bioresearch 14-19; 213-3
bit 10-6; 10-8; 144-10;
163-1; 165-18; 198-10;
209-18; 209-24; 220-19;
24-2; 32-5
bitter 25-18
Blankenship 49-15; 50-12;
50-8; 53-7; 56-18
blend 49-11
blended 71-1
block 39-13
blood 142-9; 217-25
board 195-9
boards 68-1
boat 109-14
B o b 1 0 3 - 1 0 ; 104-6;
105-20; 108-21; 109-7;
144-24; 146-21; 148-13;
148-18; 149-14; 157-13;
159-3; 173-7
BOBO 2
b o d y 102-25 ; 103-1;
135-13; 141-25; 143-2;
144-12; 144-4; 144-6;
152-1; 152-2; 152-4;
152-9; 154-14; 154-2;
155-6; 156-16; 157-13;
161-17; 177-25; 179-16;
201-24; 94-9
Boehringer 215-12; 215-14
Boehringer-Ingelheim
215-18; 215-24; 216-4
Boehringer-Mannheim
215-19
Bogart 55-20
Bond 120-9
book 167-6; 167-9; 196-6;
196-8; 63-12; 64-1; 64-4;
73-22
books 195-21; 21-16;
63-17; 73-22
bookshelves 73-21
b o m 175-5
boss 17-22; 40-25; 77-24
boss' 41-12
both 133-20; 135-16;
17-20; 183-20; 192-4;
205-23; 205-24; 206-22;
215-21; 31-2; 36-7;
MICROCopy

March 5# 1993
MOYER VS. DOW CHEMICAL COMPANY
49-16; 49-17; 61-20;
61-3; 70-16; 71-3; 78-6
bottom 83-12
bought 42-11
boy 208-13; 41-4; 49-10;
56-20; 57-7
Brain 7-18
b r a n c h 134-5; 14-6;
15-21; 16-4; 16-7; 68-11
Brand 71-4
break 118-14; 118-9;
173-1; 38-20; 39-22;
44-15; 59-3; 79-24
breakage 203-7
breast 67-3
briefly 175-9; 176-2
bring 74-14
brings 120-25
Bristol-Myers-Squibb 10-4
broad 177-1; 209-15;
211-20; 211-24; 90-22;
93-14
broader 142-24; 60-17;
91-11
broke 154-21; 154-22
brought 179-18; 45-25;
74-11; 74-16; 86-24;
87-10
Brown 4-15; 53-13; 54-15;
54-17
budget 78-4
Building 2-12; 39-13
bulk 61-21; 62-14; 62-2
bunch 41-5
burden 102-25; 103-1
burdens 154-2; 156-16
Bureau 13-11; 14-24;
14-8; 15-19; 16-2; 16-6
buried 84-16
Bumbaum 189-16
business 4-21; 4-23;
44-13; 51-24; 67-8
businesses 5-6
busy 66-14
but's 171-23
but-- 199-16; 38-20
by— 52-17
b y - p r o d u c t s 170-16;
170- 24; 171-3; 171-5;
171- 9
C
C-O-S 4-6
C-o-v-e-l-l-o 64-5
cabinet 73-20
cabinets 73-14
calculate 135-13; 135-7;

SCHULZ, CARL O.

219- 12
227-19; 32-7; 47-13;
calculated 134-18
47-15; 48-16; 48-22;
c a l c u l a t i o n 159-6;
49-19; 49-9; 50-14; 51-4;
220- 25; 221-9
5 1 - 6; 52-16; 52-17;
calculations 101-17;
5 2 - 21; 52-4; 53-16 ;
103-4; 159-9
53- 17; 55-18; 56-21;
calendar 72-6
56-23 ; 57-9 ; 67-12 ;
calender 72-18
80-11; 88-4; 88-8 ; 89-25;
California 47-5; 8-24
90- 18; 91-16; 91-23;
call 127-25; 160-19;
91- 4; 92-10; 93-13; 93-3;
160- 23; 175-24; 199-1; 93-9; 94-1; 94-2; 94-3
22-4; 44-8
cancers 164-19; 165-7;
called 103-25; 12-12;
176-4; 183-19; 202-11;
14-19; 182-18; 183-6;
93-15; 93-25; 94-7
21-12; 216-2 ; 25-9;
cannot 103-20
31-21; 35-18; 36-19;
capability 197-1
capitals 154-11
38-9; 42-5; 56-6; 64-1;
7-15; 75-9
carbaryl 13-3
came 124-24; 137-7;
Carbide 11-14
156-22; 156-25; 16-3;
carcinogen 148-2; 196-17;
21-14; 23-3; 24-2; 52-12;
196-20; 196-9; 197-25;
60-21; 72-23
199-1; 202-19; 202-8;
campus 61-13
35-19; 35-22; 91-13;
c a n ' t 103-17 ; 13-3;
92- 23; 92-25; 93-12;
132-23; 133-14; 133-23;
93- 2; 95-4
134-1; 150-25; 150-3;
carcinogenesis 112-23;
161- 12; 161-15; 173-13; 114-13; 123-13; 32-11
178-11; 182-10; 182-9;
carcinogenic 100-14;
186-3; 189-19; 19-9;
100-2; 100-22; 109-15;
191-21; 195-25; 200-17;
110-14; 111-6; 112-16;
200-19; 204-15; 205-10;
112- 20 ; 112- 22 ; 122- 20 ;
207-3; 214-18; 27-12;
122-21; 122-9; 123-2;
28-16; 32-20; 41-10;
171-10; 173-23; 174-3;
49-13; 49-20; 52-7;
196- 25; 199-2; 199-22;
56-20; 56-23; 67-13;
199-5; 97-20; 97-23;
98-6; 99-17; 99-22
67-14; 68-24 ; 71-4;
79-13; 9-21; 95-17
carcinogens 196-22;
can— 39-23
197- 21
cancer 1 0 1 --3; 104- 23;
care 127-18; 177-13
104 - 6 ; 105 - 6 ; 105 -9;
careful 200-23; 204-11;
106- 10 ; 109-■17; 1 1 0 -15;
204-12; 204-15
113--l; 113--18; 113 - 6 ; carefully 214-12; 216-19;
114-•25; 114 -8 ; 115- 16;
75-21
117-•8 ; 118-23; 119- 16;
careless 178-18; 178-22;
119-*8 ; 1 2 0 --li; 120 -4;
182-7; 186-7; 188-15
126- 13; 164--15; 164- 16;
CARL 1-14; 223; 223-3;
164- 18; 164--2 1 ; 165- 1 1 ; 226- 19; 226-5; 227-11;
165- 14; 165--20 ; 165-25;
227- 15; 227-5; 227-8;
166- 13; 166--16; 166- 18;
3-12; 3-17; 5-23; 83-25;
166- 5; 172- 1 2 ; 172- 17;
85-14; 86-7; 87-21
.
172--19; 172-6; 174 -7;
CARLTON 2
a175- 15; 175 -17; 184 -5;
Carol 192-16
196- 15; 198- 13; 198- 14;
Carolina 224-4; 225-3;
198- 18; 198 -23; 200 -3;
3-20; 5-11; 54-24; 56-16;
2 0 1 -25; 201 -3; 202 -17; 60-2; 60-20; 65-1; 7-19
2 0 2 --5; 216 - 2 ; 216 -9; Carolinas 7-17

A. WILLIAM ROBERTS & ASSOCIATES

MICROConv

<4

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

CO

,W\

Carr 49-4; 49-6
106-10; 164-24; 165-3;
carried 201-9
165-7; 48-16; 52-17;
carries 204-18
80-12; 90-18; 92-10; 92-4
carry 135-12; 153-25;
causes 165-11; 165-14;
182-12
165-24; 165-6; 166-4;
case 100-3; 107-11;
184-5; 198-13; 91-23;
1 1 2 -9; 1 2 --22 ; 127 -9
93-13; 93-14; 93-23; 93-3
13- 17; 14--l; 141- 15
causing 167-20; 199-2
148 - 2 ; 15- 15; 150- 15
cautious 67-6
CECIL 1-21; 224-3; 225
156--18; 157 - 1 2 ; 176--20
187
202
-22
20
;
cell 199-24; 199-25;
183--13;
-3;
20
7-8
200-2; 200-3; 94-7
206
; 21 -8
Center
12-4; 63-17
216 - 1 2 ; 220-5; 220 -8
12
34- 23; 45- 1 0 ; 45Central 7-16
certain 116-2; 125-23;
45- 14; 46- 17; 46- 24
47- 19; 47 -24 ; 4 7 - 8
127-7; 128-19; 139-4;
48- 17; 48 - 2 0 ; 49 - 1
155-3; 168-18; 168-19;
49- 21; 50-19; 50-4; 50-8; 173-21; 186-23; 198-16;
50- 9; 51-1; 51-3; 52-21; 213- 23; 31-24; 32-11;
53-15; 53-17; 53-21;
52-20; 93-8
53- 25; 53-7; 53-8; 54-10; certainly 121-22; 125-17;
5 4 - 16; 54-22; 54-23; 161-24; 174-6; 37-16
5 5 - 10; 55-25; 55-7; certainty 90-17; 91-22
5 6 - 19; 56-4; 57-20; CERTIFICATE 224-1; 226-9
57- 22; 57-4; 57-5; 58-15; certify 223-4; 224-20;
58- 16; 58-2; 58-22; 58-6; 224-5
58-7 ; 71-22 ; 74-18 ; chain 138-5; 164-4
74-22; 79-15; 79-19;
change 187-17; 195-4;
79-24; 80-8; 80-9; 87-11;
203-6; 209-24; 223-9
89-11; 89-19; 90-12;
changes 199-20; 54-11
changing 154-20
92-3; 95-1
case— 201-14
Chapter 185-8; 190-2;
cases 108-3; 120-21;
190-3; 191-5; 196-7;
227-25
166-15; 167-5; 202-17;
charge 16-7; 71-15; 72-15
202-18; 226-22; 44-15;
45-14; 46-15; 48-14;
chargeable 43-21; 59-10;
49-12 ; 50-1 ; 50-16 ; 59-22; 72-20
51- 20; 51-7; 51-9; 52-12; Charles 180-8
52- 15; 52-25; 52-4; 53-1; Charleston 1; 56-16
53- 9; 54-9; 55-16; 58-13; Charlotte 7-18
check 123-16; 216-21
9-1; 9-3; 9-7; 9-9
checked 103-2
catch-all 94-16
Chem 32-7; 32-8; 64-23
category 176-6; 93-24;
CHEMICAL 1; 1-10; 1-9;
94-10; 94-17; 98-7
causal 114-6; 117-12;
101-19; 101-20; 105-7;
108-22; 111-25; 112-8;
178-20
causation 172-6; 52-5
13-23; 131-11; 143-18;
cause 101-3; 105-15;
145-15; 146-16; 146-9;
105-18; 105-2; 107-12;
153-18; 166-22; 195-24;
109-16; 110-14; 114-12;
2; 2-9; 201-2; 206-25;
164-15; 164-16; 166-12;
206-3; 206-7; 207-15;
170-23; 172-12; 184-10;
211-17; 211-25; 212-15;
196-15; 198-23; 205-12;
214- 24; 215-16; 215-21;
213-24; 224-22; 91-16;
219-1 ; 30-3 ; 37-14 ;
91-4; 93-8 ; 99-22
38-12; 49-14; 50-21;
caused 102-16; 105-7;
55-22; 56-13; 57-24;

SCHULZ, CARL O.
58-17 ; 58-20 ; 65-5;
71-10; 91-3
chemically 131-13
chemicals 100-1 1 ; 100-12 ;'
100- 19; 100-20; 100-4;
101- 16; 111-7; 12-15;
121-1; 121-13; 121-23;
121-4; 122-18; 122-6;
129-13; 13-5; 144-25;
159-4; 164-14; 175-3;
207-17; 36-8; 50-17;
52-19; 52-5; 53-23;
54-13; 55-19; 56-22;
7-16; 71-12
chemist 1 1 - 1 1 ; 1 1 - 1 2 ;
11-20; 11-9; 160-12
chemistry 10 -1 1 ; 1 1 -1 2 ;
11-20; 11-6; 39-20
chemosphere 74-2
Chevron 38-5; 47-12
chief 15-20; 16-4; 68-11
children 155-2
chloracne 170-23; 171-17;
171- 22; 172-10; 172-16;
172- 18; 172-7; 213-24;
214-18; 215-1; 53-21
chloracnegenic 169-19;
169- 22; 170-17; 170-25;
170- 8
chloracnegens 170-1;
170-3
c h l o r i n a t e d 126-14;
134-12; 213-23; 57-2;
97-15; 98-2
chlorine 137-24; 98-5;
99-21
Chlorox 53-13; 54-15
Chlorox's 54-17
choose 200-24
chromated 50-20; 50-24
chromosomal 199-3
chronologically 45-2
Cl 1 •
cigarette 117-8; 221-2
C U T 206-24
CIRCUIT 1; 1-1
circulation 203-2
cirrhosis 56-25
c i t e 180-9 ; 190-18;
190-19
cited 134-24; 151-4;
188-20; 87-7
citing 190-20
civil 117-21; 3-4
,
claim 54-19
claimed 55-21

V ______________________
A. WILLIAM ROBERTS & ASSOCIATES

8

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

claiming 47-13; 50-19
college 60-8
compilers 180-18
claims 53-5; 54-17
Colojefski 17-14
Complaint 81-10; 81-11;
Clapp 150-1; 81-18
Columbia 1; 1-19; 225-3;
82-14; 82-18
class 164-18; 63-25
3-19; 5-1; 5-2; 55-4
complaints 81-6; 81-7
classes 141-14
combination 121-3; 121 -8 ; complete 116-19; 166-21;
classic 53-1; 93-12
122-18; 122-8; 138-1
224-17; 25-25; 26-11;
classification 94-17
combined 64-17
73-24; 76-12; 77-2
clean 146-17; 174-17
come 115-6; 126-19;
completed 20-20
clear 106-2; 132-25;
135-16; 178-11; 210-18;
completely 101-15; 135-20
138-14; 153-3; 172-19;
completeness 25-24
32-1; 49-20; 61-10;
205-14; 209-3; 217-1;
61-14; 61-19; 62-21; 63-7 completion 78-3
218-8
comes 152-24; 198^4;
complex 152-24
clearer 100-10
211- 15; 39-21
compliance 14-25; 15-11
clearly 105-14; 141-22;
coming 56-24; 60-22;
comply 207-16
145-9; 198-19; 205-2;
66-20
component 170-6; 50-22
26-21
comment 201-10
components 170-7
Clement 124-12; 124-16;
comments 176-19; 35-20;
compound 141-4; 186-9;
124-18; 16-23; 17-12;
35-21
217-25; 218-18; 218-2
17- 15; 17-22; 17-4; 17-6; c o m m e r c i a l 132-11;
compounds 12-19; 12-20;
1 8 - 20; 19-8; 30-23; 132-16; 133-17; 133-25;
12-24; 13-1; 137-12;
33-17; 35-17; 37-11;
97-13
161-10; 170-22; 178-20;
4 0 - 12; 40-25; 4 0-3; Commission 225
194-15; 194-19; 195-12;
4 1 - 13; 41-23; 42-10; committed 190-25
213-23; 214-25; 96-6;
4 2 - 18; 42-25; 43-10; committee 180-20; 181-1;
98-7
43- 20; 43-22; 44-12; 189-16; 189-22; 68-21
computer 31-10; 31-3;
44- 20; 44-4; 45-5; 60-16; committees 167-25; 61-16;
72- 4; 72-6
75-10; 75-8; 75-9; 78-7
68-1
Computer-Aided 1; 224-15
conceivable 102-19
Clement's 36-15; 39-3;
common 103-1; 123-18;
43-22
144-2; 28-4; 31-11
c o n c e n t r a t e 138-11;
Clements 124-21; 77-15
commonality 94-19
138-15; 220-9
client 125-5; 59-18;
companies 13-15; 166-4;
concentrate— 221-14
66 - 11 ; 66-12
215-13; 36-14
concentrated 221-12
clients 40-18; 43-11;
COMPANY 1; 1-10; 112-8;
concentration 135-5;
59-6; 64-21; 66-15
113-9; 13-6; 133-6;
143-1; 154-13; 163-1
climbed 156-24
17-15; 192-15; 2; 2-9;
concentrations 135-12;
clip 87-5
206-3; 206-7; 207-15;
140- 19; 142-12; 142-9;
closely 197-3
212- 15; 215-12; 215-16; 152-13; 217-25
clothing 102-13; 102-14;
215-8; 25-8; 25-9; 30-3;
Concepts 62-12; 62-17;
108- 19; 109-10; 109-13; 37-12; 37-21; 38-12;
63-13
109- 9; 110-1; 129-25; 41- 24; 41-25; 42-12; concern 164-11; 33-13
145-11; 145-12; 145-23;
42- 3; 42-4; 42-9; 43-24; concerned 101-13; 112-16;
145-24; 145-3; 147-21;
50-23; 58-18; 58-20
129-2; 13-25; 15-14;
147-5; 149-3
compare 156-13
15-4; 163-11; 206-11;
co-author 64-6
compared 102-21; 110-24;
73- 18; 92-23; 97-21
co-pilots 156-22
129-15; 134-8; 218-20;
concluded 115-20; 118-22;
CO. 1
221-2
119-15; 154-9
coal 48-23; 53-18
conclusion 111-22; 114-4;
comparing 127-8
cockpit 156-24
c o m p a r i s o n 156-13;
115- 7; 130-6; 137-7;
Coffee 49-14; 50-10;
218-24; 219-5; 22-25;
141- 21; 144-7; 185-lli
50-12; 50-17; 53-7; 56-12
221-5
185- 16; 185-24; 186-13?
cohort 108-2; 1 2 0 - 1 2 ; compensation 56-19
186- 25; 186-6; 187-19;
competent 114-3
127-10; 157-7; 183-14;
187- 21; 195-19; 20-7
189-1
competition 43-14
c o n c l u s i o n s 115-23;
cohorts 120-21
compilation 31-22
116- 1; 116-11; 117-1;
coincidental 34-25
compile 32-10
119-5; 182-3; 183-18;
colleagues 184-15; 185-18 compiled 134-25
184-13
A. WILLIAM ROBERTS & ASSOCIATES

n

MICROCopv

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

Cfi
CD

<=>

condition 146-12; 146-18
conditions 148-17
conducting 123-11; 15-6;
15-8
Conference 137-15; 180-5
conference. 213-19
conferences 74-3
confidence 110-4
confident 130-17; 130-19;
147-9; 26-9
confidential 35-5; 67-7
confines 65-7
confirm 205-7
confounded 120-7
confounding 187-17
confused 10-8
confusing 153-7
Congress 33-3
congressional 33-11
conjunction 61-17
connection 213-7; 214-20;
36-24; 37-1; 68-5
consider 107-25; 108-16;
112-19; 125-25; 127-21;
182-16; 183-12; 183-9;
198-5; 198-7; 87-10
considerations 102-4;
171-13
considered 108-5; 129-7;
170-4
constituents 65-6
consult 43-11
consultant 124-11; 70-10;
70- 5; 9-15
consultants 189-11; 189-7
consultations 44-3
consulting 17-6; 191-14;
4-2; 4-21; 43-13; 44-23;
44-5; 44-8; 45-1; 58-25;
64-15; 64-17; 71-16;
71- 9; 9-17
consumption 140-12
contact 202-19; 202-8;
79-17; 83-20
contacted 60-23; 74-21;
75-2; 79-15
contain 197-16; 197-18;
200-22; 96-17
contained 193-6; 197-12;
197-6
containing 87-11
contains 22-23; 95-7
c o n t a m i n a n t 101-19;
101-23; 112-10; 98-15;
98-21
contaminants 1 0 0 - 1 1 ;

SCHULZ, CARL O.

112-17; 155-20; 96-22;
179-25; 190-11; 190-21;
97- 12; 97-19; 97-6
191-3; 63-17; 70-17;
contaminated 129-22;
70-19; 73-6; 75-16;.
134-14; 178-24; 184-17;
76-22; 82-14; 82-17
'
185-20; 219-20; 220-15;
cord 56-4
95-10; 96-20
corporate 17-21
contaminating 1 0 2 -2 0 ; CORPORATION 1-9; 10-3;
103-2
12-6 ; 1 7 - 1 9 ; 17-9;
contamination 130-3;
191-13; 191-9; 2; 36-22;
130-9; 219-23; 45-12;
59-21; 8-23
98- 17
correct 1 0 - 1 1 ; 1 0 - 1 2 ;
contemplate 177-17
1 0 -2 0 ; 1 0 -2 1 ; 1 0 1 - 6 ;
Contents 31-22; 31-23;
103-11; 103-8; 105-22;
32-1; 77-13
106- 11; 106-19; 106-5;
context 142-5; 178-3;
107- 3; 108-22; 11-7;
185-1; 185-2
11- 8; 110-10; 110-15;
110- 16; 110-7; 111-19;
continuing 211-13; 62-6
continuum 116-19; 126-4
111- 3; 113-13; 113-18;
contraceptive 15-20;
113- 25; 113-7; 114-13;
16-15; 16-9
114- 25; 115-17; 115-24;
contraceptives 16-13
116-3; 116-6; 119-8;
contract 12-10; 124-22;
12- 1; 121-14; 121-24;
13-7; 18-18; 19-20;
128- 15; 128-16; 128-25;
1 9 - 21; 19-23; 20-1; 129- 16; 129-17; 129-3;
2 0 - 1 1 ; 2 0 - 8 ; 21-24; 129-9; 13-11; 13-12;
21- 25; 22-19; 24-22; 13- 8; 134-11; 136-18;
139- 7; 14-12; 14-4; 14-7;
24-24; 24-9; 25-1; 25-19;
29-17; 32-17; 33-10;
140- 13; 140-15; 140-18;
141- 6; 142-14; 145-14;
34-7; 35-15; 35-3; 36-3;
3 6 - 5; 37-18; 37-23; 146-10; 146-11; 146-20;
37- 25; 38-10; 38-7; 39-3; 148-3; 155-12; 155-13;
39-4; 42-22; 59-8; 66-1;
155-7; 155-8; 162-11;
66- 6 ; 75-19; 77-5; 79-1; 162-12; 162-14; 162-5;
162-6; 162-9; 170-18;
79-11
contracted 36-15
18-3; 182-3; 182-4;
contractor 18-21; 24-24
183-7; 189-5; 194-12;
contracts 18-24; 36-11;
194-13; 196-4; 197-2;
36-6; 37-12; 37-13; 40-4;
198-2; 20-25; 208-6;
67- 16
217- 12; 217-21; 217-7;
contractual 37-20
218- 11; 218-5; 218-6;
contrary 187-2
222-1; 222-3; 23-5; 23-9;
contribute 98-5
24-7; 31-4; 33-15; 34-1;
contributors 77-19
40-19; 42-1; 42-2; 43-1;
control 127-9; 183-20;
44-5; 44-6; 47-25; 60-4;
195-16; 200-3
63-1; 63-2; 69-21; 76-19;
controlled 68-15
76-20; 79-9; 8-11; 8-15;
converted 145-17
8-16; 8-6 ; 8-7; 80-13;
Cook 47-23; 47-5
80-14; 81-3; 81-5; 83-18;
copies 151-7; 29-4;
87-17; 89-19; 89-20;
31-15; 70-12; 73-12
89- 23; 90-1; 90-2; 90-8;
coping 63-16
90- 9; 91-24; 92-20; 92-6;
copper 50-20; 50-22;
93- 4; 93-6; 94-20; 94-21;
50-24; 51-1; 51-4; 51-5;
94- 23; 96-9
56-13
corrections 223-7
(
copy 112-2; 125-13 ; correctly 10-17; 21-24;
125-8; 150-20; 179-18;
92-7

A. WILLIAM ROBERTS & ASSOCIATES

10

MICROCopy

March 5/ 1993
MOYER V S . DOW CHEMICAL COMPANY

SCHULZ, CARL O.

y?'e

COSAR 3-22; 3-23; 4-1;
credible 168-11; 179-10;
DATE 1-15; 150-9; 178-16;
4- 10; 4-5; 44-1; 44-21; 179-2; 182-17; 183-1;
193-12; 203-24; 22-16;
5- 3
183- 10; 186-7; 188-15; 22-21; 223; 224-7; 25-3;
Cosiba 202-11; 202-12;
202-6; 203-3; 216-8; 91-1
33-6 ; 71-23 ; 83-19 ;
206-19; 207-11
CREEK 1
85-22; 86-1
could 102-11; 102-17;
crib 45-23
dated 227-12; 227-16;
103-14; 109-20; 116-11;
criteria 111-24; 12-12;
227-7; 227-9; 81-12;
125-13; 126-7; 131-11;
12-18; 192-17; 74-6; 74-8
81-13; 82-19; 82-23;
166-19; 166-20; 174-3;
critical 21-10; 21-17;
84-2; 85-16; 86-8 ; 87-21
200-11; 203-21; 205-23;
22-3; 23-1; 29-14; 77-7
David 180-8
205-24; 21-21; 213-24;
criticism 116-25; 184-18;
day 135-14; 135-9;
2 2 0 - 1 3 ; 25-4 ; 25-6;
185-21
139-13; 139-14; 139-24;
30-20; 30-7; 34-18; 37-8;
c r i t i c i s m s 176-19;
141-2; 147-11; 151-23;
44-15; 52-1; 52-2; 60-17;
177-21; 203-15
158-21; 160-9; 217-6;
68-17
criticize 204-10
218-3; 218-9; 225-2;
couldn't 205-23; 61-24
critiquer 204-6
65-24; 72-19
C o u n s e l 1-20; 2-1;
cross-contamination
day-to-day 130-8
224- 21; 3-3; 5-13; 53-25; 131-12; 131-18; 131-20
days 147-12; 210-17;
55-3
Crum 159-7
211-5; 219-22; 32-6
C O U N T Y 1-2; 100-16;
crumbles 115-5
DDT 45-12
Crump's 150-18
de 27-24
101-16; 109-8; 110-14;
110-24; 129-13; 148-22;
Cup 56-14
dead 119-7
159-5; 164-14; 175-3;
cure 165-9; 198-14
deal 141-22; 184-19;
218-17; 219-3; 221-19;
curious 46-2
185- 22; 51-4
2 2 5 - 3; 5 5 r 2 4 ; 55-9; current 199-20; 31-21;
dealing 113-10; 15-3;
32-4
84-25; 90-19; 91-20;
9-19
currently 54-8
deals 71-11
92-10; 92-2
couple 11-21; 156-10;
curriculum 5-14; 5-21
decade 214-21; 24-15
216-25; 217-1; 67-12
DECEASED 1; 2
Curt 137-4
cushy 156-22
course 120-2; 124-2;
decided 11-13
130-5; 143-17; 145-4;
cut 183-14; 203-13; 95-11 decisions 180-19
deduced 92-2
146-22; 16-22; 189-21;
CUTLER 2-11
cutting 173-12; 173-15;
deep 203-10
211-16; 25-18; 25-23;
34-17; 35-4; 61-21;
173-22; 174-10; 175-18;
defendant 112-9; 2-15;
61- 25; 62-13; 62-18; 176-10
51-2
CV 62-9
62- 2; 73-24
D e f e n d a n t s 1-12; 2;
cycle 136-22
courses 61-19; 62-4;
80-19; 85-21; 87-2
D
62-6; 63-1; 63-10; 63-6
defendants' 150-8
Court 1; 1-1; 172-25;
D 2; 226-1
defense 188-5; 47-24;
D-i-e-t-r-i-c-h 41-9
47-6 ; 49-15 ; 54-16 ;
224-3; 54-25
cousins 96-5
d a i l y 130-8 ; 135-2 ; 55-21; 56-3; 57-3; 9-10;
Covello 64-5
136-10; 136-16; 137-10;
9- 6
deficits 53-22
cover 149-10; 45-23;
138-20; 152-12; 152-7;
51-9 ; 77-12 ; 83-17 ; 217-4; 72-18; 72-6
defined 176-5; 93-24
83-22; 85-23
dairy 138-13
d e f i n i t i o n 161 - 1 1 ; *
coverage 26-8
damage 199-3; 54-10;
196-16; 198-16
H
covered 149-19; 20-12;
5 5 - 17 ; 55-25 ; 55-7 ; definitive 127-21
34-19; 71-8; 99-18
5 6 - 10; 57-20; 57-22; degree 10-10; 10-13;
covering 27-1; 74-3;
57- 4; 58-5; 7-16
10- 15; 102-18; 11-19464
77-10
d a t a 13-20 ; 134-25 ; 110-3; 126-8; 127-8;
covers 149-11; 41-22
129-2; 168-18; 173-20;
14-22; 153-23; 168-19;
covers— 82-3
179-24; 180-18; 182-10;
186- 18; 205-5; 90-17;
cows 138-6
184- 8; 185-9; 208-22; 91-22
creams 16-17
degrees 183-3
209-25; 210-23; 210-9;
created 63-16
demonstrated 118-22
213-13; 31-10; 31-11;
Denmark 182-14
credibility 179-5
34-22; 34-8; 37-4
A. WILLIAM ROBERTS & ASSOCIATES

1i

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

CO

>
\

SCHULZ, CARL O.

denture 67-9
67-3; 67-4
88-15 ; 88-20 ; 88-4;
deny 166-4
Devine 4-25
93-21; 93-23; 98-21;
Department 10-25; 123-22;
DFT 191-4; 227-24
98- 25; 99-3
60-23; 61-13; 61-2
Di 197-20
dioxins 100-7; 111-9;'
depend 129-4
diagnose 103-14
123-2; 124-7; 130-7;
depending 208-18
diagnosed 104-6
133-20; 134-13; 134-14;
depends 117-14; 127-16;
diagnosis 103-17; 104-17
136- 21; 137-18; 137-23;
127-4; 27-9
Diamond 37-15; 38-4
137- 6; 138-15; 138-2;
DEPONENT 223-1; 226-8
dibenzo 111-9; 98-2
138- 20; 141-20; 142-8;
deposed 47-22
dibenzo-p-dioxins 98-2
144-11; 154-3; 162-5;
DEPOSITION 1-14; 150-7;
dibenzofuran 197-4
162-8; 163-24; 164-8;
Dick 206-19; 207-11
157-24; 159-24; 174-19;
168-20; 178-25; 196-19;
176- 16; 176-17; 176-19; die 166-17
196- 23; 197-16; 21-4;
177- 15; 179-20; 200-10; died 49-18; 54-18; 54-19;
27-10; 32-13; 73-16;
204-14; 204-2; 221-18;
56-20; 56-25; 57-9
74- 8; 79-20; 89-1; 97-15;
222-6; 223-5; 224-16;
Diehl 57-3
99- 20
diet 136-12; 136-17;
224-6; 3-10; 3-3; 3-6;
direct 164-2; 41-15;
45-15; 5-22; 52-8; 71-19;
136-20; 138-13; 138-18;
41- 19; 61-14
81-15; 81-16; 81-17;
139- 2; 139-20; 139-25; directly 165-23; 169-25;
81-23; 83-2; 83-4; 84-19;
140- 11; 140-3; 140-6; 187- 2
86-15; 86-3; 86-4
140- 9; 141-9; 164-3; director 18-13; 19-2;
d e p o s itions 149-14;
202-14
77-14; 77-15; 77-20
149-17; 149-23; 150-5;
Dietrich 41-14; 41-9
disagree 173-21; 182-2;
d i f f e r e n c e 135-18;
169-11; 219-8
183-24; 184-20
deregulates 199-23
146-25; 173-18; 210-23;
disagreed 176-8
derivative 109-3
6-15; 95-24
discovered 165-1; 169-19;
dermatologic 54-11
differences 6-6
27-22
describe 23-19; 73-3
different 127-5; 127-6;
discuss 122-17; 122-5;
described 146-9; 32-15;
14-6; 142-21; 143-22;
197- 25
85-23
155-25; 156-15; 164-1;
discussed 119-14; 119-6;
describing 139-3; 142-22;
166-3; 18-22; 184-5;
150-15; 150-6; 179-19;
88-13; 88-3
190-5; 205-24; 60-14;
188- 21; 188-25; 189-1;
designed 173-25; 198-17;
63-19; 80-25; 94-4; 94-7;
201-20; 207-6; 216-17;
21-19
94-8; 96-6
216-5; 218-12; 221-17;
differential 187-16
detail 31-6
75- 14; 79-18
detailed 63-25
differentiating 178-23
d i s c u s s i n g 125-19;
details 49-20
difficult 142-16; 154-8;
137-17; 9-9
detect*160-4
171-2; 184-25
discussion 100-6; 198-5;
detected 111-25; 160-3
72-22; 78-12
digestive 140-13; 140-15
detection 160-10; 160-14;
d i i s o c y a n a t e 38-14;
disease 201-10
160-3; 160-9
disposal 64-25
38-17; 38-18; 39-11
determination 13-21
disposed 65-8
dioxin 111-11; 126-15;
determine 101-25; 132-2;
135-8; 137-15; 137-2;
dispute 103-9; 116-11
143-12; 165-13; 214-25;
141- 24; 143-18; 143-24; disregard 108-8
24-13
dissect 116-10
143-25; 144-5; 153-22;
develop 12-12; 65-10;
155-19; 156-8; 157-11;
distinct 141-14
66-20
162-11; 162-18; 162-24;
distress 54-18; 54-20
developing 12-17; 65-17;
d i s t r i b u t i o n 156-4;
171-23; 179-24; 180-5;
65- 18
181-10; 181-15; 181-21;
157-7; 6-24; 7-21
development 199-7; 36-10;
181-3; 193-2; 194-14;
division 18-14; 18-2;
36-9
194-18; 195-12; 195-8;
18-6; 18-8; 19-2; 42-20;
developmental 7-7
4221; 68-12
197-20; 198-13; 202-16;
d e v i c e 36-23; 37-3;
202-24; 202-7; 207-12;
divisions 18-4; 18-7
66- 22; 69-15; 69-9
207-3; 219-20; 219-25;
Diwan 78-6
,
devices 66-15; 66-19;
Dixon 74-1
220-15; 227-22; 28-23;
66-22; 67-10; 67-11;
46-12; 73-23; 74-7; 76-8;
docket 125-17
A. WILLIAM ROBERTS & ASSOCIATES

12

MICROCopy

MOYER V S .

March 5, 1993
DOW CHEMICAL COMPANY

doctor 103-14; 199-15;
Dow— 39-7
199-18; 89-21
dozen 13-4; 18-16; 51-19
doctor's 199-19
Dr 1 1 8 - 2 0 ; 14 9 -2 3 ;
doctorate 1 1 - 1 2
150-11; 150-9; 157-24;
document 111-24; 112-3;
159-7; 164-25; 176-14;
124- 17; 124-25; 124-5;
176-24; 176-8; 177-24;
125- 14; 125-8; 136-10; 179-19; 182-6; 182-9;
187-6; 191-4; 22-18;
203-15; 204-2; 227-5;
22- 22; 227-24
6-3; 75-10; 80-7; 81-14;
documentation 112-7;
81-15 ; 83-1; 83-25 ;
215-7; 89-11
84-18; 84-20; 84-21;
documents 12-13; 12-19;
84-9; 85-24; 86-2; 9-13
154-16; 178-2; 178-3;
draft 179-23; 181-5;
185-17; 185-7; 187-6;
219-19; 227-23; 30-18;
191-4; 227-24; 35-21
71-18; 74-12; 74-14;
drafted 78-9
74-17; 74-5; 74-8; 79-21;
drag 133-24
80-10; 80-21; 80-23;
86-23 ; 87-1 ; 88-25 ; dramatic 24-18
Drawer 2
89-16; 89-6
drinking 111-23; 74-7
doesn't 107-5; 108-1;
131- 13; 131-16; 166-12; dropped 128-9; 24-2
170-5; 172-24; 184-10;
Drug 13-10; 13-16; 13-18;
187-10; 193-12; 199-1;
13- 22; 14-18; 14-23;
4- 7; 95-9
1 4 - 5; 15-18; 15-21;
doing 123-10; 123-16;
16-10; 16-15; 16-16;
123- 18; 135-16; 154-14; 16-8 ; 213-14 ; 37-4;
177-16; 219-15; 221-8;
66-23; 68-10; 68-12;
68-16; 68-18; 6 8 - 2 ;
43-5; 43-6
domain 30-15
68-23; 69-10
don't— 127-3
d r u g s 13-18; 15-10;
d o n e 114-23; 120-8;
1 5 - 19 ; 16-11 ; 16-6;
124- 18; 127-19; 132-1; 213-10
132- 10; 132-6; 133-9; Drum 50-9; 57-7
due 187-15
151-8; 155-3; 156-1;
duly 224-9; 3-13
159-10; 191-25; 205-6;
dunked 147-10
215-24; 215-8; 217-16;
2 3 - 10; 23-14; 26-14; duration 105-6; 107-7
3 0 - 2 5 ; 3 2 - 16 ; 5 0 - 6 ; during 218-16; 33-16;
5 8 - 17; 58-19; 59-13; 34-4; 35-9; 40-12; 70-4
dust 202-14
59- 14; 66-13
dose 138-20; 145-10;
duties 13-13; 18-12; 61-9
E
145-18; 145-8; 146-19;
148-7
E 226-1; 226-17; 227-1;
doses 205-24
227-6; 227-9; 84-1; 85-15
earlier 119-14; 119-6;
doubt 104-2; 191-20
DOW 1 ; 112-8 ; 120-9 ; 126-4; 129-23; 147-4;
132-20; 133-5; 153-18;
184-4; 203-14; 218-12;
166-22; 195-23; 2-9;
221-17; 26-4; 99-18
206- 2; 206-24; 206-6; earlier— 216-6
207- 15; 207-2; 212-15; earliest 27-10; 27-12
212- 23; 213-13; 213-17; early 200-10; 209-10;
213- 22; 214-24; 215-6; 209-15; 209-18; 211-5;
30-3; 37-14; 38-12; 38-4;
27-13; 28-24; 32-5; 34-5;
38-8; 47-1; 47-24; 47-4;
37-17; 69-19
5 - 13; 58-17; 58-20; ears 133-9
58-22; 80-19
easier 143-3
A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL 0
East 55-14
Eastern 119-19
easy 121 -12 ; 200--19
eat 135-7; 138-12!; 138-8
139-6
Eaton 150-11; 84- 20
84-21
edition 167-12 .
educated 21-21
effect 105-19; 105 - 2
107-12; 1 1 - 6 ; 114- 12
116-16; 117-15; 122 -9
164-12; 168-6; 168 -9
199-22; 199-4; 199 -5
205-15; 205-20; 205 -8
209-9
effective 198-22
effects 117-9; 132- 12
132-21; 164-7; 180- 16
19-18; 204-21; 205- 13,
27-11; 28-17; 28-:24;
28-25 ; 30-4 ; 32-:L2 ;
32-25; 33-13; 33-9; 55-18
effort 123-15
efforts 23-21
eight 106-18; 18-16;
193-2; 73-22
either 101-19; 112-8;
121-3; 132-13; 146-22;
148-18; 169-7; 174-8;
179-10; 27-21; 45-15;
49-21; 69-18; 73-15;
96-22; 97-7; 98-22
element 39-12
elements 122-20; 122-9;
169-19; 170-10; 188-12
elevated 142-11; 155-10;
156-7; 221-20; 93-19
eliminate 48-12
e l i m i n a t e d 141-25;
144-12; 152-5; 152-6
elimination 144-9; 153-2
Ellenbecker 149-25; 81-18
Ellenbecker— 149-24
Ellenburger's 149-19
else 123-1 ; 137-20 ;
140-22; 151-12; 174-13;
174-22; 175-19; 210-15;
217-20; 219-15; 35-25*00
4-12; 40-7; 70-1; 70-23;*
80-16; 85-21; 86-13;
86-17; 89-10; 97-25
embarrassed 49-11
embarrassing 41-11
EMMANUEL 2
,
emphasis 111-10; 157-9; (\
MICROCo d v

467

March 5, 1993
MOYER V S . DOW CHEMICAL COMPANY
179-14
employed 124-12; 189-13;
3-21; 90-19
employee 195-23; 58-22;
68-10; 70-7
employees 17-18; 4-9;
71-2; 78-6
employment 11-6; 175-20;
213-8; 218-16; 44-20;
45-4; 5-7
enable 91-21
enclosing 84-8
end 127-5; 193-15; 72-18
ended 59-12
endogenous 200-1
enforcement 15-1
engaged 5-8
engagement 24-12; 37-20
engineering 18-10; 18-5;
63-22
enhances 122-19
enough 110-13; 159-9;
160-12; 172-11; 188-4;
212-3; 43-6
ensure 14-21
entire 177-25; 185-10
entirely 171-23
entirely 187-13
enunciated 203-6
e n v i r o n m e n t 137-13;
137-18; 137-23; 137-3;
137- 7; 138-11; 138-3;
138- 5
environmental 10-18;
10-22 ; 11-1 ; 123-5 ;
136-11; 142-25; 143-13;
143-19; 143-8; 152-10;
17-7;" 185-8; 190-7;
192-17; 218-21; 5-10;
60-24; 62-17; 62-25
E P A 1 1 1 - 2 3 ; 112-2;
123-21; 125-18; 125-7;
179-20; 180-16; 181-13;
181- 14; 181-20; 189-19;
190-5; 191-4; 207-22;
208-5; 210-18; 227-24;
34-8; 35-5; 36-6; 37-18;
40-17; 40-19; 74-7
epidemiologic 108-6;
116-20; 117-11; 120-3;
182- 20; 88-3
epidemiological 114-23;
116-10; 125-21; 125-23;
128-13; 129-1
epidemiologist 128-14
e p i d e m i o l o g y 108-1;

SCHULZ, CARL O.

116-22; 116-24; 117-6;
126-11; 128-20; 151-8;
179-24; 216-2; 227-19;

199-21; 20-10; 20-9;
21- 15; 22-13; 22-20;
22- 9; 32-1; 60-13; 63-6;,
88-8
63-7; 94-13
'
epidemiology/human 185-9
everybody 181-11; 191-2;
e p i t h e l i o i d 103-20;
195-9; 211-2
103-25
everything 27-1; 34-14;
equate 10-22
63- 24; 82-7
equivalence 220-16
evidence 102-23; 102-24;
era 194-25; 26-8
102-3; 107-11; 113-17;
Eriksson 151-9; 178-10
114- 21; 114-6; 115-13;
escaped 65-6
115- 4; 115-7; 126-10;
especially 138-13
126-2; 168-11; 168-12;
essential 18-7
168-23; 169-2; 172-7;
essentially 102-4; 103-6;
178-18; 179-16; 181-15;
120- 21; 120-6; 137-24; 182-12; 183-22; 184-4;
15-3; 187-25; 200-2;
184-6; 186-14; 200-18;
209-8; 22-1; 31-7; 94-12;
202- 18; 205-19; 220-5;
96-11
220-7; 91-1; 93-22
essentials 47-10
evolved 209-18
establish 119-25; 37-5;
exact 17-21; 49-20; 71-21
43-10; 43-13
exactly 19-5; 19-9; 73-7;
establishing 12-14; 36-22
98-10
ESTATE 1; 2-3
e x a m i n a t i o n 224-13;
esters 96-2; 96-4
224-19; 226-6; 3-14
estimate 101-22; 135-2;
examined 183-20; 89-24
159-2; 71-20; 71-24
example 101-1; 107-25;
estimated 162-25; 186-19;
110-6; 117-5; 122-10;
217-4
125-24; 134-20; 139-3;
estimates 135-17; 140-17;
141-10; 142-23; 143-20;
140-20
145-22; 146-16; 150-7;
ether 57-1
178-9; 201-24; 6-20;
evaluate 25-23; 36-3
64- 23
evaluated 16-16
examples 178-12; 178-13;
evaluation 7-7
203- 23; 34-2; 67-4
even 102-8; 105-12;
excellent 126-6
121- 20; 138-19; 143-19; except 117-22; 173-23;
147-21; 152-10; 154-1;
207-11; 22-24; 3-7; 51-4
166-14; 178-11; 178-2;
exceptionally 107-22
179-21; 185-1; 187-6;
excess 108-3; 120-11
191-21; 191-22; 194-22;
exclude 100-6
200-11; 203-6; 209-21;
exclusion 126-24; 127-1;
211- 5; 212-10; 220-20; 178-10
220-24; 26-7; 28-15;
e x c l u s i v e l y 134-15;
30-15; 38-21; 47-21;
182-11; 42-24; 59-15;
48-5; 48-6; 55-11; 63-6;
63-15
94-15
excrete 152-12
event 139-20; 28-21; 69-2
exercise 126-8; 147-8;
events 224-22
180-17
eventually 50-5
E X H 1 9 1 - 4 ; 22 6 - 19 ;
ever 102-7; 167-4; 192-1;
226- 21; 226-23; 227-11;
212- 20; 24-11; 25-16; 227- 14; 227-18; 227-20;
25-17; 44-13; 58-17;
227-23; 227-24; 227-3;
67-19; 71-6; 71-9
227-5; 227-8; 49-25;,
every 135-14; 135-8;
5-23; 78-14; 78-18;
137-16; 141-12; 181-8;
83-25 ; 85-14 ; 86-7 ;

A. WILLIAM ROBERTS & ASSOCIATES

14

MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

87-20; 88-18; 88-7; 89-6
114-7; 12-15; 120-5;
factual 102-23; 109-19;
exhaustive 58-12
120-6; 126-14; 127-6;
165-21; 171-11; 98-15
exhibit 157-23; 159-23;
128- 9; 129-12; 129-14; factually 90-21; 90-23
169-10; 191-1
129- 15; 130-2; 134-20; faculty 192-11; 61-22;
exhibits 81-15; 83-2;
134-7; 134-8; 136-10;
61-23; 63-4
failed 205-7
83-6; 83-9; 84-5
136-17; 140-3; 142-11;
Exide 55-6
142-18; 143-9; 145-14;
fair 111-16; 128-21;
145-25; 147-12; 147-6;
exist 25-11; 95-9
128-22; 157-2; 159-8;
existed 43-18
151-15; 153-5; 154-2;
212- 3.
existence 130-8
157-7; 157-9; 160-20;
fairly 152-23; 160-14;
160-24; 161-12; 162-2;
exists 114-16; 114-18;
176-2; 183-2; 25-25; 26-9
163- 15; 163-17; 163-21; faith 128-10; 168-18
138-1; 42-11
expect 125-6
164- 2; 168-12; 171-18; fall 74-24
expected 153-20
171-23; 172-11; 173-8;
familia 175-15
experience 102-24; 23-16;
174-14; 174-8; 186-22;
familiar 113-8; 121-23;
187-16; 201-24; 201-3;
79-19; 89-14; 90-4
133-20; 179-17; 179-20;
e x p e r i e n c e d 1 0 2 - 1 2 ; 201-4; 208-20; 220-13;
182-13; 182-22; 189-5;
221-19; 221-21; 227-21;
161-7; 90-19
206-12; 206-18; 206-6;
32-24 ; 36-4 ; 47-14 ; 207-14; 208-4; 212-1;
e x p e r i m e n t a l 168-8;
173-23; 196-15; 198-23;
48-23; 48-24; 48-25;
215-11; 48-4; 97-11;
50-20;
53-22;
55-23;
97-16
205-1; 205-21
57-2; 80-12; 87-16;
familiarity 121-20
expert 179-2; 48-21;
88-14;
88-19;
88-4;
far 1 0 1 - 1 2 ; 106-20 ;
49-15; 49-17; 52-22;
54- 16; 55-12; 55-21; 90-18; 91-15; 91-23;
108-3; 112-15; 129-1;
55- 8; 56-17; 56-3; 56-9; 92-1; 92-9
148-13; 15-4; 163-11;
exposures 139-10; 161-7;
57-15; 57-23; 57-4;
180-13; 206-10; 23-13;
25-4; 47-21; 56-15;
82-18; 82-24; 9-16
184-16; 185-19; 217-5
express 26-19
58-11; 59-23; 77-2;
expertise 167-19; 193-20;
92-22; 97-21
193-22; 212-4; 96-15
expression 200-15; 211-3
experts 150-16; 150-8;
farmer 121-10; 56-1
extension 19-25; 22-25
farming 119-24
extensive 184-18; 185-21
71-3
expired 66-8
extent 128-24; 202-7
fast 184-8
external 67-11
fat 138-11; 144-14;
expires 225
explained 183-16
extra 110-3
154-14; 155-6; 157-13;
161-17
explains 202-8
extraordinary 154-1
extrapolate 168-14
faulty 119-23; 149-4
explanation 179-13
extrapolated 205-3
Fax 226-23; 227-3; 78-14;
explore 91-6
exposed 101-24; 106-17
extremely 107-24; 147-14;
78-18
171-2; 180-4; 196-16;
FDA 213-14; 213-2; 213-5;
109-14; 109-2; 110-13
197-14; 200-14; 92-14
120 -2 2 ; 127-11; 127-13
2 1 3 - 8 ; 37-8 ; 68-13;
F
69-21; 8-14
127-14; 128-4; 130-7
February 69-13; 69-14
F 2; 227-12; 86-8
135-4; 135-6; 140-10
facilities 40-22
federal 18-18; 64-1;
140-11; 142-8; 146-16
155-24
facility 64-25; 65-3
64-3; 64-7
155-19; 155-22;
fact 103-25; 103-9;
feel 107-10; 126-9;
155-5; 159-3; 169-3
104-5; 109-9; 115-14;
142-6; 147-9; 155-17;
203-8; 218-15; 2 2 0 - 1 2
177-22; 182-7; 200-10;
89-3; 901-1; 91-19; 91-2
118-5; 129-24; 130-6;
200 -2 1 ; 2 0 1 -2 ; 202-18; 4 6 8
162-4; 163-12; 169-22;
91-9; 93-21
204-24; 93-22
exposure 100 -2 ; 100-25
173-11; 175-2; 202-5;
FEFRA 209-6
205-18; 24-3; 45-22;
101-13; 101-14; 101-18
fellow 10-18; 11-16; 39-7
1 0 1 -6 ; 1 0 2 - 1 ; 1 0 2 - 1 1
61-11; 61-23; 61-25;
fellowship 11-5
X
102-19; 102 -2 1 ; 102-25
72-23; 90-25; 92-24
104-12; 104-16; 104-23
factors 143-11; 144-21;
felony 190-23
oQ
104-7; 105-10; 105-16
felt 178-17; 216-8; 43-4
^
145-19; 148-5; 200-1
105-22; 105-6; 106-3
factory 173-12; 47-11
female 6-25; 7-22
i
few 147-12 ; 156-17 ; (\
106-9; 110-23; 110-25
facts 92-2
A. WILLIAM ROBERTS & ASSOCIATES

is

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
157-10; 179-13; 189-23;
205-6; 206-8; 216-22;
32-3; 74-20; 91-7
fiber 167-21
fibrosis 57-1
field 211-2; 31-24; 90-5
FIELDS 2
F I F R A 209-6; 209-7;

œ
œ

\

FL 2; 2-13; 2-18
flag 38-19
flaws 128-4; 183-3; 188-2
flew 156-24
flip 66-5
FLORIDA 1; 2-12; 57-11;
57-15
focus 177-14
212- 1 ; 212-10
focus— 177-8
Fifth 81-9; 82-14
focusing 101-15; 134-11
figured 151-21; 27-21
folks 185-17; 66-2
file 33-7; 73-14; 73-19
follow 65-12
filed 47-20
follow-up 183-20
files 51-24
followed 197-3
final 181-2; 187-6; 35-22
following 105-10; 223-7
Finally 187-12; 63-12
follows 3-13
find 117-7; 120-21;
Food 13-10; 13-16; 13-19;
135-1; 135-5; 149-6;
13- 23; 135-7; 136-22;
203-22; 223-5; 25-4;
138-5; 14-18; 14-23;
31-17; 60-11; 81-22
14- 5; 140-12; 143-7;
finding 108-16
15- 10; 15-18; 164-4;
fine 117-23 ; 118-2 ; 211-5; 213-13; 37-4;
118- 4; 6-4
66-23; 68-10; 68-2; 69-9
Foods 13-11
Fingerhut 127-24; 183-6;
188-22
foolish 199-10
fore 39--21
finish 130-12; 148-5;
foregoing 223-5; 224--16;
35-11
224-6
finished 176-24; 177-18;
203-14
Forgot 74-23
f i r m 17-7; 1 9 1 - 1 4 ;
form 1 01-7; 1 0 2 -:L6 ;
191-19; 47-23; 47-24;
103- 1 2 ; 104-10; 105-25;
47-4; 49-4
106- 23; 106-24; 107- 17;
first 104-16; 104-7;
107-•4; 108-11; 109- 18;
119- 20; 143-17; 149-22; 1 1 0 -8 ; 113-19; 114- 14;
114--17;! 114-8; 115 - 1 ;
151-9; 185-10; 186-17;
189- 23; 19-12; 19-7; 115- 18; 115-2; 116- 13;
190- 25; 195-6; 2-12; 116-■14; 116-21; 116 -4;
117- 18; 117-22; 119 -9;
20-11; 20-15; 20-20;
20-22; 20-3; 214-24;
120 -1 1 ; 121-15; 1 2 1 -25;
1 2 1 --5; 1 2 2 - 1 ; 1 2 2 -14;
24-21; 24-22; 26-3; 27-4;
2 9 - 17 ; 29-21; 3-13; 131-■14; 131-16; 138 -l;
30- 21; 34-6; 4-16; 41-10; 140-■15; 143-18; 144 -5;
4 4 - 25; 45-8; 46-14; 146- 9; 148-16; 153- 19;
51-17; 61-11; 62-16;
153- 7; 160-25; 165- 15;
171- 19; 172-13; 183- 1 1 ;
68-9; 7-15; 72-23; 74-21;
75-2; 87-12; 87-5; 95-19;
183- 25; 184-1; 184- 2 2 ;
96-5
185- 25; 186-10; 186 -8 ;
first-hand 132-8
187- l; 188-16; 196- 1 1 ;
first-year 62-19
198- 18; 199-13; 202 -l;
fish 138-14; 138-15;
207- 18; 209-11; 210 -1 2 ;
138-19; 138-8
2 1 1 -19; 213-25; 219- 16;
fishbowl 181-23
2 2 1 -- 1 2 ; 2 2 1 - 2 :1 ; 3 -7;
five 136-9 ; 152-16 ; 92-17; 96-13; 96-24
159-14; 160-13; 160-17;
formal 180-6
45- 23; 59-5; 61-11; 66-7 formaldehyde 36-4
five-year 51-17
formalized 210-15
A. WILLIAM ROBERTS & ASSOCIATES

16

SCHULZ, CARL O.
formas 40-17
former 195-23
forms 120-4
formulated 90-10
formulating 1 1 1 -1 2
formulation 89-12
formulations 132-14;
133-25
Fort 50-9; 57-7
forth 117-15; 130-1;
138-7; 138-9; 179-5;
199-21; 202-15; 209-25;
24-5; 34-17; 65-15;
71-18; 89-17
Forum 2-6; 67-23
forward 75-22; 76-2;
77-13
found 112-10; 112-13;
119-23; 120-10; 133-5;
155-10; 162-5; 171-1;
63-12; 96-22; 97-12;
97-17; 97-19; 97-6
Foundation 27-23; 27-24;
36-18
founded 192-11
four 16-19 ; 181-13;
193-15; 58-24; 67-25;
68-3; 98-4; 99-21
four-year 35-13
fourth 167-12; 48-20
frame 73-16
frankly 117-18; 177-12;
9-22
free 144-4; 177-22
frequently 207-10
friend 166-17
from— 143-4
front 158-9; 189-20;
190-16; 76-23
fuel 56-15
full 102-13; 176-16
fully 164-4; 179-4; 184-2
function 105-5; 107-7;
117-2; 117-3; 152-9;
168-13; 181-4
functions 43-6
fungicides 34-15
funnily 187-25
furan 143-19; 197-8
furans 1 0 0 - 6 ; 1 1 1 - 1 0 ;
123-3; 126-15; 134-13;
136-21; 137-18 ; 137-6;
138-15; 138-2; 138-20;
144-11; 154-3; 168-21;
73-17; 89-2; 97-15; 98-3;
99-11; 99-17; 99-19
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
furnish 191-2
furnished 81-1; 81-4;
81-6; 83-16; 85-20;
86-13; 86-18; 87-2
further 224-20
future 177-17

6
G 209-20; 210-25; 210-3
G-e-h-r-i-n-g 207-5
galley 167-17
Gallo 143-20
gallons 220-10
galls 2 2 1 - 1 1
Garwood 227-6; 227-9;
.75-3; 84-1; 85-15
Gary 41-14
gasoline 57-10; 57-14;
57-18
gastrointestinal 15-20;
16-9
gave 106-22; 139-3;
179-7; 4-22; 4-24; 40-10;
48-14; 5-12; 5-13; 52-8
gear 148-13
Gearheart 71-4
Gee 132-18; 207-1
Gehring 207-4; 207-5
gel 6-25; 67-2; 68 - 6 ;
69-24; 7-22; 7-8; 70-13;
8-10; 8-14; 8-25; 8-4
gels 16-16 .
gene 199-24; 199-3
general 105-7; 110-25;
111-2; 112-23; 116-23;
125-20; 129-15; 134-19;
134-8; 136-11; 152-13;
156-19; 157-8; 177-21;
178-14; 203-21; 205-21;
207-13; 209-14; 209-15;
218-21; 218-24; 219-7;
25-25; 61-16; 67-8;
79-18; 89-2
general— 140-7
generalization 116-16
generally 121-2; 152-10;
174-16; 204-13; 73-4;
90-12; 90-23; 94-14
generating 90-6
generically 101-14
generous 43-15
genetic 199-24; 54-11
genetically 175-17
genotoxic 199-1
geographic 60-17
geometric 154-13; 170-21
Georgia 49-3; 54-5; 58-10

SCHULZ, CARL O.

German 215-11; 215-13
133-17; 16-5; 97-13
Germany 182-23; 28-5;
gradually 43-2
28-7
graduate 62-19
Gerson 48-3
gram 139-19
gets 140-13; 143-1;
grams 139-17
152-1; 164-3
grandfather 212-19
getting 100-9; 109-2;
graph 24-4
144-24; 219-4; 63-11
grasp 177-25; 179-5
GI 142-23
graze 138-6
give 104-1; 109-20;
great 102-18; 141-11;
161-15; 172-14; 203-21;
141-22; 141-7; 184-19;
210-16; 23-23; 26-15;
185-22; 186-21; 31-6
34-2; 41-6; 47-9; 5-16;
greater 221-20
62-3; 63-1; 63-5; 67-3;
Greenville 55-24
71-20; 80-2
Greg 120-9
given 105-15; 137-3;
grew 33-10; 33-12
142-18; 153-10; 184-11;
groundwater 65-11; 65-19
62-2; 62-9; 67-21
65-9
gives 110-3; 94-22
g r o u p 114-3 ; 119-1
glance 46-8; 80-2
119-19; 127-20; 143-20
glycol 57-1
155-11; 155-22; 156-14
goes 144-6; 146-3; 146-8;
164-22; 170-21; 186-20
152-25; 152-8; 207-11;
212-19; 53-9; 8-18; 88-11
groups 164-21
207-15; 83-11; 85-3
going 118-15; 132-22;
growth 200-1; 200-3
140-12; 144-14; 155-24;
guarantee 136-5
158-17; 158-18; 165-17;
guard 166-25
167-14; 173-3; 174-9;
guess 11-25; 126-16;
128-17; 151-17; 154-5;
175-10; 176-13; 180-1;
180-19; 181-1; 191-22;
17-18; 176-16; 176-9;
193-17; 193-19; 193-25;
200-18; 45-7; 73-23;
203-10; 219-14; 27-14;
78-11; 82-23; 85-25;
27-18; 27-7; 31-7; 38-7;
95-15
4 1 - 12; 46-14; 5-18; guessing 27-3
80-10; 82-21; 84-7
guest 63-5
Gold 56-14
guidance 211-7
gone 169-15; 216-13;
g u i d e l i n e s 209 - 1 6 ;
80-21
209-20; 210-25; 210-4
g o o d 1 1 4 - 2 ; 11 5 - 6 ;
gun 201-17; 201-21
127-24; 128-2; 128-8;
g u y 144-16; 144-18;
135-24; 137-1; 161-23;
155- 20; 162-17
guys 155-21; 156-17;
166-17; 172-16; 172-25;
177-24; 182-1; 183-13;
207-10; 210-19
183-4; 193-11; 216-20;
H
24-1; 30-17
H 2-17; 226-17; 227-1
Gosh 152-19
habits 175-23
gotten 179-25; 65-8; 9-8
had— 35-8
A *70
government 123-8; 13-7;
h a l f 106-19; 130-5 ;
4 ‘u
15-9; 18-19; 18-21;
153-2; 153-4; 173-3;
18-22; 18-24; 189-18;
180-5"
42- 22; 59-14; 59-7; 64-2; HALVORSON 2
64-3; 64-8
Hamberg 216-3
governmental 67-20
hand 147-11; 156-20;
Grace 37-25
156- 3; 157-4; 157-7;
gracious 60-25
225-1; 63-25
grade 132-11; 132-16;
handed 6-7

A. WILLIAM ROBERTS & ASSOCIATES

17

MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
handers 156-13; 156-16;
156-7
handle 2 1 1 - 1
handled 102-4; 102-7;

J?-Sòr

471

1 0 2 -8

handling 102-10
hands 30-20
handshake 66-13
H a n d w r i t t e n 226-21;
45-22; 49-25
happened 165-8
happens 143-25; 199-12;
199-6; 199-9
h a r d 176-4 ; 190-11;
31-15; 49-10
Harden 178-10; 179-8;
179-9; 184-15; 185-18;
187-15; 188-2; 188-5
Hardell's 182-10; 182-6;
186-19; 204-2; 85-24;
86-3
Hardin 47-23; 47-5
Harrisburg 133-13
hasn't 187-7; 95-15
haven't 1 1 2 - 1 1 ; 112-14
123-15; 134-18; 137-13
149-21; 150-6; 167-23
176-24; 179-25; 181-24
181-25; 193-4; 203-18
2 1 1 - 1 2 ; 216-17; 38-21
47-22; 71-14
having 103-21; 110-17
178-12; 212-4
Haynes 192-16
Hayward 3-19
Hazardous 62-12; 63-13
head 14-25; 80-2
headache 103-21
headed 189-16
headquarters 192-5
H e a l t h 11-2 ; 117-9
12-12; 12-5; 13-22
132-12; 132-21; 164-11
164-7; 180-15; 19-18
190-7; 27-11; 28-17
28-24; 28-25; 30-4
32-25; 33-13; 33-9
35-16; 5-10; 55-18
60-24; 62-17; 74-6
healthy 146-17; 174-17
hear 168-25; 91-9
heard 188-5; 191-8; 48-6
hearing 124-3
hearings 125-17; 125-2;
71-1
heat 137-25

SCHULZ, CARL O.

heavily 129-4; 142-8;
154- 23; 155-18; 155-21;
62-10; 93-20
heavy 111-10; 171-23;
178-8; 19-10; 63-22
Heidi 227-6; 227-9; 75-3;
84-1; 85-15
HELENA 1-10; 2; 57-5
help 172-24; 196-14;

64-25 ; 67-7 ; 72-23 ;
74-21; 75-15; 76-17;
76-9; 80-21; 81-22;.
82-13; 82-22; 82-25;*
88-1; 91-18; 91-7
here's 37-9; 77-13; 84-8
hereby 223-4; 224-5; 3-6
hereunto 225-1
hesitant 28-15
66-20
hesitate 126-22; 73-7;
helped 35-21; 89-12
93-21
helps 172-22
hexa 162-21
heptacholorodibenzo
Hexacholorodibenzo
162-10; 98-21
162-18; 98-24
herbicide 101-22; 120-23;
high 138-19; 156-18;
129-21; 136-24; 156-25;
157-10; 157-11; 160-14;
19-3; 194-20; 34-22;
161-25
37-14; 38-1; 38-25; 40-5;
higher 138-19; 145-10;
45-10; 46-11; 46-15;
156-16; 157-9; 161-18;
71-10
178-25; 197-17; 24-1;
herbicides 12-21; 120-5;
72-15
120-7; 121-2; 121-21;
highest 138-10
Hill 54-24
13-25; 130-1; 15-14;
155- 19; 161-10; 17-1; Hills 47-13
178-23; 184-17; 185-20;
himself 149-2; 177-13
hired 8-17
19-11; 19-13; 19-18;
19-7; 197-13; 20-24 ; historian 60-7
2 0 - 5 ; 2 0 1 - 5 ; 2 1-4;
H i s t o r i c a l l y 96-19;
218-16; 226-25; 227-22;
96-21; 98-17
227-4; 23-11; 23-17;
history 121-13; 14-17;
24-17; 27-11; 28-18;
173- 7; 173-9; 174-14;
28-25; 30-4 ; 32-14 ; 174- 23; 174-25; 175-1;
32-24 ; 33-19; 33-25;
175- 14; 175-20; 175-24;
33-9; 34-18; 45-11; 59-9;
175-4; 181-6; 192-10;
73-19; 78-16; 78-20;
195-22
79-20; 8-5; 88-15; 88-20;
hit 200-14
90-1
Hoarizom 113-9; 128-7
here 10-6; 10-9; 105-19;
Hoarizom's 113-23; 118-25
110-18; 113-16; 114-11;
Hold 150-25; 193-25
home 4-24; 73-1
115-10; 119-7; 125-20;
127-6; 134-5; 135-21;
honest 200-19; 204-15
hope 61-2
136-7; 139-23; 140-18;
hoped 99-18
140-24; 141-19; 144-19;
Hopefully 62-1
145-7; 151-20; 153-1;
153-8; 158-2; 158-23;
Hopkins 10-19; 11-15;
159-16; 159-22; 160-2;
11-25
165-18; 169-25; 169-9;
horse 119-7
179-18; 180-9; 185-15;
hour 173-3; 71-17; 71-19
185-16; 189-1; 191-10;
hourly 43-12
194-19; 198-1; 20-17;
hours 118-16; 203-19;
200-24; 206-8; 21-1;
72-19; 72-2; 72-20
216-14; 216-17; 219-6;
h u m a n 101-3; 13-22;
29-8; 30-1; 46-9; 48-9;
154-12; 164-18; 179-24;
49-13; 49-17; 49-19;
9 1 - 13; 91-4; 92-22;,
49-24; 5-14; 55-3; 56-2;
92- 25; 93-2; 93-4; 95-4 }
56-9; 60-22; 61-12;
human's 201-24

A. WILLIAM ROBERTS & ASSOCIATES

18

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
humans 100 -2 2 ; 168-10;
168-13; 168-15; 168-22;
168-24; 169-3; 174-3;
181-15; 205-13; 205-7;
208-16; 208-20; 97-24
humor 136-2
hundreds 155-23
hydrocarbon 57-2
hydrocarbons 137-25
Hygiene 10-19; 167-13;
175-11; 175-24
hygienist 38-12
hypothesis 200-20; 203-3;
203-5
hypothesized 91-3
hypothetical 105-20;
106-12
hypothetically 109-7
I
I 'd 104-19 ; 141-15 ;
151-19; 167-21; 190-11;
203-17; 203-24; 209-13;
43-10; 43-12; 45-7;
48-18; 99-18
I've 110-20; 117-17;
124-1; 142-20; 151-21;
163-25; 167-16; 167-6;
168- 12; 168-22; 169-15;
169- 2; 169-9; 17-20;
184-8; 188-5; 190-25;
191-25; 192-25; 20-18;
207-1; 216-12; 216-15;
45-21; 48-6; 50-6; 58-19;
59-12; 59-13; 59-14;
61-15; 62-9; 66-10;
66-11; 67-25; 67-6; 71-7;
71-8; 80-21; 9-22; 98-15
I-- 151-5; 185-13; 214-3
I-A-R-C 128-2
Ian 124-10; 124-4; 124-9
IARC 128-2; 189-1
ICF 42-11; 42-13; 42-20;
42-5
idea 25-15; 26-16
identical 96-8
identification 76-5
identification. 191-6;
5-25; 50-2; 78-17; 78-21;
84-3; 85-18; 86-11;
87-23; 88-21; 88-9; 89-7
identified 137-13; 137-5;
165-5; 170-25; 26-5;
75-24; 76-1; 97-16
identifies 170-5
identify 170-6; 184-23;
198-17; 31-13

identifying 30-18
identity 17-21
ideology 164-17; 166-14
if— 142-3
II 1-5; 2; 62-13; 63-14
III 38-9; 39-4
immediately 65-9
immune 168-13; 168-22;
168-7; 168-9; 204-21;
205-13
immuno 205-20
immunostimulatory 205-16;
205-17
immunosuppressive 205-15;
205-22
i m m u n o t o x i c 171-5;
204-25; 2Q5-2
inpact 122-20
imperfect 116-22; 132-18
implant 56-5; 66-17;
67-3; 68-6 ; 7-8; 9-7
implantable 67-10
implanted 6-25; 7-21;
7-9; 8-9
implants 69-11; 8-21
implementation 37-2
implementing 14-19
important 137-12; 137-19;
144-23; 144-6; 147-6;
148-11; 152-25; 195-6;
205-25; 26-6
inpossible 120-21
impressed 127-17
inpression 177-10; 177-23
impressions 178-15;
203-21
impressive 39-17
impurities 102-20
impurity 103-2
in— 168-4; 95-10
Inc 17-4
INC. 1-11; 17-5; 18-20;
40-4; 44-1
incidence 105-5; 93-19
incidences 107-24
incidentally 149-13;
75-14
include 12 -20 ; 208-16
included 118-21; 119-1;
119-13; 119-3; 195-21;
26-2; 26-4; 51-3; 62-8;
71-3. 73-9
includes 156-21; 157-2;
157-3; 98-6
including 130-7; 149-1;
154-3; 167-11; 55-18;

A. WILLIAM ROBERTS & ASSOCIATES

19

SCHULZ, CARL O.

91-4
income 72-10
i n c o n s i s t e n t 142-6;
179-14; 179-15
incontinence 69-17
Inc o r p o r a t e d 17-12;
17-16; 3-22; 3-24; 4-1;
44-21; 5-4; 64-24
increase 152-13; 16-5;
24- 18
increased 119-23; 126-12;
172-17; 186-18
incumbent 25-23
i n d e p e n d e n t 124-11;
217-16; 217-20; 30-13;
4-2; 43-13; 70-10; 90-6
independently 111-23
INDEX 2-21; 226-12
indicate 100-19; 169-17
indicated 112-9; 186-21
indicates 100-20; 102-24;
205-19
indication 133-5; 69-17
indicator 172-16
indirectly 38-7
individual 101-3; 141-10;
141-17; 142-17; 148-8;
151-18; 153-20; 153-9;
160-20; 160-21; 160-5;
162-1; 174-17; 201-7;
25- 12; 8-19; 9-3; 94-14;
98-7
i n d i v i d u a l s 13-15;
141-23; 142-10; 191-19;
75-23
induction 165-20; 198-18
industrial 13-1; 13-4;
167-13; 30-12; 38-12
industry 181-7; 206-25;
8-18
inexpensive 64-9
informal 211-4
i n f o r m a t i o n 103-5;
109-20; 12-18; 131-25;
132-4; 132-8; 132-9;
155-16; 157-22; 178-1;
195-18; 195-21; 195-25;
207- 22; 208-11; 208-14;,^o
208- 4; 209-3; 211-14;*
211-15; 226-12; 226-14;
4 5 - 18; 45-21; 67-23;
W
67-8; 87-11; 98-14; 98-16 J«
ingest 135-14; 135-8
C?
ingested 102-18; 143-23
j
ingredient 68-18
f\
inhaled 102-18; 144-1
V
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
inherent 117-12
initial 105-10; 105-16;
105-22; 114-9; 134-6;
16-1 ; 24-12 ; 24-24 ;
26-14; 40-25; 79-17;
83-20
initially 133-8; 145-14;
148-13; 79-16; 8-13;
81-22; 81-5; 83-16
initials 4-7
initiate 199-2; 200-11
initiated 181-18; 68-13
initiating 198-24
initiative 68-14
initiator 198-22; 198-8
injectable 69-16
Injected 56-8
injection 56-3
i n j u r y 50-19; 53-1;
5 3 - 15; 53-21; 53-8;
54- 10; 54-16; 7-18
input 180-2
insect 34-12; 34-14
inside 202-23
inspected 213-3; 213-5
inspections 14-21; 15-7
inspector 213-5
installment 23-6
instance 117-8; 135-8;
168-15; 45-9
Institute 12-11; 12-6;
124-15; 192-10; 206-25;
32-7; 68-22; 68-23
Institutes 190-7; 38-10
institution 12-9; 123-8
intact 220-21; 220-23;
221-10

CO

intake' 137-10; 140-7;
151-24; 152-11; 152-8;
217-5
intakes 135-3
integrity 14-22
intend 176-20
intended 208-18; 208-19
intense 105-17; 126-14;
160-24; 161-11; 161-7;
171-18; 171-20
intensity 105-5; 107-7
intensive 123-11
inter-individual 144-10
interaction 199-5
Interactions 62-24
interest 26-23
interested 213-11; 224-22
i n t e r e s t i n g 143-21;
205-14

SCHULZ, CARL O.

Interestingly 198-21
Irrespective 110-12
interim 181-16
is— 212-6; 9-12
internal 145-10; 145-18;
isn't 128-11; 136-4;,
145-8; 215-6
141- 8; 181-10; 184-10;'
International 137-15;
189- 20; 189-22; 198-21
207-12; 38-9; 42-11; 74-1
Isocyanide 38-9; 58-21
interpreted 134-1
isomer 162-20
interpreting 146-7
isopropyl 13-3
interrogatories 81-12;
issue 108-18; 1 1 0 - 2 ;
81- 13; 82-19; 82-23; 110-6; 122-17; 122-5;
82- 25
128-10; 130-17; 153-8;
interrupt 156-9
166- 3; 167-4; 179-7;
intervals 102-9
195-22; 201-20; 206-1
interviews 9-5
issues 178-16; 207-7;
into 12 -18; 137-2; 138-3
66- 18; 9-9
140--14; 143-1; 144 -4
It'd 120-16; 131-2
144--6 ; 152-1; 152 - 2
it'll 190-3; 45-19; 46-7
153- 7; 156--24; 158- 12
it's 102-2; 103-21;
158--25; 164-3; 17- 19
106-12; 106-25; 107-21;
180- 2 ; 202 --14; 202 -25
120-20; 121-11; 127-25;
203- 1 0 ; 210 -18; 218- 13
128-3; 134-14; 136-12;
31-6 ; 41-25; 42-3; 44--14
137-4; 138-21; 138-23;
48-7 ; 65-8 ; 67-14
139-16; 139-19; 141-15;
introduction 76-25
142- 15; 143-3; 144-1;
introductory 62-18
144-4; 144-5; 146-10;
intubated 202-12
146-8; 150-9; 152-23;
investigate 30-11; 32-23;
152-6; 153-1; 154-15;
36-6; 69-21
154-7; 156-6; 159-16;
investigated 36-17
159-23; 160-10; 160-16;
investigation 123-19;
163- 1; 164-23; 164-24;
23-18
164- 25; 166-21; 167-10;
invited 35-20
167- 11; 169-5; 17-18;
involve 13-25; 144-21;
172-6; 173-21; 176-22;
15-13; 17-1; 33-24;
176-4; 177-17; 179-22;
40-13; 48-15; 49-8; 8-4
182-18; 183-3; 183-6;
involved 119-4; 12-21;
184-25; 185-1; 188-12;
131-1; 14-20; 144-8
188-3; 189-15; 190-2;
156-2; 156-3; 189-8
190- 4; 192-15; 192-23;
190-8 ; 20-4 ; 206-9
193-14; 193-2; 194-10;
207-8; 2 1 1 - 1 2 ; 23-24
195-20; 202-23; 203-3;
30-22; 33-16; 34-20
204- 18; 205-1; 205-17;
34-3 ; 44-25; 48-17
205- 21; 210-9; 216-1;
50-15; 50-17; 52-16
216-2; 217-14; 217-17;
52-4 ; 5 7 - 2 3 ; 58-13
218-14; 219-18; 22-13;
58-25; 67-4; 67-9; 71-22;
2 2 - 17; 221-2; 221-5;
79-8; 80-13
23- 20; 25-23; 27-20;
involvement 180-6; 19-10;
28-4; 28-5; 28-7; 34-25;
19- 12; 19-6; 35-1; 44-22; 39-13; 4-19; 4-2; 42-12;
44-23; 45-9; 51-17; 66-17
42-19 ; 44-12 ; 47-1;
involvements 45-14
47-14; 47-17; 47-21;
involves 126-2; 53-15
47-4; 47-8; 53-16; 54-10;
involving 184-17; 185-20;
5 5 - 15; 56-10; 56-24;
20- 23; 45-12; 54-12; 56- 6; 61-2; 61-7; 61-8;
55-7; 57-5
64-6; 64-7; 64-9; 65-25; ,
IOSH 127-24; 183-6
67- 14; 68-22; 7-3; 71-24;
Iron 55-20
73-4; 75-16; 75-21; 76-2;

A. WILLIAM ROBERTS & ASSOCIATES

20

MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
76-9; 77-3; 79-12; 82-16;
84-17; 92-12; 92-13;
92-8; 93-24; 93-25; 93-4;
95-14
its 116-10; 116-11;
123-10; 123-12; 123-23;
131-14; 153-7; 167-19;
187-22; 198-25; 199-22;
199-5; 200-2; 211-17;
215-1; 220-15
itself 112-19; 198-23;
211-21; 36-10

171-4; 172-8; 175-13;
176-7; 179-1; 179-11;
182-12; 188-3; 189-19;
190-15; 197-9; 203-19;
203-6; 207-12; 210-9;
212-3; 216-21; 216-25;
219-6; 220-17; 220-2;
221-18; 221-9; 23-15;
27-3 ; 2 8 - 1 5 ; 29-11;
29-24; 30-8; 31-22; 31-5;
32-10; 37-6; 39-2; 39-25;
4- 8; 41-6; 46-5; 46-8;
5 - 18; 56-20; 57-23;
. J
J-u-n-k-o 4-17
61-10; 61-19; 67-13;
Jacobs 1
67-8; 7-3; 73-3; 74-20;
January 81-12; 81-13;
75-16; 76-11; 76-16;
82-19; 82-20; 82-23
78-3; 79-18; 80-1; 81-21;
Jay 41-20
81-25; 81-8; 82-13; 87-4;
jet 56-15
87-9; 94-16
job 135-24; 136-1; 30-17;
just- 159-19
just— 214-11; 33-20
60-19; 60-9
Joe 17-24; 41-8; 57-8
justified 128-11
John 17-14; 48-20; 53-10
K
Johns 10-18; 11-15; 11-25 K 1-21; 212-17; 212-18;
j o i n 104-19 ; 106-1;
224-3; 225
106- 13; 106-8; 107-18; K-r-u-m-e-t 196-2
107- 8; 108-12; 109-22; Kaposi 164-22; 164-25
keep 158-17; 166-25;
110-9; 116-5; 117-25;
118-6; 121-16; 121-6;
190-11; 72-16; 72-17;
72-25; 72-3
161-1; 165-16; 171-21;
Kelley 57-21
185-4; 187-23; 187-8;
190-22; 202-3; 214-1;
Kenny 150-18; 151-7
219-17
kept 148-22; 41-17
Journal 227-18; 88-2;
key 124-3; 152-25;
88-7
180-18; 75-11
journals 30-19; 31-24;
kid 137-16
kidding 152-18
31-25
killers 34-13; 34-14
JR. 1
JRB 25-10; 25-13; 25-17;
kills 56-20
kilogram 151-22
26-15; 29-21; 29-4
judgment 134-17; 134-19
KIMBERLY 1-4; 2
Kimmig 28-10
JUDICIAL 1
Kiiranig-Schulz— 27-16
July 74-25
Junko 4-15
kind 125-20; 135-11;
jurisdiction 55-1
135-14; 157-6; 173-15;
jury 136-4; 136-6
175-16; 203-16; 208-22;
j u s t 10-5; 1 0 1 - 1 5 ;
209-17; 221-5; 26-15;
106-22; 107-9; 110-3;
37-7; 41-10; 51-6; 53-15;
53-5; 55-10; 64-22;
115-22; 117-5; 120-22;
126-9; 127-2; 128-8;
65-23; 65-24; 70-14;
71-1; 71-7; 73-3; 74-9;
131-13; 136-3; 139-11;
139-3; 142-6; 144-8;
80- 23 ; 82-5 ; 93-13 ;
93-14; 94-16
147-15; 152-18; 156-18;
158-13; 16-23; 160-1;
kinds 160-15; 173-22;
50-14
161-16; 162-16; 163-14;
166-22; 167-17; 171-14;
k n e w 124-24; 165-1;
A. WILLIAM ROBERTS & ASSOCIATES

SCHULZ, CARL O.
25-16; 40-3; 60-22
know 103-14; 105-13
107-10; 107-19; 120-6
121-10; 123-17; 125-10
127-5; 130-11; 131-24
133-25; 134-3; 135-11
146-21; 146-24; 147-7
148-12; 149-2; 154-21
154-22; 156-21; 156-25
157-12; 157-2; 158-13
159-2; 160-17; 164-17
164-23; 165-24; 166-15
170-22; 173-15; 177-5
179- 22; 180-1; 180-22
180- 8; 189-10; 189-9
19-5; 191-12; 191-18
191-20; 191-22; 191-23
191-24; 192-16; 192-8
193-8; 198-3; 199-15
199-9; 200-24; 203-9
206-13; 206-14; 207-1
209-24; 212-11; 212-14
212-18; 213-21; 214-15
214-24; 216-18; 22-10
22-25; 220-25; 221-3
25-13; 32-15; 32-17
33-5; 36-19; 37-21
39-12; 39-24; 39-25
41-11; 42-13; 42-7; 42-9
45-18; 46-3; 48-2; 53-2
54-25; 55-15; 56-22
58-12; 6-11; 63-21; 63-7
71-7; 75-21; 75-5; 79-10
84-7; 9-11; 9-19; 9-25
90-21; 95-21; 97-18
98-23; 99-1
know— 192-14
knowledge 134-20; 174-12;
180-12; 192-12; 211-11;
214-4; 214-9; 70-24
known 137-10; 137-8;
142-11; 154-1; 162-2;
199-8; 207-1; 91-3
Krommel 169-5
Krumel 158-14; 169-5
Krumet 195-22; 196-2
L
Lab 159-1
Lab— 157-25
laboratories 15-7
laboratory 15-1; 15-2;
162-4; 213-12; 213-6;
40-21
Labs 158-1
lack 113-17; 114-11; 22-4
lag 193-14

474

MICROConv

March 5# 1993
MOYER vs. DOW CHEMICAL COMPANY

K

\r>

$l

laid 216-18
landfill 55-25; 65-4
language 21-12; 29-19
l arge 120-2; 165-4;
224-5; 31-14
larger 17-19
largest 57-13
Larry 212-14; 38-11;
58- 21
last 121-14; 152-16;
168-25; 193-15; 203-19;
206-20; 23-21; 26-10;
40-2; 45-22; 45-23;
47-20; 58-24; 58-6;
59- 14; 59-16; 59-5; 62-9;
74-23; 74-24; 79-7; 80-6;
88-23
late 2 19-24; 26- 24 ;
42-10; 61-24; 69-18
latencies 105-12; 105-9;
107-23
latency 104-16; 104-22;
104- 25; 105-1; 105-14;
105- 20; 105-4; 107-10;
107- 15; 107-21; 107-6;
108- 15; 108-4; 108-9
later 167-16; 178-15;
186-19; 190-12; 203-24;
209-21; 214-20; 31-1;
38-2; 85-22; 86-1
lateral 98-3;
latter 142-21
Laurinburg 57-17
47-23
-19
lawyers' 9-22
lay 21-12; 21-2] ; 29-19
lead 55-7; 57-5
leakage 201-11
leaked 201-9
leaking 201-21 55-25;
57-18
leap 128-10
least 114-22; 128 -24;
133-4; 162-7; 177 -21;
216-14; 217-2; 30 -17;
72-25
leave 159-7
lecture 61-10; 62 -14;
62-20; 63-5
lecturer 62-4
lectures 61-1 ; 6 1-6;
62-2
lecturing 61-21
Lee 6-23; 7-6
l e f t 1 1 - 1 4 ; 16- 2 2 ;

legal
50-1"
.9; 58-25; 64-15
64-1.7; 67-19; 71-16
72-12Ì
legally 37-19
legislation 33-4
length 75-14
lenqth
lengthy 184-24
Leoni 27-24
‘5’7
lesjs 108-15; 130130)—19 ; 130-25; 143144
^4-3; 157-15; 159160-11; 210-10; 210220-17; 221-13
Let 10-5; 104-11; 105114-1; 130-12; 132135-23; 139-21; 153
158-25; 159-19; 160169-4; 172-2; 172
172-9; 180-21; 197
200-25; 204-1; 204208-24; 216-21; 216216-3; 220-2; 3235-11 ; 39-2 ; 39-:
39-25; 48-8; 48-9; 495- 14; 5-16; 53-14; 6
6- 5; 74-19; 76-4; 82
85-11; 86-5; 91-11; 9]
Let's 108-18; 109 -6
109-9; 11-11; 114 -9
134-5; 159-12; 161-■18
190-10; 190-14; 190--20
209-14 ; 38-23; 44- 19
5-20; 80-23; 89-4
letter 139-11; 151 -3
217-3; 227-11; 227-•14
227-5; 227-8; 82- 21
83-17; 83-22; 83- 25
84-6; 84-8; 85-14; 85--23
8 6-7; 87-12 ; 87- 13
87-20; B7-6
letters 4-4
leukemia 57-9; 94-2
level 100-25; 101- 10
101-5; 130-3 ; 130 -9
131-2; 135-15; 138- 16
148-1; 160-17; 176 -2
211-2; 220-16 ; 60 -8
64-24; 91-15; 92-3
levels 132-2; 135- 11
138-10; 153-24; 156-•14
156-18; 156-7; 157- 10
157-11; 161-14; 163- 18

A. WILLIAM ROBERTS & ASSOCIATES

22

SCHULZ, CARL O.
164-10; 197-14; 89-1;
98-15
Lexington 225-3
library 112-5; 29-5;
31- 8; 72-24
life 139-6; 153-11;
153-15; 153-2; 18-10;
18-14; 18-2; 19-2; 49-19
like 101-1; 103-21;
105-4; 119-22; 137-15;
14-3; 140-5; 144-14;
144-18; 15-19; 151-20;
18- 9; 190-11; 192-10;
207-15; 21-19; 210-25;
3 2 - 11; 43-10; 43-12;
46-3; 48-13; 61-1; 64-19;
74-6; 91-9
liked 4-8
likely 144-3; 154-23;
178- 24; 92-12; 92-21;
98-8
limit 160-14; 160-9
limit a t i o n s 117-13;
179- 12
limited 116-22; 129-20;
50-25
limits 160-10
Linda 189-16
line 177-7; 223-9
line-by-line 177-16
Ling 182-14
lingo 48-12
lining 146-4
link 104-22; 115-16;
115-20; 32-24; 36-17
linkage 182-19
linked 174-10
linking 113-18
liquid 65-5
li st 100-19 ; 135-4 ;
189-22; 226-21; 45-13;
48-14 ; 4 9-25 ; 53-9 ;
58-12; 62-17; 68-15; 77-1
listed 190-1; 191-9;
20- 18; 21-1; 51-22; 51-8
l i t e r a t u r e 105-15;
107-24; 111-22; 119-13;
121-11; 132-20; 132-5;
141-3; 172-2; 172-5;
19- 16; 19-17; 20-16;
2 1 - 11; 21-3; 213-22;
214-13; 217-10; 217-15;
22- 23; 226-24; 227-4;
24-10; 25-2; 26-4; 30-10;
31-2; 32-4; 33-7; 33-8;
40-14; 40-15; 40-20;
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
loose 184-8
loses 200-2
lost 17-20; 25-19; 26-20;
38-24; 61-23
lot 138-1 2; 138-23;
141-13; 149-1; 153-23;
155-1
Louisiana 7-24
low 130-4; 163-2; 174-6;
176-2; 196-16; 197-14;
64-24
lumped 94-13
lunch 118-9
luncheon 118-17
lung 146-4; 166-12;
166-13; 166-16; 166-18;
166-5; 202-17; 94-1
LUTZ 104- 19 ; 106-1;
106 -13; 106-24J; 106 "8;
107 -18; 107-8; 108- 12;
109 -22; 110-9; 115 -2;
116 -14; 116-5; 117- 24;
118 -3; 118-6; 121- 16;
121 -6; 122-1; 122- 14;
161--l; 165-16; 171- 21;
184 -l; 185-4; 186- 10;
186 -2; 187-23; 187 -8;
1902; 2-17 ; 202!-3;
214--l; 219-17; 221-23;
38-21
lymphoma 113-6; 119178-■19
lymphomas 94-23
Lyons 55-14
M
M-a-n-z 182-23
made 101-21; 110- 23
116-2; 123-15; 128- 10
129-20; 159-6; 176 -9
180-20; 187-13; 213-■10
214-19; 218-24; 224-•12
224-18; 45-22
Main 1; 134-5; 18- 10
41-6; 59-18
maintain 33-6
maintained 61-12
major J.38-24; 139 -1
23-21; 35-15; 39- 13
majority 105-9; 155- 18
52-25; 73-7
make 100-9; 101-2 ; 103-3
114-10; 116-15; 13-21
130-13; 134-16; 134- 19
139-12; 142-16; 146-25
148-14; 148-16; 15- 11
173-18; 173-25; 181 -2

A. WILLIAM ROBERTS & ASSOCIATES

to
•£>

i
to
t•o

75-13 ; 75-9 ; 77- 11 ;
78-15; 78-19; 79-5;
88-13; 89-15; 90-5; 90-7;
92-24; 98-20
litigation 44-11; 45-1;
9-7
l i t t l e 10 -6; 10-8 ;
102-10; 124-1; 132-4;
142-11; 144-15; 147-8;
152-11; 160-8; 163-1;
165-18; 165-20; 180-4;
184-7; 195-15; 196-12;
197-10; 198-10; 199-10;
202-6; 204-14; 21-18;
211-6; 220-19; 24-2;
3 9-19 ; 45-22 ; 5-17;
61-10; 63-18
live 153-11
lived 166-19; 166-22;
60-10
liver 56-25
living 174-17; 174-25;
175-1; 175-14; 175-4
loaded 156-23
Loads 110-8
lobbying 181-12
local 54-17; 55-3
LOCATION 1-17; 224-8;
42-15
locations 175-5
logic 188-13
lo ng 117-18; 165-1;
193-8; 213-21
long-term 126-14; 32-25;
64-22
long-winded 172-15
longer 105- 12; 206--23;
95-14
look 119-17; 143- 12;
145-13; 151 -19; 155--25;
205-6; 210 -21; 24--li;
24-13; 29- 17; 31- 16;
32-4; 46 "5; 48-18; 48-8;
59-20; 60- 17; 74- 23;
75-20; 76-11 ; 76 -7; 77-4;
80-21
looked 120--9; 149- 21;
24-20; 26- 13; 30- 24;
60-9; 75-15; 89-10
looking 127 -6; 132--23;
136-7; 141- 18; 153--21;
154-5; 179 -6; 194 -3;
213-11; 215 -17 26--16;
31-21; 32--2; 52- 14;
60-18; 8-12
looks 14-3; 15-19

SCHULZ, CARL O.

9?

183-18; 187-10; 190-14;
203-17; 209-2; 217-2;
218-23; 22-24; 50-23;
65- 13; 71-8; 78-3
makers 181-17
making 140-18; 140-21;
140-22; 219-6; 221-10;
221-9
malathion 13-2
malpractice 56-4
mammary 66-17; 67-3;
68-6; 69-10; 7-8; 8-21;
9-7
man 132-13; 205-4; 217-7;
218-10; 4-18
management 18-9; 43-9;
62-12; 63-14
manager 39-6
mandate 25-1; 33-11;
33-12
mandated 32-19; 33-5
manual 31-19; 31-20;
31-3; 31-7
Manually 72-7
m a n u f a c t u r e 127-15;
131- 14; 161-8; 169-24;
195-17; 66-15
manufactured 213-24;
50-21; 95-19
manufacturer 121-22;
123-10; 209-4; 210-17;
211-15; 211-25; 38-2;
71-10; 8-20; 8-22
manufacturers 132-1;
132- 11; 207-21; 215-22;
37-14 ; 38-25 ; 40-5;
66- 19; 67-16; 9-11; 9-25;
9-4
manufacturing 127-23;
128-4; 131-17; 208-14;
211-16; 215-16; 215-2;
37-21; 39-14; 93-20
manuscripts 85-24
Many 164-1; 184-5; 33-22;
36-1; 4-9; 64-21
Manz 182-23; 216-3
476
Marathon 56-9
March 1-15; 225-2; 2 2 5 -9 $ ¡$ í
7-24 '
m a r k 16 9-13; 191-1 /
48-15; 49-23; 76-15
76-5; 78-12; 86-6; 88-16
88-6; 89-4
marked 136-8; 169-10
Vi?
191-6; 194-4; 5-21; 5-24
A)
50-1; 6-8; 78-16; 78-20 / b
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O

CO
CN
1
00

CO
1

83-22 ; 84-18 ; 84-3;
206-13; 214-8; 218-24;
m e t h o d o l o g y 117-13;
85-12; 85-17; 86-10;
219-6; 27-9; 45-17; 56-5;
127-18; 36-7
87- 19; 87-23; 88-20; 67-21; 84-20; 93-4; 95-11 methods 129-25; 132-7
88- 9; 89-7
meaning 122-18; 187-22
methyl 13-2
marker 163-16; 171-18;
meaningful 102-1; 109-21;
metropolitan 60-10
171- 19; 171-22; 172-10; 91-10; 91-2
Michigan 212-21; 213-17
172- 11
means 157-19
middle 20-12; 24-3; 27-2;
measurable 154-2
market 123-25; 152-18
27-5; 45-4
marketed 66-25
measured 131-10; 161-14
Midland 212-20; 213-17
marks 203-18
m e a s u r e m e n t 157-13;
might 101-23; 110-5;
Marshall 58-1; 58-7
159-13; 217-24; 219-9
123-10; 129-21; 135-4;
Mary 124-13; 124-4
measurements 158-20;
160-18; 177-8; 18-7;
material 100-3; 195-16;
158-21; 163-11; 163-7
200-22; 202-5; 205-15;
199-24; 200-21; 203-25;
measures 162-7
205-18; 211-17; 216-20;
7-8
meat 138-13
37-7; 80-1; 92-10
materially 221-20
mechanism 165-13; 165-20;
Mike 143-20
materials 130-14; 169-23;
165-24; 165-9; 198-13
MILL 1
62-12; 65-20; 65-4;
mechanistic 198-12
Miller 54-20; 55-6
66-21; 67-9
Med-Line 31-11
million 130-18; 130-20;
Mathews 6-23
media 143-19
130-25; 219-25; 220-17;
matter 123-22; 123-9;
Medical 10-2; 103-13;
221-13
138-6; 144-2; 45-10;
173- 6; 173-9; 174-13; mills 138-22; 138-23
70-13; 80-13
174- 22; 199-15; 199-18; mincing 115-9
matters 45-1; 69-21;
199-19; 33-8; 36-23;
mind 103-18; 126-19;
72-12
37-3; 56-4; 59-21; 66-15;
177-12; 177-19; 217-2;
maximum 220-8
66-19; 8-23; 83-10; 89-21
221-6; 70-25
may 111-6; 122-20; 122-9;
medical/legal 44-22; 44-7 mine 164-3; 86-21
125- 11; 125-12; 126-12; medicine 10-18; 10-23;
minimal 102-12; 147-14;
133-14; 140-3; 147-17;
11-1; 14-25; 14-9; 16-3
61-8
148-6; 171-14; 190-22;
medium 146-8; 201-5
minimum 101-5; 108-4
202-19; 202-9; 212-9;
meet 66-22
minor 137-22; 137-23
214-25; 31-18; 41-19;
Meeting 7-23
minus 139-17
66-7 ; 81-24 ; 82-25 ; meetings 207-12
minute 104-11; 108-19;
84-16; 99-17
member 191-16; 61-22;
218-17
Maybe 106-2; 115-9;
61-23
minutes 216-22; 91-7
126- 17; 145-13; 153-7; members 108-2; 189-17;
mis-remembering 20-19
161-24; 204-11; 209-22;
189-22; 63-4
miscellaneous 74-5
27-13'; 48-12; 63-5;
memo 169-6
misclassification 187-16
75-16; 82-2
m e m o r a n d u m 1 6 9-14;
miscommunication 22-11
McCracken 54-2
169-17; 170-4; 171-14
mislead 133-1
McCutchen 55-4
memory 119-16; 119-23;
miss 117-11
M c G h a n 10-2 ; 59-20
133-24; 154-15; 30-1
missed 31-18
59-24; 64-15; 64-16
mention 136-9; 139-10;
Missing 109-19
69-25; 70-2; 70-23; 70-4
140-18; 148-6; 188-24;
mist 102-17; 110-13;
70-5; 70
201-7; 87-13
110-7
mean 100-15; 106-20
mentioned 129-11; 143-15;
mistake 16-20
114-16; 114-21; 121-1
167-3; 171-4; 175-19;
misusing 145-6
-A.
121-12;
121-10;
127-2
176-7; 183-5; 188-21;
mix 170-7
;•£*>*
128-18; 134-17; 140-13
206-8 ; 39-9 ; 40- 16 ; mixed 75-23
141-8; 146-15; 150-1
40-24; 41-23
mixing 50-23
152-7; 154-13; 156-14
mesenchymal 94-20
model 200-14; 200-16
156-9; 160-21;' 165-12
M e s o t h e l i o m a 165-2;
moderately 174-17
165-7; 166-2; 166-3
167-20; 167-3
moderates 123-1
168-16; 177-4; 177-5
messed 158-7
modem 111-25
Vv
vS,
Methanol 13-2
modifies 123-1
i<\ 179-3; 180-25; 183-2
189-12; 201-6; 203-13
methodological 117-6
molecule 200-11

vVS

A. WILLIAM ROBERTS & ASSOCIATES

24

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
moment 109-6; 176-7;
216-12; 49-24
monitoring 14-20; 213-4;
65-11; 65-19
monographs 73-23
MONSANTO 1-9
Montana 57-6
month 193-13; 199-21;
32-1; 65-24
monthly 32-9
months 157-6; 193-15;
193-16
m o r e 125 -25 ; 129-7 ;
131-8; 140-5; 143-23;
144-16; 152-11; 152-23;
153-3; 153-4; 154-23;
155-1; 164-20; 186-23;
19-24; 195-11; 195-16;
202-6; 210-15; 210-16;
25-11; 36-1; 5-17; 53-2;
61-10; 89-14; 95-9
moreover 187-12
morning 72-1; 72-23
mortality 216-9
Moss 57-9
m o s t 114-5; 137-19 ;
144-2; 151-8; 164-18;
165-6; 200-16; 216-13;
28-4; 40-13; 47-3; 65-24;
76-7; 78-24; 78-25; 82-8
mostly 164-3; 18-21;
195-20
mouth 66-13
m o v e 137-20; 138-5;
15-25; 161-16; 44-14
moved 13-10; 65-16
MOYER 1-4; 1-5; 100-1;
103-10} 129-12; 130-14;
134-7; 146-21; 148-13;
148-18; 149-2; 159-3;
164-14; 164-8; 173-7;
174-20; 2; 203-8; 218-15;
219-19; 220-12; 58-16;
81-17; 91-19; 92-1
Moyer's 101-12; 104-6;
105-20; 108-21; 109-7;
144-24; 149-14; 151-22;
157-13; 160-13; 201-13;
202-22; 80-11; 81-11;
82-18; 90-17; 92-9; 95-1
Mr 100-1; 100-15; 100-17;
100-23; 101-11; 101-12;
101-7; 103-12; 103-23;
104-10; 104-14; 104-18;
104-19; 104-24; 105-24;
106-1; 106-11; 106-13;

106-16; 106-2; 106-23;
106-24; 106-5; 106-6;
106-8; 106-9 ; 107-1;
107-14; 107-17; 107-18;
107-4; 107-8; 108-11;
108-12; 108-17; 108-24;
108-7; 109-18; 109-22;
109-23; 109-5; 110-11;
110-19; 110-21; 110-8;
110-9; 113-19; 113-22;
114-14; 114-15; 114-17;
114-20; 115-1; 115-18;
115-2; 115-21; 115-8;
116-13; 116-14; 116-17;
116-4; 116-5 ; 116-7;
117-16; 117-20; 117-24;
118-11; 118-15; 118-18;
118-2; 118-3; 118-4;
118-6; 118-8; 119-11;
119-9; 121-15; 121-16;
121-18; 121-25; 121-5;
121-6; 121-9 ; 122-1;
122-11; 122-14; 122-15;
122-3; 129-12; 130-14;
134-24; 135-24; 135-25;
144-18; 144-20; 148-20;
148-21; 149-1; 150-13;
152-20; 152-21; 153-14;
153-16; 159-23; 159-25;
160-25; 161-1; 161-2;
163-18; 163-19; 163-22;
164-14; 164-8; 165-15;
165-16; 166-1; 166-24;
167-2; 171-19; 171-21;
171-25; 172-13; 172-20;
173-2; 173-5; 174-20;
176-22; 176-25; 177-11;
177-3; 178-5; 183-11;
183-17; 183-25; 184-1;
184-12; 184-22; 185-25;
185-4; 185-5; 186-10;
186-15; 186-2; 186-5;
186-8; 187-1; 187-11;
187-20; 187-23; 187-8;
188-10; 188-14; 188-16;
188-19; 188-6; 189-12;
189-14; 189-24; 190-13;
190-14; 190-18; 190-19;
190-22; 190-24; 190-9;
191-7; 193-25; 194-2;
196-11; 196-18; 199-13;
199-14; 202-1; 202-3;
203-4; 206-12; 206-14;
206-17; 207-18; 207-24;
208-12; 208-23; 208-8;
208-9; 209-11; 210-1;

A. WILLIAM ROBERTS & ASSOCIATES

O C

SCHULZ, CARL O.
210-12; 211-19; 211-9;
212-13; 212-2; 212-7;
213-20; 213-25; 214-1;
214-2; 214-4; 214-7;
215-3; 215-5; 216-20;
216-24; 218-15; 219-16;
219-17; 219-19; 22-12;
22-13; 22-15; 22-9;
220-1; 221-23; 221-25;
222-2; 222-4; 226-7;
3-15; 3-18; 38-16; 38-21;
39-1; 39-16; 39-20;
44-14; 44-16; 44-18;
46-1; 46-3; 49-22; 50-3;
54-2; 6-1; 74-17; 75-4;
78-11; 78-22; 79-23;
79-25; 80-1; 80-11; 80-5;
81-20; 82-1; 82-11;
82-12; 83-21; 84-10;
84-12; 84-16; 84-20;
84-21; 84-23; 84-6;
85-11; 85-19 ; 85-6;
86-12 ; 86 -1 5 ; 86-5;
87-14; 87-18; 87-24;
87-6; 88-10; 88-16;
88-22; 88-5; 89-4; 89-8;
9-13; 9-23; 90-17; 91-19;
92-1; 92-17; 92-19; 92-9;
94-25; 96-13; 96-16;
96-24; 97-10; 97-2; 97-8
m u c h 126-4; 127-17;
132-8; 135-13; 135-7;
135-8; 141-23; 149-10;
149-11; 152-9; 165-19;
17-19.; 181-22; 182-12;
190-10; 195-16; 209-24;
24-16 ; 2 6 - 2 3 ; 43-5;
60-25 ; 6 1-4 ; 66-12 ;
67-14; 67-7; 71-15; 71-22
multiple 55-22
Muskegon 55-9
must 119-3; 214-19; 39-16
mutation 199-3; 54-12
myself 153-8; 43-23
mystery 166-21
N
’
N 226-1
N-H-A-T-S 154-10; 154-11
naked 147-10
na me 167-8; 191-22;
206-20; 215-14; 25-9;
28-2; 3-16; 4-14; 4-16;
41-10; 41-12; 41-14;
41-18; 42-9; 48-3; 68-25;
75-12; 75-17; 75-6; 75-7;
76-19; 79-13

4

MICROCopy

479

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
names 206-8; 36-13; 9-22
106-15; 193-3; 220-14
nasal 202-10; 202-14
NINTH 1
National 12-11; 154-11;
Nisbet 124-10; 124-18;
190-6; 32-6; 38-13;
124-4; 124-9
68-22; 68-23
nisthology 103-19
nature 117-14; 117-4;
nobody 123-17; 161-14;
205-20; 24-8; 40-18; 5-7;
38-3
non-EPA 189-12
75-19
nature— 168-1
non-Hodgkin's 113-6;
119-24; 178-19
NCI 128-6
non-occupational 139-9;
Neal 127-20
nearly 116-9; 43-6
217-5
Nebraska 119-20
non-prescription 16-15
non-radioactive 65-19
necessarily 30-16; 76-6
necrosis 56-25
non-target 208-15; 208-16
need 117-25; 119-17;
none 100-20; 144-18;
143-12; 147-15; 169-13;
163-16; 163-18; 22-23;
195-7; 198-9; 199-17;
220-13; 46-11
39-22; 48-18; 55-11;
nor 123-18; 224-21; 89-24
75-10; 79-24; 93-5; 96-25 normal 142-10; 151-16;
needed 209-25
153-11; 153-14; 153-24;
needs 208-5; 209-4
155-11; 156-4; 156-6;
negative 108-14; 108-16
157-19; 161-21; 161-22;
negligible 102-22; 218-19
162- 17; 162-23; 163-12;
neither 224-20; 89-24
163- 21; 30-19; 31-9
Nervous 7-17
North 2; 7-18
not— 217-17
nets 147-8
not-yet-published 167-12
neurologic 54-10
neurological 53-21
Notary 224-4; 225-8
notation 10-9
n e v e r 109-8; 109-9;
166-18; 166-19; 183-15;
note 162-3; 190-15
184-25; 184-8; 192-24;
noted 98-20
192-25; 38-4; 52-12;
notes 216-21; 63-25;
56-14; 62-1; 63-12 ; 70-15; 87-4
noteworthy 175-8
66-10; 66-11; 9-8
nevertheless 92-16
nothing 118-7; 169-25;
N e w 1 2 7 - 1 9 ; 1 3 - 1 7 ; 224-10
137-17; 189-2; 192-3;
notice 16-21; 24-21; 3-5;
192-5; 22-17; 22-22;
35-19; 35-21
23-3; 23-7; 29-16; 43-10;
noticed 110-20; 172-5;
5- 16; 5-20; 6-10; 6-12; 8-12
6- 7; 6-9; 7-23
noticed— 27-19
newer 173-24
November 227-13; 69-13;
Nexsen 1
69-14; 74-25; 86-9
next 117-17; 166-22;
Now 10-10 ; 101-15 ;
174-9; 186-16; 191-1;
112-22; 114-1; 119-22;
85-12; 87-25; 88-11
123-4; 124-11; 128-12;
NHATS 154-8
129-11; 130-20; 132-15;
nice 64-9
135-11; 137-4; 144-24;
Nick 159-7; 81-19
147-20; 15-19; 152-15;
NIDA 68-23
16- 21; 160-15; 166-24;
NIEHS 190-6
17- 18; 171-4; 175-13;
Nigg 150-13
191-21; 192-13; 194-16;
night 203-20; 45-22;
194-3; 20-21; 200-18;
74-23
206-24; 212-6; 212-8;
nine 105-21; 106-14;
23-16; 28-16; 32-21;
A. WILLIAM ROBERTS & ASSOCIATES

26

SCHULZ, CARL O.
38-6; 42-12; 42-16;
42-24; 53-11; 56-25;
57-8; 62-21; 63-18;/
65- 16; 66-14; 66-18;
66- 8; 67-13; 7-13; 70-25;
72-21; 94-25
NTP 202-10; 202-13; 38-13
Nuclear 64-23
nuisance 53 -4; 55- 10;
55-17; 56-10
number 102 -3; 12- 19 ;
120-2; 136- 8; 153- 19;
154-6 ; 154 -7; 157 -2 ;
159-17 ; 161- 12; 162--13;
180-1 5; 21 -5; 219 -9 ;
23-18 ; 24- l; 26- 18 ;
31-14; 32-22; 66-■14; 7-3;
71-21; 74-8; 79-21; 85-13
numbers 134-18; 161-15;
219-12

0
O 1-14; 2; 223; 223-3;
226- 19; 226-5; 227-11;
227- 15; 227-5; 227-8;
3-12; 3-17; 5-23; 83-25;
85-14; 86-7; 87-21
o'clock 72-1
Oakland 47-5
Obj ect 101--7; 103- 12
104--10; 105--24; 106-23
106 -24; 107 -17; 107-4
108 -il; 109 -18; 110-8
113--19; 114-■14; 114- 17
115 -l; 115- 18; 115 -2
116 -13; 116 -14; 116-4
117 -17; 119 -9; 121- 15
121 -25; 121 -5; 122 -1
122--14; 160-•25; 165- 15
171--19; 172--13; 183- 11
183 -25; 184 -l; 184-22
185 -25; 186 -10; 186-8
187 -l; 188- 16; 196- 11
199 -13; 202 -1; 207- 18
209--li; 210--12; 211- 19
213--25; 219-■16; 221-23
92-17; 96-13; 96-24
objection 104-11; 104-18;
104-20; 106-7; 108-24;
185-3; 186-2; 187-20;
188-10; 208-12; 208-8;
212-7; 215-3; 9-20; 97-8
o b j e c t i o n s 11 7-19;
117-21; 224-12; 224-18;
3-5; 3-7
obligation 211-14
observations 103-5
MICROCopy

MOYER

V S .

DOW CHEM ICAL

observed 114-2
observer's 114-22
obtained 125-14; 217-24
obvious 93-5
obviously 140-10; 77-1;
89-22
occasion 149-12; 19-3;
39-23
occasions 69-7
OCCIDENTAL 1; 2; 5-13;
80- 19
O c c u p a t i o n a l 12-11;
12-14; 12-4; 120-8;
162-2; 17-8; 35-16; 36-3;
47-14; 48-24; 48-25
occupationally 47-11;
89-3
occupied 98-4; 98-5;
99-20
occur 94-8
occurred 195-8
occurring 107-21; 201-10;
201-11

octachloro 170-13
octachlorodibenzo 162-24;
99-2
October 150-23; 151-3;
217-4; 227-16; 227-9;
85-16; 87-14; 87-21
odd 164-18; 177-6; 41-12
of-- 139-4; 42-16
Off-the-record 213-19
offer 176-20; 63-6; 63-8
offered 204-5
office 112-4; 150-18;
180-15; 34-7; 37-19;
4-25; 61-12; 64-8; 73-1;
73-2; 75-4
officer 192-17; 192-21;
38-11
officers 156-22
Offices 1-17; 190-5;
192-4; 43-22; 5-3
official 225-2
often 121-7; 132-6
Oh 145-4; 178-11; 195-21;
201-19; 207-1; 208-13;
209-21; 33-22; 41-4;
57-7; 68-22; 70-25; 74-5;
81- 22
oil 1 7 3 - 1 2 ; 173-16;
174-10; 175-18; 176-10;
56-11; 56-15
oils 173-22
O k a y 10-16 ; 100-24;
101-12; 101-25; 103-24;

March 5, 1993
COMPANY
103-3; 106-20; 106-6;
107-15; 11-18; 110-22;
111-12; 112-25; 113-3;
114-9; 115-9; 116-18;
117-19; 117-25; 118-25;
118-3; 119-5; 120-17;
126-16; 13-24; 131-24;
133-22; 134-4; 135-22;
136-6; 139-18; 139-2;
139-20
139-9 ; 14-8;
140-17; 140-2; 141-1;
142-7; 143-14; 144-21;
145-21; 145-24; 145-5;
146-1; 147-15; 148-4;
151-24; 153-6; 158-12;
159-16; 159-19; 159-8;
160-4; 160-7; 161-13;
162-22; 163-16; 166-10;
167-8; 169-10; 169-8;
170-15; 172-24; 175-12;
175-18; 179-3; 182-25;
185-15; 194-9; 195-3;
20-18; 200-9; 203-13;
209-1; 21-23; 210-20;
214-16; 215-15; 215-20;
216-11; 217-13 ; 22-8;
220-11; 221-4; 222-4;
23-2 ; 28-12 ; 2 8 - 2 1 ;
30-21; 34-16; 34-24;
35-23; 35-6; 39-15; 4-9;
4 0-1; 10-24 ; 41-21;
43-2 5 ; 4 3 - 3 ; 45-24 ;
46-13 ; 46 -2 2 ; 47-9 ;
48-11; 48-24; 49-12;
49-22 ; 50-12; 50-7 ;
51-14; 51-16; 51-21;
51-25; 52-24; 53-24;
53-6; 54-14; 54-6; 55-2;
56-7; 58-23; 59-17; 59-3;
6-14; 6-22; 62-15; 62-23;
66-9; 69-12; 69-6; 70-6;
70-9; 71-15; 71-6 ; 72-14;
72-16; 74-11; 77-17 ;
77-9; 78-1; 78-8; 79-4;
82-21; 82-22; 82-25;
82-6; 83-13; 83-15 ;
83-2 1 ; 83-5 ; 84-17 ;
84-24; 85-11; 85-20;
85-5; 86-20; 87-12 ;
87-18; 87-8; 88-5 ; 89-18;
89-4; 9-24; 90-21 ; 91-25;
91-6; 91--8; 92-13; 92-15;
93-7 ; 94 -2 5 ; 95-24 ;
97-11; 97-4; 98-1; 99-8
old 2 1 0-17; 2 1 0 - 2 2 ;
213-5; 42-18

A. WILLIAM ROBERTS & ASSOCIATES

0*7

SCHULZ, CARL 0.
omissions 26-1
on-going 123-14; 62-25;
63-10; 65-25
onc e 13 8-4 ; 177-17 ;
20-10; 62-20; 66-12
One 10-2; 120-22; 121-3;
122-24; 123-20 125-14;
126-18; 127-16 137-19;
139-19; 145-18 148-10;
149-18; 153-19 155-20;
162-10; 169-12 171-15;
173-10; 176-12 ; 176-3;
176-9; 182-19; 183-18;
184-7; 188-1; 190-25;
191-15; 193-22; 198-18;
20-12; 200-11; 200-14;
201-8; 202-20; 205-13;
207-6; 208-24, 209-2;
21-1; 21-16; 2 1-17 ;
216-1; 219-21; 219-25;
221-2; 23 -2 0 ; 25-6;
30-24; 32-5; 33-18; 33-2;
34-22; 36-16; 40-16;
41-18; 41-19; 46-16;
47-22; 5-16; 53-14; 54-8;
56-17; 57-13; 57-8; 58-8;
59-17; 6-10 ; 60-15 ;
61-21; 61-23 ; 62-1;
62-10; 62-14; 62-16;
62-3; 63-12; 63-19 ;
64-12; 64-13; 65-24;
66-12; 68-17; 68-9; 7-15;
71-2; 75-25; 76-18 ;
76-23; 77-10 ; 77-5;
81-18; 86-16; 87-5; 9-12;
93-13; 98-10
one-third 59-7
one-year 19-25; 60-12
ones 120-18; 126-20;
126-24; 144-23; 149-20;
173-24; 197-18; 216-14;
73-17; 81-2; 99-6
ones— 190-1
o n l y 117-2 ; L2 0 - 18 ;
120-5; 126-10 j 128-2;
131-11; 137-8; 139-24;
146-2; 147-20; 151-21;
16-15; 164-24; 173-21;
174-1; 178-18 ; 18-6;
203-20; 27-5; 51-11;
6-15; 64-12; 6 4 - 1 3 4 8 0
71-24; 9-14; 93-13; 94-9
onto 201-21; 220-18;
220-19
1^
open 146-15; 146-23;
204-15; 67-23

(4

MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
operate 4-21; 4-22
operates 198-20; 64-24
Operation 156-2
operational 198-11
opine 101-2
opinion 100-13; 100-24;
101-9; 103-7; 104-5 ;
110-4; 111-13; 126-20;
126-21; 130-24; 134-10;
134-22; 134-6; 147-1;
147-23; 148-1; 161-23;
163-23; 164-13; 164-15;
169-20; 169-21; 171-17;
178-4; 196-10; 197-19;
197-22; 200-4; 2 0 1 -2 2 ;
202-4; 205-9; 2 1 1 -2 1 ;
216-14; 216-17; 217-2;
218-14; 90-16; 90-24;
90-25; 91-18; 97-21;
98-1; 98-12 ; 98-16;
99-16; 99-25
opinions 122-23;: 129-2;
164-6; 179-6; 67-22;
89- 12; 89-13; 90-11;
90- 15
opportunity 16-3; 174-18
opposed 110-7; 112-24;
141-4; 146-17; 177-15;
81-2; 9-15; 90-6
or— 149-17; 27-8
O R A N G E 1-2; 100-16;
101-16; 109-8; 110-14;
110-24; 129-13; 155-5;
156-4; 159-4; 164-14;
175-3; 218-17; 219-3;
221-19; 33-14; 73-23;
84-25; 90-19; 91-20;
92-1; 92-9
oranges 127-8; 158-23
order 101-1; 145-17;
153-3; 158-8; 165-13;
207-16; 208-5; 35-22;
47-3; 71-25; 80-20
organic 10-10; 213-23;
39- 20
^ organisms 138-8; 208-17;
OO 208-21
organization 36-20; 71-11
organizationally 41-13
organized 73-5
organs 94-8
original 184-14; 185-18;
192-9; 23-10; 26-12;
40- 23
originally 186-21
originated 30-12; 30-2

Orleans 7-24
OSHA 35-18; 35-22; 36-3
OTC 68-12
other— 97-22
others 113-12; 125-25;
126-24; 127-2; 129-8;
144-22; 148-11; 178-11;
186-20; 207-1; 49-8;
62- 21; 67-12; 71-4; 87-9
others' 136-14; 136-15
Otherwise 130-13; 7-25
ought 205-11
our 100-6; 130-8; 135-12;
135-15; 137-9; 138-12;
24-8; 26-8; 29-17; 30-20;
38-10; 62-18
out 106-2 1; 109-12;
11-24; 114-21; 115-14;
126-22; 133-24; 135-17;
152-25; 152-8; 156-22;
158-5; 166-13; 178-3;
184-24; 185-2; 200-17;
21-15; 216-19; 23-3;
30-12; 30-3; 32-1; 32-6;
32-9; 33-10; 33-12; 54-4;
6-13; 6-19; 61-2; 63-15;
63- 17; 63-25
out— 82-5
outfit 79-12
outlined 37-6
output 22-2
outset 75-15
outside 189-10; 189-13;
189-7; 44-5; 67-25; 68-1;
71-3
over 121-13; 144-7;
147-10; 147-13; 147-8;
201-1; 21-25; 211-19;
219-2 ; 24-7 ; 25-22 ;
30-18; 49-12; 58-24;
78-2; 97-13
over-the-counter 16-11;
16-8; 68-18
overall 147-23; 156-11;
156-12; 177-23; 177-9;
179-16; 190-8; 32-16
overlap 128-19
overlies 203-1
overnight 195-5
overrun 78-4
overseeing 65-18
oversight 78-2
overview 102-2
own 110-17 ; 1 1 1 - 2 1 ;
123-10; 199-11; 4-2;
43-13; 71-2; 90-7

A. WILLIAM ROBERTS & ASSOCIATES

28

SCHULZ, CARL O.
owned 65-2
P
P 2
P/H 6-25
P/N 7-1; 7-22; 7-8
packages 210-22
packet 87-25; 88-23
page 114-10; 159-16;
159-17; 159-18; 184-23;
185-10; 185-6; 186-18;
194-16; 223-9; 224-8;
226-18; 226-3; 227-2;
6-10; 6-12; 6-13; 62-9;
76-23; 77-12
pages 177-6; 189-23;
29-10; 6-17
paid 181-12; 70-10; 70-5
Palm 2
pamphlet 21-18; 22-3
panel 69-16; 69-25; 70-4
panels 69-20; 69-9; 71-3
paper 138-21; 138-23;
181-17; 181-7; 199-21;
24-4; 27-12
papers 150-18; 150-19;
150-24; 216-1; 24-5;
27-10
Para-Chem 57-21
Paragraph 139-10; 139-23;
185-10; 186-17; 194-18
paraphrase 92-8
parathion 13-2
Pardon 22-12
paregoric 68-14
parent 42-12
parents 175-15; 54-19
park 162-21
parked 157-1
part 120-15; 124-21;
130-18; 130-20; 130-25;
130-8; 131-8; 138-12;
147-21; 15-2; 160-11;
169-1; 190-15; 213-3;
219-25; 220-17; 221-13;
23-1; 31-18; 31-20;
44-13; 7-3; 77-3; 82-9;
83-7
partial 76-21; 77-6
participate 61-16
p a r t i c i p a t e d 207-2;
208-2; 212-5
particular 125-5; 142-17;
145-15; 163-17; 164-11;
180-17; 187-9; 191-18;!
196-5; 211-16; 5 2 - 5 ; V
59-17; 63-9; 8-18
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
p a r t i c u l a r l y 175-8;
207-10; 37-17
particulate 144-1
parts 154-14; 157-15;
159-14; 161-25; 18-11;
212-1
party 224-21
passages 202-15
passed 32-21
passing 121-20
past 142-9; 95-13; 95-9
paste 56-6; 69-16; 69-17
pathologist 103-17
patients 89-25
pattern 172-4; 98-17
Patties' 167-12
Paxton 124-13; 124-18;
124-4
peak 105-11; 105-12;
107-20
pending 224-22 ; 49-2;
54-22; 58-6; 58-9
pe n t a c hloro 197-11;
197-5; 197-6
people 113-14; 114-3;
114-5; 1 2 0 -2 2 ; 124-2;
127-11; 127-13; 127-14;
132-21; 141-14; 142-7;
149-1; 150-16; 150-6;
153-24; 153-25; 154-1;
154-25; 155-22; 155-23;
157-4 ; 157-5
16-8 ;
161-8; 180-10; 180-20;
180-25; 182-7; 189-13;
190-1; 190-4 ; 190-6;
191-24; 207-2; 2 1 - 2 1 ;
214-9; 34-21; 41--2; 41-6
p e r TO 3-4 ; 1 3 0 - 1 8 ;
130-20; 130-25; 131-8;
139-12; 139-14; 139-24;
141-2; 151-23; 154-14;
157-15; 158-21; 159-14;
160-11; 161-18; 161-25;
217-6; 218-9; 219-25;
220-17; 221-13 ; 24-5;
26-18; 28-18; 61--6 ; 63-1
percent 137-9; 140-4;
140-5; 140-6; 161-18;
18-24; 18-25; 2 2 0 - 2 0 ;
43-20; 59-2; 59-4; 61-8;
64-18; 64-20; 72-13; 73-8
percentage 108-2; 58-23;
61-7; 72-10; 72-9; 73-8
percentage-wise 143-24
perform 19-16
performed 178-4

perhaps 102-6; 117-11;
132-20; 157-20; 194-22;
71-21; 96-5
period 104-16; 104-25;
105-2; 105-21; 207-19;
218-22; 22-18; 35-13;
43-20
period— 51-18
periodically 65-14
periods 108-9
permanent 60-11
permit 134-21; 92-4
Perry 207-4
person 144-14; 172-17;
172-19; 214-5
PERSONAL 1-4; 175-11;
175-23; 2; 53-1; 53-20;
53-8; 54-15; 54-9; 57-19
personally 206-13; 206-15
personnel 157-3
persuasive 187-13
pesticide 207-21; 208-6;
34-7; 34-9; 37-21
pesticides 137-22; 34-10;
34-11; 34-12; 37-19; 8-6
petition 13-14; 13-21;
207-22
Petroleum 124-15
pg 139-12
Ph.D 1-14; 10-10; 226-5
Ph.D. 3-12
phenol 197-11; 197-5;
197-6
phenoxy 120 -2 2 ; 120-7;
121-2; 155-19; 161-9;
178-23; 184-17; 185-20;
19-11; 19-13; 194-20;
197-13; 20-23; 20-4;
201-5; 21-4; 226-25;
227-21; 23-11; 23-17;
24-17; 27-11; 28-18;
28-25; 30-4; 32-13;
33-19; 33-24; 38-1;
38-25; 46-11; 46-15;
59-9; 78-16; 79-19;
88-14; 88-19; 90-1
Phil 207-4
Philadelphia 79-12
physical 105-8; 143-18
pick 144-15; 26-2
Pickering 47-1; 47-4;
53-6; 58-16
picogram 139-15; 139-16
Picograms 139-14; 139-24;
141-1; 151-23; 158-21;
217-6; 218-9

A. WILLIAM ROBERTS & ASSOCIATES

O O

SCHULZ, CARL O.
piece 107-11; 220-3
piecemealed 71-7
Piedmont 54-13; 54-8;
58-2; 58-3; 58-9
Pierce 127-20
pile 154-16; 182-24; 82-4
pilots 156-21
pitch 48-23; 53-18
place 12-15; 144-16;
173-1; 181-22; 19-9;
195-4; 2-6; 216-21; 36-4
placed 182-5
places 192-5
Plaintiff 1; 1-20; 2-2;
48-1
Plaintiff's 136-8; 142-4;
150-21; 194-16; 194-4;
217-3; 48-15; 48-21;
49-17; 49-23; 5-21; 51-8;
53-25; 55-11; 5 5-8;
5 6 - 16 ; 56-9; 57-15;
57- 22; 6 -8 ; 76-16; 78-13;
78-23; 81-12; 82-22;
83-23; 85-12; 8 6 - 6 ;
87-19; 88-17; 88-6 ; 89-5
plaintiffs 49-16; 49-18
Plaintiffs' 81-9
plane 156-23; 157-1
plankton 138-7
Plant 153-18; 166-23;
212-23; 57-24
plants 136-25
played 124-3
player 75-11
playing 184-7; 211-2
Plaza 50-9; 57-7
please 185-14; 3-16
pleasure 118-11
P L F 226-19; 226-21;
226- 23; 227-11; 227-14;
227- 18; 227-20; 227-23;
227-3; 227-5; 227-8;
49-25; 5-23; 78-14;
78-18; 83-25; 85-14;
86-7; 87-20; 88-18; 88-7;
89-6
plus 63-25; 73-14
PM. 222-7
point 1 1 0 -2 2 ; 120-25;
124-25; 131-11; 133-11;
133-15; 133-23; 14-1
147-13; 149-18; 149
169-6; 173-8; 176-23;
177-17; 19-6; 195-18;
202-19; 202-7; 203-14; f\
204-10; 209-2; 219-10;
?

$

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

cn

00
^

24-18? 41-19; 43-24;
6-19; 9-8
points 102-6? 127-5
Poisons 7-16; 8-9
policy 35-19; 35-22
political 193-6
Pollard 1-18
pollutant 36-8
Pollution 53-3; 53-4?
55-7; 57-24
polychlorinated 111-9
polyester 39-14
Pool 180-8
poorly 164-20; 176-5;
93-24
Pope 49-6
p o p u l a t i o n 136-11;
153-25; 154-24; 155-25;
156-20
population's 152-13
populations 127-7; 128-5;
155-4; 89-3
portion 65-22; 77-8
portions 63-16
position 181-10? 3-23;
60-12; 60-18
positions 98-3; 98-4;
99-21
positive 153-21
possibility 92-11? 92-13;
92-15
possible 126-10; 160-17;
161-3; 161-5; 178-20;
181-8? 210-14; 32-24
possibly 129-20; 190-6;
197-2? 54-11
p o s t d o c t o r a l 10-17;
11-16; 11-23? 11-5
potent 168-9; 196-13;
196-17; 196-9
potential 108-4? 120-3;
123-12? 123-24; 138-1;
170-8; 172-10; 176-14;
179-12; 19-18; 205-25;
55-17; 68-16; 9-6; 99-22
p o t e n t i a l l y 100-13;
108-23; 174-2
potentiates 122-8
pound 217-7; 218-10
practice 4-3; 43-14
precise 198-11
precursor 58-2
precursors 131-15
predicate 103-13; 104-12?
106-7; 107-6? 113-20?
186-11; 202 -2 ? 209-12;

SCHULZ, CARL O.

211-20; 214-2
prisoners 133-12
predicates 109-19
private 1 2 - 6 ; 123-8;
predict 143-4
13-6; 17-9; 18-25;,
predictability 168-18
192-15; 36-11; 42-24;'
predispose 175-17
59-15; 59-6
preface 75-22; 76-2
pro 40-17
prefer 203-24
probability 174-6
p r e l i m i n a r y 176-23?
probable 148-2; 163-24
179-23? 48-7; 74-20? 9-5
92-9
p r e p a r a t i o n 149-20;
probably 116-24 ; 116-3
189-8; 194-21; 194-22;
118-16? 1 22 -2 ; 124-21
219-20; 220-9; 28-19;
125-7; 138-21; 143-15
71-17
148-10; 149-21; 164-20
preparations 194-21
165-9; 167-16; 168-21
prepared 124-17; 125-1;
17-17; 172-15; 174-7
125-4? 134-23; 178-15;
179-4? 18-23 ; 19-9
179-4; 203-20; 98-9? 99-5
190-24; 192-11; 193-14
preparing 177-15; 9-6
195-9? 196-7; 200-16
prescription 16-14; 68-19
213-1? 220-16; 22 0 -8
present 111-7? 194-20;
27-12; 27-2; 27-9; 29-25
200-4; 59-19? 79-11?
29-9; 37-17? 41-18? 45-3
98-10; 98-11; 98-8
46-13; 46-8; 47-2? 48-13
presentation 6-11; 7-17
51-19; 52-6; 69-5; 72-1
presentations 6-12; 6-13;
73-12 ; 73-22 ; 73-8
7-13; 8-8
76-13; 83-19; 95-10
presented 67-24; 67-25;
96- 19; 98-18
68-20? 71-2
problem 160-13; 186-1;
Presently 46-18
187-5; 204-14
preservative 50-21
problems 128-1? 183-13
preservatives 34-15
procedure 117-21; 3-4
preserving 53-23; 54-12;
proceedings 67-19; 70-16;
55-15; 55-19
70-20; 74-1
president 17-14; 3-25
process 131-17; 141-12;
presumptuous 199-9
169-23? 169-25; 170-2;
pretty 117-5; 117-6;
180- 1; 180-22; 180-3;
119-2? 121-12; 135-17?
181- 16; 181-18; 181-22?
148- 21; 148-24; 149-10; 193-5; 199-2; 207-14;
149- 11? 149-4; 149-7; 208-3; 211-13; 211-4;
149-8; 172-15; 172-16;
212- 5; 215-2
177-1; 183-13? 183-3?
produced 170-2; 24-23
23- 25; 30-17; 58-12? produces 21-19
71-13
producing 13-19
previous 22-23
product 132-11; 133-18;
primarily 127-12; 136-12;
166-4; 181-16? 20-3;
18-18; 180-17; 44-3;
208-19; 21-24; 24-6;
55-16
39-12.
primary 136-16
production 1 2 0 - 1 0 ;
prime 170-12; 170-13
127-15; 161-9
principal 77-16
P R O D U C T S 1? 100-20;
principles 171-8
138-13; 15-21; 16-10;
printed 32-4; 64-7
213- 15? 36-23; 37-6;
Printing 64-8
50-15; 66-25; 68-18;
Prior 210-2? 215-8? 23-4;
97- 13
24- 15; 26-8; 27-5? 71-25 professor 5-10; 60-2
prioritizing 36-8
professorship 61-18
Prison 133-13
profile 163-5

A. WILLIAM ROBERTS & ASSOCIATES

30

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

• N.

VO
1
o
0
0

program 14-20; 14-9;
published 120-13; 124-6;
15-1; 15-2; 16-1; 18-11;
125- 15; 132-19; 133-21;
18-7; 38-14; 62-19; 65-14
134-3; 167-15; 20-10;
Programs 34-7
20- 13; 20-5; 209-20;
prohibited 37-19
2 1 - 13; 21-7; 22-20;
project 12-17; 192-20;
23-11; 23-15; 24-4; 25-2;
213-4; 30-22; 33-21;
26-22; 26-7; 27-6; 29-23;
3 4 - 20; 38-11; 39-6; 30-10; 30-11; 30-14;
59-11; 77-14; 77-20
30-16; 30-19; 30-2;
project's 59-12
35-18; 64-6; 77-11; 88-13
projects 18-22; 19-4;
pull 158-5; 178-2
33-18; 33-22; 33-23;
pulp 181-17; 181-6
35- 6; 40-11; 40-13; 43-22 puncture 203-10
promoter 198-1; 198-10;
purchase 63-19; 63-20
198-15; 198-20; 198-6
purchased 41-24; 42-4;
promotion 14-15; 14-16;
42-8
15-22
purely 176-23; 198-5;
promulgation 210-24
55-10
pronounced 169-6
purports 79-4
proofs 167-17
purpose 100-5; 105-19;
properties 211-18
94-17
property 53-5; 54-8;
purposes 76-5; 78-12
5 5 - 17 ; 55-25 ; 55-6 ; pursuant 209-5
5 6 - 10; 57-19; 57-22; put 124-5; 135-3; 144-16;
57- 23; 57-25; 57-4; 58-4 155-22; 161-12; 180-10;
propionic 96-3
180-25; 185-17; 191-2;
proposal 19-14; 19-16;
217-20; 26-7; 32-6; 32-8;
37-8
33-3; 47-2; 65-4; 72-19;
propose 37-9
76-16; 80-23; 94-16
proposed 81-10
Q
proposition 1 1 1 -2
qualification 58-21
Protection 123-5; 185-8
qualified 103-15; 115-15;
p r o t e c t i v e 102-13;
130-16; 211-23; 43-7
102-14; 108-19; 109-8;
qualify 114-1
110-1; 129-25; 145-11;
quality 116-20; 117-3;
145-12; 145-3; 147-5;
126- 5; 126-8; 14-21
quantitative 101-21
149-3
provide 211-14
q u a n t i t i e s 148-23;
provided 103-6; 107-6;
197-16; 97-14
208-11; 44-10; 44-11;
quantity 147-7; 91-10;
67-22; 69-1; 74-17
91-2
provides 172-18; 183-21
quarters 156-23
provisions 32-22
que 160-19
proximity 20 1-1 1
question 100 - 1 0 ; 100 -5
Pruitt 1
102 -7; 103-18; 105- 20
P u b l i c 11-1; 224-4 ; 105--25; 108- 14; 114- 10
117--17; 122 -13; 126- 16
225-8; 32-19; 84-25;
84-8; 89-2
126 -18; 129--6 ; 130- 12
publication 20-15; 20-20;
130 -2 1 ; 133--16; 133 - 2
20-22; 210-2; 24-22;
134 "I; 134- 6 ; 142- 15
33-5; 7-5
153 -15; 165--2 2 ; 172 -9
174 -1 0 ; 177--2 ; 177- 22
publications 32-9; 6-20;
6-23; 6-9; 7-10; 8-3;
185 -23; 204--1 ; 214- 12
87-10
218 -23; 2 2 1 --24; 26- 12
34- 18; 35- 1 1 ); 39--2
publicly 132-5; 30-15
publish 35-2
46-14; 48-10; 71A. WILLIAM ROBERTS & ASSOCIATES

31

SCHULZ, CARL O.
9-24; 91-12; 97-1
questioning 40-2; 45-20
questions 147-17; 158-18;
173-10; 194-7; 217-1;
222-5; 74-20; 90-22
quibbling 147-8
quick* 44-15
quickly 141-24; 82-4
quite 105-14; 126-9;
128-22; 130-18; 130-4;
144-10; 168-9; 209-18;
209-24; 26-11; 32-5;
52-20; 61-8
quote 190-16; 190-18;
190-19
quote/unquote 151-16
quoting 190-20
quoting— 214-10
R
rabbit 133-9
radioactive 64-24; 65-3
raise 34-18
raised 121-1; 173-10;
175-5
Raleigh 180-6
Rampy 38-11; 58-21
ranch 156-13; 156-15;
156- 20; 156-3; 156-7;
157- 4; 157-7
randomly 154-25
range 105-9; 107-20;
139-11; 142-10; 151-20;
154-6; 161-20; 161-22;
217-14; 220-14
ranges 217-6
ranking 126-8
r a r e ‘107-22; 107-24;
94-14
rarely 102-5; 102-8
rate 108-22; 119-24;
144-11; 145-19; 145-21;
146-2; 146-7; 148-7
rates 72-15
rather 198-11; 203-17;
212-10

rats 143-23; 6-25; 7-9
Rats. 7-22
Raven 55-24
raw 195-16
re-awarded 79-1
re-competed 19-23
re-registration 34-10
re-review 181-14
re-reviewed 203-20
reached 111-22; 114-5
reaction 200-12; 55-23
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

VO
GO

r e a d 124-24; 124-4;
149- 12; 149-14; 149-16;
150- 1; 150-5; 185-12;
185-15; 187-3; 190-9;
192-24; 199-21; 203-18;
21-21; 223-4
reading 110-17; 142-4;
184-24; 185-9; 187-5; 3-9
real 195-6; 205-7
realize 29-25
really 110-1; 115-3;
128-9; 132-22; 132-8;
143-21; 147-2; 154-7;
161-23; 187-24; 188-12;
4-7; 48-5; 49-10; 51-3;
53-1; 70-18; 75-20
REAR 2-21
reason 104-1; 141-18;
15-24; 223-9; 32-16;
75-17
reasonable 107-2; 90-16;
91-21
reasons 138-14; 60-15
rebuttal 176-14
recall 133-14; 148-21;
149-4; 149-6; 188-1;
189-19; 19-13; 28-13;
29- 23; 29-24; 30-1; 30-5;
30- 7; 34-19; 34-3; 35-7;
37-24; 40-8; 45-8; 47-16;
50-14; 50-7; 52-16
recalling 178-13
received 110-23; 149-22;
167-17; 82-14
recent 151-8; 47-19;
47-4; 76-8; 78-24; 78-25
recently 123-16; 166-18;
207-11;" 86-17
receptor 199-6
recess 118-17; 173-4;
216-23; 44-17; 80-4
reciting 140-24
reclassify 68-14; 68-16
recollection 120-19;
120-23; 132-18; 190-4;
20-2; 42-23; 49-18;
52-13; 58-19
recommendations 65-13
reconsider 181-20
reconstruct 51-23; 52-1;
52-2
record 182-19; 190-21;
224-17; 72-17; 72-22;
84-9
recorded 224-13
records 133-6; 148-22;

149-7; 51-24; 51-25;
52-14; 72-3; 84-25; 85-1
recourse 181-8
reduce 195-7
refer 169-4
reference 125-16; 169-21
referenced 27-15
references 134-24; 151-4;
31-17; 74-9; 87-15
referred 164-19; 170-3;
185-16; 190-10; 197-9;
22-24; 43-19
referring 104-13; 115-13;
122-7; 139-21; 139-24
150-19; 150-21; 178-18
178-7; 178-8; 187-14
194-16; 215-15; 220-4
28-13; 28-22 ; 34-12
7-11; 93-3; 97-24
refinery 56-11
reflect 163-14; 164-10
193-12
regard 101-18; 111-5
1 1 1 -6 ; 123-12; 123-23
125-24; 131-25; 132-10
133-17; 133-7; 148-17
154-17; 155-6; 164-7
172-6; 176-20; 181-3
20-4; 215-7; 216-9
2 2 0 - 6 ; 39-3 ; 80-10
89-11; 90-12; 94-25
regarding 10-9; 104-5;
206- 3; 206-9; 24-16;
8-14; 8-9; 87-16
registered 208-6
registration 207-16;
207- 22; 208-3; 210-22;
34-10; 63-8
Registry 189-1
regs 2 1 2 -1
regular 61-18
regulate 205-12
regulated 213-15
regulates 199-23
regulations 15-12; 209-5
regulatory 211-23; 63-23
regurgitate 39-17
Reichardt 77-21; 77-22
reject 200-19
relate 158-20; 73-16
related 105-14; 119-18;
120-1; 124-7; 136-21;
137-6; 161-10; 168-20;
172-7; 224-21; 27-25;
28-9; 30-3; 48-22; 55-16;
88-4; 96-5

A. WILLIAM ROBERTS & ASSOCIATES

32

SCHULZ, CARL O.
relationship 105-19;
105-3; 107-13; 113-5;
114-12; 114-24; 114-7;r
118-23; 119-15; 119-8;'
142-25; 152-24; 154-19;
167-20; 171-13; 201-23;
43-11; 43-17
relationships 170-23
relative 164-7
relatively 141-16; 147-9;
160-23; 161-6; 171-18;
171-20; 23-17
relevant 178-18; 178-19;
202-21; 211-17; 22-20;
28-17; 31-14; 32-10;
32-13; 33-19; 33-7; 33-8;
34-23; 67-14; 74-17;
87-11; 89-1
reliable 125-25; 126-24;
129-8; 171-24
reliably 131-9
reliance 178-9; 182-6
relied 148-25
rely 126-20; 128-25;
182-9
relying 179-7
remainder 41-16
remember 13-4; 134-2;
150- 3; 151-10; 173-13;
191- 21; 195-6; 196-1;
196-5; 196-8; 207-3;
214-18; 214-21; 27-12;
28-16 ; 30-8 ; 32-20 ;
36-13; 36-16; 40-12;
41-10; 49-13; 51-5;
56-21; 56-24; 71-5;
79-13; 9-21
remembering 20-21
remote 92-14
removal 123-24
render 134-21
rendered 51-9; 67-22
reorganizing 41-17
repeat 96-25; 97-3; 97-5
replace 61-24
report 134-23; 136-7;
136-9; 158-14; 170-25;
171-2; 181-1; 181-24;
181-4; 182-5; 184-14;
185-18; 185-6; 188-21;
192- 24; 193-2
REPORTED 1-21; 107-23;
151- 20
R e p o r t e r 1; 172-25;,
224-1; 224-3; 226-9
reporters 180-18
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY
reporting 181-1
reports 73-25
represent 141-3; 218-1
REPRESENTATIVE 1; 2-3;
70-4; 77-6
represented 209-23; 72-11
representing 10-1; 47-24;
9-11
represents 48-1
reproductive 32-12
request 14-14; 14-17;
19-16
requested 125-7; 226-12;
226-14
require 37-3
required 196-14; 208-11;
9-16
requirements 207-17;
209-14; 209-9; 210-8;
211-24; 212-11; 212-9;
66-23.
research 1 1 - 1 1 ; 1 1 -20 ;
11-25; 11-9; 119-1; 12-5;
123-11; 158-1; 159-1;
184-19; 185-22; 186-20;
191-13; 191-9; 192-10;
206-9; 215-23; 217-17;
23- 10; 23-15; 23-21;
2 4 - 16 ; 24-19 ; 24-7 ;
26-22; 29-24; 30-12;
30-13; 30-2; 40-22;
40-23; 61-14; 72-25; 90-7
researcher 114-3
reserve 188-17
reserved 117-22; 3-7
residence 54-25
resins 39-14
resource 64-10
resources 72-25
respect 104-12; 169-18;
204-2; 215-24
respirable 102-17
respiratory 54-18; 54-20
respond 177-22
responds 200-1
response 19-15; 99-22
responsibilities 18-13;
61-5
responsibility 25-14;
61-25
responsible 51-1; 75-23
rest 165-4
restate 122-12
result 156-5; 160-21;
162-4; 199-23; 208-20;
218-15; 35-3

results 113-24; 114-2;
117-4; 155-9; 65-13
r e s u m e 10-16; 2 1 - 2 ;
226- 19; 5-23; 6 -6 ; 6-7;
7-14; 8-1; 8-13
retain 142-17
retained 152-4; 153-1;
153-21; 157-14; 161-17;
218-19; 53-24; 69-25;
70-12; 70-23; 9-14
retention 151-17
retrained 11-15
retrospectively 24-14
reveal 9-17
reverse 202-9; 47-3
reversing 152-15
review 100-18; 100-3;
103-17; 111-21; 120-16;
123-17; 125-6; 126-2;
13-14; 136-15; 141-2;
155-15; 16-8; 172-2;
172-5; 176-15; 176-18;
179-23; 185-7; 187-5;
19- 17; 193-18; 21-10;
21-18; 213-22; 214-13;
217-10; 217-14; 22-3;
227- 3; 23-1; 23-14; 23-3;
24-9; 25-1; 26-10; 26-8;
33-4; 33-6; 34-8; 40-14;
52-11; 65-12; 71-18;
73-11; 75-9; 77-16; 77-8;
78-10; 78-19; 79-22;
80-20; 80-9; 89-14; 90-5;
98-20
reviewed 121-11; 123-20;
13-19; 169-14; 177-20;
187-7; 23-8; 34-21;
35-20; 38-13; 89-9; 9-3
reviewer 115-6
reviewing 72-11
revised 179-22
Reye's 36-18
RICHARD 2
r i g h t 10-5; 100-17;
100-18; 101-15; 106-18;
11-22; 11-3; 112-15;
114-16; 123-4; 125-19;
130-22; 134-16; 136-1;
138-22; 139-8; 14-11;
140- 19; 140-24; 141-21;
141- 7; 146-5; 15-17;
153-17; 159-12; 159-8;
16-12; 162-3; 163-19;
167-1; 17-3; 177-9 ;
193-21; 193-23; 193-24;
20- 21; 201-15; 204-20;

A. WILLIAM ROBERTS & ASSOCIATES

33

SCHULZ, CARL O.
209-7; 21-6; 214-11;
217-22; 217-23; 22-15;
22-7; 221-1; 221-22;
221-7 ; 39-15 ; 39-8;
42-25; 44-2; 45-4; 46-10;
47-2; 48-8; 49-1; 49-22;
49-8; 51-7; 53-19; 55-5;
58-11; 58-15; 6-18; 6-22;
64-11; 64-14; 65-21;
6 6 - 14; 66-4; 67-13;
67- 18; 7-25; 7-4; 72-21;
76-15; 77-13; 78-11;
79-14; 8-10; 84-24;
86-17; 86-5; 89-9; 90-10;
92-12; 98-19
ring 98-3; 98-4
rise 148-1; 92-3; 94-22
risk 124-10; 126-12;
17- 8; 172-17; 180-14;
181-14; 181-20; 186-18;
36-7; 62-24; 64-1; 64-2
risks 120-11
road 134-4
ROBERT 1-5; 2
ROBERTS 1
Rock 54-24
Rodricks 17-25; 41-8
ROGER 2-17
role 124-3
roughly 161-24; 24-13;
58-24; 73-8
routine 160-10
Row 212-17
rubber 88-24
Ruffin 53-20
rule 117-20; 99-19
ruled 200-17
rules 209-5; 3-4
running 17-11
rushed 130-20
Rutgers 143-21
S
S 226-17; 227-1; 69-9
S-c-h-w-e-t-z 206-21
safe 101-10; 101-5; 13-22
Safety 12-11; 12-5; 15-9;
209-24; 34-9;
35-16; 36-23; 37-5
s a i d 1 0 1 - 8 ; 101-9;
103-13; 107-19; 110-5;
129-23; 142-6; 147-4;
154-19; 159-14; 16-10;
18- 1; 181-14; 184-3;
184-9; 196-23;
28-25; (X1
33-6; 43-10; 50-8; 60-25; V
75-10; 97-5
CV

486

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

r>CO

salary 16-5
Same 104-18; H O - -5
114 -10 ; 119 -19; 128 - 1
130--24 ; 131--2 1 ; 143-25
151 -l; 157--6 ; 185- 25
186--17 ; 186-18; 186 -2
187--20 ; 187 -5; 188- 10
204 - 1 ; 208--1 2 ; 208 - 8
209 - 8 ;
r 2 1 - 13; 2 1 2 -7
214--14 ; 215 -3; 218- 22
28-:2 ; 72-13 ; 8 - 1 ; 8 -8
84- 17 ; 84--9; 94-22
95- 22 ; 96- 1 1 ; 97--8
99-10; 99-13;; 99--19
sample 160-13
samples 154-23
Sanjivani 78-5
Santa 8-23
Sarasota 2-18
sarcoma 103-10; 103-21
104-1; 104-2; 164-22
164-23; 165-2; 174-11
176-3; 176-5; 178-21
183-21; 184-11; 184-16
189-2; 47-18; 91-5; 92-5
93-16; 93-20; 93-23
93-25; 94-5; 94-6
sarcomas 164-19; 165-5
Sassick 81-18; 81-19
Sassick's 148-21
satisfactorily 183-16
satisfactory 63-13
sav e 2 03-24 ; 45- 17;
45-19; 46-8; 6-2; 6-5
saw 134-2; 173-7; 175--22 ;
26-E
say 101 -9; 108-3; 1 1 1 --16;
1 1 2 --2 2 ; 113-14; 115- 1 2 ;
115--13; 117-25; 118 -5;
118 -7; 1 2 2 - 6 ; 127 -l;
128--2 2 ; 131-7; 132-23;
139--1 1 ; 141-15; 145-7;
148--9; 151-20; 153- 20 ;
155--l; 160-16; 161- 18;
161 -19; 161-3; 161 -5;
167 -2 1 ; 171-6; 175 -4;
176 -4; 182-10; 182 -9;
184 -6 ; 185-1; 186- 16;
187--1 2 ; 190-17; 191- 2 2 ;
197--24; 204-12; 204- 17;
205--li; 206-12; 209- 13;
210 --19; 210 -20 ; 218- 14;
220-3; 23-20; 24-14;
26-25; 27-2; 37-8; 39-16;
4-20; 46-20; 51-4; 52-6;
59-20; 67-21; 73-7; 85-6;

91-21; 92-4; 93-2; 95-18;
97-23; 98-11; 99-5
say-- 122-11
saying 103-21; 117-17;
140-3; 140-4; 142-19;
143-3; 181-18; 188-3;
210-11; 217-11; 218-7;
221-8; 221-9; 92-8
s a y s 15 - 2 0 ; 160-2;
181-11; 187-4; 190-16;
194-19; 20-17; 21-2;
77-14
SC 1; 1-19
scan 32-12
scattered 147-13
School 10-19; 11-1
SCHULER 100-17; 100-23
101-11; 103-23; 104-14
104-24; 106-11; 106-16
106-5; 107-1; 107-14
108- 17; 108-7; 109-23
109- 5; 110-11; 110-21
113-22; 114-15; 114-20
115- 21; 115-8; 116-17
116- 7; 117-20; 118-15
118-18; 118-2; 118-4
118-8; 119-11; 121-18
121-9; 122-15; 122-3
135-25; 144-20; 152-21
153-16; 159-25; 161-2
163-19; 163-22; 166-1
167-2; 171-25; 172-20
173 -2 ; 173-5; 176-25
177 -3; 178-5; 183-17
184 -1 2 ; 185-5; 186-15
186 -5; 187-11; 188-14
188 -19; 188-6; 189-14
189--24; 190-13; 190-18
190 -24; 191-7; 194-2
196--18; 199-14; 2; 203-4
206--14; 206-17; 207-24
208 -23; 208-9; 2 1 0 - 1
2 1 1 -9; 212-13; 2 1 2 - 2
213 -2 0 ; 214-7; 215-5
216 -20 ; 216-24; 2 2 - 1 2
2 2 -15; 2 2 0 - 1 ; 221-25
2 2 2 -4; 226-7 ; 3-15
38- 16; 39-1 ; 39-20
44- 16; 44-18 ; 46-3
49-22; 50-3; 6-1; 78-11
78-22; 79-25; 80-5; 82-1
82- 1 2 ; 83-21; 84-10
84-20; 84-23; 85-11
8 6 - 12 ; 86-5 ; 87-18
87- 24; 88-10; 88-16
88- 22; 88-5; 89-4; 89-8

A. WILLIAM ROBERTS & ASSOCIATES

34

SCHULZ, CARL O
9-23 ; 92-19 ; 96-16 ;
97-10; 97-2
SCHULZ 1-14; 118-20; 223;,223-3; 226-20; 226-5;
227-11; 227-15; 227-5;
227-8; 27-17; 28-10;
28-3; 28-9; 3-12; 3-17;
3-18; 5-24; 6-23; 6-3;
7-6; 75-11; 80-7; 84-1;
85-15; 85-19; 8 6 - 8 ;
87-21; 9-13
Schwetz 206-19; 206-21
science 117-13; 128-19;
168-2; 168-3; 168-4;
60-24
sciences 18-1 0 ; 18--14
18-2; 19-2; 190-7'} 5-10
62-18; 62-23
s e i e n tifi c 1 :L2 - 1 2
113-17 ; 114 -li; 115-6
12-13; 165--2 1 ; 19--17
21-3; 226- 24; 30- 10
30-13 ; 30--19; 3 1 - 2
31-23; 33-7; 40-15; 43-7
78-15 j: 89- 15; 90- 17
91-22; 92-24
s e i e n tist s 115- 15
115-16 ; 18- 16; 18--17
78-9
screen 31-25
screwed 153-15
scrutiny 187-4
se 103-4; 28-18; 63-1
seal 225-2
search 19-17; 30-23;
31-11; 31-7; 75-13
searches 31-1
searching 31-19; 31-20
second 150-25; 158-6;
171-15; 208-24; 220-2;
25-6; 53-14
second-hand 195-20
secondary 74-9
seconds 187-3
section 141-20; 141-21;
185-11
sections 193-1; 78-10
see 103-24; 107-22
11-11; 121-12; 153-6
158-14; 159-13; 16-21
160-14; 171-14; 174-18
189-25; 209-14; 24-14
25-2 ; 38-23 ; 44-19
75-16; 76-11; 81-25
84-6; 85-8; 85-9
seeking 207-23; 207-25
MICROCopy

severe 179-12
sewage 55-12
Shamrock 37-15
Shamrock— 38-4
shape 170-21
share 61-22
Sharon 78-5
She's 114-2; 124-14
sheet 45-23
sheets 72-16; 84-13
Sheila 113-23; 113-9;
118-25; 128-7
shifting 41-17
ship 131-21
shipping 131-21
shock 36-25
short 104-22; 105-13;
106- 25; 107-10; 107-15;
107- 16; 147-6
shorter 108-9
should 121-23; 129-4;
204-11; 51-2
show 141-19; 160-18;
219-19; 5-14; 76-4
shown 100-2 1 ; 126-11
shows 114-6
side 134-4; 203-16
signature 104-17; 223-1;
226-8
signed 66-7
s i g n i f i c a n c e 104-4;
157-17; 162-15; 162-22;
163-10; 163-3; 172-1;
174-1
significant 108-2; 128-3;
163-13; 173-8; 174-14;
174- 23; 175-2; 175-20;
175- 25; 26-22
significantly 130-19;
156-15
signify 161-19
signing 3-9
SILICATES 167-10
SILICONE 167-10; 56-2;
6-25; 66-17; 67-2; 68-6 ;
69- 10; 69-24; 7-22; 7-8;
70- 13; 8-10; 8-14; 8-20;
8-25; 8-4; 9-7
Silverstein 212-14
silvex 102-19; 102-5;
102-7; 109-16; 122-19;
1 2 2 -2 1 ; 122-7; 123-24;
130-10; 130-21; 130-23;
132-17; 132-3; 134-13;
146-23; 148-18; 152-17;
200 -2 2 ; 219-21; 219-23;

A. WILLIAM ROBERTS & ASSOCIATES

35

220-9; 80-12; 95-19;
95- 22; 95-3; 95-6; 95-8;
96- 2; 96-22; 97-17; 97-7;
98-13; 98-17; 98-22
silvex— 133-18
similar 131-2; 135-17;
191-15; 96-7; 98-18
simplest 153-7
simply 198-15; 199-25
since 149-21; 152- 17
176 -23; 176 -4; 179- 22
184 -25; 190-20 ; 190-9
193 -1 0 ; 193--14; 194- 12
202 -15; 204 - 1 2 ; 204 -3
208 -2 ; 209209 -9
26- 13; 44- 13; 58- 14
58- 24; 59- 1 2 ; 60- 20
61-3; 94-1; 95-16
single 126-22; 204-16
sister 68-24
sit 210-18; 49-19
site 201-24; 201-5;
65-11; 65-9; 93-12
sites 126-13; 184-6;
65-17; 65-20
situation 131-18; 144-25;
181-6; 70-15
six 155-21; 193-13;
220-14
Sixth 81-10; 82-17
size 128-2 ; 151-22;
17-21; 183-14
sizeable 72-24
skewed 154-23
skin 146-12; 146-17;
146- 3; 146-8; 147-22;
202-25; 202-5; 203-8;
220-18; 220-19; 220-21;
220-22; 221-10; 48-22;
53-16; 53-17
skinny 144-16; 144-18
sloppy 117-6
slowly 152-7
small 102-20; 110-24;
129-14; 130-2; 134-7;
147- 25; 147-7; 197-16;
219-1; 219-22; 220-4;
36-2; 97-14
smaller 156-18; 21-18 488
smelled 55-12
smelter 57-5
Smith 127-19; 150-9;
179-19; 2-11; 28-6; 28-7;
84-18; 84-9
smoke 117-8; 166-12;
166-19; 166-20; 166-21

S'/Z'

seem 147-17; 152-15
seemed 149-3; 174-16
seems 187-2; 91-10
seen 1 1 2 - 1 1 ; 1 1 2 - 1 2 ;
112-7; 113-4; 124-1;
159-9; 168-12; 168-22;
169-2; 181-24; 184-25;
192- 24; 192-25; 193-1;
193- 4; 212-23; 215-23;
215-6; 48-6; 98-14; 98-15
Segal 78-5
selected 81-15
selection 187-15
selectively 178-2
semester 61-7; 62-21;
62-3; 63-21
semesters 62-13
send 80-10
senior 12-16; 43-19
sense 130-13; 135-18;
187-10; 195-14; 205-19;
43-23; 53-2; 60-17; 77-25
sensitivity 193-7; 195-7;
55-22
sent 150-17; 150-18;
150-20; 151-7; 213-4;
79-20; 83-19; 84-17;
84-7; 85-1; 87-6
sentence 184-24; 185-12;
186-17; 187-10; 187-3
separate 198-17; 22-22
separated 102-5; 102-9
September 179-21; 185-7;
191-5; 193-10; 227-25;
227-7; 83-17; 84-2
sequentially 36-6
series 14-20; 227-18;
227-23; 41-1; 88-12;
88-2; 88-25; 88-7; 89-6
serious 188-2
served 61-15
Service 32-8; 57-14
services 36-15
set 16-2; 21-8; 26-3;
69-20; 73-24
sets 83-19
setting 154-15
settled 58-8
settlement 58-4
Sevaso 188-24
Seven 105-23; 106-19;
153-3; 20-1; 60-13; 60-9
sever 60-16
several 134-24; 186-20;
190-5; 215-13; 36-5;
65-17; 71-4

SCHULZ, CARL O.

>->
0
>0
>•

March 5# 1993
MOYER vs. DOW CHEMICAL COMPANY

MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

l is - a

smoked 166-18; 175 - 8 ;
176-1
smoker 221-3
smoking 176-4
Smoller 48-3
snapshot 59-20
So— 220 -2 1
so-called 94-10
soapbox 165-18
Society 7-23
soft 1 03-10 ; 104 - 2 ;
164-19; 164-23; 165-2;
165-5; 174-11; 176 -3;
176-5; 178-21; 183-■2 1 ;
184-10; 184-16; 202 --2 2 ;
203-10; 203-2; 47- 17;
91-4; 92-4; 93-16; 93--19;
93-23; 93-25; 94- 1 1 ;
94-4; 94-6
soil 143-20; 143--22
solid 56-5; 93-22
some 1132-7; 1 03- 18;
105-11; 107-23; 113- 1 2 ;
113-14; 113-15; 114--2 2 ;
116-25; 124-25; 126 -8 ;
128-24; 128-3; 128 - 6 ;
129-2; 129-7; 133- 1 1 ;
133-12; 133-5; 133 - 6 ;
133-8; 134-2; 136 - 2 ;
137-17; 140-15; 141- 14;
141-15; 142-7; 143- 15;
143-21; 147-17; 150- 18;
155-4; 158-18; 173- 20 ;
177-17; 177-6; 178- 15;
179-11; 183-13; 191- 24;
194-6; 194-7; 195- 24;
198-24; 200-25; 201 -7;
2 0 1 - 8 ; 201-9; 2 0 2 -17;
202-18; 202-7; 203- 2 2 ;
203-7; 205-19; 205 -5;
210 -2 1 ; 211-15; 218- 24;
219-9; 24-17 ; 26--l;
26-15; 26-4; 31-8 ; 34-2;
34-3; 36-21; 38-3; 4--23;
40-11; 40-17; 41- 1 2 ;
44-10 ; 44-12 ; 44--4;
45-10; 45-17; 45- 19;
46-8; 5 1-9; 6 -2 ; 6 -5;
62-5; 65-3; 65-6 ; 66--18;
67-4; 72--21; 74-11; 74-3;
80-10; 84-24; 8 6 - 23;
87-15; 90-11; 91--15
somebody 138-18; 219--14;
47-10
somehow 168-21
Someone 140-22; 217- 20 ;

69-25; 9-15
something 101 -1 ; 119--21
121-19; 131-13; 137--20
14-19; 161-17; 165-■14
165-24; 166-14 ; 18 -9
190-16; 190-23; 211 -8
213-11; 31-21; 32- 21
32-6; 35-18; 38-8; 75--18
97-25
sometime 45-3
somewhat 17-20; 193 -6
72-24; 91-11
somewhere 154-16; 209--23
24-4; 27-25; 31-8; 45--13
45-19; 51-22; 84-■15
soon 148-9
sooner 190-12
sores 146-23; 147 -10
sorry 149-15; 151 - 6
154-21; 168-25; 26- 20
35-12 ; 46-23 ; 66 -5
69-14; 81-23; 85- 24
95-11
sort 82-5
Soublis 48-21; 53- 10
53-12; 53-15
sound 4-8 ; 48-4
Sounds 64-19
source 136-16; 137- 16,
137-17; 137-2; 137-23,
138-24; 139-1; 139- 2 1 ,
140-2; 143-13; 144 "3,
163-24; 215-1
sources 123-18; 136- 1 2 ,
137-12; 137-6; 137 - 8 ,
139-25; 140-1; 152- 1 1 ,
164-1; 164-2; 218- 13,
218-21
South 224-4; 225-3; 3-•20
5-11; 54-24; 56-16; 60-2,
60-20; 65-1
SOUTHERN 1; 54-13; 54-7,
57-21; 58-1; 58-3 ; 58-9
speak 30-20; 70-15
speaking 111-4; 1 1 1 "5,
112-23; 117-18
special 69-24
specialist 14-10
specialization 10 -25
species 208-15; 208-16
specific 113-1; 123- 18
126-23; 133-1; 165 - 6
178-12; 178-13; 178- 16
194-7; 201-6; 203- 23
204-16; 33-2; 51- 2; 65-7
78-9; 9--9; 93-12 ; 95 - 1

A. WILLIAM ROBERTS & ASSOCIATES

36

SCHULZ, CARL O.
99-6
spec i f i c a l l y 1 1 1 - 4 ;
111- 8 ; 120- 20 ; 122 - 7 ;,
124-7; 124-8; 125-1;
133-16; 133-24; 134-11;
142-22; 156-2; 173-24;
178-6; 190-15; 215-15;
219-5; 27-10; 28-14;
31-12; 70-3; 73-18;
80-18; 95-17; 99-1
specifications 33-3
specifics 179-6; 216-11;
90-13; 90-23
spectrum 106-21
speculate 180-24
speculation 165-19
spell 191-23; 196-3;
206-20; 28-4; 38-19; 4-16
spelled 28-3
Spells 28-2
spend.61-4
spending 43-4
spent 13-9; 43-21; 72-19
spermicidal 16-16
spill 56-15; 57-10
spills 57-14
spirobixanthene 170-14
spoken 206-2
sponsor 211-7
sporadically 219-1
spot 61-19; 62-3
spray 102-15; 102-17;
110-6; 148-16
sprayed 102-15; 111-14;
148-22; 149-4; 175-3
sprayers 127-20; 201-8
spraying 100-16; 101-16;
109-13; 129-13; 130-15;
144-25; 146-22; 153-18;
159-4; 47-10
sprays 16-17
Springs 56-14
SRI 12-10
staff 18-15; 18-16; 18-17
stage 200-10
stamp 181-9
stance 181-3
stand 113-2; 4-4; 4-7;
42-6; 7-1; 71-19
standard 36-10; 36-9
standards 12-14; 14-21;
210-24
standpoint 128-23; 174-15
stands 42-14
Stanford 12-5; 192-10
start 177-11; 201-1;
MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
31-10; 80-2; 91-12
started 11-24; 214-25;
28-18; 38-21; 43-25;
44-4; 60-15; 63-15; 74-19
starts 6-13
state 141-2; 184-13;
217-23; 224-4; 3-16;
90-11
state-of-the-art 117-10
stated 224-8
statement 1 1 1 -1 ; 128-21;
142- 13; 142-16; 142-2;
166-11; 179-8; 184-3;
187-25; 188-8; 192-23;
194-15; 194-24; 204-16;
217-3; 219-7
statements 176-9; 178-3;
194-7; 218-25; 219-8
states 141-22; 181-7;
185-7; 194-11; 65-17;
66-25
statistically 156-14
status 168-13
stay 202-25
stayed 14-4
Stealth 7-15; 8-9
steam 110-7
Steel 55-21
stenographically 224-13
step 199-7
Stephen 180-9
stick 82-13
sticker 191-2
stickler 66-10
sticky 159-21
S t i l l 113-2; 117-7;
124-23; 137-12; 147-12;
147-22; 15-18; 156-4;
161-20; 166-4; 191-25;
210-8; 25-22; 42-11;
42-21; 44-11
stipulated 3-2
STIPULATION 226-4; 3-1
stomach 142-23; 143-5;
143- 6; 146-4; 202-16
stood 184-18; 185-21
stop 208-24; 216-21;
220-2; 25-6; 38-7; 53-14
stopped 123-16; 51-13
storage 57-19
stored 144-13
strange 42-8
strategy 36-22; 65-11;
65-12; 66-21
stream 110-13
Street 1; 3-19; 4-25

strict 154-15
strike 139-22; 160-22;
172-3; 95-1
stringent 210-10; 210-14
strong 107-11
stronger 184-7
strongest 183-22; 196-20;
196-24
strongly 126-9
structural 170-20
structurally 96-5; 96-7
structure 170-22; 171-12;
171-8
STS 185-19
students 61-14; 62-19;
63-20
studied 123-4
studies 108-8; 113-15;
113-4; 114-23; 116-20;
116-21; 116-3; 120-3;
122-16; 122-4; 123-15;
125- 20; 125-21; 125-24;
126- 12; 126-19; 126-23;
126- 3; 126-5; 127-10;
127- 19; 127-21; 127-23;
127- 9; 128-13; 128-7;
128- 8; 129-1; 129-7;
132-19; 133-20; 143-22;
151-8; 155-3; 160-15;
168- 15; 168-19; 168-23;
169- 3; 178-9; 179-13;
179-8; 179-9; 182-20;
182-6; 183-21; 186-19;
187- 14; 187-15; 188-2;
188- 20; 189-4; 201-8;
202-9; 205-6; 207-3;
209-17; 88-14; 88-3;
88-4; 93-18
study 108-1; 108-14;
108-5; 108-6; 116-10;
116- 24; 117-1; 117-11;
117- 3; 117-7; 119-18;
120-13; 120-5; 120-8;
126- 5; 126-6; 127-24;
127- 25; 128-2; 128-3;
128- 6; 156-1; 156-11;
156-12; 156-21; 159-13;
182-13; 182-17; 182-19;
182- 22; 183-1; 183-13;
183- 15; 183-19; 183-4;
183-6; 188-22; 188-24;
188-5; 189-2; 202-10;
202-11; 202-13; 210-19;
216-3; 216-4; 216-5;
216-9
stuff 120-8; 153-18;

A. WILLIAM ROBERTS & ASSOCIATES

37

SCHULZ, CARL O.
84-17
stumbled 39-19
Sturgis 55-20
style 153-11
sub-part 209-19; 210-25;
210- 3
subcategory 167-22
subcommittee 70-24
subcommittees 123-23
subcutaneously 6-24;
7-21; 7-9
subject 116-25
submit 13-16; 211-8;
212-9; 37-4; 40-18
submitted 13-20; 14-22;
15-8; 19-14; 213-13; 34-8
subscribe 184-3
s u b s e q u e n t 173-13;
184-19; 185-22
subsequently 146-19
subset 48-9
substance 174-3; 48-16;
93-3
substances 68-15
substantial 65-22
such 10-14; 113-6; 119-3;
132-5; 200-22
Sudderam 81-20; 81-24
sufficient 105-1; 109-15;
172-11; 201-4; 63-8;
91-19
suggest 113-15; 164-11;
93-18
suggesting 113-16
suggests 105-15; 137-11;
211 21
summaries 149-16; 150-2;
150-4; 81-17
summarized 21-11; 29-20
summary 10-9; 118-19;
119-13; 120-15; 141-19;
149-15; 20-10; 20-16;
21-13; 2 1 - 2 0 ; 22-3;
29-14; 30-9; 79-5; 81-24;
83-22; 84-12; 85-7
summer 74-24
.
summers 90-20
4
superficially 169-15
supervised 18-15; 34-21;
41-2
supervisor 41-15; 41-19
supplied 208-5; 210-9;
80-18; 85-25
supply 209-4
support 114-12; 15-9;
195-19; 34-9; 44-11 ; 47-6
-

MICROCopy

MOYER V S .

March 5, 1993
DOW CHEMICAL COMPANY

supported 178-4; 186-13
supports 117-1; 92-24
suppose 113-14; 126-7;
41-15; 66-16; 66-3
supposed 192-9
supposedly 155-5; 156-3
sure 114-10; 117-20;
119-2; 119-25; 132-24;
139-12; 15-11; 161-6;
169-5; 190-13; 190-3;
206-16; 207-3; 44-16;
46-6; 48-19; 71-13; 71-8;
78-3; 79-25
surgery 154-25; 155-1
surname 28-4
surprised 160-8
surprising 162-1; 28-5
Survey 154-12
suspect 101-2; 56-21
Swanson's 148-20; 86-15
sweeping 116-16
sworn 224-9; 3-13
Symposia 74-2
Symposium 7-18
syndrome 36-18; 54-19;
54-20; 55-22
synopses 73-25; 75-25;
76-1
synopsis 194-3; 198-1;
21-12; 21-3; 22-5; 22-6;
226-23; 29-15; 29-16;
29-18; 76-12; 76-8; 78-15
synopsized 23-8; 29-20
Syracuse 191-12; 191-8;
192-3; 192-5
system 140-14; 143-2;
168-22; 168-7; 168-9;
204-21 "
System. 7-17
systemic 102 -12 ; 202-20 ;
203-2
Systems 64-23
T
T 226-17; 227-1
T-u-r-i-m 41-20
Tabb 49-6
Tabb— 49-5
table 31-25; 77-12
tables 31-23
tag 160-1; 169-12
take 116-9; 118-8; 126-1;
153-9; 155-20; 159-20;
177-13; 181-2; 182-10;
188-8; 203-22; 210-16;
23-23; 39-22; 44-15;
46-5; 48-8; 76-7; 77-4;

79-24; 80-20
TAKEN 1-20; 141-5; 150-8;
152-17; 154-24, 162-7;
174-19 ; 181-7; 203-1;
224-6; 21-3; 86-16
takes 65-21; 65-24
taking 181-22
talk 1 08-18 ; 136-9 ;
137-3; 150-25; 166-2;
198-1; 198-9; 207-13;
207-9; 211-23; 25-17;
75-10; 90-3; 95- 8; 97-25
talked 148-15; 180-4;
56-12; 56-18; 9- 22
talking 1 1 1 -8 ; 119-22;
12-25; 120-19; 120 -20 ;
127-2; 128-12; 132-14;
142-24; 148-15; 156-10;
158-22; 175-13; 175-4;
178-14; 195-14; 203-23;
209-4 ; 29-2;
209-16
29-7; 44-19; 85- 10
Tallahassee 2-13
Tamiami 2
Tampax 36-21
tank 147- 1 1
tanks 57-19
tar 48-23; 53-18
target 208-15
taught 62-6; 63-4
TCDD 100 -1 ; 101-1 ; 101 -6 ;
106-4; 111-14; 111-17;
111-24; 111-5; 1 1 2 - 1 0 ;
112-13; 125-24; 129-14;
129-16; 131-6; 132-2;
133-13; 133-8; 134-11;
134-21; 134-9; 135-12;
136-11; 136-17; 136-20;
137-6; 139-4; 140-10;
140-9; 147-25; 151-15;
151-16; 154-13; 155-10;
155-6; 157-14; 159-3;
160-21; 160-5; 161-17;
168-12; 168-6; 168-8;
171-18; 183-23; 184-17;
184-4; 184-5; 184-9 ;
185-20; 186-22; 196-9;
197-24; 198-19; 200 -1 1 ;
200 -2 1 ; 200-23; 201-4;
204-24; 215-25; 215-8;
217-5; 218-15; 221-19;
2 2 2 - 1 ; 87-16 ; 91-13;
91-20; 92-22; 92-25;
93-11; 93-7; 95-10; 95-7;
96-18; 96-21; 97--6 ; 99-9
teach 60-8 ; 61-18; 61-6;

A. WILLIAM ROBERTS & ASSOCIATES

38

SCHULZ, CARL O.
62-10
teaching 60-12; 60-9;
61-5; 61-9; 64-16; 64-17
technical 50-19; 77 -15;
78-3
teflon 56-2; 56-3; 56-5;
56-6; 69-16
T e i t e l b a u m 173- 2 1 ;
176-15; 176-24; 176-8;
177-20; 177-24; 203-15
Teitelbaum's 157- 24 ;
159-24; 81-14; 81--16;
83-1; 84-5
tell 180-22; 208- 1 0 ;
29-24; 41-1; 43-3; 45-2;
46-10; 68-8 ; 76-13; 77-4
Telling 55-12; 91-25
tells 170-1
ten 152-16; 220- 1 0 ;
221-11; 23-21; 61 - 6 ;
73-22; 89-13
tend 136-21; 138- li;
138-19; 141-24; 152--li;
153-25; 20-19; 49-11
Tennessee 49-14; 50--1 0 ;
50-18; 50-21; 56-13
tens 98-7
tense 95-9
tenth 220-16
term 101-13; 142- 2 0 ;
145-9; 147-6; 196- 13;
198-11; 198-12; 198-4;
91-11
terminology 103-20
terms 128-12; 129- 1 2 ;
129-14; 132-12; 142--24;
165-11; 167-19; 194--14;
196-25; 200-25; 207--13;
26-18; 45-1; 67-9
terrestrial 138- 17;
208-17; 208-20
terrible 128-10
terribly 162-1
test 119-17; 153-21
tested 213-15
testified 167-4; 3--13;
45-15; 52-8; 67- 20 ;
67-21; 69-15; 69-7; 69-8;
8-13; 8-25
testified-- 167-23
testify 176-13; 224-9;
52-3; 70-23; 9-15; 98-9;
99-6
testifying 168-3; 70-3;
72-11; 89-18
testimony 123-21; 149-1;
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

_______ SCHULZ, CARL O.

176-14; 176-21; 177-6;
6-4; 60-21; 62-14; 63-12;
207-17; 208-18; 21-7;
6 3 - 2 ; 64-13 ; 64-16 ; 32-9; 38-19; 46-15;
201-13; 204-6; 204-9;
223-6; 224-11; 224-17;
65-23; 67-7; 70-18; 73-2;
48- 13; 49-11; 49-16;
75- 12; 75-18; 76-12; 49- 17; 51-7; 51-8; 52-25;
50-25; 51-10; 52-12;
67-19; 69-1; 69-23; 70-13 76- 20; 76-23; 77-5; 79-9; 54-8; 55-15; 58-11; 66-1;
69-21; 79-21; 80-21;
testing 132-1; 132-10;
8-11; 8-16; 8-7; 81-3;
132- 6; 133-12; 133-17; 81-5 ; 82-24 ; 83-18 ; 80-23; 80-24; 82--8 ; 83-3;
84-25; 86-21; 87--1; 87-9;
133- 6; 214-25; 215-7; 84-11; 86-16; 86-19;
89- 11; 89-20; 89-23; 88-25; 89-16; 90-22 ;
29-25; 37-7; 66-21
90- 2; 91-24; 92-6; 93-6; 98-11
tests 133-9; 15-8
they'd 210 -20 ; 210-21
94-21; 96-14; 97-21; 99-4
tetra 197-17
They're 121-7; 126-25;
that's-- 152-16; 219-12;
tetrachlorinated 178-24
137-17; 138-4; 138-6;
tetrachlorodibenzo 1 1 1 - 1 1
64- 3
138-7; 144-12; 150-4;
that— 12-25; 177-10;
text 184-24; 184-25;
154-24; 156-18; 163-12;
204-3; 35-9; 46-5; 6-3;
63-20; 63-9
163-13; 170-20; 171-7;
texts 63-16; 63-19; 64-11 76-8; 81-2; 95-12
180-14; 180-19; 187-25;
the'40s 27-7
That's 10-12; 103-6;
The— 138-25; 150-21;
188-3; 189-17; 189-18;
106-11; 106-20; 106-6;
191-14; 191-9; 192-12;
II- 8; 110-16; 110-25; 201-16; 27-22; 48-18;
215-21; 29-1; 29--9; 53-2;
III- 19; 111-3; 112-5; 76- 13; 80-24
theme 94-9
55-16 ; 62-8 ; 63-22 ;
113-25; 114-1; 115-24;
78-25; 80-25; 84-14 ;
117- 19; 117-20; 117-22; theory 199-11; 199-20;
94-16; 96-6
118- 2; 118-4; 119-18; 200- 6; 200-7
They're-- 63-3
therapy 67-12
120-24; 121-12; 128-16;
they've 193-9
there'd 131-10
128-22; 129-6; 131-9;
things 135-6; 136-25;
there's 101-5; 102-6;
133-19; 136-1; 136-14;
142-21; 16-10; 205-14;
105-13; 115-4; 115-7;
136-16; 138-18; 138-2;
217-1; 221-16 ; 32-4;
116-19; 126-4; 127-7;
138-23; 14-7; 140-1;
128-19; 132-4; 133-4;
34-3; 40-17; 41-12; 46-4;
140-12; 141-9; 142-14;
49-11; 64-22; 73-24;
137-11; 141-7; 144-9;
142-6; 144-1; 149-5;
145-14; 145-23; 16-20;
82-8; 87 -9
151-13; 151-25; 152-7;
153-14; 153-17; 154-17;
163- 10; 165-19; 168-5; think 1 0 2 - 6 ; 105-4 ;
107-22; 1 1 0 -2 2 ; 113-12;
169-11; 169-12; 169-21;
155-13; 159-8; 16-14;
115-3; 115-5; 116-21;
169-25;
177-5;
190-3;
161- 11; 161-20; 162-25;
116-24; 117-5; 118-13;
162- 6; 163-14; 165-3; 193-13; 194-15; 200-25;
201- 23; 201-7; 201-9; 119-2; 119-22; 122-25;
167-1; 169-24; 170-18;
210-22; 215-18; 22-10;
124-5; 126-25; 126-3;
175-16; 177-1; 18-3;
127-17; 127-23; 128-22;
182- 24; 182-25; 182-4; 220-19; 26-1; 27-2; 41-5;
128-6; 128-8; 129-10;
183- 15; 184-11; 185-2; 51-19; 63-7; 76-25;
77- 12; 91-1; 93-19; 93-22 131-10; 135-20; 137-21;
187-24; 189-21; 190-2;
thereafter 224-14
141-13; 141-20; 143-25;
193-11; 195-5; 196-4;
therefore 105-8; 218-1;
144-9; 145-8; 148-10;
197-5; 198-17; 199-18;
148-25; 149-18; 149-5;
51-2
20-21; 200-13; 200-4;
therein 101-23; 151-5
150-20; 150-3; 150-9;
200-6; 202-21; 203-11;
thereof 224-23; 96-2;
151-9; 154-12; 155-14;
205-14; 205-25; 207-23;
156-12; 158-19; 159-14;
96-4
207-25; 212-3; 216-3;
these 105-11; 111-7;
164-9; 165-19; 168-16;
216-5; 217-16; 217-9;
12-18; 121-1; 121-13;
169-11; 169-12; 169-23;
220-17; 221-22; 222-4;
170-7; 171-1; 171-13;
23-11; 23-25; 23-5; 31-4;
121-23; 122-18; 122-6;
172-23; 173-12; 174-5;
34-1; 41-10; 41-14;
126-11; 126-5; 128-4;
175-7; 175-9; 176-1;
4 1-22; 4 2 - 1 2 ; 42-2 ; 133-8; 137-12; 139-23;
140-20; 144-25; 156-17;
176-3; 179-11; 179-9;
43-17; 44-6; 47-25; 5-1;
5-17; 5-18; 52-13; 53-17;
160-15; 163-18; 164-10;
18-6; :L82-25; 183-5;
5 6 - 13; 56-15; 56-19; 164- 9; 179-13; 180-25; 184-4; 184-9; 186-13;
57- 13; 57-4; 58-25; 58-8; 182-7; 183-2; 187-14;
186-6; 188-25; 189-15;
59-13; 59-18; 59-6; 6-15;
193-8; 197-21; 201-5;
189-16 j; 19-5; 193-3;

492

A. WILLIAM ROBERTS & ASSOCIATES

39

MICROCopy

n

4

/

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

195-24; 195-6; 196-4
146-8; 148-12; 169-15;
71-1; 94-13
198-14; 199-22; 199-8
177-7; 199-5; 20-12;
told 134-17; 158-19;
2 0 - 11; 20-14; 20-18
201- 4; 203-22; 207-15; 176- 13; 176-22; 177-12;.
200-13; 201-18; 201-7
21-5; 216-13; 220-21;
177- 14; 177-21; 46-l;(
204-16; 204-18; 206-7
25-2; 26-10; 29-18;
80-8
209-19; 209-20; 212-6
51-11; 73-10; 80-2 ; toluene 38-14; 38-17;
212-8; 214-23; 215-17
80-22; 81-8; 82-4; 84-7
39-11
216-13; 216-18; 218-12
ties 60-16
tomes 29-7
220-24; 221-18; 24-1
TIME 1-16; 101-16; 102-5;
took 134-4; 16-6; 195-4;
25- 11; 25-16; 28-16
1 0 9 - 7 ; 11-2; 11-5;
30-18
28-19; 28-24; 30-16
123-20; 124-12; 124-16;
tool 116-22
133-15; 137-24; 151-1;
30-24; 30-25; 34-25
top 47-2; 6-10; 6-11;
34-4; 36-2; 37-10; 37-25
151-23; 17-17; 18-23;
6- 13
38-2 ; 40-10 ; 40-15
203-22; 205-10; 207-18;
topic 148-5; 69-2
40-24 ; 40-5 ; 4 1-11
tort 53-2
207-6; 211-20; 213-16;
219-2; 224-12; 224-19;
42-23; 44-10; 44-19
total 102-10; 111-13;
47-17; 47-3; 48-5; 50-8
224-7; 25-11; 3-8; 33-16;
113-17; 114-11; 140-7;
36-12; 40-12; 41-13;
52-7; 54-23; 54-9; 57-8
155-25; 162-21; 163-9;
6-10; 64-5; 67-13; 68-24
41-16; 43-21; 43-5;
218-20; 22-10; 22-14;
71-13; 72-22; 74-24
45-17; 45-19; 46-8;
27-6
75-1; 76-14; 8-2; 80-6
49-12; 58-23; 59-10;
totally 126-23; 126-6;
80-8; 81-21; 82-7; 83-11
59-19; 59-22; 6-2; 6-5;
130-16; 138-14
83-24; 84-14; 84-4; 85-6
toto 186-4
61-4; 61-7; 61-9; 64-18;
touched 200-9; 204-21
86-21; 88-5; 93-10
65-22; 71-16; 71-19;
93-11; 93-14; 97-14
71- 22; 72-10; 72-16; toward 154-23; 63-22
97-9; 99-4
7 2 - 17 ; 72-3 ; 73-16 ; tox 209-20
think— 154-9
79-21; 91-20
Tox-Line 31-12
thinking 19-22
times 138-16; 67-25; 68-3 toxic 36-25; 53-2
thinks 199-8
timing 119-3
Toxicants 62-25
third 110-22; 59-10;
tired 166-25
toxicity 206-10; 208-14;
tissue 103-10; 104-2;
7- 7
59-21
this— 57-10
154-12; 164-19; 164-23;
toxicological 123-19;
though 10-17; 126-16;
165-2; 165-5; 174-11;
210-9; 211-18
15- 5; 156-1; 195-25; 176-3; 176-5; 178-21;
tox i c o l o g i s t 1 1 - 1 0 ;
26- 13; 26-7; 9-24
183-21; 184-11; 184-16;
11- 14; 12-16; 124-14;
thought 101-18; 104-21;
202- 22; 203-11; 203-2; 128-24; 13-15; 168-17;
177-8; 178-22; 204-14;
47-17; 89-1; 91-4; 92-5;
204-13; 211-12; 55-11;
26-6; 38-24; 81-23; 94-15
93-16; 93-19; 93-23;
89-19
thousand-fold 135-18
93- 25; 94-20; 94-4; 94-6 toxicologists 206-22
thousands 155-23
tissues 135-15; 138-17;
toxicology 10-13; 10-23;
three 126-19; 137-4;
141-20; 218-1; 94-11;
10-24; 11-16; 11-24;
138-16; 155-20; 157-5;
94- 22; 94-8
12- 17; 128-20; 13-20;
16- 24; 181-13; 189-25; titles 41-17; 62-5
14-22; 15-2; 15-7;
19-24; 193-13; 193-15;
to-- 112-24; 118-1;
167-13; 167-22; 17-8;
21- 14; 219-22; 220-13; 181-19; 197-9
206-25; 210-3; 213-6;
227-20; 67-24; 69-6;
tobacco 166-12; 166-3
38-13; 4-3; 43-19; 63-24;
today 149-20; 158-3;
69-8; 88-12; 88-18
7-23; 83-10
three-quarter 118-16
179- 18; 184-9; 189-1; trace 160-19
three-quarters 73-13
203- 21; 216-17; 222-5; track 17-20; 26-20
three-volume 22-1
27-19; 28-20; 49-20;
tracked 203-16
three-year 19-23; 20-8
59-20; 71-25; 74-12;
tract 140-13; 140-15;
through 10-5; 126-7;
74-15; 87-10; 91-18
142-23
127-12; 127-15; 132-23;
toe 103-22
trade 36-19; 71-11; 8-18
136-17; 137-5; 140-10;
together 124-5; 135-3;
Trail 2
140-12; 140-14; 141-9;
180- 10; 180-25; 185-17; train 38-24
144-12; 146-3; 146-4;
217-21; 220-3; 49-12;
training 103-19; 199-19
A. WILLIAM ROBERTS & ASSOCIATES

40

MICROCopy

March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
transcribed 224-14
TRANSCRIPT 2-21; 203-18;
224-8; 83-1; 86-1; 86-2
Transcription 1; 223-6;
224-15
transcripts 70-16; 70-19;
81-14
transfer 14-14
T r a n s m i t t a l 226-23;
227-3; 78-14; 78-18
tra n s p i r e d . 118-17;
173-4; 216-23; 44-17;
80-4
Travis 137-5
treat 205-12
treated 89-25
treating 67-10
tremendous 210-23
trenches 65-7
trespass 53-5
trial 3-8; 45-15; 54-22
Triangle 157-25; 158-1;
159-1
trichlorodibenzo 197-20
trichlorophenol 133-14;
133-7; 161-9
tried 26-2
trillion 154-14; 157-16;
159-15; 160-11; 161-18;
161-25
trillionth 139-19
trouble 110-17; 178-13;
196-13
true 108-16; 117-11;
165-6; 223-5; 224-16
truth 224-10; 224-11
try 193-19; 196-13; 48-9;
6-2
trying 128-17; 158-20;
177-5; 209-19; 40-3
TSCA 212-10
Tucker 54-7; 58-3; 58-9
tumor 105-14; 199-7
tumors 105-12; 201-10
Turim 41-20
turnpike 57-11; 57-12;
57-15
twelve 73-22
twisted 188-13
two 107-16; 118-16; 12-3;
12-9; 123-17; 124-2;
126-18; 13-9; 135-3;
142-21; 151-7; 157-4;
170-6; 171-3; 18-10;
18-6; 187-3; 19-8; 2;
21-16; 213-2; 218-22;

29-20; 29-21; 29-22;
34-6; 4-11; 40-16; 47-20;
49-12; 55-16; 59-14;
59-16; 59-25; 59-7; 6-12;
6-20; 6-9; 62-13; 62-3;
63-19 ; 69-10 ; 7-10 ;
70-25; 73-21; 75-22;
76-3; 77-10; 8-4; 83-20;
83-3
two-a-day 221-3
two-thirds 59-6; 62-11;
73-13
two-volume 20-10 ; 21-8
t y p e 1 OS- 6 ; 113 - 1
126 -2 1 ; 131 -18; 131--25
16- 1 1 ; 166- 19; 170--21
174 - 6 ; 175 -6 ; 200 -■ 12
203 -7; 209 -3; 2 1 1 -•10
2 1 1 -13; 219-5; 2 IS -9
26- 17; 39- 1 2 ; 40- 14
42- 22 ; 45 -l; 47- 15
51- 1 0 ; 55-- 2 2 ; 56 -4
60- 18; 67- 2 1 ; 67- 22
67- 23 ; 7 1--16 ; 94 - 1
94-14; 94-2; 94-20; 94-3
typed 224-16
types 105-11; 113-5;
12-24; 139-4; 143-22;
16-10; 182-20; 198-19;
208-10; 208-4; 50-15;
93-8; 94-6; 94-7
typewritten 85-7
typical 105-1
typically 160-18; 193-12;
193-13; 31-15; 31-9; 63-5
U
U 69-9
Uh- huh 1 0 - 7; 1 0 0 -- 8
108--20 ; 109- 1 1 ; 125- 22
133 -1 0 ; 136--13; 139 -5
145 -l; 166- 6 ; 171- 16
176--1 1 ; 180-23; 188- 23
189 -3; 194- 17; 194 -5
204 -23; 204 -4; 204 - 8
210 -5; 218- 4; 2 2 1 -15
42- 17; 44-24; 46- 19
77-23; 79-6; 83-14
ultimate 164-1; 201-3
ultimately 133-8; 148-7;
152-5
unable 60-11
uncertain 205-10
unclear 171-20
uncommon 163-6
under 107-23; 148-18;
175-11; 209-5; 212-10;

A. WILLIAM ROBERTS & ASSOCIATES

41

SCHULZ, CARL O.
219- 25; 24-24; 34-19;
6-22 ; 82-16
undergoing 155-1
underground 57-13; 57-17;
57-18
underlying 65-9
underneath 202-23
undersigned 223-3
understand 10-16; 103-20;
11-17; 117-23; 128-14;
128-18; 139-12; 146-5;
147-15; 160-12; 164-5;
165-12; 165-23; 166-2;
171-2; 172-21; 176-25;
177-4; 179-3; 198-12;
21-22; 21-23; 211-11;
218-8; 219-11; 221-7;
67-15; 75-7; 90-3; 92-7;
95-14
understandable 204-18
understanding 137-1;
194-10; 195-3; 199-19;
220- 5; 220-7
u n d e r s t o o d 133-19;
164-20; 165-7; 165-8;
94-15
underway 183-15
undue 153-12
unifying 94-9
Union 11-14
United 181-7; 185-7;
194-11; 66-25
universities 60-14
university 192-11; 192-8;
5-11; 60-19; 60-2; 60-23
unknown 166-14
unless 203-14; 97-24
unlikely 131-7; 179-1;
200-14; 99-4
unnumbered 6-17
unpublished 133-21
unquestionably 142-8
unreliable 149-7
until 16-22; 3-7; 59-7
unusual 135-19; 149-5;
160-4; 160-6; 163-15;
64-7
updated 5-17
upon 126-21; 219-7
upset 63-18
upstanding 127-22
urinary 69-17
use 1 0 2 - 1 0 ; 1 2 0 - 1 ;
121- 13; 121-21; 122-18;
122- 6; 127-13; 129-20;
13-22; 136-24; 137-22;
MICROCopy

March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

145-9; 188- 18; 200 -25
208-18; 208 -19 ; 211 -3
48-13 ; 63--25 ; 63 -9
64-12; 67-11
used li00-13 ; 1 0 0 -4
1 2 1 -2 ; 1 2 1 --7; 129- 25
13-18; 131--22 ;! 132 -7
142-20; 147-■il; 147-■13
148-23; 164 -14 ; 178 - 1
19-19; 191- 2 1 ; 191-23
194-11; 198-3; 2 1 0 -18
218-25; 219 -l; 219- 20
220-9; 2 2 1 - 1 1 ; 32 -5
33-9; 34-22 ; 36-7; 50--22
96-12
uses 123-10
using 101-13; 131- 20

57- 21; 57-3; 58-1; 58-3; 29-5; 30-9; 73-9; 74-2;
58- 9
76-3; 77-10
versus— 54-21
W
very 102-10 ; 102-5 ; W 1-5; 2
(
W-a-t-a-n-a-b-e 207-5
104-22; 105-16; 106-25;
W.R 37-25
110-25; 124-1; 126-13;
126- 4; 127-17; 127-21; WAGNER 100-15 ; 101-7
127- 24; 128-3; 128-8; 103-12; 104-10 ; 104-18
105-24; 106-2; 106-23
129-19; 129-4; 130-17;
132-4; 137-22; 153-1;
106-6; 106-9; 107-17
155- 21; 156-7; 157-19; 107-4; 108-11; 108-24
162- 16; 162-23; 163-4; 109-18; 110-19; 110-8
166-17; 178-2; 179-10;
113-19; 114-14 114-17
179-2; 181-22; 182-18;
115-1; 115-18 116-13
116-4; 117-16
186-7; 188-15; 195-15;
118-11
197- 10; 197-2; 198-19; 119-9; 121-15 121-25
198- 21; 200-18; 200-9; 121-5; 1 2 2 - 1 1
134-24
221-12
204-13; 205-25; 207-10;
135-24; 144-18 152-20
usually 62-20
211-4; 211-6; 219-1;
153-14; 159-23 160-25
V
219-22; 31-9; 43-15;
163-18; 165-15 166-24
V 212-17; 212-18
48-6; 50-18; 50-25;
171-19; 172-13 176-22
VA 21-19; 33-4; 59-8;
56-14; 60-25; 62-8; 64-9;
177-11; 183-11 183-25
66-14; 67-6; 67-7; 79-18;
73-10; 73-25
184-22; 185-25; 186-8
vague 186-9; 187-21;
93-22; 93-24; 94-14; 99-4
187-1; 187-20; 188-10
vessels 131-21
188-16; 189-12 ; 190-14
91-11; 92-18
Veteran's 118-20
vaguely 37-24
190-19; 190-9; 193-25
valid 108-5 ; 108-9 ; veterans 155-18; 155-4;
196-11; 199-13; 2 ; 202-1
111-25; 117-2
156- 19; 19-15; 21-2; 206-12; 207-18 208-12
21- 25; 24-25; 32-17; 208-8; 209-11; 2 1 0 - 1 2
value 53-5; 57-23
Vanderlaan 56-8
32- 23; 33-1; 33-14
211-19; 212-7; 213-25
v a r i a b i l i t y 141-12;
Veterinary 14-24; 14-9;
214-2; 214-4; 215-3
141-13; 141-23; 141-8;
16-3
219-16 ; 22-13; 22-9
144-10; 195-12; 195-13;
vices 153-12
222 -2 ; 227-12; 227-14
195-15
videotape 174-19
3 9 - 16 ; 44-14 ; 46-1
variable 141-16
Vienna 42-13; 42-15
74-17; 75-4; 79-23; 80-1
varied 194-21
Vietnam 127-14; 155-18;
81-20; 82-11; 84-12
variety 13-1; 18-17;
155-4; 156-19; 19-19;
84-16; 84-21; 84-6; 85-6
64-21;“66-19; 93-14
194-25; 32-25; 33-10;
86-8 ; 87-14; 87-20; 87-6
various 113-3; 120-4;
33- 14; 34-23; 73-18
9-13; 92-17; 96-13
view
114-22;
131-11;
96-24; 97-8
96-1; 96-4
vasculature .203-1
163- 7; 168-7; 173-8; Wait 104-10
vast 105-8; 155-17
waive 3-9
174-15; 174-4
vegetable 138-6
waived 3-6
Virginia 42-13; 42-15
vegetables 136-25
virtually 185-10
walked 157-1
vendor 79-2
visibility 66-18
Walnut 47-13
verbal 200-15
vocal 56-3
WANDA 1-21; 224-3; 225
verifying 168-23; 169-2
volatile 144-4
wanted 11-13; 60-8
version 31-1
wanting 211-8
volatiles 48-23; 53-18
versions 30-25; 78-24;
volume 189-21; 21-6;
WARD 2
78-25
22- 22; 26-25; 27-4; 29-1; Warren 195-21
versus 47-1; 47-4; 49-14;
Washington 17-7; 192-2;
29-10
volumes 189-21; 193-3;
49-16; 50-10; 50-18;
25-10; 60-10
53- 13; 53-20; 54-15; 193-8; 21-14; 21-20;
wasn't 110-13; 145-10;
5 4 - 7; 55-14; 55-20; 2 1-5 ; 24-23 ; 25-2 1;
145-3; 156-1; 166-19;
55- 24; 55-6; 55-9; 56-1; 26-13; 26-14; 26-3; 26-5;
195-5; 26-5; 27-15;
5 6 - 12; 56-18; 56-8; 29-18; 29-20; 29-21;
27-21; 45-11
A. WILLIAM ROBERTS & ASSOCIATES

42

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY
waste 169-24; 63-13;
64-25
W atan ab e 207-4
w a tc h 152-20
w a te r 111-24; 74-7
w a y 102-11; 103-10;
111-12; 122-24; 131-11;
135-10; 135-23; 145-13;
146-6; 172-9; 174-23;
186-4; 199-23; 199-25;
200-23; 21-21; 21-7;
211-7; 26-19; 27-7; 28-3;
43-4; 62-11; 80-24; 82-2;
83-11; 97-24
W ayne 77-20
w a y s 128-6; 135-16;
135-3; 135-4
we'd 165-9; 198-14; 32-12
we'll 135-8; 190-25;
220-3; 76-15; 78-12;
88-5; 90-13; 90-22
we're 114-10; 115-9;
12-21; 120-18; 120-19;
127- 6; 13-25; 130-6;
135-6; 145-6; 147-7;
148-4; 15-14; 190-20;
204-19; 207-7; 48-6
We've 118-15; 125-19;
128- 12; 133-5; 136-8;
143-15; 169-10; 173-2;
190-9; 194-4; 206-7;
29-1; 60-21; 75-14
weakest 182-20; 188-4
weaning 43-23
wearing 145-11; 145-12;
145-3
VJEBB 2
week 167-17; 213-4; 83-20
week's 200-6; 200-7
weekly 32-9
weight 126-1; 153-10;
182-11; 182-12
Weisberger 119-21
Weisenberger 119-21
Weissman 56-1
We l l 10-24; 102-2;
105 -18; 109-6; 1 1 - 10
113--13; 113-25; 115- 15
117 -4; 119-18; 120 -25
124 -2 0 ; 125-6; 128- 16
129--19; 130-12; 131-7
134--1 2 ; 134-23; 136- 20
137--3; 139-16; 139- 21
143--17; 145-24; 145 -6
148 - 2 0 ; 148-9 ; 15 - 6
151--19; 151-21; 152 -6

SCHULZ, CARL 0.

153- 1; 153-23; 154-5; 146-24; 147-4; 150-3
154- 7; 155-11; 158-22; 165-24; 172-6; 179-22
16-1; 161-6; 162-20;
185-1; 189-18; 201-22
163-25; 165-11; 165-17;
205-15; 207-2; 24-14
166-15; 168-16; 168-5;
24-15 ; 24-17 ; 33-5
17- 13; 17-17; 170-20; 70-19; 76-12; 97-18
170-5; 172-2; 173-9;
99-17
175-10; 176-1; 176-16;
which 102-11; 104-1
177-9; 178-12; 178-8;
109-20; 111-6; 12-13
18- 15; 18-5; 180-14; 126-2; 127-16; 127-18
180-21; 188-9; 192-4;
133-25; 138-12; 14-20
195- 13; 195-20; 196-12; 144-11; 144-2; 146-3
196- 21; 197-8; 198-3; 146- 7; 148-18; 149-2
198- 8; 198-9; 199-11; 151-22; 16-5; 165-6
199- 17; 202-20; 203-11; 167-22; 170-7; 182-19
204-11; 204-7; 205-5;
188-1; 188-25; 188-4
206-19; 209-14; 209-22;
197-18; 198-13; 199-20
21- 6; 212-18; 213-1; 200-1; 200-15; 203-1
214-8; 215-17; 219-24;
203-11; 204-21; 206-24
22- 17; 24-20; 27-9; 28-3; 21-13; 21-19; 25-22
29-21; 29-9; 30-13; 31-3;
26-1; 31-14; 31-22; 37-3
32-19; 4-6; 43-2; 44-5;
42-11; 48-14; 48-22
46-13; 5-16; 5-9; 51-23;
53-22; 59-8; 59-9; 65-7
53-10; 59-19; 59-5; 61-2;
77-5; 82-15; 95-8; 98-10
61-20; 61-4; 62-8; 66-11;
98-3; 98-8; 99-6
67-6; 68-9; 69-5; 72-17;
who's 191-20; 75-3
73-6; 75-10; 75-18; 75-3;
w h o l e 128-9; 172-8;
76-4 ; 79-17 ; 84-22 ; 181-21; 182-11; 193-5;
89-13; 93-10; 93-11;
212-19; 22-17; 224-10;
95-1; 97-22
41-5; 61-9; 66-22
Well— 20-6
whom 3-21; 9-17
went 11-15; 11-23; 12-18;
widely 102-5; 102-9;
124-22; 137-5; 14-8;
147- 13
148-12; 16-6; 17-13;
wife 60-7
WILKERSON 2
17-3; 203-19; 213-2;
26-17; 29-19; 35-17; 58-4 WILLIAM 1
were— 35-7
WILLIAMS 2-5
weren't 155-23; 98-10
willing 43-15
West 2
wish 204-10; 40-8
Whaley 55-4
within 10-25; 107-2;
what's 141-5; 143-4;
116-2; 161,-20; 164-22;
180-19; 182-18; 201-21;
19-7'; 212-4; 2 15-8;
220-4 ; 42-19 ; 80-3;
47-20; 68-i3; 83-20;
91-21
88-11; 94-4; 95-24; 97-17
Whatever 118-11; 127-25;
without 109-13; 132-22;
134-25; 208-21; 26-16
153-12; 153-7; 154-17;
whatsoever 180-7
221-8; 52-13; 68-19
Whenever 173-14; 79-2
withstood 187-4
4QP
where's 54-4
WITNESS 100-18; 101 “8 ,
whereas 142-10; 142-23;
103 -16; 104-21; 106- 1 2 ;
202-11
106 -14; 106-25; 107- 19;
whereby 43-11
107 -9; 108-13; 108-25;
whether 102-7; 1 1 0 - 1 2 ; HO--1 0 ; 113-21; 114- 18;
\Q
116-25; 122-17; 122 -5;
115 -19; 115-3; 116- 15;
rtf
iu
129-7; 13-21; 132 - 6 ; 116 -6 ; 118-13; 119- 1 0 ; vn
134-2; 145-23; 146- 2 1 ; 1 2 1 -17; 121-7; 1 2 2 - 1 2 ;

A. WILLIAM ROBERTS & ASSOCIATES

43

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March 5, 1993
MOYER vs. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

1 2 2 --2 ; 163- 20 ; 165- 17;
167--1 ; 171- 2 2 ; 172- 14;
177 -l; 177--23; 179 -2 ;
183--1 2 ; 184-2 ; 186- 1 2 ;

wounds 146-23
worker 56-19
write 72-18
workers 120-10; 214-18;
93-20
writing 110-18; 195-22;
working 124-23; 174-2;
40-21
(
18-21; 43-21; 44-8;
186--3; 187--24; 187 -9;
written 167-6; 195-24;
46-16; 53-11
21-20; 211-7; 216-15
188--1 1 ; 188--17; 189- 15;
works 151-11
w r o n g 128-25; 14-4;
196--1 2 ; 202 -4; 206- 16;
world 24-7; 74-6
204-17; 66-12
207--20 ; 208--13; 209- 13;
X
2 1 0 --13; 2 1 1 -2 2 ; 212 -8 ; world's 24-9; 57-13
worthless 126-6
X 226-1; 226-17; 227-1
214 -3; 214 - 6 ; 215 -4;
xanthone 170-12
219--18; 222 -3; 224- 1 1 ; would 100-1; 100-25;
1 0 1 - 1 0 ; 1 0 1 -2 ; 102-16; xanthones 100-6; 99-14;
224--18; 224-9; 225 -l;
104- 1; 104-7; 105-1; 99-24; 99-25
3-8; 38-18; 38-23; 39-■19;
Y
105- 21; 106-18; 108-3;
81- 2 1 ; 84- 1 1 ; 84- 14;
Y'all 118-8
109-12; 109-14; 111-1;
84-4 ; 85i-9; 9-21 ; 96-■14;
Y e a h 103-16 ; 109-4 ;
115-6; 116-8; 121-19;
96-25; 97-9
113-14; 118-13; 124-20;
125-16; 126-20; 126-22;
woman 4-18; 4-19
133-3; 147-16; 147-19;
128-20; 13-22; 130-24;
women 16-13
147-24; 152-23; 152-3;
131-17; 131-7; 134-21;
won 19-24
140-14; 142-1; 144-3;
157-15; 158-16; 158-24;
won't 172-19; 188-17;
16-20; 162-2.5; 163-13;
145-10; 145-11; 145-2;
218-13; 38-1
145- 7; 146-12; 146-13; 20- 17; 200-6; 209-13;
wonderful 158-7
146- 14; 146-18; 146-25; 210-13; 211-22; 216-1;
wood 34-15; 50-20; 53-22;
5 4 - 12; 54-13; 54-7; 147- 14; 149-6; 15-8; 219-13; 28-7; 35-10;
38-23; 41-8; 50-13;
55- 15; 55-19; 58-1; 58-3; 154-25; 16-21; 160-21;
52-23; 53-4; 57-1; 57-12;
160-23; 161-19; 161-25;
58-9
64-2; 76-24; 77-3; 80-25;
w o r d 1 4 5 - 7 ; 1 4 5 - 8 ; 166-11; 166-20; 166-8;
86-22
166-9; 17-18; 173-18;
179-14; 186-4; 210-14;
174- 1; 174-7; 175-16; year 107-16; 137-16;
22-4; 6-22; 66-13
175- 20; 182-6; 184-22; 137-19; 167-16; 180-5;
worded 186-12; 214-12
185- 23; 186-24; 186-4; 193-15; 20-10; 20-9;
words 104-15; 115-9;
188-18; 200-24; 22-21;
186- 6; 186-7; 187-18; 21- 13; 21-15; 213-1;
196- 7; 196-8; 197-10; 214-19; 218-22; 22-13;
91-9
197- 15; 197-18; 20-13; 2 2 - 16; 22-18; 2 2 - 2 0 ;
words— 104-9
22-9; 23-16; 23-2; 23-4;
20-16; 202-24; 202-25;
wore 102-13; 109-10;
24-21; 24-5; 26-10;
203-6; 203-9; 204-17;
109-8; 129-24; 147-5;
26-17; 26-18; 47-20;
205-11; 208-19; 21-8;
149-3
59-10; 60-13; 61-23;
214-14; 218-18; 218-19;
work 11-23; 114-6; 118-9;
61-24; 63-6; 63-7; 69-4;
12- 15; 12-8; 124-22; 219-21; 219-24; 221-19;
77-11; 79-3; 79-7
13- 24; 135-10; 136-14; 23-19; 23-2; 23-20; 23-6;
yearly 25-3
26-25; 27-2; 3-16; 30-9;
136-15; 15-13; 153-12;
years 105-10; 105-22;
31-13; 31-15; 31-16;
153-17; 16-25; 17-13;
105- 23; 106-14; 106-15;
31-20; 31-6; 32-10; 32-8;
187-4; 19-3; 191-25;
106- 18; 106-21; 107-16;
20-3; 21-7; 213-2; 25-24;
37-3; 38-3; 40-22; 41-9;
107- 20; 107-23; 108-10;
35- 17; 35-5; 36-21; 36-4; 42-18; 45-17; 51-21;
108- 15; 108-4; 11-21;
37-11; 38-24; 40-21;
52-11; 54-23; 55-1;
119-14; 119-4; 12-3;
42-22; 42-24; 43-7; 44-8;
59-20; 59-23; 60-25;
12- 9; 121-14; 123-17;
I>- 58-17; 58-20; 59-15;
68-21; 69-18; 72-13;
O i 64-14; 64-16; 66-13; 74-25; 76-9; 77-7; 79-2; 13- 9; 137-4; 152-16;
9-20; 92-23; 92-3; 93-1;
153-3; 157-5; 16-19;
’
"'t* 71-16; 75-19
w o r k e d 11-20; 12-4;
93-16; 95-6; 99-10; 99-13
16-24; 180-16; 181-13;
124-2; 161-8; 173-11;
wouldn't 116-15; 130-13;
19-24; 19-8; 20-1; 213-2;
147-22; 166-7; 173-19;
2 2 - 1; 22-24; 23-21;
173-14; 173-16; 180-15;
182-1; 188-12; 190-24;
187-25; 19-8; 192-20;
2 3 - 23; 25-22; 34-6;
3 6 - 11; 36-14; 41-7; 22 -2 1 ; 220-18
37-17 ; 38-3 ; 45-23 ;
47-11; 47-12; 50-23; 61-2 wound 146-15; 203-10
58-24; 59-14; 59-16;
A. WILLIAM ROBERTS & ASSOCIATES

44

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March 5, 1993
MOYER VS. DOW CHEMICAL COMPANY

SCHULZ, CARL O.

H* i
GO to

59- 25; 59-5; 59-8; 60-13;
60-9; 61-11; 65-2; 66-7;
89-14; 90-20; 97-13
yellow 159-21
y e t 13 7-1 4 ; 18 0 - 1
181-24; 38-22
York 192-3; 192- 5
y o u 'd 143- 23; 31- 24
31-25
you'll 24-21
y o u 're 1 0 0 --1 2 ; 103 -6
104-13; 106 -3; H O - 19
112-17; 113 -16; 113 -3
1 2 1 - 1 0 ; 122 -16; 122 -4
136-3; 139--2 ; 139- 21
139-24; 140--1 0 ; 140- 1 1
140-18; 140
140 -3
140-4; 142146 - 6
153-21; 179 -4; 181- 18
184-23; 189 -4; 193- 17
196-20; 199--15; 205- 10
207-23; 209 -3; 2 1 0 - 1 1
2 1 1 -1 1 ; 214215- 17
217-11; 218 -7; 220 -22
2 2 1 - 8 ; 2 2 1 -9; 28- 13
28-22; 28-9; 53-24; 67-4
7-11 ; 85-1 0 ; 89-18
89-21; 9-16; 9-19
you've 121-11; 129-10;
134-17; 135-20; 146-9;
153-15; 157-8; 158-7;
172-4; 203-5; 204-5;
208-2; 213-16; 216-13;
221-16; 23-14; 23-24;
26-13; 27-22; 30-25;
32-15; 40-5; 45-14;
45-18; 51-7; 51-9; 58-13;
62-6; 69-7; 7-5; 8-13
Young 195-24
your— 59-24
yours 164-2; 43-14
Yourself 4-12; 70-22;
87-14
youth 27-23
Z
Zealand 127-19; 189-2
zero 220-10 ; 2 2 1-11
O
rH

49$

225-7
223

A. WILLIAM ROBERTS & ASSOCIATES

Of
u

45

MICROCopy

AA Department of
W Veterans Affairs

Synopsis of Scientific
Literature on Phenoxy
Herbicides and
Associated Dioxins
No. 9-(Volumes XIX and XX)

Veterans Health Administration

50 Ö
9

6 * -1

VA CONTRACT NO. V101(93)P-1333

SYNOPSIS OF SCIENTIFIC LITERATURE
ON PHENOXY HERBICIDES
AND ASSOCIATED DIOXINS
NO. 9 - (Volumes XIX and XX)
Prepared for:
Lawrence B. Hobson, M.D., Ph.D., Director
Environmental Agents Service and
Layne A. Drash
Contracting Officer Technical Representative
Veterans Health Administration
Department of Veterans Affairs
810 Vermont Avenue, NW
Washington, DC 20420

Information Ventures, Inc.
1500 Locust Street, Suite 3216
Philadelphia, Pennsylvania 19102

501

PREFACE
This synopsis is the ninth in a series of lay language summaries of the Review of Literature on
Herbicides, Including Phenoxy Herbicides and Associated Dioxins. Synopsis No. 1 of Volumes I-IV was
published in July 1985. Subsequent synopses were published as follows:

October 1985 (Synopsis No. 2 - Volumes V and VI)
October 1986 (Synopsis No. 3 - Volumes VII and VIII)
July 1987 (Synopsis No. 4 - Volumes IX and X)
September 1988 (Synopsis No. 5 - Volumes XI and XII)
October 1989 (Synopsis No. 6 - Volumes XIII and XIV)
May 1990 (Synopsis No. 7 - Volumes XV and XVI)
August 1991 (Synopsis No. 8 - Volumes XVII and XVIII)
This current synopsis, a review of Volumes XIX and XX, continues the effort of the Department of
Veterans Affairs (VA) to provide for the general public a summary in laymen’s terms, of the scientific
literature published during 1991 related to the possible health effects of exposure to phenoxy herbicides
and dioxins.

Environmental Agents Service
Department of Veterans Affairs
Washington DC
August 1992

502

CONTENTS
Preface

Page

1. Introduction...................................................................................................................................1
2. Description of the literature published in 1991..........................................................................1
3. Studies of Vietnam v eteran s....................................................................................................... 2
4. C an ce r...........................................................................................................................................4
5. Genetic effects.............................................................................................................................. 7
6. Reproductive e ffe c ts....................................................................................................................7
7. Effects on the immune system ...................................................................................................8
8. Other effects .................................................................................................................................8
9. Dioxins in human tissues ........................................................................................................... 9
10. Basic research on the mechanism of dioxin to x ic ity ............................................................. 9
11. Summary and conclusions..................................................................................................... 10

503
9 ' ^

1. Introduction
In May 1992, Information Venture, Inc., a scientific information company in Philadelphia,
Pennsylvania, completed a review of the literature published during 1991 on the health effects of Agent
Orange and related compounds. A critical review and an annotated bibliography of this literature have been
published as Volumes XIX and XX of the ongoing Review o f Literature on Herbicides, Including Phenoxy
Herbicides and Associated Dioxins. This synopsis summarizes the important new information that became
available during 1991.

Phenoxy herbicides are a group of structurally-related chemicals that have been used in agriculture
and forestry to kill weeds in cultivated crops and unwanted tree species in coniferous forests, and to clear
vegetation from road beds and fence lines. The phenoxy herbicides that have been most frequently used in
the United States are 2,4-D and 2,4,5-T. The latter has not been used in the United States for a number of
years, and its use has been banned in most countries around the world. Another phenoxy herbicide, MCPA,
has been used extensively in Scandinavian countries. Several herbicides were used by the U.S. Air Force in
Vietnam from 1963 to 1971 in Operation Ranch Hand to remove leaves from trees in heavily forested areas
so as to be able to see enemy troop movements and supply operations. Agent Orange, a mixture of 2,4-D
and 2,4,5-T was, by far, the herbicide used most frequently.

Commercial phenoxy herbicide preparations manufactured from the 1940s until the early 1970s
contained small quantities of chlorinated dibenzo-p-dioxins as contaminating impurities. The terms
’’dioxins” or ’’dioxin” have frequently been used as shorthand for this family of chemical compounds. The
exact dioxin compounds and the amounts of them that were present in phenoxy herbicide preparations
varied from preparation to preparation and perhaps even from batch to batch. Commercial preparations of
2,4,5-T contained small amounts of one particular dioxin, 2,3,7,8 -tetrachlorodibenzo-p-dioxin, which is
frequently abbreviated as 2,3,7,8-TCDD or just TCDD. TCDD was present in the Agent Orange that was
used in Vietnam. The effects of TCDD on experimental animals have been extensively studied since it is
believed to be the most toxic member of the dioxin family of compounds. While 2,4-D contained small
quantities of dioxins, TCDD was not one of them. When it was recognized that phenoxy herbicides were
contaminated with dioxins, manufacturing processes were changed so as to reduce or eliminate them.
Some other herbicidal preparations that were used in Vietnam contained cacodylic acid and/or picloram.
These herbicides were used in much smaller quantities than Agent Orange, however, and they were not
contaminated with dioxins.

2. Description of the literature published in 1991
There were 350 papers published during 1991 about the health effects of phenoxy herbicides and other
herbicides used in Vietnam. This is a slightly larger number than the year before and above the average of
the last five years. It indicates that there continues to be a high level of scientific interest in this area of
investigation. Public controversy surrounding the dioxins has if anything increased over the past year.
Consistent with previous years, much of the literature described studies of the effects of dioxins and related
compounds in animals and various experimental systems because scientists are very interested in learning
how this family of compounds causes the wide variety of toxic effects that it does. At the same time, the
results of a number of studies of possible health effects in humans who may have been exposed to phenoxy
herbicides and/or dioxins were published in 1991. Furthermore, many papers reported on studies in which

1

504

the concentration of dioxins in human blood, body fat, and breast milk were measured, and attempts were
made to relate these concentrations to past exposure to phenoxy herbicides or dioxins and to any adverse
health effects that were experienced.

3. Studies of Vietnam veterans
The past 10-15 years has seen much research devoted to the issue of whether the health of Vietnam
veterans has been adversely affected by their service in Vietnam, in general, and by exposure to phenoxy
herbicides, in particular. The question of lasting effects of Vietnam service in general is easier to address
than that of the effects of herbicide exposure, because it is much easier to determine whether a veteran
served in Vietnam, and to locate detailed service records, than to determine whether he or she was exposed
to herbicides while there.
It is difficult, if not impossible, to answer the question of whether there is an association between
exposure to herbicides in Vietnam and adverse health effects, especially cancer. One reason for this is the
difficulty of accurately determining any given individual’s exposure to herbicides, and to phenoxy
herbicides in particular, so many years after the war. Another reason is that exposure to herbicides is just
one aspect of military service in Vietnam that might have had a long lasting impact on health, and it is not
possible to separate all the factors. For example, careful study of the available information on herbicide
application missions in Vietnam, indicates that the ground troops that were most likely to have been
exposed to herbicides during, or just after, their application were the same troops that were most likely to
have been involved in combat. The stress of constant exposure to combat situations is known to have
adverse consequences for physical health.
How can exposure to phenoxy herbicides be assessed among Vietnam veterans? Three basic
approaches have been attempted. The first is to ask veterans whether they were sprayed with herbicides.
This method is inaccurate for several reasons. First, other chemicals such as insecticides, were sprayed in
Vietnam, and ground troops had no way of knowing what was being sprayed. Second, a number of
independent studies have shown that a veteran’s recall of herbicide exposure is influenced by his or her
belief regarding lasting health effects of that exposure, i.e., veterans who do not believe that they are in poor
health as a result of herbicide exposure are less likely to remember being exposed, even if objective
evidence indicates that they were. Finally, troops could have entered an area that had been sprayed only
several hours or a day or two earlier, in which case they would not have realized that they were exposed.
A second approach to assessing herbicide exposure is to combine records of herbicide application
missions with individual service records in order to determine if an individual was in a specific area at the
same time that a herbicide application mission took place. This method also is not completely reliable.
Service records identify only the military units to which individuals were posted and may not reflect such
details as temporary assignments. Second, unit records are unlikely to identify the areas in which patrols
and small units might have operated, and the individuals who participated in these actions. Finally, even the
accuracy of data on herbicide spray missions may be questionable, since for example, aircraft often
jettisoned the herbicide when they came under enemy fire.
The development of sensitive and specific methods for the analysis of TCDD and other dioxins in
biological specimens such as blood and body fat, has provided the opportunity for a third approach to

2

assessing herbicide exposure in Vietnam, since many of the phenoxy herbicides used in Vietnam were
contaminated with TCDD. While it might seem unlikely that there would be enough of this substance still
remaining in the body to measure after so many years, in fact the body content only drops by half in about 6
to 10 years. As a result, individuals who were heavily exposed in Vietnam still might have elevated levels
of this compound in their blood.

Over the past six years a number of studies have been conducted in which blood samples from Vietnam
veterans, from workers who were exposed to dioxins in chemical manufacturing plants, from civilian
populations exposed to dioxins as a result of accidental environmental pollution, and from members of the
general population, have been analyzed to determine their TCDD content. These studies have shown that:
a significant portion of the general population of industrialized countries has measurable concentrations of
TCDD in their blood, without evidence of unusual exposure; a number of individuals who did experience
relatively heavy exposures to phenoxy herbicides or dioxins and related compounds in the past currently
have concentrations of TCDD in their blood that are clearly higher than those found in the general
population; and, many individuals who were unquestionably exposed to these substances in the past have
levels of TCDD in their blood that are no higher than those found in people with no known unusual
exposure.

Because of these findings, measurements of the concentration of TCDD in the blood of Vietnam
veterans cannot be used as the sole basis for estimating their exposure to herbicides. Elevated levels of
TCDD in the blood do occur in Vietnam veterans who experienced exposure to phenoxy herbicides, but the
vast majority have blood TCDD concentrations that are no different from those found in the general
population, even in some cases where other evidence indicates that they indeed suffered such exposure. A
good example of this is provided by the results of the analysis of blood samples taken from 888 Air Force
veterans who participated in the herbicide application program (Operation Ranch Hand) in Vietnam. The
concentrations of TCDD in the blood of these veterans were compared to those in blood samples from 856
Air Force veterans who did not participate in Operation Ranch Hand. While the average concentration of
TCDD in the blood of Ranch Hand personnel was higher than in the blood of comparison subjects, even
within this group which was responsible for spraying herbicide there was considerable variation. Officers,
who on the whole did not actually handle the material, had average blood TCDD levels that were only
slightly above those of personnel unassociated with the operation, as would be expected. The highest levels
were found in the enlisted groundcrew, followed by enlisted flyers, but even among these two
unquestionably exposed groups, there was a 25-fold variation between individual blood levels.

Studies of mortality and health status among Vietnam veterans have fairly consistently indicated that
there are differences between these individuals and military veterans of the same era who did not serve in
Vietnam, as well as between Vietnam veterans and the general population of the United States. In earlier
surveys, Vietnam veterans believed that they had more health problems than do other veterans and the
general population. There has been a marked decline in the expression of such feelings. Other objective
findings have for the most part not indicated any major health problems associated with service in Vietnam,
and exposure to phenoxy herbicides in particular, but some changes have been recorded. The general
health study of U.S. Air Force personnel involved in the Ranch Hand operation, for example, has not shown
major problems among this group which was clearly associated with herbicide exposure. It has revealed,
however, a correlation between a higher percentage of body fat and elevated levels of TCDD in the blood,
suggesting that the dioxin may be affecting fat metabolism. Another finding has been that higher blood
3

TCDD levels are associated with changes in properties of components of the blood which suggest that some
type of immune reaction is occurring.
While Vietnam veterans are not dying at a greater rate than other veterans or the population at large,
they are still more likely to die from certain causes of death. These include a group of causes such as motor
vehicle accidents and homicide that are lumped together as “external causes of death.” Overall, however,
Vietnam veterans in general do not appear to experience more diseases or to be more likely to die of any
specific disease than other veterans or the U.S. population as a whole.
Most studies of cancer mortality among Vietnam veterans have shown them to be at little or no
increased risk, but a few studies have reported increased risks for certain types of cancer in those who
served in Vietnam. There is a problem with deriving clear-cut conclusions from such studies in which very
few veterans actually contract these cancers, so that a 50% increase in incidence may in fact describe six
individuals with the specific cancer in the veterans versus four among the controls, a difference which may
not always be meaningful. For example, an epidemiologic study that was published by scientists at the
Veterans Administration 1988 found significantly increased mortality from two types of cancer,
non-Hodgkin’s lymphomas and lung cancer, in U.S. Marine veterans of Vietnam but not in U.S. Army
veterans. Subsequently, in the 1991 follow-up publication from the same source, it was the Army veterans
who were shown to have an increased death rate from cancers of the lung and larynx, while the increases
previously found among Marine veterans appeared to reflect the very low incidence of these cancers in the
non-Vietnam veterans with whom they were compared. If they were compared with the general U.S.
population there was no excess. Another study conducted on behalf of the U.S. Centers for Disease Control
found that Vietnam veterans were at 50% greater risk of developing non-Hodgkin’s lymphoma than were
veterans who did not serve in Vietnam. However, this increased risk could not be tied to any of the factors
such as military region, unit, or dates of service, which might indicate that they were exposed to Agent
Orange. Risks for five other cancers covered in this study were not increased.
Similar conclusions were evident in the complete report on the 1987 follow-up of the Operation
Ranch Hand personnel who worked with Agent Orange daily, compared with a control group of veterans.
In this study of 995 Air Force veterans, few differences between these groups were seen in objective
measures of health status. The only one of these that was of clinical importance was a significantly
increased incidence of basal cell carcinoma (a type of cancer of the skin) among the Ranch Hand veterans, a
difference which had also been noted in the two previous studies of their health status. This type of skin
cancer is known to be related to exposure to the sun, but the excess of such cancers among the Ranch Hand
group as a whole could not be accounted for by known differences in exposure to the sun, neither was it
associated with their blood dioxin levels. With respect to other types of cancer, no differences could be
determined between the Ranch Hand and comparison groups. However, blood TCDD levels were related
to the incidence of benign, non-cancerous tumors 75% of which were lipomas.
These recently reported studies fit into the same patterns established in earlier ones, such as that
undertaken on members of the U.S. Army Chemical Corps who had been involved in other missions
involving herbicide application, such as clearing vegetation from military installations in Vietnam. This
group of veterans also showed no overall trends in the relatively few cancers they developed.

4. Cancer
The question of a possible association between cancer and exposure to phenoxy herbicides and their
dioxin contaminants, which has received no consistent answer from the studies with veterans, has met a
4

similarly ambivalent response in the civilian area. There has been a large number of studies of workers who
may have been exposed to these compounds during their manufacture or in the course of their application in
agriculture, forestry, and highway and railroad maintenance. Over the past 10 years, more than 50
publications in the scientific literature have described over 30 epidemiologic investigations of all types,
including proportionate mortality, historical cohort studies, and case control studies. These studies have
been conducted in many countries in addition to the United States, and have in some cases been
international in scope. They have shown no consistent evidence of an association between herbicide
exposure and the risk of cancer, either in general, or of any specific type.

Attempts to explain the apparent inconsistencies among these studies have been hampered by the
numerous differences between them in terms of how they were carried out, and by the existence of many
potential interfering factors. As an example of the latter, in assessing possible associations between
herbicide exposure and cancer in agricultural workers, it is notable that while farmers as a group are at
lower risk of dying of cancer than the general population, they appear to be at a higher risk for cancers of the
lymphatic system, particularly non-Hodgkin’s lymphoma. While at first sight this might imply a
relationship to herbicide exposure, several studies have not found any such association with the types or
amounts of herbicide used by those farmers. Here we may be seeing the effects of the many other factors
which may be unique to farmers, such as exposure to a wide range of other agricultural chemicals and plant
and animal pathogens, or even as yet unsuspected features of diet and lifestyle in a rural environment.

Several studies were published during 1991 in which possible associations between cancer and
occupational exposure to dioxin were examined. The most significant of these was conducted by the
National Institute for Occupational Safety and Health (NIOSH), and has been in progress for a number of
years as part of the NIOSH Dioxin Registry. This study, published in early 1991 presented the results of a
cohort mortality study of 5,172 workers at 12 chemical plants in the United States, who were exposed to
dioxins while employed in the manufacture of chlorinated phenols or phenoxy herbicides. The NIOSH
investigators identified the cause of death in 1,037 of the 1,052 who had died, and found that death rates
within this group were what might be expected for the general U.S. male population. When considering
specific causes of death, they found fewer deaths from diseases of the digestive system (specifically
cirrhosis of the liver) and significantly more deaths from accidental causes than would be expected. The
number of cancer deaths in the cohort also was slightly but significantly above what would be expected.
This excess cancer risk was greatest in those workers who had been exposed to dioxins for one year or more,
and whose first exposure occurred at least 20 years previously. In this group the mortality ratio was 145 as
percent of control. Overall excess mortality was not due to a marked increase in any particular form of
cancer, a finding that is rather unusual for chemical carcinogens, which typically show some organ
specificity. Instead, mortality rates for a number of cancers, such as soft tissue sarcomas and respiratory
cancers, were slightly greater than expected, but only the rate for cancers of “other and unspecified” sites
was significantly elevated. This category was simply an arbitrary grouping of a number of cancers that do
not fit other categories, and which are individually rather rare. It is difficult to ascribe significance to
changes in such a nebulous category. A limitation in the study design was that it did not take account of the
effect of smoking habits or the presence of other chemicals in the workplace.

A multi-site study carried out under the aegis of the International Agency for Research on Cancer,
involved 18,910 production workers and herbicide sprayers from ten countries. Through a combination of
factory records, work histories, questionnaires, and recorded data from sprayings, it was found this large
group showed a doubled risk of soft tissue sarcoma, relative to cause-specific national death rates. There
5

were also small increases in testicular, thyroid and nasal cancers, but the numbers were too small to be
meaningful. Unfortunately, this study presents a number of problems. First, the deaths from soft tissue
sarcoma, four in all, took place exclusively for the time period 10 to 19 years after first exposure. In
addition, two of these deaths occurred after less than one, and the other two after 10 to 19 years of exposure.
This clustered pattern is what might be expected for random, non-significant variation in the distribution of
a rare disease. Second, not only are national death rates based on less accurate reporting of causes of death
than medical records, but their use in comparisons may be misleading, because they do not reflect specific
risk factors which are associated with other chemicals and workplace conditions to which these workers are
exposed. For these reasons, the conclusions of this study are not very convincing; a longer follow-up may
strengthen the study, but will not eliminate the problem of the control comparison.

A study of mortality among workers at a herbicide plant in Germany where the products had been
heavily contaminated with dioxin prior to 1954, showed increases in overall cancer mortality compared
with both German national statistics and a comparison group of workers in the gas industry. Rates were
highest for those with 20 or more years of employment, and women showed an increase in breast cancer.
Two major problems with this study were the use of mortality data from national statistics and death
certificates for the control groups, compared with more accurate medical records in the study group, and the
80% higher rate of smoking among the herbicide workers than the general population. Both factors could
severely affect the findings.

In a region of northern Italy in which heavy spraying with phenoxy herbicides had occurred over
several decades, there was a higher incidence of lymphomas of all types. This increased incidence also was
related to higher measured soil levels of these herbicides in the areas where the subjects lived.
Unfortunately, no attempt was made to look at the occupations of the study subjects or their length of
residence in the particular area. Men did show a higher incidence than women, however, suggesting that
occupation might be a factor. Also in Italy, further follow-up of those involved in the industrial accident at
Seveso in 1976, which released large amounts of dioxin, showed that even among individuals who were
most heavily exposed on the basis of their blood TCDD values and areas of residence, there were no
statistically significant increments in cancer incidence.

The inconclusive nature of the studies attempting to associate exposure to dioxins with cancer in
humans stands in stark contrast to the results of studies in experimental animals, where TCDD has been
found to be a carcinogen in many strains and species. No additional animal studies of the production of
cancers by conventional long-term administration over the course of eighteen months to two years were
published in 1991. There was however, an important réévaluation of 1978 work on the production of liver
cancer in rodents, based on the fact that since that time the criteria used by pathologists to define what is or is
not liver cancer have changed. The 1978 data are very important because they serve currently as the basis
on which such agencies as the Food and Drug Administration and the Environmental Protection Agency
calculate the hazard that dioxin presents to human health. Using the new criteria, it was found that the risk
to humans may be between ten and one hundred times less than had been calculated earlier. This does not
mean that it is no longer considered to be a carcinogen, however. Another advance seen in 1991 papers, has
been the use of tests that are based on biological indicators of precancerous changes that occur before a
tumor appears, and which can evaluate carcinogenic potency more rapidly, and with the use of fewer
animals, than conventional methods.
6

509

5. Genetic effects
Extensive testing of TCDD and related compounds over the last 10-20 years in various strains of
bacteria, in animal and human cells in culture, and in whole experimental animals, has produced no
convincing evidence that these compounds cause genetic mutations. Despite some conflicting findings,
the smaller amount of information available suggests that the same is true of phenoxy herbicides. On the
other hand, some studies in experimental animals have suggested that TCDD can cause damage, other than
mutations, in chromosomes. There is no reliable evidence of genetic damage or changes in chromosomes
from studies of humans exposed to phenoxy herbicides or dioxins.
No studies implicating either phenoxy herbicides or dioxins in producing genetic damage in humans
were published in 1991. Two studies of TCDD, one in the bacterial Ames’ test, and the other in an animal
cell culture, confirmed that TCDD is inactive in producing mutations at the highest concentrations at which
it would dissolve. Another study with animal cells found that the phenoxy herbicide 2,4-D did cause
mutations at high concentrations.

6. Reproductive effects
The cumulative body of research undertaken to date provides a few definitive answers to the question
of whether exposure to phenoxy herbicides or dioxin causes adverse reproductive effects. It is fairly certain
that delayed development of young children can occur when women are exposed to TCDD and related
compounds before or during pregnancy. An example of this is a study published in 1991 of 128 children
bom in Taiwan to women who had been exposed to high levels of various polychlorinated compounds
contaminating the cooking oil which they had been using. Developmental delays, and speech problems
were much more frequent in these children than in a comparison group, and persisted over a prolonged
period. There was, however, no evidence of the frank physical abnormalities that have been well
documented in experimental animals exposed to these compounds.
Further instances of such physical findings appeared in 1991 reports describing the production of cleft
palates and a kidney abnormality called hydronephrosis in the offspring of mice exposed to TCDD and
similar substances having bromine substituted for chlorine. Even when normal newborn mice were
exposed to TCDD through their mothers’ milk, abnormal kidney development occurred. Interference with
development also was demonstrated when embryonic tissue from the palate region was exposed to TCDD
in vitro. An interesting result here was that tissue from humans or from rats was 200 times less sensitive
than that from mice, which might provide an explanation of why the physical abnormalities, which are so
prevalent in mice, have not been clearly demonstrated to occur in humans. It is true that a number of studies
have been described in the Review over the past few years in which the authors concluded that there is a
correlation between a large number of adverse reproductive consequences, including spontaneous
abortions and birth defects, and exposure of civilian Vietnamese women to herbicides during the war in that
country. All such studies have suffered from deficiencies that included lack of an appropriate historical
basis or control groups with which to compare the incidence rates, and the absence of unequivocal evidence
of exposure to Agent Orange.
Two recent studies have reported damage to the testicles, one in phenoxy herbicide sprayers using
2,4-D, and the other in rats exposed to TCDD. The damage led to diminution in sperm count and increases

7

in abnormal or inactive sperm. However, another study undertaken in male rats exposed to TCDD
disclosed no significant effects of this testicular damage upon the number or health of the offspring. The
authors concluded that the data did not demonstrate any “biologically significant paternally-mediated
developmental toxicity.” Previous volumes of this Review found no evidence of an association between
spontaneous abortions and a history of military service in Vietnam by the father, beyond a slightly, but not
statistically significant, increased risk of congenital anomalies in one study of children fathered by such
men. The ongoing Ranch Hand study has given no evidence of such adverse effects.

7. Effects on the immune system
The available evidence indicates that the phenoxy herbicides do not affect the immune system.
Dioxins, however, are another matter. They have clearly been shown to alter the immune system in
experimental animals, but studies of humans exposed to these substances have not disclosed significant
effects. In humans, the Air Force Health Study, for example, did find changes in blood proteins suggesting
that some mild chronic inflammation was at work, but white blood cells, the core of the immune system,
were unaffected. Some abnormal reactions to skin tests did not appear to be related to concentrations of
TCDD in the blood. Another study with patients suffering from AIDS indicated that those who had the
highest amounts of TCDD in their blood also experienced many more other types of infection, termed
opportunistic infections, than did patients with lower levels. This suggests that dioxin was making their
immune system even worse, but the fact that these patients had an immune defect from the underlying
AIDS to begin with, makes interpretation of the results difficult. Another recent study on white cells taken
from either humans or monkeys showed that TCDD changed the proportions of various subset types of
these cells, but despite this, monkeys given TCDD showed no signs that their immune system was
defective.

An effect of TCDD, related to the immune system, which has been known for a long time, is that it
causes the thymus gland to shrink and cease functioning. Papers published in 1991 indicate that this effect
is not due to an action of dioxin on the active immune cells that make up much of the weight of the gland, but
rather to damage to the supporting structure. Once the latter was repaired, fresh cells returned from the
bone marrow and the thymus recovered.

8. Other effects
While it is clear that the potential human health effects of most concern are cancer, adverse
reproductive effects, and alterations in the immune system, there have been some recent publications
dealing with other potential adverse effects both in humans and in animals. Chief among these have been
reports of effects on the nervous system. Ranch Hand personnel showed evidence of some changes in their
coordination and gait that could be correlated with levels of TCDD measured in their blood. Similarly,
among the children of the Taiwanese women, discussed above, who had consumed contaminated cooking
oil, there was evidence of a lag in the development of their coordination skills.

In animals, the most conspicuous result of a single large dose of TCDD is that they stop eating, and in
susceptible strains, waste away till they die. A 1991 study suggests that this refusal to eat results from a
disturbance in the balance of substances in the brain which control the sensations of hunger and satiety.
8

Dogs are rather sensitive to phenoxy herbicides, and a study appearing in 1991 reported on the changes in
brain waves and muscle strength of dogs exposed to 2,4-D.

Another area of toxicity restricted to humans is the skin disorder known as chloracne. This is very
characteristic to exposure to dioxin, and a follow-up of those exposed to TCDD in the accident that
occurred at Seveso in Italy, showed that development of chloracne was tied closely to high blood levels of
TCDD. Among other toxic symptoms of dioxin exposure that were reported during 1991, were effects on
the liver, manifested as alterations in fat metabolism, and some interference in blood coagulation.

9. Dioxins in human tissues
A topic of continued active research interest is the relationship between concentrations of TCDD in
blood, body fat, or breast milk, and past exposure to dioxins or phenoxy herbicide preparations that
contained dioxins. This activity has been made possible by the development of sensitive methods for
analysis of TCDD that can detect levels of this and related substances in the parts per trillion range.
Elevated levels of TCDD in blood or fat tissue samples from Air Force veterans who participated in
Operations Ranch Hand in Vietnam, workers exposed to dioxins in 12 different chemical manufacturing
plants in the United States, and workers who were exposed to dioxins as byproducts of a manufacturing
process in a German chemical company more than twenty years after exposure. In one case published in
1991, TCDD and a related compound were measured in the blood of a chemist who had made these
substances 34 years previously! This technology has also shown that dioxin can cross the placenta and
enter a growing fetus, or pass in the breast milk from mother to child.

Despite this sensitivity, some caution is needed in relying on these measurements as indicators of past
exposure to dioxins and related compounds. There must clearly be a great deal of variation among
individuals as to how much dioxin they absorb and how quickly they eliminate it from their bodies. While
the finding of high average concentrations of TCDD in the blood may serve to identify groups of people
who experienced unusually heavy exposure in the past, levels no higher than those in the general population
do not necessarily indicate that those individuals did not undergo at least moderate exposure.

10. Basic research on the mechanism of dioxin toxicity
As has been true for a number of years, a large proportion of the scientific literature published during
1991 has described basic research on TCDD and closely related compounds. Most of these studies are of
little direct relevance to potential human health effects. They have, however, served to outline in greater
detail the means by which these substances produce their toxic effects, and in this way have laid the ground
work for a better understanding of the true extent of the hazard they present for human health.

Studies published in 1991 confirmed that most of the effects of dioxin arise from its interaction with a
particular component (known as the Ah receptor) in the cell, which helps to transport it to the cell nucleus
and attach it to special sites on the cell’s DNA. It can then turn on various processes within the cell that lead
to the adverse changes. A few effects of dioxin, especially those related to the immune effect, may not use
this particular receptor, but it is not yet clear how this happens.

9

Another area of basic research that received considerable attention during 1991 as in the past few
years, was the antiestrogenic and antiandrogenic activity, that is, the effects on female and male hormone
action, of TCDD in a number of experimental models. The antiestrogenic action seems to depend on direct
effects on tissues of the breast and uterus, whereas androgens are antagonized indirectly through effects on
hormones from the pituitary gland in the brain.

Basic research has also implicated some involvement of dioxin in the action of Vitamin A, but there is
no clear picture as yet of how this antagonism occurs. It may be because the Ah receptor to which dioxin
attaches is related in structure to the receptor for the vitamin. Doubtless many other basic research findings
will be made over the next few years which will finally elucidate the different mechanisms by which this
“environmental hormone”, as dioxin has been termed, exerts all its varied actions.

11. Summary and conclusions
Clearly, the most important research results relevant to the potential human health effects of phenoxy
herbicides and dioxins to become available during 1991 have confirmed and extended those reported in
1990, in which there was a small but significant increase in the risk of cancer among men who were
occupationally exposed to relatively large amounts of dioxins more than 20 years ago. These data were to
some extent tied to blood dioxin levels, and could be said to reflect the likelihood that dioxins promote
cancer, rather than initiate it.

In contrast to studies of dioxin-exposed workers, those carried out among Vietnam veterans, were
either negative or equivocal. These studies found no increased risk of cancer except for sun-related skin
cancers among Air Force personnel who participated in Operation Ranch Hand, and these could not be
associated with dioxin levels. Benign tumors did show an increased incidence.

Human studies which were published during 1991 provided no convincing evidence for the existence
of an association between exposure of males to phenoxy herbicides or dioxins and adverse reproductive
outcomes. Exposure of females to related chlorinated furans and PCBs, however, did lead to slowed
development of their children. In mice, frank malformations such as cleft palate were produced by TCDD
and many related compounds, but studies with human tissue suggested that humans are less sensitive to this
action.

It is clear that many questions remain regarding the potential human health effect of phenoxy
herbicides and their dioxin impurities. This is especially true of the immune system and hormone
regulation. In addition, further basic studies are needed, not merely for the theoretical satisfaction of
elucidating the detailed mechanism of action, but more importantly, to help define the relative sensitivity of
human tissues, and thus resolve the ongoing debate on how harmful dioxin is to human health.

10

Another area of basic research that received considerable attention during 1991 as in the past few
years, was the antiestrogenic and antiandrogenic activity, that is, the effects on female and male hormone
action, of TCDD in a number of experimental models. The antiestrogenic action seems to depend on direct
effects on tissues of the breast and uterus, whereas androgens are antagonized indirectly through effects on
hormones from the pituitary gland in the brain.

Basic research has also implicated some involvement of dioxin in the action of Vitamin A, but there is
no clear picture as yet of how this antagonism occurs. It may be because the Ah receptor to which dioxin
attaches is related in structure to the receptor for the vitamin. Doubtless many other basic research findings
will be made over the next few years which will finally elucidate the different mechanisms by which this
“environmental hormone”, as dioxin has been termed, exerts all its varied actions.

11. Summary and conclusions
Clearly, the most important research results relevant to the potential human health effects of phenoxy
herbicides and dioxins to become available during 1991 have confirmed and extended those reported in
1990, in which there was a small but significant increase in the risk of cancer among men who were
occupationally exposed to relatively large amounts of dioxins more than 20 years ago. These data were to
some extent tied to blood dioxin levels, and could be said to reflect the likelihood that dioxins promote
cancer, rather than initiate it.

In contrast to studies of dioxin-exposed workers, those carried out among Vietnam veterans, were
either negative or equivocal. These studies found no increased risk of cancer except for sun-related skin
cancers among Air Force personnel who participated in Operation Ranch Hand, and these could not be
associated with dioxin levels. Benign tumors did show an increased incidence.

Human studies which were published during 1991 provided no convincing evidence for the existence
of an association between exposure of males to phenoxy herbicides or dioxins and adverse reproductive
outcomes. Exposure of females to related chlorinated furans and PCBs, however, did lead to slowed
development of their children. In mice, frank malformations such as cleft palate were produced by TCDD
and many related compounds, but studies with human tissue suggested that humans are less sensitive to this
action.

It is clear that many questions remain regarding the potential human health effect of phenoxy
herbicides and their dioxin impurities. This is especially true of the immune system and hormone
regulation. In addition, further basic studies are needed, not merely for the theoretical satisfaction of
elucidating the detailed mechanism of action, but more importantly, to help define the relative sensitivity of
human tissues, and thus resolve the ongoing debate on how harmful dioxin is to human health.

514

Sy\ Department of
W

Veterans Affairs

Synopsis of Scientific
Literature on Phenoxy
Herbicides and
Associated Dioxins
No. 7 - (Volumes XV and XVI)
Veterans Health Services
and Research Administration

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VA CONTRACT NO. V101(93)P-1136

SYNOPSIS OF SCIENTIFIC LITERATURE
O N PHENOXY HERBICIDES
AND ASSOCIATED DIOXINS
N O . 7 - (Volumes XV and XVI)
Prepared for:
Lawrence B. Hobson, M.D., Ph.D., Director
Environmental Medicine Office and
Layne A. Drash
Contracting Officers Technical Representative
Veterans Health Services and Research Administration
Department of Veterans Affairs
810 Vermont Avenue, NW
Washington, DC 20420

Submitted by:
Clement Associates, Inc.
9300 Lee Highway
Fairfax, VA 22031

5l6
9

PREFACE
This synopsis is the seventh in a series of lay language summaries of the Review o f Literature
on Herbicides, Including Phenoxy H erbicides and Associated Dioxins. Synopsis No. 1 of Vol­
umes I and IV was published in July 1985, Synopsis N o. 2 of Volumes V and VI was published in
October 1985, Synopsis No. 3 of Volumes VII and VIII was published in O ctober 1986, Synop­
sis No. 4 of Volumes IX and X was published in July 1987, Synopsis No. 5 of Volumes XI and
XII was published in September 1988, and Synopsis N o. 6 of Volumes XIII and XIV was pub­
lished in O ctober 1989.
This current synopsis, a review of Volumes XV and XVI, continues the effort of the D epart­
ment of Veterans Affairs to provide for the general public a summary in laymen’s terms, of the
scientific literature published during 1989 related to the possible health effects of exposure to
phenoxy herbicides and dioxins.

Environm ental Medicine Office
D epartm ent of Veterans Affairs
W ashington DC
M ay 1990

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CONTENTS
Preface

Page

1. Introduction..................................................................................................................................

1

2. Description of the literature published in 1989 ....................................................................

1

3. Studies of the general health of Vietnam veterans ................................................................ 2
4. Cancer ........................................................................................................................................... 3
5. Genetic e ffe c ts.............................................................................................................................. 6
6. Reproductive e ffe c ts.................................................................................................................... 6
7. Other effects ................................................................................................................................ 8
8. Dioxins in hum an tissu e s........................................................................................................... 9
9. Summary and c o n c lu sio n s.......................................................................................................

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1.

Introduction

In M ay 1990, Clement Associates, Inc. a research firm in Fairfax, Virginia, completed a
review of the literature published during 1989 on the health effects of Agent Orange and related
compounds. A critical review and an annotated bibliography of this literature have been
published as Volumes XV and XVI of the ongoing Review of Literature on Herbicides,
Including Phenoxy Herbicides and Associated Dioxins. This synopsis summarizes the key new
information that became available during 1989.
Phenoxy herbicides are a group of structurally related chemicals that have been used in
agriculture and forestry to kill weeds in cultivated crops, to kill unwanted tree species in
coniferous forests, and to clear vegetation from road beds and fence lines. Historically, the
phenoxy herbicides that have been m ost frequently used in the United States are 2,4-D and
2,4,5-T . The latter has not been used in the United States for a num ber of years, and its use has
been banned in most countries around the world. Another phenoxy herbicide, MCPA, has had
extensive use in Scandinavian countries. Several herbicidal preparations were used by the U.S.
Air Force in Vietnam from 1963 to 1971. A m ajor purpose of this operation (known as
Operation Ranch Hand) was to remove leaves from trees in heavily forested areas of Vietnam in
order to be able to see enemy troop movements and supply operations. While several herbicidal
preparations were used in this operation, Agent Orange, a mixture of equal parts of 2,4-D and 2,4,5-T
was, by far, the one use most frequently.
Commercial phenoxy herbicide preparations manufactured from the 1940s until the early
1970s contained small quantities of contam inating impurities known as chlorinated
dibenzo-p-dioxins. The terms “dioxins” or “dioxin” have frequently been used as shorthand
for this family of chemical compounds. The exact dioxin compounds and the amounts of them
that were present in phenoxy herbicide preparations varied from preparation to preparation and
perhaps even from batch to batch. Commercial preparations of 2,4,5-T contained small
am ounts of one of these dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); this
contam inant was present in Agent Orange in Vietnam. The effects of TCDD have been
extensively studied in experimental animals, and it is believed to be the most toxic member of the
dioxin family of compounds. While 2,4-D contained small quantities of dioxins, TCDD was
not one of them. W hen it was recognized that phenoxy herbicides were contam inated with
dioxins, manufacturing processes were changed to reduce or eliminate dioxin contamination.
Some other herbicidal preparations that were used in Vietnam contained cacodylic acid and/or
picloram. These preparations were used in much small quantities, however, and they were not
contam inated with dioxins.
2. Description of the literature published in 1989
Just under 400 scientific papers about the health effects of phenoxy herbicides, dioxins, and
other herbicides used in Vietnam were published during 1989. This is an increase over the

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number of papers published in each of the three preceding years. While some of this increase can
be attributed to m ore research activity, most of it can be attributed to the fact that the
proceedings of tw o International Symposia on Chlorinated Dioxins and Related Compounds
that were held in 1987 and 1988 were published in 1989. M uch of the information contained in
the symposia presentations was contained in articles published in other journals. Thus, the
increased num ber of citations in the bibliography is not indicative of a proportionate increase in
unique scientific inform ation.

As judged by the num ber of publications addressing these issues, several topics are attracting
undiminished and even increased scientific attention. These include epidemiologic studies of
long-term health effects (especially cancer) from exposure to phenoxy herbicides and/or dioxins
in various groups of people including Vietnam veterans, agricultural and forestry workers, and
chemical m anufacturing workers. O ther areas of interest are the mechanism by which TCDD
and related dioxins cause adverse effects such as cancer and birth defects in animals and the
interrelationships between concentrations of dioxins in blood and fat, exposure to phenoxy
herbicides and/or dioxins, and resulting health effects.

3. Studies of the general health of Vietnam veterans

Tw o studies that examined a num ber of possible adverse health effects among Vietnam
veterans were published in 1989. One of these was an update of an ongoing study of causes of
death among men w ho were involved in Operation Ranch H and (the herbicide application
program) in Vietnam. The Air Force has identified a group of 1,247 men who were assigned to
some aspect of this operation. By the end of 1987, 74 of these men had died. The relative
frequency of death by specific cause within this group was compared to the relative frequencies
of causes of deaths for 1,039 men who had died in a com parison group of 19,101 men who had
similar assignments in the Air Force in Vietnam but were not involved in the application of
herbicides. At that time the death rate in the Ranch H and group was not different from that in
the com parison group, but there has been a trend tow ard a higher death rate in this group in
recent years. Closer exam ination indicates that this trend is seen mostly among flying officers
and may reflect an unusually low death rate for this subgroup prior to 1986. The only specific
cause of death that was more frequent in Ranch H and personnel than in the comparison group
was digestive disease. O f the six deaths attributed to digestive diseases among Ranch Hand
personnel, five were diagnosed as alcoholic liver disease. Therefore, it is unlikely that the
increased num ber of deaths from digestive diseases seen in the Ranch Hand group was caused by
exposure to herbicides.

In a study conducted by the Armed Forces Institute of Pathology (AFIP), pathology specimens
taken from Vietnam veterans at Veterans Adm inistration hospitals throughout the United States
were collected and examined by pathologists who were unaw are of either the original diagnosis
or the military service history of the persons from whom the specimens were taken. A total of

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1,828 cases were diagnosed in this study. O f these, 1,053 were veterans who had served in
Vietnam, and the remainder were veterans of the same era w ho had not served in Vietnam. The
frequencies of diagnoses were com pared between these tw o groups. Two skin conditions,
epidermal inclusion cysts and dermatitides, were diagnosed more frequently in Vietnam
veterans than in non-V ietnam veterans. Both of these conditions are relatively common, are not
life-threatening, and cannot be considered to be serious health problems. Two benign tum ors,
derm atofibrom a and seborrheic kertosis, were more com m on in Vietnam veterans, but these
also are fairly common and not serious. There was no excess of cancer among Vietnam veterans,
although there were slightly more basal cell carcinomas and lymphomas in this group. These
increases were not statistically significant. There were no other differences between Vietnam
veterans and non-V ietnam veterans in the frequencies of specific diagnoses.

Together, these studies did not indicate any im portant differences in the long-term health
status of Vietnam veterans. The Ranch H and study is designed to identify long-term effects
attributable to herbicide exposure, but because of the small num ber of deaths in the study group
through 1987, only dram atic differences between Ranch H and personnel and the com parison
group in terms of causes of death would be evident. The AFIP study was designed to relate
diagnoses to military service in Vietnam; no attem pt was made to investigate possible
connections to herbicide exposure. W hether or not the m inor differences between Vietnam and
non-V ietnam veterans seen in this study are attributable to herbicide exposure is a m atter for
speculation.

4. Cancer

Two studies of cancer among individuals who served in Vietnam were published during
1989. One of these, the Ranch H and study, was described in Section 3 above. Twelve men in the
Ranch H and cohort had died of cancer as of the end of 1987. This is slightly fewer than expected
based on the incidence of cancer deaths in the com parison group. None of the twelve cancers
was a lymphoma or a soft tissue sarcoma. While this study suggests that there is no connection
between Agent Orange exposure and death from cancer, small differences in cancer m ortality in
the two groups may become apparent as more deaths occur in both groups.

Another study of cancer in Vietnam veterans was published in early 1990; because of its
importance, it was included in this volume of the review. This study, known as the Selected
Cancers Study, was conducted as part of the Vietnam Veterans Health Studies by the U.S.
Centers for Disease Control (USCDC). It was designed to see if there was any connection
between military service in Vietnam and the later diagnosis of any of six forms of cancer that
other studies had suggested might be associated with exposure to phenoxy herbicides and/or
dioxins. The six forms of cancer were non-H odgkin’s lymphoma (a cancer of the lymphatic
system), H odgkin’s disease (another type of cancer of the lymphatic system), sarcomas
(including soft tissue sarcomas), nasal cancer (cancer of the nose), nasopharyngeal cancer

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(cancer in the nose and throat), and liver cancer. This study was not designed to see if there was a
connection between these forms of cancer and exposure to Agent Orange. The USCDC had
concluded two years earlier that there was no reliable way to determine Agent Orange exposure
am ong Vietnam veterans.

This study was a case-control study, meaning that men who were between the ages of 15 and
39 in 1968 and were diagnosed between 1985 and 1989 as having these types of cancer were
com pared to men of the same age who did not have any of these types of cancer but were as
similar as possible in other respects. If the men with the cancer were more likely to have served in
Vietnam than the men w ithout cancer, there is an apparent association between that form of
cancer and military service in Vietnam. As case-control studies go, this study was quite large.
There were 1,157 cases of non-H odgkin’s lymphoma, 310 cases of H odgkin’s disease, 342 cases
of sarcom a, 62 cases of nasal cancer, 89 cases of nasopharyngeal cancer, and 130 cases of liver
cancer. These were com pared to 1,776 controls.

For five of the cancers studied, men with the cancers were no more likely to have served in
Vietnam than men without. However, men with non-H odgkin’s lymphoma were more likely to
have served in Vietnam than the controls. USCDC found no evidence, however, that the
increased risk of non-H odgkin’s lymphoma was related to exposure to Agent Orange. The risk
of non-H odgkin’s lymphomas was highest among Navy veterans who served on ships off the
coast of Vietnam and slightly lower in troops w ho were stationed in the III Corps region where
Agent Orange was m ost heavily used than in troops stationed in other areas of Vietnam. Only
one of the 99 Vietnam veterans who had non-H odgkin’s lymphoma reported that he had
handled herbicides in Vietnam, and none of the 99 was involved in the application of herbicides.
In fact, USCDC was unable to identify any specific aspect of the Vietnam experience that might
explain the increased risk of non-H odgkin’s lymphoma that was seen in this study. It is
interesting to note that a study of cancer m ortality am ong Vietnam veterans that was published
by the Veterans Adm inistration in 1987 found an increased m ortality due to non-H odgkin’s
lymphoma among Vietnam M arine veterans com pared to M arine veterans who did not serve in
Vietnam. This difference was not seen in Army veterans. Thus, two independent studies suggest
that there is a small but significant relationship between some aspect of military service in or
near Vietnam and non-H odgkin’s lymphoma. It is highly unlikely that the aspect of the
Vietnam experience is exposure to herbicides (Agent Orange). It is also possible that the difference
in cancer risk is attributable to some undiscovered difference, not related to military service, between
men who served in Vietnam and those who did not.

There have been a num ber of studies over the past ten years looking at possible associations
between cancer and exposure to phenoxy herbicides during there use in agriculture and forestry.
Some studies conducted in Scandinavia and the midwestern United States have suggested that
there is an association between exposure to phenoxy herbicides and non-H odgkin’s lymphoma.
The midwestern studies, one of which was published in 1989, suggest that the association is with
2,4-D , a phenoxy herbicide th at is not contam inated with TCDD. The Scandinavian studies

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have also shown an association between phenoxy herbicide exposure and soft tissue sarcoma.
No other studies including those in the midwestern United States have replicated the soft tissue
sarcoma findings of the Scandinavian studies. Moreover, studies of the relationship between
non-H odgkin’s lymphoma and herbicide exposure in New Zealand and western Washington
State have failed to find an association. The authors of these latter two studies both published
articles during 1989 in which they reported the results of reanalysis of their data and still found
no evidence of an association.

Three new studies of cancer in relation for occupations in which there is potential exposure to
phenoxy herbicides were published in 1989. In a study of licensed and pesticide applicators in
three agricultural provinces of northern Italy,the authors found excess risks of lymphatic cancers
and of cancers of the skin. A case-control study of non-Hodgkin’s lymphoma among white males in
Hancock County, Ohio, showed an increased risk of this form of cancer associated with the occupation
of fanning, but because of the small number of cases in this study the finding was not statistically
significant. Finally a study of highway maintenance workers in Minnesota found a trend toward an
increased risk of cancers of the lymphatic system with duration of employment; this increased risk was
statistically significant among men with 30-39 years of employment. There was no analysis of
non-Hodgkin’s lymphoma separate from other lymphatic cancers in this study. In only one of these
three studies, the one in northern Italy, was there an attempt to ascertain herbicide exposure. The
criterion for exposure in that study was the possession of a license to apply pesticides. Individuals with
a pesticide applicator’s license certainly differed from those without a license in more ways than
exposure to herbicides. In the Ohio and Minnesota studies, there were no direct or indirect measures of
herbicide exposure. These studies are of interest in that they continue to add to a large and growing body
of evidence that there is an association between some aspect of agriculture and lymphatic cancers, and
specifically non-Hodgkin’s lymphoma. At the present time, attempts to identify the reason for this
association have not been successful.

Previously published reports describing studies of causes of death among workers who were
exposed to dioxins during the m anufacture of phenoxy herbicides and related compounds at the
Dow Chemical Company plant in M idland, Michigan have indicated no association between
exposure to dioxin and cancer. The results of an additional tw o years of follow -up of this group
of workers were published during 1989. The total cohort of dioxin-exposed workers comprises
2,192 people. As of the end of 1984, there were 406 deaths in this group compared to 445
expected on the basis of m ortality statistics for the U.S. population as a whole. There were 95
cancer deaths com pared to 92 expected. The authors concluded that there was no clear evidence
of a causal association between any cause of m ortality and potential occupational exposure to
dioxins. However, there were 8 deaths caused by stom ach cancer in this cohort compared to 4.2
expected. Furthermore, there was a statistically significant trend tow ard an increased risk of
stomach cancer with increased intensity and duration of exposure to dioxins. Taken by itself,
this finding may not be noteworthy. However, two other studies have shown an increased risk
of stomach cancer in workers who were exposed to dioxins and/or phenoxy herbicides, two
studies (one of which was conducted in this same Dow cohort), have shown an increased risk of
non-cancer stomach disease in workers exposed to dioxins, and animal studies have indicated

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that ingestion of dioxins causes significant effects in the stomach. Taken together these results
suggest that cancer and other diseases of the stomach should be studied in populations that have
been exposed to dioxins. The results of a large mortality study among all workers in the United States
who have been exposed to dioxins has not yet been published.

Scientists in Italy published the results of a study of causes of death among nearly 200,000
residents of 11 villages in the vicinity of a chemical plant, where a reactor accident in 1976
resulted in the release of a cloud that contained high concentrations of dioxins, among other
chemicals. Causes of death were analyzed in relation to place of residence at the time of the
accident, with the entire study area being divided into four zones based on levels of dioxin
contam ination measured one m onth after the accident. While some increased risk of death from
cardiovascular disease, cancers of the lymphatic system, and cancers of the gallbladder and bile
ducts appeared to be associated with residence in the more contam inated areas of these towns, it
is unlikely that these findings were indicative of a cause-and-effect relationship because of the
short time (10 years) th at has elapsed since the accident, inconsistencies in the timing of excess
deaths by cause, and uncertainties regarding the reliability of exposure estimates based solely on
place of residence. This study serves mainly to provide justification for further study of residents
of this area.

5. Genetic effects

The weight of the scientific evidence gathered over a period of years from experiments in
animals and in cultured cells indicates that neither the phenoxy herbicides nor their dioxin
impurities cause gene m utations. There is no evidence that these compounds cause gene
alterations that can be inherited by subsequent generations and become manifest as an
abnorm ality or disease in the offspring. No articles were published during 1989 that would
change this point of view. O n the other hand, there is some evidence from experiments with
animals that TCDD and perhaps some related dioxins may cause damage other than mutations
to chromosomes or the DNA in them. N o studies of the effects of dioxins on human
chromosomes or DNA were published in 1989. Several studies indicating the TCDD may
increase a form of chrom osom al damage known as sister chrom atid exchanges in experimental
animals were published. At the present time, the significance of these findings for human health
is not clear.

6. Reproductive effects

Over the years there have been isolated reports that exposure to phenoxy herbicides and/or
their dioxin contam inants may interfere with reproduction or lead to birth defects. However,
the overwhelming majority of studies designed to detect such effects have shown no association
between phenoxy herbicide or dioxin exposure and adverse reproductive effects. Studies in

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experimental animals, on the other hand, indicate that TCDD and some closely related compounds have
the potential to interfere with reproduction at relatively high exposures, and at lower doses, cause birth
defects in the offspring of exposed females. There is no evidence that exposure of male animals to
dioxins causes defects in the offspring of unexposed females to which they are mated.

One group of studies that have suggested adverse reproductive effects in hum ans who may
have been exposed to phenoxy herbicides are those conducted by scientists in Vietnam among
civilian and military personnel who may have been exposed to Agent Orange during the U.S.
military action in that country. Several of these studies were published in 1989. The authors
reported a num ber of adverse reproductive effects including spontaneous abortions, stillbirths,
and m ajor birth defects in groups of people w ho were exposed to Agent Orange. It is difficult, if
not impossible, to assess the validity of these studies. Because of the long-term political and
military upheaval in that country, the keeping of health statistics and medical records has been
haphazard. The type of baseline inform ation on reproductive outcomes that is so im portant for
conducting meaningful epidemiologic studies is not available. Data on the background
incidence of adverse reproductive outcomes in the Vietnamese population in general are
inconsistent. Furtherm ore, all of the published reports lack inform ation on the specific methods
used to select the study population and ascertain exposure and reproductive outcomes. The
potential for bias and uncontrolled factors to influence the results of these studies is quite high.

The results of a case-control study of spontaneous abortions in relation to military service by
the father in Vietnam were published in 1989. Spontaneous abortions in the first 27 weeks of
gestation may reflect m utations that are induced in the germ cells of the male parent prior to
conception. In this study, the military service history of the husbands of 201 women in the
Boston area who had spontaneous abortions was com pared to that of the husbands of 1,119
women w ho had norm al pregnancies and deliveries during the same time period. H usbands of
the women who had spontaneous abortions were slightly less likely to have served in Vietnam
than men who fathered norm al pregnancies, suggesting that there was no association between
military service of the father in Vietnam and spontaneous abortion. No attem pt was made in
this study to ascertain herbicide exposure of the fathers.

A study of reproductive outcomes among people who may have been exposed to dioxins and
related compounds as a result of an electrical transform er fire in Binghamton, New York, found
no increased risk for spontaneous abortion, stillbirth, or birth defects. The num ber of people
included in this study was small, and for many of them there was little evidence that they were
actually exposed.

The experimental anim al studies that were published during 1989 were primarily studies of
the mechanism(s) by which dioxins cause birth defects in mice. Some of these studies indicated
that TCDD alters the estrogen receptor in several tissues and that it may interfere with
reproduction as a indirect result of interfering with the normal mechanisms by which sex

horm ones regulate the function of the reproductive organs. A series of studies suggested that a
commercial mixture of the herbicides 2,4-D and picloram caused birth defects in mice either
when the fathers were treated prior to m ating or when the mothers were treated during
pregnancy. The doses of herbicide used in this experim ent were high and caused toxic effects in
the parents. It is possible that the defects were an indirect result of the toxic effects on the
parents. Overall the new inform ation on reproductive effects of phenoxy herbicides and/or
dioxins did not significantly change the conclusions based on the overall body of evidence prior
to 1989.

7. O ther effects

Studies in experimental animals have indicated that TCDD and closely related compounds
change the way that the immune system responds to foreign materials in the body. In mice, very
low doses of TCDD suppress the defense mechanism against a variety of foreign materials
including allergens, disease-causing organisms, and cancer cells. There is no evidence that
phenoxy herbicides affect the immune system. Very few epidemiologic studies of humans who were
potentially exposed to phenoxy herbicides and/or dioxins have included a careful evaluation of the
status or function of the immune mechanism. Over the past several years, however, evaluation of
immune status has been included in several such studies. Studies of Ranch Hand personnel have failed
to indicate any differences in immune status between Ranch Hand personnel and the comparison group.

In 1986 a series of publications described studies of a group of people who resided in areas of
Missouri that were contam inated with relatively high levels of dioxins when chemical wastes
from a phenoxy herbicide m anufacturing plant were mixed with oil and used to control dust on
unpaved roads. The initial studies of this group of people found that they were less likely to
exhibit an allergic response when exposed to a group of materials that often provoke such a
response. These people also had subtle differences in the relative numbers of specific types of
white blood cells that are thought to be indicators of immune status. Subsequent studies have
indicated that the methods used to evaluate the response to allergens in the first study were
flawed, and a repeat of the study failed to show a difference between exposed-and unexposed
people. Since that time, blood samples collected from most of the people in the original study
group were analyzed for their dioxin content. A new health study was conducted in which
health status was evaluated in terms of dioxin concentration in the blood. The results of this
study were published in 1989. This study did not show any indication of an impaired allergic
response to the test substances. It did, however, continue to show the subtle differences in white cell
types seen in the earlier study. These differences were correlated with dioxin concentration in the
blood. These subtle differences were not accompanied by any signs or symptoms of altered immune
function. Unfortunately, immunologists do not yet know whether these subtle differences reflect any
actual differences in the function of the immune system.

In another study among dioxin-exposed residents of a mobile home park in Missouri,
scientists found that concentrations of a horm one associated with the thymus were different in

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the blood of residents than in the blood of an unexposed control group. The thymus is the organ
where the specialized white blood cells that play a role in many immune functions are formed.
The scientists found no evidence of altered immune function in this study. Together these
studies and the animal studies that were reported during 1989 did little to resolve the question of
whether dioxins have the potential to alter immune function in humans. The ways in which the
hum an immune system functions are extremely complex and poorly understood at the present
time. It may be some time in the future before the hum an health significance of subtle alterations
in cell populations and altered immune function in experimental animals is demonstrated.

A study designed to assess the relative psychological status of Vietnam veterans who reported
that they were exposed to herbicides in Vietnam found significant differences in several
measures of psychological well-being when compared to Vietnam veterans who reported that
they were not exposed. The poorer psychological status of veterans who reported being exposed
could not be accounted for by differences in upbringing, educational level, or demographics.
The authors of this study made no attem pt to determine actual herbicide exposure in Vietnam by
objective methods.

Studies were published during 1989 that indicated that when female monkeys were fed diets
containing quite low concentrations of TCDD, their offspring exhibited subtle differences in the
ability to learn. These learning differences correlated more closely with the am ount of TCDD in
body tissues than with the am ount of TCDD in the m other’s diet. The significance of these
studies is that very small am ounts of dioxins can produce subtle effects on learning behavior that
would be difficult to detect and that some, if not all, of the health effects of dioxins may be
determined by the am ount of dioxin in the body rather than the daily intake. While these two
indicators of exposure are related, they may differ from individual to individual based on how
the body absorbs and eliminates the dioxins to which it is exposed.

8. Dioxins in human tissues

One area of scientific inquiry that accounted for some of the increase in literature that was
published in 1989 was the m easurement of TCDD and related dioxins in hum an tissues. This
area of investigation has become increasingly active since the methodology to measure very small
concentrations of dioxins in human blood and fat was developed four or five years ago. If levels of
dioxins in human tissues can be correlated with past exposure to dioxins or dioxin-containing
chemicals, on the one hand, and with adverse health effects, on the other, the measurement of these
levels becomes an extremely important tool for the conduct of epidemiologic studies were published
during 1989. Dioxins were determined in blood and fat samples of Vietnam veterans, individuals who
were exposed to dioxins during the manufacture of chemicals containing dioxins, civilian populations
exposed to dioxins as a result of environmental contamination, and the general population.

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Taken together, the results of these studies indicate that, in general, humans have detectable
concentrations of dioxins in their blood and fat. The source of these compounds is not entirely
clear, but dioxins in the diet, especially in animal fat, may represent the major source. Studies of
people with abnormally high dioxin exposures in the past indicate that elevated concentrations
of dioxin in either the blood or the fat is a reliable indicator of past exposure. Once in the body,
dioxin is eliminated very slowly. In the absence of additional exposure it is estimated that it
takes approximately seven years for the body to eliminate half of the dioxin that it has stored.
Thus, among people who were relatively heavily exposed, it is possible to detect elevated dioxin
levels in blood or fat 15-30 years after the exposure. Studies published within the last year or two
have identified several groups of people with significantly elevated concentrations of dioxin in their
tissues. These include workers who were exposed to dioxins during the manufacture of phenoxy
herbicides and related compounds, people who were exposed to dioxins as a result of the accident in
Seveso, Italy, in 1976, some of the people who live in a dioxin-contaminated area of Missouri, people
who consumed cooking oil that was contaminated with dioxins and related compounds in two separate
incidents in Japan and Taiwan, and a few Vietnam veterans who were relatively heavily exposed to
herbicides in Vietnam. Studies of dioxin levels of Vietnamese who may have been exposed to Agent
Orange during the war give inconsistent results but are generally supportive of elevated tissue levels
among people who may have been heavily exposed. In general, Vietnam veterans do not have higher
concentrations of dioxins in their tissues than non-Vietnam veterans. This suggests that exposures of
most U.S. military personnel in Vietnam were not great and that adequate time has passed for elevated
body burdens to decrease to background levels.

Several health effect studies published in the last year attem pted to correlate observed effects
with tissue body burdens of dioxins. Among these were a study of health effects among people in
Missouri and a study of the health effects in monkeys born to mothers who had been treated
with dioxins. It is anticipated th at more studies will be designed to relate health status to dioxin
body burden in the future. Also, measurements of dioxins in tissue may be used to identify
populations for epidemiologic study. This should help to overcome the problems with many
epidemiologic studies in the past where people with little or no exposure were included in the
“exposed” group.

9. Summary and conclusions
The num ber of articles about potential health effects of phenoxy herbicides and /or dioxins
published in the scientific literature during 1989 was greater than in each of the preceding
several years. M uch of this increase was attributable to the publication of the proceedings of
two symposia, and there was a fair am ount of duplication and overlap. Increases were seen,
however, in the num ber of articles published about concentrations of dioxin in human tissue and
about the mechanism(s) by which dioxin and related compounds affect the body.

By and large the results of research published during 1989 were consistent with the general
body of inform ation that had been developed prior to 1989. In other words, no new health

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effects were identified, and no breakthroughs were made in resolving apparent inconsistencies
among several human health effects studies or in understanding why effects of dioxin seen in
experimental animals have not been observed in humans who have been exposed to dioxins.

One of the more notew orthy findings in this year was the association between military service
in Vietnam and an elevated risk of non-H odgkin’s lymphoma. This is the second independent
study that has suggested the possible existence of such an association. While these studies
suggest an association, they provide no evidence that the increased risk is related to exposure to
herbicides and, in fact, the study conducted by the USCDC suggests that it probably is not. Five
other types of cancer did not appear to be associated with military service in Vietnam. Several
studies of non-H odgkin’s lymphoma published in 1989 and earlier suggest that this type of
cancer is associated with some aspect of agricultural employment. W hether or not this aspect
includes exposure to herbicides is unresolved at present and needs to be the focus of continued
investigation in the future.

Another result that might prove to be of importance was the observation of a trend toward an
increased risk of stomach cancer within a cohort of workers who were exposed to dioxins while
employed at the Dow Chemical Company in M idland, Michigan. While this observation may
not be of great significance by itself, it becomes significant when coupled with the results of other
epidemiologic and experimental evidence that suggests that the stomach may be an important
target for the effects of dioxins in primates.

Several studies of reproductive outcomes among Vietnamese civilians and military veterans
reported an association between exposure to Agent Orange and spontaneous abortions,
stillbirths, and birth defects. The validity of these conclusions is questionable because of
methodological weakness. A study in the United States of a possible association between
spontaneous abortion and military service of the father in Vietnam indicated that there was no
such association. Several studies of humans exposed to environmental dioxin contamination in
Missouri suggested an association between dioxin exposure and subtle changes in the
proportions of some blood cells th at have a role in the immune system, but there was no evidence
of impaired immune function or clinical disease in these individuals.

Research has indicated th at concentrations of dioxins in the blood or fat are reliable
indicators of relatively heavy past exposure to dioxins or to phenoxy herbicides contaminated
with dioxins. The correlation may prove extremely useful for identifying populations for
epidemiologic studies and for relating health risks to body burdens. This finding is not useful for
identifying health effects among U.S. military veterans who may have been exposed to Agent
Orange in Vietnam, however, because only a few heavily exposed individuals have
concentrations of dioxins in their fat or blood that are significantly different from the general
U.S. population.

11

529

ig

f

w

Department of
Veterans Affairs

m

Review of Literature on
i Herbicides, Including
/ Phenoxy Herbicides and
^Associated Dioxins
i
-

Volume XIX
Analysis of Recent Literature on
Health Effects
Mand ^Volume XX
^Annotated Bibliography of Recent
Literature on Health Effects

V eterans Health S ervices
and R esearch A dm inistration

•

»

Jfc D epartm ent of

▼ « » V e t e r a n s Affairs

Review of Literature on
Herbicides, Including
Phenoxy Herbicides and
Associated Dioxins
Volume XIX
Analysis of Recent Literature on
Health Effects
and
Volume XX
Annotated Bibliography of Recent
Literature on Health Effects

Veterans Health Administration

V A Contract Number: V101(93)P-1333

REVIEW OF LIT ER A T U R E ON H ER B ICID ES,
INCLUDING PHENOXY H ER B ICID ES
AND A SSO CIA TED DIOXINS
Volume XIX: Analysis of
Recent Literature on Health Effects
Published in 1991

Prepared for:
Lawrence B. Hobson, M.D., Ph.D.
Director and
Contracting Officer’s Technical Representative
Environmental Agents Service
Veterans Health Administration
Department of Veterans Affairs
810 Vermont Avenue, N.W.
Washington, D.C. 20420

Submitted by:
Information Ventures, Incorporated
1500 Locust Street, Suite 3216
Philadelphia, Pennsylvania 19102

June 1992

532
D-56I

TABLE O F C O N T E N T S

Foreword

Page

I.

Introduction

1

II.

Summary and Conclusions

3

General Health Studies of Vietnam Veterans
Cancer
Genetic Effects
Reproductive and Teratological Effects
Immunological Sequelae
Neurobehavioral Effects and Appetite Suppression
Other Toxic Effects
Tissue Residues and Pharmacokinetics
Basic Studies

3
4
8
8
9
10
11
11
12

Health Effects of Phenoxy Herbicides and Contaminants

13

A.
B.
C.
D.
E.
F.
G.

13
20
38
41
47
59
67

A.
B.
C.
D.
E.
F.
G.
H.
I.

General Health Studies of Vietnam Veterans
Cancer
Genetic Effects
Reproductive and Teratological Effects
Immunological Sequelae
Neurobehavioral Effects and Appetite Suppression
Other Toxic Effects

Health Effects of Other Herbicidal Active Ingredients
A.
B.

Picloram
Cacodylic Acid

Tissue Residues and Pharmacokinetics of Chlorinated
Dibenzo-p-dioxins and Related Compounds
A.
B.
C.
D.

Studies of Vietnam Veterans
Studies of Other Exposed Populations
Studies of Dioxins in Milk
Pharmacokinetic Studies in Animals

74
74
75

77
77
81
85
88

J)- b

VI.

Basic Studies Relevant to Health Effects

94

A.
B.
C.
D.
E.

94
96
101
104

F.
G.

Introduction
The Ah Receptor
Mechanism of Ah Receptor Interaction with T C D D
Induction of Cytochrome P450
Interaction of T C D D with Other Receptors and
Effects on Expression of Other Genes
General Metabolic Effects of Dioxins
Summary and Conclusions

107
110
116

534

FO REW O RD

Public Law 96-151, enacted December 20, 1979, mandated the Veterans Administration
to conduct "a comprehensive review and scientific analysis" of the worldwide literature on
Agent Orange and other phenoxy herbicides. This mandate was in response to an
increasing awareness among veterans, the Congress, and the public of the potential long­
term health consequences of exposure to these herbicides and their dioxin contaminant.
In October 1981, the Veterans Administration published a two-volume "Review of
Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins."

Because of continued active research, a two-volume update covering the literature
through December 1983 was published in 1984. The Review has been updated each
year since that time. The present two-volume update covers literature that became
available during 1991.

This report was prepared by Information Ventures, Incorporated. It is an independent
assessment of the current state of knowledge about the health effects of phenoxy
herbicides, their contaminating polychlorinated dibenzo-p-dioxin impurities, and two other
herbicides (picloram and cacodylic acid) that were used in Vietnam. The publication of
this document by the Department of Veterans Affairs (VA) does not signify that the
contents necessarily reflect the views and policies of the VA.

The project director for Information Ventures and principal author of this update to the
Review was William A. Creasey, D.Phil. Phyllis Guinivan, Ph.D. was co-author. Consulting

advice was provided by Michael A. Gallo, Ph.D., William F. Greenlee, Ph.D., David E.
Lilienfeld, M.D., M.P.H., M.A.C.E., and Alan P. Poland, M.D.

535

P 5?

b

I. INTRODUCTION

This report consists of a bibliography and critical review of the scientific literature
that became available during 1991 on the health effects of the herbicides (including
contaminants) that were used as defoliants during the Vietnam conflict. It comprises
Volumes XIX and XX of an ongoing series of publications entitled "Review of Literature on
Herbicides, Including Phenoxy Herbicides an d Associated Dioxins." Volumes Iand IIof

this series were prepared by JRB Associates and published by the Veterans
Administration in October 1981. Volumes III and IV, covering literature published from
1981 through 1983, were prepared by Clement Associates, Inc., and published by the
Veterans Administration in June 1984.

Subsequent volumes also were prepared by

Clement Associates and published by the Veterans Administration: Volumes V and VI,
covering literature that became available in 1984, were published in 1985; Volumes VII
and VIII, covering literature that became available in 1985, were published in 1986;
Volumes IX and X covering literature that became available in 1986, were published in
1987; Volumes XI and XII, covering literature that became available in 1987, were
published in 1988; Volumes XIII and XIV, covering the literature that became available in
1988, were published in 1989; Volumes XV and XVI, covering the literature that became
available in 1989, were published in 1990; and Volumes XVII and XVIII, covering the
literature that became available in 1990, were published in 1991.

In this update,

Information Ventures, Inc., has identified and reviewed the scientific literaturethat became
available during 1991 relevant to the potential adverse health effects of exposure to these
herbicides and their contaminating impurities.
An attempt has been made to identify all scientific literature (including unpublished
material) relevant to the potential adverse health effects of the herbicidal preparation
commonly referred to as Agent Orange, its active ingredients, 2,4-dichlorophenoxyacetic
acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and their esters, as well as
the polychlorinated dibenzo-p-dioxins (primarily 2,3,7,8-tetrachlorodibenzo-p-dioxin or
TCDD) known to be present as contaminating impurities in some herbicidal preparations,
and the herbicides, picloram and cacodylic acid. The scope of this review extends
1

537
d

-5U>

beyond health effects in humans to encompass studies of the biological effects of these
compounds in animals or in vitro systems, their basic mechanisms of action, and their
pharmacokinetic disposition. However, literature dealing exclusively with their chemistry,
analysis, or environmental issues is not included.
In order to identify relevant literature, Information Ventures utilized searches of on­
line databases, screening of primary journals and various ancillary sources. Searches of
on-line databases covered the MEDLINE database of the M E D L A R S on-line information
systems of the National Library of Medicine, BIOSIS, CA, EMBASE, Japan Technology,
and the Life Sciences, NTIS, PASCAL, and SCISEARCH files of DIALOG.
Since there is a significant time delay between publication of scientific reports and
their entry into on-line databases, it was necessary to screen the primary scientific
literature for optimal coverage of research that became available during 1991. Personnel
from Information Ventures routinely screened over 600 scientific journals, both in our
library and at the libraries of five local Medical Schools, and retrieved articles within the
scope of this Review.

In addition, the biweekly issues of C A Selects: Carcinogens,

Mutagens, an d Teratogens, and C A Selects: Herbicides, published by Chemical Abstracts

Service, Columbus, Ohio, were screened in order to identify articles in journals not
covered by the primary screen. Finally, information was obtained regarding unpublished
reports, or material not in the open literature, from scientific meetings and from interaction
with Information Ventures’consultants and other scientists actively engaged in research
on the health effects of herbicides and dioxins.

2

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V-5k7

II. SUM M ARY AND CO N CLU SIO N S

The annotated bibliography that accompanies this review contains 340 citations to
literature relevant to the human health effects of the herbicides used in Vietnam. This
represents an increase from the previous year, undoubtedly due in large measure to the
growing effort to elucidate the mechanism of action of chlorinated dibenzo-p-dioxins such
as T C D D and related compounds. In addition, a significant number of review articles,
abstracts and editorials are included to reflect the widespread interest in and controversy
surrounding these substances.

A.

General Health Studies of Vietnam Veterans
Two studies of the general health status of Vietnam veterans, or of veterans who

had served in the vicinity, were published in 1991. The first of these was a second report
on the 1987 follow-up of U.S. Air Force personnel who were involved in the herbicide
application program in Vietnam (Operation Ranch Hand). A notable feature of the 1987
follow-up had been the inclusion of accurate measurements of serum dioxin, made
possible by recent technological advances. These were integrated into the 1991 report,
in which clinical findings in the Ranch Hand cohort and the comparison group were
correlated with current and estimated initial T C D D serum levels, using three models with
differing pharmacokinetic assumptions. Itwas evident that the Ranch Hand cohort was
indeed heterogeneous with respect to the extent of exposure to Agent Orange, in terms
of both the military ranks and the individuals composing it. When dioxin levels were used
as a basis for comparison, it was found that among Ranch Handers, both higher
percentage body fat and increased erythrocyte sedimentation rates were positively
correlated with higher current or initial T C D D levels. Since there was also a relationship
between deduced initial dioxin levels on the one hand, and elevated IgA, leukocyte and
platelet counts on the other, it appears that there is a long-term subtle inflammatory
response among these subjects. This is in agreement with reports of earlier follow-ups.
Cardiovascular, renal, hepatic, dermatologic, neurologic and psychological findings were
negative or inconclusive with respect to any association with dioxin. There was some
3

539

suggestion that dioxin may accelerate the development of a diabetic or prediabetic state.
The incidence of benign and malignant neoplasms, and serum T C D D levels are discussed
below.
In a study based on monozygotic twins that addressed the question of service in
and around Vietnam, rather than exposure to Agent Orange per se, there were increases
in self-reported hearing problems, skin problems and stomach conditions with the combat
index, a composite measure of involvement in the conflict.
Health studies reported during 1991 have contributed no new findings to those of
earlier reports, which provided no indications of any marked differences in disease
incidence or mortality resulting from service in Vietnam, or from exposure to the
herbicides used there, although there was some increase in deaths from external causes.
Indications of a subtle inflammatory response, and an association with a historical
diagnosis of chloracne, have been the only consistent findings for the Ranch Hand cohort
as a whole.

The use of serum and adipose tissue levels of T C D D permits greater

discrimination in analyzing data, but the limited sizes of the study populations limit the
statistical power to detect any differences that might be small but significant.

B.

Cancer
A large number of studies relevant to the potential carcinogenicity of dioxins

appeared in 1991.

They included seven reports that looked at the incidence of

neoplasms in Vietnam veterans, and five occupational health studies of civilian
populations. In addition to these primary publications, there were several in-depth reviews
and a meta-analysis of earlier Swedish data.
In a report on the 1987 Air Force Health Study follow-up, in which correlations with
measured T C D D levels were sought, an elevated incidence of basal cell carcinomas and
sun-related cancers, previously ascribed to the Ranch Hand cohort as a whole, could not
be associated with dioxin exposure as reflected in intragroup variations in serum dioxin
levels. There was, however, a correlation between such levels and the incidence of benign
neoplasms (75% were lipomas), for which the adjusted relative risk ratio for those with
current dioxin levels greater than 33.3 ppt was 2.13.
4

540

Three case-control reports appeared on cancer incidence encountered in the
Centers for Disease Control’s Vietnam Experience Study. This comparison of randomlyselected groups of Army Vietnam and non-Vietnam veterans, also included a group of
controls, identified by random digit dialing in the areas where veterans with cancer lived,
who were frequency-matched by age to the cases.

There was no evidence of any

association between service in Vietnam and the incidence of non-Hodgkin’s lymphoma,
soft tissue tumors and other sarcomas, Hodgkin’s disease, nasopharyngeal carcinoma,
and primary liver cancer. Although serum or tissue dioxin levels were not measured,
there was no evidence of association of these tumors with surrogate measures of
possible exposure to Agent Orange, such as rank, combat role, military branch or military
region of Vietnam in which service occurred. The design of this study had sufficient
power to detect a doubling of risk for all soft tissue tumors and sarcomas as well as for
alltypes of lymphomas. The Department of Veterans Affairs proportionate mortality study
of Army and Marine Vietnam-era veterans (Watanabe et al. 1991) reported excessive
deaths from laryngeal cancer among Army veterans, but in the case of Marine veterans,
elevated proportionate mortality ratios for lung cancer and non-Hodgkin’s lymphoma were
due to deficits among the non-Vietnam comparison group.

In addition to the usual

limitations of proportionate mortality studies, this study provided no information on the
smoking and drinking habits of the study groups, factors of critical importance in
considering the occurrence of laryngeal and lung cancers.
Among other studies of veterans that were published in 1991, one was based on
findings that military working dogs who served and died in Vietnam exhibited elevated
frequencies of testicular dysfunction and tumors. Patients of the age group that would
have included those liable for service in Vietnam, and who had been admitted to
Washington, DC, area hospitals with testicular cancer, were compared with a group of
patients with non-genitourinary cancers. It was found that there was an approximately
two-fold increase in risk for testicular cancer in Vietnam veterans, with the largest increase
in subjects aged below 35 years. A study of 4,600 w o m e n Vietnam veterans indicated
that standardized mortality ratios were elevated in veteran nurses for pancreatic and
uterine cancers compared with U.S. w o m e n in general, but only a small number of deaths
5

541
J7-570

were involved. Finally, a study based on the Massachusetts Cancer Registry, discloser
an elevated odds ratio for mortality from soft tissue sarcomas, but not from non-HodgkinV
lymphomas.

However, since this study provided no demographic data or details c

military service, it is of limited value.
The largest and best executed of the civilian occupational studies was that o
Fingerhut et a/.(1991) who analyzed data obtained from 5,172 male workers at 12 plants
in the U.S. that produced chemicals contaminated with dioxin. The data also includec
measurements of serum T C D D levels in 253 members of the surviving cohort. Mortality
from all forms of cancer was elevated to a slight but statistically significant extent, with the
largest increase (standardized mortality ratio of 145) in the subcohort with > 1 year o'
exposure and > 20 years of latency. Amo n g individual tumor types, small increases in
soft tissue sarcomas and respiratory system cancers were seen in this most highly
exposed subcohort. The study did not exclude possible contributions from smoking or
exposure to other chemicals in the workplace, but did address many other concerns that
can be raised regarding studies carried out at multiple sites. Another multi-site study was
undertaken by the International Agency for Research on Cancer on 18,910 production
workers and herbicide sprayers from ten countries. There was an apparent overall two­
fold increase in the risk for soft tissue sarcomas, which was not, however, statistically
significant. Slight increases in the risk for other cancers involved numbers too small to
serve as the basis for definitive conclusions.
A mortality study of workers employed at a herbicide plant in Germany where the
products had been contaminated with dioxin prior to 1954, showed increases in overall
cancer mortality as compared with German national statistics and a cohort of workers in
the gas industry. The increases were more pronounced in those with 20 or more years
of employment, and wom e n showed an increase in death from breast cancer. The
significance of the study was diminished by the use of mortality data from death
certificates for controls, rather than the more accurate medical records used for the
cases, and by confounding due to a more than 80 % higher prevalence of smoking among
the subjects compared with the general population.6

6

542
V - S 7 I

Two studies carried out in Italy were related to environmental exposures. In an
area of northern Italy in which heavy spraying with phenoxy herbicides had taken place
over several decades, the mortality rates for Hodgkin’s and non-Hodgkin’s lymphomas
were elevated. There was a correlation with living in areas which had higher measured
soil levels of the herbicides 2,4-D and 2,4,5-T. The authors did not attempt to stratify for
length of residence or for occupation, but since rates were higher for men than for
women, some contribution from occupational factors is probable. No conclusions could
be drawn regarding mortality from soft tissue sarcomas. The Seveso incident, in which
an industrial accident released a large amount of dioxin over a several square mile area
in 1976, has been one of the best documented from the point of view of soil and human
tissue levels of TCDD.

Even among the most contaminated group, only small, non­

significant increases in soft tissue sarcomas, leukemia and melanoma have been noted
in males, and of biliary cancer in females.

Among the latter, however, an almost

statistically-significant decline in breast cancer has been registered.
The chief value of animal carcinogenesis studies is their relevance to defining the
risk of dioxins to human populations. There is an extensive data base of results from
animal studies indicating that T C D D and related dioxins are multi-site, complete
carcinogens for a number of species and strains. Official recommendations for limiting
exposure to these compounds rely primarily on linearized extrapolation from data for
induction of liver cancer in rodents, which was originally obtained over the period 1978 1982. Two réévaluations of these older experiments, and of the models used to estimate
human risks, based on updated histopathologic criteria, have appeared during 1991.
They suggested, in general, that the human risk may be between 10 and 100 times less
than that presently accepted by regulatory agencies in the U.S. However, further study
is needed to define this risk more exactly. Another advance achieved through animal
studies, and emphasized in 1991 publications, has been the establishment of assays
based on surrogate markers of carcinogenesis, biochemical and biological changes that
precede overt cancer development, and thus afford a more rapid method for evaluation
of carcinogenic potential, and one requiring fewer animals.

7

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X7-Î73-

In summary, the human data, taken in conjunction with findings made in animals,
is indicative of a moderate carcinogenic risk to humans, associated with the highest levels
of exposure to which humans are likely to be subjected occupationally or environmentally.
There is no clear evidence that Vietnam veterans were in general exposed to these higher
levels.

C.

Genetic Effects
No new studies implicating phenoxy herbicides or dioxins as causative agents in

producing genetic effects in humans became available during 1991.

Experiments

associated with a study of the mutagenic potential of fish contaminated with a variety of
polychlorinated compounds, showed that pure T C D D is non-mutagenic at levels up to the
toxicity limit for Salmonella typhimurium in the Ames test. In a study that used a mouse
lymphoma forward mutation assay, T C D D was inactive up to its solubility limit of 1 pg/m\.
These data further confirm the large body of earlier findings indicating that T C D D is
essentially inactive as a genotoxin. On the other hand, the phenoxy herbicide 2,4-D was
found to be both mutagenic and cytotoxic for V79 hamster cells in culture.

Earlier

literature does report scattered findings of modest genotoxicity associated with this
herbicide.

D.

Reproductive and Teratological Effects
In a study of organ cultures of human and rodent palatal shelves, itwas evident

that T C D D interfered with differentiation, but that humans and rats required concentrations
200 times higher than those effective in mouse tissue.

Both T C D D and 2,4-D were

reported to produce testicular damage and abnormal spermatogenesis in rats and
humans, respectively, but there was no evidence of paternally-mediated developmental
toxicity in rats administered TCDD.

Finally, one report added to the evidence for

teratogenicity in mice by showing that T C D D and tetrabrominated dioxins and furans
produced cleft palate and hydronephrosis. Interestingly, cleft palate was not induced by
T C D D in embryos that had been made exencephalic by exposure to cadmium chloride.

8

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D - S 7 3

E.

Immunological Sequelae
While there is a significant body of literature suggesting that T C D D and related

compounds produce a variety of actions on the immune system in animals, evidence that
this occurs in humans is equivocal. In the recent report on the Air Force Health Study,
for example, the only immunological parameter that could be related to serum dioxin was
an increased IgA level. Abnormal delayed hypersensitivity skin test data seen in the
Ranch Hand cohort as a whole did not correlate with dioxin levels. However, another
study found that when human and non-human primate lymphocytes were cultured in the
presence of T C D D there was a pronounced decrease in the CD 4 subset, a finding seen
also in monkeys who were given this compound. These changes in lymphocyte subsets
did not appear to lead to immunosuppression, but in one study with AIDS patients, those
with the highest body dioxin burdens also were more susceptible to opportunistic
infections, a finding suggestive of some type of immune deficit.
Thymic involution is a well known result of dioxin intoxication whose mechanism
is only now beginning to be clarified. Three studies carried out in rodents established that
thymic involution is an indirect effect, since changes in lymphocyte subsets did not occur
rapidly, nor to the extent that would have been expected ifthis were the primary site of
action.

It appeared that involution resulted from reversible damage to the epithelial

component of the thymus, and that this change in the cellular microenvironment in turn
led to impairment of lymphocyte differentiation. Once the epithelial damage was repaired,
there was an influx of progenitor elements from the bone marrow, leading to full recovery
of thymic architecture and function. An interesting finding made in a study that compared
T C D D high-responder and low-responder mouse strains, was that thymic involution
following acute exposure was mediated by the Ah receptor, whereas with a subchronic
regimen some other mechanism appeared to be involved.
While the results of two studies in rodents suggested that any effects of T C D D on
B cells were secondary to alterations in T cell function, several others showed that this
agent may act directly on B cells. As with thymic involution, studies on TCDD-induced
immunodepression indicated that acute dioxin effects were mediated by the Ah receptor,
while those associated with subchronic exposure to lower doses were not. The nature
9

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P-57<f

of such alternate mechanisms is as yet unknown, but one early biochemical effect of
exposure to T C D D which has been reported was increased tyrosine kinase activity, the
timing and magnitude of which were correlated with inhibition of antibody synthesis.

F.

Neurobehavioral Effects and Appetite Suppression
Earlier human and experimental animal data have shown that heavy exposure to

T C D D can give rise to neuropathies. In the recent report from the Air Force Health Study,
a significant correlation was demonstrated between current and extrapolated initial levels
of serum dioxin and abnormalities in the C N S index, a composite of coordination, tremor
and gait. In the portion of the report devoted to psychological assessment, results of the
tests employed were somewhat at variance, but overall there was no convincing evidence
of a significant psychological deficit ascribable to exposure to Agent Orange and its
associated dioxins in these Vietnam veterans. In a follow-up of children of wom e n in
Taiwan who had consumed cooking oil contaminated with polychlorinated biphenyls and
benzofurans, there was evidence of significant delays using standard criteria for
developmental status.
A highly characteristic result of dioxin intoxication in animals is hypophagia and
wasting, a phenomenon which shows extreme variations in species and strain sensitivity.
Strain differences in one study were shown to reflect recovery from anorexia in the
resistant but not the sensitive rat strain, and some intestinal factor was involved in the
development of hypophagia. Other reports, however, are compatible with central effects
involving alterations in hypothalamic histamine and/or /S-endorphin.
Dogs are relatively more sensitive to 2,4-D than many other mammals, and a threepart study published in 1991 defined the dose-response relationship for development of
electroencephalographic changes and myotonia in this species. Itwas found that dogs
running loose on a plot heavily treated with 2,4-D did not develop any neuromuscular
abnormalities.

10

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G.

Other Toxic Effects
A characteristic symptom of heavy exposure to dioxin in humans isthe appearance

of chloracne. This relationship has been strengthened by the demonstration of a clear
correlation between elevated serum T C D D levels and this dermatological condition, in the
recent follow-up of the subjects involved in the Seveso incident in Italy. Some degree of
hepatotoxicity occurs both in humans and in animals, with itsprinciple manifestation being
altered lipid metabolism. Other toxic effects that were reported on during 1991, included
an anticoagulant effect based on thromboxane-mediated inhibition of platelet aggregation,
and a hypergastrinemia seen in rats in the dioxin-induced hypophagic state.

H.

T issu e R esidues and Pharm acokinetics
This has been an active area of research in the literature reported during 1991.

Perhaps most important has been the extension of serum T C D D measurements in the
Ranch Hand cohort, and the correlation of these levels with military rank and occupational
classifications. There has been some controversy regarding the validity of conclusions
about exposure to Agent Orange based on measurements of serum concentrations made
many years after the fact; alternative pharmacokinetic models for humans have also been
suggested.

However, several recent studies have indicated that such factors as

increasing body fat do not have the major repercussion that might be expected on the
disposition of TCDD, which over most of its time course can best be expressed by single
compartment kinetics. Other data from recent studies of occupational and environmental
exposure to polychlorinated dioxins, benzofurans and biphenyls are indicative of the long­
term retention of these compounds. These data support those obtained in veterans in
indicating that even after many years, the prolonged half-life of these compounds means
that high current serum and adipose tissue levels reflect earlier heavy exposure.
Moderate or low exposures, however, may not be reflected in increased levels.
This year has seen continued activity with regard to the transport of T C D D and
related compounds transplacentally, and more especially through excretion in breast milk,
with its clear implications for the health of infants. This is emphasized by studies in rats,

11

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V - S K &

where the amounts of TCDD secreted in milk or transported across the placenta were
sufficient to induce hydronephrosis in nursing pups.
I.

Basic Studies
The large body of literature on basic studies that became available during 1991 has

served to further document the importance of the role played by the Ah receptor in
mediating the toxic effects of dioxin. This primary interaction serves as the basis for
intervention in many other systems, most notably xenobiotic metabolism, steroidogenesis
and lipid metabolism. However, there is evidence for the existence of other sites of dioxin
intervention that are independent of the Ah receptor, especially in relation to immunologic
effects . Although T C D D induces a vitamin A-deficient state, this does not appear to be
a primary mechanism for dioxin toxicity. Basic studies of dioxin toxicity are playing, and
will continue to play an important role in establishing the sensitivity of humans to this
agent. This is an essential step in defining the hazard presented by dioxin and the most
appropriate recommendations for its regulatory control.

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III.

A.

HEALTH E F F E C T S O F PHENOXY H ER B IC ID ES AND CONTAMINANTS

General Health Studies of Vietnam Veterans
1. The Ranch Hand Study
The United States Air Force has been conducting an ongoing prospective

epidemiologic study of the cohort of Air Force personnel assigned to the herbicide
application program in Vietnam between 1962 and 1971, inclusive. This program was
known as Operation Ranch Hand, and during its execution, 10 to 12 million gallons of
Agent Orange, containing an estimated 368 pounds of the contaminant dioxin TCDD,
were sprayed in various areas of Vietnam (Gough 1991). In this "Ranch Hand" study,
mortality and general health status of members of the study cohort have been compared
to those of Air Force personnel who served in Vietnam during the same period, but
lacked the opportunity for exposure to herbicides because of different duty assignments.
The first mortality results of this cohort were published in 1983 and reviewed in Volume
IIIof this Review in 1984. The mortality portion of the study has been updated twice since
that time, and these updates were covered in Volumes IX and XV of this Review,
published in 1987 and 1990. The most recent of these two updates also was published
as a journal article by Michalek etal. (1990). The cohort of Ranch Hand personnel (called
"Ranch Handers") was characterized by a greater incidence of external causes of death,
such as accidents or homicides, a finding also noted in the recently-updated Army and
Marine Vietnam-era Veterans Study (proportionate mortality ratio of 1.16 for homicides)
from the Department of Veterans Affairs (Watanabe et al. 1991), and a study of women
Vietnam veterans (relative risk for accidents 1.33) compared with non-Vietnam veterans
(Thomas et al. 1991).
The results of the baseline general health status (morbidity) study of this cohort
were published in 1984 and reviewed in Volume V of this Review. The first follow-up of
the general health status portion of the study was published in 1987, and the findings
were discussed in Volume XI of this Review in 1988. There was little difference between
the cohort and the comparison group in terms of overall general health, except for a
consistently elevated incidence of basal cell carcinoma (skin cancer) in the Ranch
13

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o

?

n

Handers. The self-perception of health had been worse In Ranch Handers in the first
follow-up; this cohort also had a more favorable proportion of body fat but a higher
proportion of abnormal erythrocyte sedimentation rates than did the comparisons.
The second follow-up of the general health status portion of this study was
released and published as a journal article (Wolfe etal. 1990) in 1990, and discussed at
length in Volume XVII of this Review. Over the intervening years, there had been 33
deaths from among the original cohort of 1,208 subjects, and another 13 individuals had
been identified and enrolled for a 1987 total of 1,188. Participation in the second follow­
up was 8 4 % (995 individuals) of w h o m 944 had participated in the baseline study. A
concern expressed by the reviewers was that the incomplete participation in the study in
both follow-ups introduced a possible bias, and this, together with the inclusion as Ranch
Handers of individuals who had experienced little or no abnormal herbicide exposure,
detracted from the power of the study to detect differences in health status between the
exposed members of the cohort and controls. The variability in exposure to dioxin among
the members of the Ranch Hand cohort was documented by current serum T C D D
measurements. Clinical findings were very similar to those noted at the first follow-up.
For example, more members of the Ranch Hand group had experienced chloracne, but
at the time of follow-up there were no observable dermatologic lesions compatible with
a history of that condition. As in the first follow-up, there were significantly more Ranch
Hand individuals with abnormal erythrocyte sedimentation rates, but other health
parameters showed no preponderance of abnormalities in the exposed cohort. However,
compared with the earlier follow-up, there was a greater than 5 0% decline in the
proportion of veterans who reported their health status as fair or poor.
A

major feature of this second follow-up was the inclusion of accurate

measurements of serum dioxin levels; the complete data have since been published in
a report (Roegner et al. 1991). The findings on serum levels are discussed in Chapter
V, but here we are concerned with correlations between those levels and observed health
status (except for cancer which is discussed in Section III B). The lipophilic nature of
T C D D and its very limited metabolism combine to give the compound a prolonged
biological half-life, of the order of 7 years. This permits the determination of dioxin in
14

550
D-S7?

serum and adipose tissue many years after exposure to abnormal levels, using the
extremely sensitive assay systems that are now available.

In this way, such

determinations provide an independent marker of significant past exposure to dioxins, and
thus a way of stratifying the Ranch Hand cohort. Accordingly, this report attempted to
associate clinical findings with measured dioxin levels. Three statistical models were used
in evaluating any possible associations:

o

Model 1, estimated initial T C D D levels using Ranch Hand participants only;

o

Model 2, current dioxin levels and time since military service in Vietnam in
Ranch Hand participants only;

o

Model 3, categories of current dioxin levels using both Ranch Hand and
Comparison cohorts.

These models differed in their assumptions and utility. Model 1 assumed that there had
been first-order elimination of dioxin at a constant decay rate, whereas model 2 made no
such assumptions about the kinetics by which body burdens decreased. These two
models were applied under either the minimal (only those Ranch Hand participants with
more than 10 ppt serum dioxin, n = 521) or the maximal (all Ranch Handers with current
levels above 5 ppt, n = 742) assumptions. Model 3 used all participants in both Ranch
Hand and Comparison cohorts, and related health consequences to current dioxin levels
only. This multi-model approach helped to increase the discrimination of the analyses.
Ranch Handers had higher levels of body fat and increased erythrocyte
sedimentation rates, both of which parameters exhibited significant positive relationships
with current and estimated initial serum levels of TCDD.

The continued elevation in

sedimentation rates over this long period implies the existence of a subtle chronic
inflammatory response, a conclusion supported by a correlation between deduced initial
dioxin levels and elevated IgA (although other immunoglobulins did not show this
relationship), and by increased leukocyte and platelet counts in Ranch Handers with the
15

551
D -5 2 0

highest dioxin levels. However, earlier conclusions regarding abnormal skin-test reactions
in the Ranch Hand cohort, were not supported by analysis based on a relationship to
dioxin levels.
The findings of percent body fat are consistent with an observed positive
association between dioxin levels on the one hand, and serum triglycerides and high
density lipoprotein cholesterol, on the other.

However, it could be argued that the

correlation reflects the larger storage compartment for dioxin provided by the greater
amount of body fat, thus leading to more prolonged retention, rather than a stimulatory
effect of T C D D on lipid formation. This question will only be resolved by further follow-up
and basic studies. The^e lipid changes may have led to reductions in vital lung capacity
in the high current dioxin category, but the abnormalities in spirometric results observed,
although significant statistically, were not clinically important.
A new finding resulting from analysis of the health data in terms of serum T C D D
concentrations related to the incidence of diabetes. Ranch Handers were classified on
the basis of 2-hour postprandial glucose levels as normal (<140 mg/dl), impaired (>140
to <200 mg/dl), or diabetic (>200 mg/dl, or medical history of diabetes). Stratified in this
way, there was a strong positive correlation (p = 0.001) with current (13.5,14.8 and 21.9
ppt for the three groups, respectively) and initial (112.8,123.7 and 169.9 ppt, respectively,
under the maximal assumption) serum dioxin levels. Under the minimal assumption, the
correlation with initial dioxin levels (174.4,176.2 and 221.9 ppt) was marginally significant
(p = 0.095), as itwas also for the comparison cohort (3.4, 4.0 and 4.5 ppt; p = 0.026).

These correlations are interesting, but do not necessarily infer a causal relationship
between dioxin and the development of diabetes. The same survey noted a significant
correlation between both initial and current dioxin levels and increase in body fat, as we
have mentioned above, and Ranch Handers classified as obese (>25% body fat) also
had significantly (p <0.001) higher current (22.4 versus 12.9 ppt for normal/lean) and
initial (161.1 versus 110.2 ppt, under the maximal assumption) dioxin concentrations in
their sera. Obesity is a known risk factor for the development of late-onset diabetes, so
that the dioxin relationship to diabetes could merely reflect a c o m m o n association with
body fat. Itis apparent that this important health aspect of the Ranch Hand Study merits
16

552

further detailed examination, and ideally should be accompanied with correlative studies
in experimental systems.

Diabetes has not been described in experimental animals

exposed to TCDD, but the disturbances in the satiety response, and the enzymatic
evidence of impaired gluconeogenesis, which are described on pages 62-64 and 114,
respectively, could be of possible relevance. Itis possible that such changes might serve
to accelerate the manifestation of developing, but not yet clinically overt, disease.
All three dioxin concentration models supported the existence of a positive
association between testicular size and serum dioxin levels. There was a significant
negative correlation between dioxin levels and serum testosterone when no allowance
was made for body fat. However, it is possible that the lipid changes discussed above
impinged upon this finding, since when the latter were factored in, there was no significant
relationship between dioxin and abnormally low testosterone levels.
Cardiovascular findings were inconclusive. Thus, although there was a significantly
increased risk of essential hypertension in Ranch Handers with high current T C D D levels
(>33.3 ppt) relative to background comparisons (<10 ppt), and their adjusted mean
continuous levels of diastolic and systolic blood pressures were higher also (without
considering body fat), the fraction of participants exhibiting abnormally high blood
pressures showed no correlation with dioxin. Furthermore, the adjusted relative risk of
verified heart disease was less than 1 in Ranch Handers with high current dioxin levels.
Other attempts at correlation with dioxin levels in the areas of renal or hepatic function,
dermatologic or neurologic findings, and psychological status (Symptom Check List-90Revised and the Millon Clinical Multiaxial Inventory) led to null or inconsistent results.

2. Other Studies
A study that addressed the question of service in and around Vietnam, rather than
exposure to Agent Orange per se, was reported by Eisen et at. (1991). It is relevant to
this Review, because itis difficult to dissociate the effects of exposure to Agent Orange
in Vietnam from those attributable to the health hazards of the location alone, or the
sequelae of military combat. This study, based on mail and/or telephone interviews,
surveyed the impact of military service in Southeast Asia on 13 categories of health
17

553

problems among 2,260 male-male monozygotic twin pairs.

The reliability of this

epidemiologic approach was validated in a preliminary trial of 150 Connecticut-born twin
pairs. A combat index, based on 18 specific activities, such as serving as a "tunnel rat"
or being in a unit patrol that was ambushed, was employed to evaluate the degree of
combat exposure. This index ranged from 0 for no Southeast Asian exposure to >7 for
heavy combat in the area. The year of data collection was 1987. Among the twins,
service in Southeast Asia was associated with an increased current incidence of selfreported hearing problems (odds ratio (OR) = 1.9, 9 5 % confidence interval (Cl) 1.3-2.7)
and persistent skin problems (OR = 2.1, Cl 1.4-3.2). The odds ratios for these problems
increased as the combat index rose. Odds ratios for ever having hearing problems (OR
= 1.8, Cl 1.3-2.5), persistent skin problems (OR = 2.1, Cl 1.5-3.0), or having been
hospitalized for stomach conditions (OR = 2.6, Cl 1.4-4.9), also were elevated. There
were marginal elevations in the odds ratios for ever having stomach (OR = 1.4, Cl 1.01.9) or urinary (OR = 1.5, Cl 1.0-2.1) conditions. The design of the study, and the
identification of monozygotic twins without prior knowledge of exposure or disease state,
helped eliminate some potential confounders. In summary, the general physical health
of veterans who served in Southeast Asia is similar to that of their twin siblings who did
not, with two exceptions. Hearing impairment has been observed in military personnel
under combat conditions in other theaters of action, and is most probably associated with
loud noise, known to produce similar effects in various civilian occupations. The skin
conditions experienced at such a long interval of time after combat, cannot readily be
explained, but their existence could be a confounding factor in investigating claims of
association of such conditions with exposure to Agent Orange.

Three other studies have been concerned with measurements of the serum lipid
and adipose tissue contents of T C D D and related compound in veterans. These will be
described in detail in Section V. Seven other reports have described the occurrence of
various benign and malignant tumors in Vietnam veterans; these will be the subject for
discussion in Section III B.

18

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5-5* 3

REFERENCES

Eisen, S.A., J. Goldberg, W.R. True and W.G. Henderson. (1991) A co-twin control study of the
effects of the Vietnam war on the self-reported physical health of veterans. A m J
Epidemiol 134(1): 49-58.
Gough, M. (1991) Agent Orange: exposure and policy. Am. J. Public Health 81(3): 289-290.
Michalek, J.E., W.H. Wolfe and J.C. Miner. (1990) Health status of Air Force veterans
occupationally exposed to herbicides in Vietnam. JAMA 264: 1832-1836.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson. (1991) An
epidemiologic investigation of health effects in Air Force personnel following exposure to
herbicides. Introduction, background and conclusions. Air Force Health Study Chapters
1-5, 18, 19: 1-133.
Thomas, T.L., H.K. Kang and N.A. Dalager. (1991) Mortality among women Vietnam veterans,
1973-1987. Am. J. Epidemiol. 134(9): 973-980.
Watanabe, K.K., H.K. Kang and T.L. Thomas. (1991) Mortality among Vietnam veterans: with
methodological considerations. J. Occup. Med. 33(7): 780-785.
Wolfe, W.H., J.E. Michalek, J.C. Miner, A. Rahe, J. Silva, T. W.F., W.D. Grubbs, M.B. Lustik, T.G.
Karrison, R.H. Roegner and D.E. Williams. (1990) Health status of air force veterans
occupationally exposed to herbicides in Vietnam. 1. Physical health. JAMA 264(14):
1824-1831.

19

5
V'

B.

Cancer
The results of a number of epidemiologic studies became available during 1991,

which described possible correlations between exposure to phenoxy herbicides and their
contaminant dioxins, or at least of the opportunity for experiencing such exposure, with
the development of neoplastic diseases. They include further updates of the U.S. Air
Force’s Ranch Hand Study and the Centers for Disease Control’s Vietnam Experience
Study, other articles describing observations in veterans, and some epidemiologic work
in civilian populations. In addition, a significant amount of data was reported for studies
carried out in experimental animals, which will be described because of its relevance to
interpreting the human data.

1. Studies of Vietnam Veterans
Seven reports which became available during 1991 have looked at the general
incidence of cancers and other neoplasms in Vietnam veterans, but only one specifically
searched for a definitive correlation with exposure to Agent Orange. This was the Air
Force Health Study correlating health status with measured and estimated dioxin levels,
which was outlined in Section III A above. When dioxin levels were used as reference,
the higher incidence of basal cell carcinoma and sun exposure-related skin neoplasms
in general, described in both earlierfollow-ups and the previous report of the 1987 survey,
could not be substantiated. An increased incidence of basal cell carcinoma of sites other
than the ear, face, head or neck was noted in the enlisted flyer category. However, this
was thought to be an artifact, since the association was not seen in the enlisted ground
crew who had higher serum dioxin levels. This question merits further study, not only in
terms of future follow-up, but also with respect to the models used for estimating initial
dioxin levels as discussed in Section V. Furthermore, the number of cancers involved is
small, so the study may not have sufficient power to achieve statistical significance. The
risk for development of systemic malignant neoplasms was not elevated. Ranch Hand
participants did have a significantly higher incidence of benign neoplasms than the
comparison cohort, and the effect was related to estimated initial levels, falling from 9.7%
at high, to 5.7% at medium and 1.6% at low levels. The adjusted relative risk for those
2 0

556^,

with the highest current dioxin levels (>33.3 ppt) was 2.13. Lipomas comprised 75% of
Ranch Hand and 70% of comparison group benign neoplasms (Roegner et al. 1991).
Watanabe et al. (1991) published an update (through 1984 for a total of 62,068
veterans) of the Department of Veterans Affairs’proportionate mortality study of Army and
Marine Vietnam-era veterans. They reported significant excesses of deaths from laryngeal
and lung cancer among the Army veterans, with calculated proportionate mortality ratios
(PMRs) of 1.53 and 1.08, respectively.

However, among Marine Vietnam veterans,

apparently elevated PMRs for lung cancer and non-Hodgkin’s lymphoma, resulted from
deficits in the non-Vietnam comparison group. A survey carried out as an extension of
routine surveillance of the Massachusetts Cancer Registry for cases diagnosed between
1982 and 1988 (Clapp et al. 1991), disclosed an elevated odds ratio (OR) for mortality
from soft tissue sarcomas among Vietnam veterans (OR = 3.08, 95 % confidence interval
(Cl) of 1.07-8.73), but no significant increase for non-Hodgkin’s lymphoma, a malignancy
considered to be associated with exposure to dioxins on the basis of earlier studies by
the National Cancer Institute and by Swedish workers.

However, since the

Massachusetts study involved no interviews, questionnaires or other interaction with the
study participants, and no information was obtained regarding the timing or duration of
military service or any other demographic data, its value is quite limited. In a study of
4,600 w o m e n Vietnam veterans, standardized mortality ratios (SMRs) for cancers of the
pancreas (five deaths) and uterine corpus (four deaths) were elevated, at 3.27 and 4.05,
respectively, in Vietnam veteran nurses compared with U.S. w o m e n in general (Thomas
ef al. 1991).
The specific topic of non-Hodgkin’s lymphoma was addressed in three reports.
O ’Brien et al. (1991), as part of the Centers for Disease Control’s Vietnam Experience
Study (VES), used data from a randomly-selected group of 9,324 Army Vietnam veterans
and 8,989 non-Vietnam veterans. Of these two groups, 246 Vietnam veterans and 200
controls had died between discharge from active duty and the close of the mortality study
(December 31,1983). Telephone interviews, medical records and review of such records
by a panel of physicians, were used to establish causes of death and diagnosis of current
disease. Seven Vietnam veterans and 1 non-Vietnam veteran developed non-Hodgkin’s
21

P

lymphoma, a difference that was significant (p = 0.07). However, none of the cases had
military job titles suggesting that they were exposed to herbicides during their tour of duty
in Vietnam. Also as part of the VES study, the Selected Cancers Cooperative Study
Group utilized the population-based cancer registries for five metropolitan areas and three
states for a case-control study restricted to men born between 1929 and 1953. A total
of 1,157 non-Hodgkin’s lymphoma patients were frequency-matched by age to 1,776
controls who were identified by random-digit dialing from these regions. The risk of
developing non-Hodgkin’s lymphoma was elevated in Vietnam veterans (OR = 1.47, Cl
= 1.1-2.0) compared to those men with no Vietnam service; these veterans were also at
higher risk than other veterans, contemporary veterans who had not served in Vietnam,
and those individuals with no military service. The relative risk increased with length of
time in Vietnam, but showed no correlation with factors such as military region, unit, or
dates of service that could be associated with exposure to Agent Orange (Selected
Cancers Cooperative Study Group 1990a). A hospital-based, case-control study of 201
Vietnam-era veterans treated for non-Hodgkin’s lymphoma between 1969 and 1985,
disclosed no increased risk of non-Hodgkin’s lymphoma relative to a group of 358
Vietnam-era patents with a diagnosis other than lymphoma (OR = 1.03, Cl = 0.7-1.50).
Neither was there any correlation with surrogate measures of potential exposure to Agent
Orange, such as specific military branch, combat role or region of Vietnam in which the
subjects served (Dalager et al. 1991).
Soft-tissue sarcomas have also been claimed to be associated with exposure to
dioxins. As part of the VES study, and using the matching procedures indicated for nonHodgkin’s lymphoma, 342 men with soft tissue and other sarcomas were compared with
1776 controls (Selected Cancers Cooperative Study Group 1990b). The study design had
the power (97%) to detect a relative risk of 2.0 for all sarcomas. Relative risks for these
tumors were not increased, either for total sarcomas (OR = 1.0, Cl = 0.6-1.6), or for soft
tissue sarcomas only (n = 254, O R = 0.9, Cl = 0.5-1.6). There was no evidence of
overrepresentation of specific histologic subtypes of sarcoma, or of increased risk to
those whose military service included activities that might have exposed them to Agent
Orange.
22

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In a third segment of the VES study, the incidence of four other cancers was
studied, using the same Cancer Registry-based, case-control matching procedure
(Selected Cancers Cooperative Study Group 1990c).

The cancers studied were

Hodgkin’s disease (310); nasal carcinoma (48); nasopharyngeal carcinoma (80); and
primary liver cancer (130). All were matched to 1,776 controls. Risks relative to controls,
and to other veterans or men who never served, were: 1.1 (Hodgkin’s); 0.7 (nasal); 0.5
(nasopharyngeal); and 1.2 (liver). None of these risks differed statistically from unity, but
only in the case of Hodgkin’s disease, was the power of the study (96%) sufficient to
detect a doubling of the risk; for other tumors the ability to detect a similar difference
ranged from 3 8 % to 75%.
Based on findings that military working dogs, who served and died in Vietnam,
exhibited significantly elevated incidences of testicular dysfunction and testicular tumors,
data from a previously reported case-control study of human testicular cancer were
reexamined by Tarone et al. (1991). Subjects aged 18-42 years, newly diagnosed with
testicular cancer during the period January 1, 1976 to June 30, 1981, and referred to
Washington DC-area hospitals, were compared with patients newly diagnosed with
cancers of non-genitourinary sites. A standardized questionnaire was employed, and
exclusions made for cryptorchidism, low birth weight, non-Hodgkin’s lymphoma, and birth
prior to 1955, in order to reduce problems from confounding factors, for example, the
known association of crytorchidism with testicular cancer. The ORs for Vietnam service
were 2.6 for cases diagnosed before age 35, 3.0 for those diagnosed between 30 and
34 years, and 1.1 for subjects diagnosed after 35 years of age. For Vietnam service the
O R was 1.8 (Cl = 0.6-5.1) for seminomas, and 2.4 (Cl = 1.1-5.4) for nonseminomas.
This approximately two-fold increase in risk was similar to that described in dogs, as was
the relatively greater risk for younger subjects. Itis well to bear in mind when considering
both the dog and the human data that many confounding factors could have been at
work in addition to herbicides. They include infectious agents and parasites endemic to
Vietnam, the use of chemotherapy, including tetracyclines which are known to cause
testicular dysfunction, to treat those infections, and the effects of stress itself.

23

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The INSERM North-South Network for Environmental Epidemiology in Vietnam is
conducting three studies in Vietnam regarding wartime exposure to Agent Orange, and
the subsequent development of non-Hodgkin’s lymphoma, molar pregnancy and
choriocarcinoma, and primary liver cancer, using a case-control design (Abenhaim et al.
1991). These studies, while not involving former U.S. military personnel, will provide data
that might help to shed light on some of the inconsistencies in the studies with veterans.

2. Other Studies of Human Subjects
Most of the reports dealing with cancer in humans not involved in the Vietnam
conflict have dealt with occupational exposures. Perhaps the largest compendium of
such data was provided by Fingerhut and her coworkers (Fingerhut et al. 1991), who
analyzed data from 5,172 male workers at 12 plants in the U.S. that produced chemicals
contaminated with TODD.

This study is part of the National Institute of Occupational

Safety and Health’s (NIOSH) Dioxin Registry. Occupational exposure was based upon
job description, supplemented with measurements of serum T C D D in 253 members of the
surviving cohort; mortality data was derived from death certificates. Of the subjects
entered into the study, 202 were included in the overall mortality analysis, but excluded
from analyses based on duration of exposure because these data were unavailable.
Mortality from all forms of cancer combined was raised to a slight but statistically
significant extent (standardized mortality ratio, SMR, of 115, Cl = 102-130), and to a
greater degree in the subcohort (n = 1,520) with > 1 year of exposure and > 20 years
of latency (SMR = 146, Cl = 121-176). There was no elevation in the incidence of
Hodgkin’s disease, non-Hodgkin’s lymphoma, stomach, liverand nasal cancers, diseases
that have been reported to be associated with dioxin toxicity. However, there was a
slight, but not significant, increase in deaths from soft tissue sarcoma (SMR = 338, Cl =
92-865, four deaths). There was a significant increase for this latter disease only ifthose
workers with > 1 year exposure and > 20 years of latency were considered (SMR 922,
Cl = 190-2,695, three deaths); respiratory system cancers also were increased in this
group (SMR = 142, Cl = 103-192). This study did not exclude the contribution of factors
such as smoking or exposure to other chemicals in the work place, and two deaths were
24

misclassified in the soft tissue sarcoma group. Furthermore, objections can be raised to
combining data obtained at so many sites, a practice somewhat resembling meta­
analysis, although in this case the authors did not merely combine the results of separate
studies, but rather identified the individual subjects, coded and analyzed data under a
c o mmon protocol, and reviewed the procedures used at each work site, procedures
which negate most of the problems of meta-analysis. If there is any conclusion to be
drawn, it is surely that the study indicated a relatively low order of cancer risk from
occupational exposure to TCDD. Nevertheless, itprovoked considerable discussion, and
its data were used by others as conclusive support for both the standard linear model
used by the EPA for cancer risk assessment (Goldman et al. 1991), and for the receptorbased, practical effect threshold model (Carlo et al. 1991) that is a currently-favored
alternative.
Another study of a large multi-site nature was carried out by the International
Agency for Research on Cancer (IARC), and involved 18,910 production workers or
herbicide sprayers from ten countries (Saracci et al. 1991). Estimates of exposure were
obtained by a combination of questionnaires, recorded durations and frequency of
spraying, factory records, and work histories; cause-specific national death rates were
used as reference for each country’s contribution. There was a two-fold increase in
overall risk of soft tissue sarcoma (SMR = 196, Cl = 53-502), which lacked statistical
significance, however.

The increase was concentrated so as to become statistically

significant only for the time period 10-19 years after first exposure, both for the total
cohort (SMR = 606, Cl = 165-1,552), and for the subgroup of sprayers (SMR = 882, Cl
= 182-2,579). There appeared to be small increases in the risks for testicular, nasal,
thyroid and other endocrine-related cancers, but the numbers were too small to draw any
definitive conclusions. Peto (1991) has questioned the conclusions that were drawn from
the data of the IARC study, pointing out that there were four deaths from soft-tissue
sarcoma in the group classified as 10-19 years since first exposure, but none for those
associated with any other time interval. Similarly, two of these deaths occurred after less
than one, and the other two after 10-19 years of exposure. This clustered distribution
pattern does not support any specific statistical conclusions regarding subgroups. A
25

separate description of part of the British contribution to this IARC study was published
by Coggon et al. (1991). Among a total of 2,239 men at four chemical manufacturers,
there were two deaths from non-Hodgkin’s lymphoma with 0.87 expected, and a further
living case with this disease, a non-significant excess of lung cancer (19 deaths with 14.2
expected) possibly due to confounding factors or chance, but no cases of soft tissue
sarcoma or Hodgkin’s disease.
The Swedish group which has carried out a number of studies of the association
between dioxins and soft tissue sarcomas over the past 15 years, published a meta­
analysis of four of their studies (Harden et al. 1991), using the criteria of the Fingerhut
study (Fingerhut et al. 1991). There were two stratifications, first between subjects with
less than one and more than one year of exposure, and second between those with 5-19
years and 20 or more years of latency. There were 352 cases and 865 controls in the
study. A significant trend for increased incidence with increased exposure to dioxins was
noted (Chi squared test = 18.2, p, 0.001). Volume XVII of the Review presented a
detailed analysis of the most recent of the Swedish studies, in which itwas pointed out
that there had been a steady decline in the apparent risk from 5.3 in the first study
(Hardell and Sandstrom 1979) to 1.34 in the more recent publications (Eriksson et al.
1990; Hardell and Eriksson 1988). The most marked association was with chlorophenols
rather than phenoxy herbicides, and there also were inconsistencies in the use of normal
or cancer case controls. In general, the risk ratios were smaller when cancer cases were
used as controls, and itwas speculated that recall bias was operative here. In view of
such objections, and the limitations of meta-analysis, this most recent study from the
Swedish group cannot be said to clarify the issue.
Other studies have been restricted to single plants or occurrences. A mortality
study of 1,184 men and 399 wom e n employed between 1954 and 1984 at a chemical
plant in Germany that produced herbicides, and involved products contaminated with
TCDD, was described by Manz et al. (1991). Dioxin production was curtailed at the plant
after an outbreak of chloracne in 1954. SMR s were calculated using as references the
national mortality statistics for West Germany, and deaths among a cohort of gas
workers. As of 1989, there had been 313 deaths among men and 54 among women, of
26

562
p

which 93 and 20, respectively, resulted from malignancies. Total cancer SMRs for men
were 1.24 (Cl 1.00-1.52) versus national data, and 1.39 (Cl 1.10-1.75) compared with gas
workers. These risks for cancer deaths rose to 1.87 and 1.82 against the two references,
respectively, for those men with 20 or more years of employment, and to 1.61 and 1.87
for men hired before 1955. For men employed in areas with the highest probability of
T C D D exposure, S M R s were 1.42 and 1.78 compared with national and gas worker
figures. Adipose tissue levels of T C D D were measured in only 48 individuals, with figures
of 296 ± 479 and 83 ± 73 ng/kg for the two classes of high and lower exposure. Of the
men, 39.6% worked in high exposure locations compared with 7 % of women. Among
wom e n there was no increased overall risk of cancer mortality, but mortality from breast
cancer was raised (SMR = 2.15). There are a number of concerns regarding this study.
National mortality data is based on death certificates, whereas deaths among the study
population were documented by medical records which are likely to provide more
accurate causes of death. Other concerns, raised by Triebig (1991), relate to the failure
to document which of the subjects experienced chloracne, a good indicator of heavy
dioxin exposure, determinations of T C D D in such a small, possibly unrepresentative,
fraction of the study population, and the unusually high percentage of smokers among
the chemical workers (73%) compared with the general male population of Germany
(40%). This latter factor could confound comparisons with national statistics, and also
could affect the results through a process of multiplicative interaction with carcinogens
such as benzene and asbestos, which were present at the site.
One study evaluated the relationship between mortality from lymphomas and soft
tissue sarcomas, and environmental exposure to phenoxy herbicides in the provinces of
Novara and Vercelli in northern Italy (Vineis et al. 1991). These areas are noted for
cultivation of rice, and phenoxy herbicides have been used heavily there since 1950. A
survey of four local hospitals, and others to which residents of the two provinces would
have been admitted, identified 43 cases of Hodgkin’s disease, 141 of non-Hodgkin’s
lymphoma and 30 cases of soft tissue sarcoma in men; for w o m e n the corresponding
figures were 20, 112 and 19 cases. Age-adjusted, standardized incidence rates were
calculated with the world population as reference. Determinations of the soil and water
27

563
P-

3-

concentration of 2,4-D and the propionic ester of 2,4,5-T (2,4,5-TP), carried out in several
areas of each province in 1974 and 1975, were used to define two categories of
exposure: A, in which these compounds were detected by at least one measurement; and
B, the areas where greatest contamination of water was recorded (2.4-D, 0.07-0.46 ppm;
2,4,5-TP, 0.10-0.19 ppm). Annual incidence rates (with 95% confidence intervals) for nonHodgkin’s lymphomas were elevated for men aged 17-74 years from 8.8 per 100,000 (Cl
= 7.4-10.4) for the region as a whole to 11.7 (Cl = 6.5-19.3) for those living in category
A areas, and to 18.2 (Cl = 11.1-28.0) in area B. For w o m e n the corresponding figures
were: 5.8 (Cl = 4.7-7.0); 6.2 (Cl = 2.8-11.8); and 7.4 (Cl = 3.5-13.6). The rate ratio for
men in category B areas was 2.2 (Cl = 1.4-3.5). Annual incidence rates for Hodgkin’s
disease were 3.3 (Cl = 2.4-4.4) in men and 1.5 (Cl = 0.9-2.3) in women; for soft tissue
sarcomas the corresponding rates were 1.8 (Cl = 1.2-2.6) and 0.9 (Cl = 0.5-1.4).
Numbers for these latter two tumor types were too small to permit any conclusions to be
drawn. The study is of potential value because it included objective measurements of
environmental herbicides. However, no attempt was made to dissect out the contribution
from occupational elements, such as the contribution to overall mortality of those subjects
who were herbicide sprayers, neither was there any stratification for length of residence
in the area. Furthermore, although on its face value this study suggests that phenoxy
herbicides themselves are associated with non-Hodgkin’s lymphomas, the measurements
made may in actual fact reflect the activity of any accompanying dioxin contaminant,
which was not determined.
Bertazzi (1991) has reviewed the latest status of the follow-up of subjects exposed
to dioxins during the Seveso incident in Italy on July 10, 1976, when rupture of a safety
valve in a plant producing trichlorophenol, released a cloud that deposited its contents
over a several square mile area. T C D D was a prominent component of the deposited
material. This episode is discussed further in Section V in connection with studies of
tissue levels of TCDD. In the period ending 1986, cancer mortality findings for both males
and females in Zone B, where dioxin levels were high but the population remained, were
essentially negative, with ORs below unity. However, there were non-significant increases
for soft tissue sarcoma (but only two cases), leukemia and melanoma among males. In
28

564
P-57-?

females, there was an increase in biliary cancer, and a noticeable decrease in breast
cancer incidence that approached statistical significance. This latter finding should be
viewed in the context of the antiestrogenic action of dioxins, discussed in Section VI. It
is necessary to emphasize that the breakdown into specific diseases leftvery few tumors
in each category, making statistical evaluation unreliable.

Further follow-up of this

population is important, because this incident represents, perhaps, the best opportunity
to correlate disease prevalence with actual measurements of environmental and tissue
T C D D levels, and thus provide definitive estimates of the hazards from dioxins.
Several reviews and commentaries on the epidemiologic evidence for an
association with cancer became available during 1991. The NIOSH study has been
criticized for inclusion of data obtained by both "new" and "old" procedures, leading to
internal inconsistencies (Collins etal. 1992). This claim has been refuted by Fingerhut et
al. (1992), and on balance it would appear that the overall uniform review of data that

took place in the preparation of the NIOSH report made itessentially a "new" study. Two
reviews have examined the whole area. Gough (Gough 1991) has recently discussed the
conflicting claims of health effects from occupational exposure to dioxin. He reviewed the
inconsistent results of epidemiologic studies linking several cancers and exposure to
dioxins, and pointed out that nearly all the positive associations relate to herbicide
applicators. Workers in chemical plants, who have generally shown higher serum and
adipose tissue levels of T C D D and a greater incidence of chloracne, both indicators of
heavy exposure to dioxin, have not shown the expected major increase in cancer
incidence. Tollefson (Tollefson 1991), examining the problem from the point of view of
the 1,600-fold range in acceptable T C D D intakes set by regulatory agencies in the U.S.,
Canada and Europe, stressed that this reflected the degree of uncertainty in the scientific
data.

He considered the best studies were those in which actual exposures are

emphasized, backed where possible by adipose tissue and serum levels. He feltthat the
studies of the participants in the NIOSH Dioxin Registry and the Seveso incident follow-up
offer the best prospect of future definition of the human carcinogenic risk from dioxin.
Taken together with the animal data, current information suggests that at most the

29

565
J>

51

calculated increased risk from T C D D exposure is moderate, bearing in mind high
prevalent background cancer rates.

3. Studies in Animals
Dioxins, and especially TCDD, the one which has been studied most intensively,
are generally recognized as trans-species, trans-strain, trans-sex, multi-site complete
carcinogens. In the U.S. National Toxicology Program (NTP), T C D D is listed as an agent
causing cancer in both mice and rats (Huff et al. 1991a); see also the analysis by Ashby
and Tennant (1991). The original basis for this classification may be found in the feed
study of Sprague-Dawley rats by Kociba et al. (1978) and the NT P ’s gavage study of rats
and mice (National Toxicology Program 1982), both of which described the induction of
liver tumors.

Although subsequent work has extended these observations to other

species, tumors, and routes of administration, these original studies have been widely
applied as the standards for estimating human cancer risks from exposure to TCDD. The
evidence from studies in experimental animals for the carcinogenicity of T C D D and related
compounds has been reviewed recently by Huff et al. (1991b). Experimental data now
indicates that T C D D produces neoplasms of the lung, oral and nasal cavities, thyroid,
adrenal gland and liver in rats, of the liver, subcutaneous tissue, thyroid and thymus gland
in mice, and in hamsters it induces squamous cell carcinomas of the facial skin. This
review also included a detailed presentation of the Kociba and NTP studies. The Kociba
study has also received attention and réévaluation, because of the significant changes
that have taken place in the histopathological criteria used for classifying proliferative
lesions of the liver since 1978. Two réévaluations were published in 1991 by the same
investigating group, both based on reexamination of the original slides by an independent
board of pathologists (the Pathology Working Group, which published itsfindings in 1990)
using the current NTP criteria for hepatic lesions. Amo n g their findings were two-thirds
fewer malignant tumors in female rats, and the redefinition of many adenomas as
hyperplasias. In the first of these réévaluations, the no-observed-adverse-effect level for
hepatocellular carcinomas was calculated as 0.01 rather than 0.001 /vg/kg/day, as
determined in the original study. This new estimate was applied to the task of deriving
30

566

V 'S 'ît Î

risk-specific doses (RsDs) for humans, using body weight rather than surface area as the
basis for scaling rodent data to humans because of the implications of a receptor-based
mode of action. For the standard linearized multistage model, the RsD for a 10^ upper
bound (95% confidence) lifetime incremental cancer risk was calculated as 370 fg/kg/day
for carcinomas, and 100 fg/kg/day for all hepatic tumors combined. These risks are 16fold lower than those calculated from the original Kociba data (Keenan et al. 1991). In
the second paper, the data were reviewed using a stochastic two-stage, biologicallybased model of carcinogenesis, the Moolgavkar-Venzon-Knudson model, rather than the
linearized multistage model (Paustenbach et al. 1991). Whe n this model was applied to
data which had been adjusted to current pathologic criteria, the RsD for hepatocellular
carcinoma soared to 25,000 fg/kg/day, although it remained at a comparable figure of
80 fg/kg/day for hepatocellular carcinomas and adenomas combined. When applied to
the unadjusted Kociba findings, this model predicted RsDs for hepatocellular carcinoma
and of carcinomas plus adenomas of 150 and 10 fg/kg/day, respectively, close to the
values of 130 and 35 based on the linearized multistage model. These reanalyses do
provide a toxicologic basis for reevaluating the estimates of carcinogenic risk to humans
used by regulatory agencies, but do not negate the carcinogenic potential of dioxins.
Several of the reports that became available during 1991 in the area of dioxin
carcinogenicity described studies using various surrogate measures or intermediate
endpoints of carcinogenesis.

Such markers are widely recognized as being closely

associated with eventual malignant transformation, and offer the significant advantage of
permitting evaluation of carcinogenic potential in much less time than is required for
conventional carcinogenesis studies. In these studies, T C D D served in most cases as
a standard reference for promoting activity. For example, Massa et al. (1991) described
a host-mediated in vivo/in vitro assay of peritoneal macrophage transformation to
demonstrate the carcinogenicity of T C D D in mice. Macrophages were harvested from
control and treated mice and cultured for 5-6 days on soft agar, after which time normal
and transformed cells could be distinguished. Carcinogenic potential was expressed as
an index based on the frequency of clone sizes of defined classes; the test was positive
at least at the 5 % significance level by the f-test. T C D D alone exhibited a concentration31

567

dependent carcinogenic potential, while a cocarcinogenic effect in combination with
phenytoin, was only seen when the two compounds were applied together. Dragan et
al. (1991) described an initiation-promotion assay in rat liver that followed the activity of

four enzymes (placental glutathione-S-transferase (PGST); y-glutamyltranspeptidase
(GGT); canalicular ATPase; and glucose-6-phosphatase) in altered hepatic foci. T C D D
was an effective promoter when used with diethylnitrosamine, and 100% of the altered foci
were scored by the combination of PGST and G G T together.

A

number of

polychlorinated dibenzo-p-dioxins and dibenzofurans were compared in an altered hepatic
foci assay, to determine their relative promoting activity in combination with the initiator
diethylnitrosamine when administered to Sprague-Dawley rats (Waern etal. 1991). While
the pentachlorodioxin analog was of similar activity to TCDD, the furans had only a tenth
of the activity, but showed more prolonged tissue retention. Lucier et al. (1991) studied
the female sex-dependence of hepatocarcinogenicity in Sprague-Dawley rats, by following
altered hepatic foci in a two stage model with initiation by diethylnitrosamine.

The

percentage of the liver occupied by GGT-positive foci was 0.37 in normal versus 0.08 in
ovariectomized rats; similar data were obtained for PGST-positive foci.

In addition,

proliferative indices obtained by the bromodeoxyuridine technique, indicated that cell
division was enhanced by carcinogen treatment of normal, but not of ovariectomized rats.
These differences were seen in the absence of any effect of ovariectomy on the
distribution of TCDD, or its Ah receptor-dependent induction of cytochrome P450. This
latter finding adds emphasis to the caution expressed by Silbergeld (1991) that more
information is needed about the intervention of dioxins in such functions as gene
expression, immune surveillance and endocrine regulation, before a complete and
definitive réévaluation of the overall risk assessment for these compounds can be made.
Finally, in connection with the major herbicidal components of Agent Orange, a
case-control study of canine malignant lymphomas in dogs, associated the occurrence
of the tumor with the use of 2,4-D by their owners (Hayes et al. 1991). A total of 491
cases were compared with 466 nontumor and 479 tumor controls, and the odds ratio
(OR) was significantly elevated to 1.3 in those whose owners applied the herbicide, or
employed a lawn service to do so, more frequently. The O R was about 2 in dogs whose
32

568
0 -5 1 7

owners carried out four or more applications of 2,4-D themselves every year. Another
report, also described in Section IV, indicated that exposure to Tordon 202C, a mixture
of 200 g of 2,4-D and 12 g of picloram per liter, raised the incidence but not the size of
adenomas in female CD-1 mice induced with urethan (Adams et al. 1991). The data in
these two reports support claims of a carcinogenic effect of 2,4-D made on the basis of
agricultural exposure studies in humans, although in the earlier of the human studies a
contribution to the overall effect from the higher levels of contaminating dioxins then
prevalent is highly likely. In marked contrast to 2,4-D, chronic administration of 2,4,5-T
to MRC-Wistar rats (600 mg/kg diet) was not carcinogenic, neither did itaffect in any way
the carcinogenicity of diethylnitrosamine (Mirvish et al. 1991).

33

569

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Consequences of Agent Orange on health - the INSERM study in Vietnam. Arch.
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effects of Tordon 202c exposure on urethan-induced lung adenom a formation in female
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Ashby, J. and R.W. Tennant. (1991) Definitive relationships among chemical structure,
carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res.
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Bertazzi, P. (1991) Long-term effects of chemical disasters. Lessons and results from Seveso.
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Carlo, G.L., K.G. Sund, R.W. Morgan, L. Hardell, M. Erikkson, O. Axelson, L.R. Goldman, D.
Hayward, D.M. Siegel, R.D. Stephens et al. (1991) Dioxin and mortality from cancer
[Letter], N. Engl. J. Med. 324(25): 1809-1812.
Clapp, R.W., L.A. Cupples, T. Colton and D.M. Ozonoff. (1991) Cancer surveillance of veterans
in Massachusetts, USA, 1982-1988. Int. J. Epidemiol. 20(1): 7-12.
Coggon, D., B. Pannett and P. Winter. (1991) Mortality and incidence of cancer at four factories
making phenoxy herbicides. Br. J. Ind. Med. 48(3): 173-178.
Collins, J.J., J.F. Acquavella and B.R. Friedlander. (1992) Reconciling old and new findings on
dioxin. Epidemiology 3(1): 65-69.
Dalager, N.A., H.K. Kang, V.L. Burt and L. Weatherbee. (1991) Non-Hodgkin’s lymphoma among
Vietnam veterans. J. Occup. Med. 33(7): 774-779.
Dragan, Y.P., T. Rizvi, Y.-H. Xu, J.R. Hully, N. Bawa, H.A. Campbell, R.R. Maronpot and H.C.
Pitot. (1991) An initiation-promotion assay in rat liver as a potential complement to the
2-year carcinogenesis bioassay. Fundam. Appl. Toxicol. 16: 525-547.
Eriksson, M., L. Hardell and H.O. Adami. (1990) Exposure to dioxins as a risk factor for soft
tissue sarcoma: a population-based case-control study. JNCI 82: 486-490.
Fingerhut, M.A., W.E. Halperin, D.A. Marlow, L.A. Piacitelli, P.A. Honchar, M .H. Sweeney, A.L.
Greife, P.A. Dill, K. Steenland and A.J. Suruda. (1991) Cancer mortality in workers
exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N. Engl. J. Med. 324(4): 212-218.
Fingerhut, M.A., K. Steenland, M.H. Sweeney, W.E. Halperin, L.A. Piacitelli and D.A. Marlow.
(1992) Old and new reflections on dioxin. Epidemiology 3(1): 69-72.
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Goldman, L.R., D. Hayward, D.M. Siegel and R.D. Stephens. (1991) Dioxin and mortality from
cancer (Letter). N. Engl. J. Med. 324(25): 1811.
Gough, M. (1991) Human health effects: what the data indicate. Sci. Total Environ. 104(1-2):
129-158.
Harden, L. and M. Eriksson. (1988) The association between soft tissue sarcomas and exposure
to phenoxyacetic acids: a new case-referent study. Cancer 62: 652-656.
Hardell, L., M. Eriksson, O. Axelson and M. Fredriksson. (1991) Increased risk of soft tissue
sarcoma in persons exposed to dioxin. Lakartidningen 88(47): 4005-4006.
Hardell, L. and A. Sandstrom. (1979) Case-control study: soft-tissue sarcomas and exposure
to phenoxyacetic acids or chlorophenols. Br. J. Cancer 39: 711-717.
Hayes, H.M., R.E. Tarone, K.P. Cantor, C.R. Jessen, D.M. McCurnin and R.C. Richardson. (1991)
Case-control study of canine malignant lymphoma: positive association with dog owner’s
use of 2,4-dichlorophenoxyacetic acid herbicides. JNCI 83(17): 1226-1231.
Huff, J., J. Cirvello, J. Haseman and J. Bucher. (1991a) Chemicals associated with site-specific
neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents. Environ.
Health Perspect. 93: 247-270.
Huff, J., A. Salmon, N. Hooper and L. Zeise. (1991b) Long-term carcinogenesis studies on
2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins. Cell Biol. Toxicol.
7(1): 67-94.
Keenan, R., D. Paustenbach, R. Wenning and A. Parsons. (1991) Pathology réévaluation of the
Kociba et al. (1978) bioassay of 2,3,7,8-TCDD: implications for risk assessment. J.
Toxicol. Environ. Health 34(3): 279-296.
Kociba, R.J., D.G. Keyes, J.E. Beyer, C. R.M., D.A. Wade, D.A. Dittenberger, R.P. Kalnins, L.E.
Frauson, C.N. Park, S.D. Bernard, R.A. Hummel and C.G. Humiston. (1978) Results of
a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin
in rats. Toxicol. Appl. Pharmacol. 46: 279-303.
Lucier, G.W., A. Tritscher, T. Goldsworthy, J. Foley, G. Clark, J. Goldstein and R. Maronpot.
(1991) Ovarian hormones enhance 2,3,7,8-tetrachloro-dibenzo-p-dioxin-mediated
increases in cell proliferation and preneoplastic foci in a two-stage model for rat
hepatocarcinogenesis. Cancer Res. 51(5): 1391-1397.
Manz, A., J. Berger, J.H. Dwyer, D. Flesch-Janys, S. Nagel and H. Waltsgott. (1991) Cancer
mortality among workers in chemical plant contaminated with dioxin. Lancet 338(8773):
959-964.
Massa, T., A. Esmaeili, B. Schlatterer, H. Hagenmaier and P. Chandra. (1991) Carcinogenic and
co-carcinogenic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a host-mediated in
vivo/in vitro assay. Chemosphere 23(11-12): 1855-1868.
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Mirvish, S.S., J. Nickols, D.D. Weisenburger, D. Johnson, S.S. Joshi, P. Kaplan, M. Gross and
H.Y. Tong. (1991) Effects of 2,4,5-trichlorophenoxyacetic acid, pentachlorophenol,
méthylprednisolone, and Freund adjuvant on 2-hydroxyethylnitrosourea carcinogenesis
in MRC-Wistar rats. J. Toxicol. Environ. Health 32(1): 59-74.
National Toxicology Program. (1982) Bioassay of2,3,7,8-tetrachlorodibenzo-p-dioxin forpossible
carcinogenicity (gavage study). Technical Report Series 209.
O ’Brien, T.R., P. Decoufle 2nd and C.A. Boyle. (1991) Non-Hodgkin’s lymphoma in a cohort of
Vietnam veterans. Am. J. Public Health 81 (6): 758-760.
Paustenbach, D.J., M.W. Layard, R.J. Wenning and R.E. Keenan. (1991) Risk assessment of
2,3,7,8-TCDD using a biologically based cancer model: a réévaluation of the Kociba et
al. bioassay using a 1978 and 1990 histopathology criteria. J. Toxicol. Environ. Health
34(1): 11-26.
Peto, R. (1991) Occupational exposure to chlorophenoxy herbicides and chlorophenols [Letter].
Lancet 338(8779): 1392.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson. (1991) An
epidemiologic investigation of health effects in air force personnel following exposure to
herbicides. Air Force Health Study 1-9(Mar).
Saracci, R., M. Kogevinas, P.-A. Bertazzi, B.H. Bueno de Mesquita, D. Coggon, L.M. Green, T.
Kauppinen etal. (1991) Cancer mortality inworkers exposed to chlorophenoxy herbicides
and chlorophenols. Lancet 338(8774): 1027-1032.
Selected Cancers Cooperative Study Group. (1990a) The association of selected cancers with
service in the US military in Vietnam. I. Non-Hodgkin’s lymphoma. Arch. Intern. Med.
150(12): 2473-2482.
Selected Cancers Cooperative Study Group. (1990b) The association of selected cancers with
service in the US military in Vietnam. II. Soft-tissue and other sarcomas. Arch. Intern.
Med. 150(12): 2485-2492.
Selected Cancers Cooperative Study Group. (1990c) The association of selected cancers with
service in the US military in Vietnam. III. Hodgkin’s disease, nasal cancer,
nasopharyngeal cancer, and primary livercancer. Arch. Intern. Med. 150(12): 2495-2505.
Silbergeld, E.K. (1991) Carcinogenicity of dioxins [Editorial]. JNCI 83(17): 1198-1199.
Tarone, R.E., H.M. Hayes, R.N. Hoover, J.F. Rosenthal, L.M. Brown, L.M. Pottern, N. Javadpour,
K.J. O ’Connell and R.E. Stutzman. (1991) Service in Vietnam and risk of testicular cancer
(brief communication). JNCI 83(20): 1497-1499.
Thomas, T.L., H.K. Kang and N.A. Dalager. (1991) Mortality among women Vietnam veterans,
1973-1987. Am. J. Epidemiol. 134(9): 973-980.

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Tollefson, L. (1991) Use of epidemiology data to assess the cancer risk of 2,3,7,8tetrachlorodibenzo-p-dioxin. Regul. Toxicol. Pharmacol. 13(2): 150-169.
Triebig, G. (1991) Is dioxin carcinogenic? Lancet 338(8752): 1592.
Vineis, P., F. Faggiano, M. Tedeschi and G. Ciccone. (1991) Incidence rates of lymphomas and
soft-tissue sarcomas and environmental measurements of phenoxy herbicides. J. Natl.
Cancer Inst. 83(5): 362-363.
Waern, F., S. Flodstrom, L. Busk, T. Kronevi, I.Nordgren and U.G. Ahlborg. (1991) Relative liver
tumor promoting activity and toxicity of some polychlorinated dibenzo-p-dioxin- and
dibenzofuran-congeners in female Sprague-Dawley rats. Pharmacol. Toxicol. 69(6):
450-458.
Watanabe, K.K., H.K. Kang and T.L. Thomas. (1991) Mortality among Vietnam veterans: with
methodological considerations. J. Occup. Med. 33(7): 780-785.

37

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C.

Genetic Effects
No studies specifically associating phenoxy herbicides or their dioxin contaminants

with human genotoxicity became available during 1991. One report described statistically
significant elevations in the incidences of chromosome aberrations and sister chromatid
exchanges in lymphocytes from 32 healthy individuals working in the flower industry, who
were exposed to 48 insecticides, fungicides and herbicides, including 2,4-D, and 32
patients with bladder cancer and similar occupational exposure, compared with 31 normal
controls (DeFerrari et al. 1991). However, without information on the actual individual
usage of the various compounds by the subjects, this study, while of interest from the
point of view of occupational hazard assessment, is of no value for the purposes of this
Review.

While there have been some conflicting claims in the literature regarding the
mutagenicity of T C D D ,the bulk of the evidence does not support such an activity (Fahrig
1991). This forms the basis for the negative listing given to the compound by the U.S.
National Toxicology Program (Huff et al. 1991). Two studies reported in 1991 lend further
support to this conclusion. In the course of assessing the mutagenic potential of fish
from the Pigeon River, Tennessee, which are contaminated with T C D D and other
compounds, Blevins (1991) reported that pure T C D D was not mutagenic for strains TA97,
TA98 and TA100 in the Salmonella typhimurium assay at the highest non-toxic level of 825
ng/ml of top agar; above this concentration itwas highly toxic for all three strains. Acidic
extracts of the fish were mutagenic, but since the maximum level of T C D D in the fish was
117 pg/kg of wet weight, it was evident that other contaminants, individually or in
combination, were responsible for this activity. In the L5178Y tk+/tk- mouse-lymphoma
cell forward mutation assay, in which the cells were exposed to T C D D at 1 pg/kg (the
solubility limit) for 4 hours, and then cultured for 2 days before plating in soft agar with
or without trifluorothymidine (3 jug/ml), the dioxin exhibited no toxic or mutagenic effects.
This was true in the presence or absence of an enzyme activation system (McGregor et
al. 1991).

In contrast to the apparent absence of mutagenic activity in the case of TCDD, the
phenoxy herbicide 2,4-D showed both mutagenic and cytotoxic effects on V79 hamster
38

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g-C. o 3

fibroblast cells in culture at concentrations of 10 /jg/ml and greater. Structural changes
in the chromosomes and chromatin, as well as altered cell cycle characteristics and
mitotic activity were evident in shallot root tip cells in culture exposed to 2,4-D (Pavlica et
al. 1991).

39

575

REFERENCES

Blevins, R. (1991) 2,3,7,8-Tetrachlorodibenzodioxin in fish from the Pigeon River of eastern
Tennessee, USA: itstoxicity and mutagenicity as revealed by the Ames Salmonella assay.
Arch. Environ. Contam. Toxicol. 20(3): 366-370.
DeFerrari, M., M. Artuso, S. Bonassi, S. Bonatti, Z. Cavalieri, D. Pescatore, E. Marchini, V. Pisano
and A. Abbondandolo. (1991) Cytogenetic biomonitoring ofan Italian population exposed
to pesticides: chromosome aberration and sister-chromatid exchange analysis in
peripheral blood lymphocytes. Mutat. Res. 260(1): 105-113.
Fahrig, R. (1991) Genetic effects of dioxin. Environ. Mol. Mutagen Suppl. (19): 24-25.
Huff, J., J. Cirvello, J. Haseman and J. Bucher. (1991) Chemicals associated with site-specific
neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents. Environ.
Health Perspect. 93: 247-270.
McGregor, D.B., A.G. Brown, S. Howgate, D. McBride, C. Riach and W.J. Caspary. (1991)
Responses of the L5178Y mouse lymphoma cell forward mutation assay .5. 27 coded
chemicals. Environmental and Molecular Mutagenesis 17(3): 196-219.
Pavlica, M., D. Papes and B. Nagy. (1991) 2,4-Dichlorophenoxyacetic acid causes chromatin and
chromosome abnormalities in plant cells and mutation in cultured mammalian cells.
Mutat. Res. 263(2): 77-81.

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D.

Reproductive and Teratological Effects
Earlier volumes of the Review have documented the work undertaken to evaluate

both the reproductive effects and the teratologic potential of the dioxins and related
compounds.

Most of the studies which have been carried out in humans have been

subject to methodological problems such as recall bias, and various confounding factors
which have served to prevent the studies from reaching definitive conclusions. Among
the experimental systems that have been used to evaluate this activity have been the
induction of cleft palate and hydronephrosis in mice at doses that are not overtly toxic to
the dams or offspring. A few scattered studies concerning the reproductive toxicity and
teratologic effects of 2,4-dichlorophenoxyacetic acid (2,4-D) and dioxin became available
during 1991. Couture etal. (1990) reviewed studies related to this topic, and discussed
the issues of species and organ specificity, and the possible mechanisms responsible for
the observed teratologic effects.

1. Human studies
Lerda and Rizzi (1991) studied the reproductive function of 32 male farm sprayers
who were occupationally exposed to 2,4-D. The level of exposure was estimated by
measuring the concentration of 2,4-D in urine samples (mean level 9.02 mg/l). Sperm
samples obtained from exposed and control subjects were analyzed for asthenospermia,
necrospermia, and teratospermia. Exposed workers exhibited a significant degree of
asthenospermia (49.0 millions/ml), necrospermia (37.1% alive), lowered motility (24.8%
motile) and teratospermia (72.9% abnormal). Corresponding values for the control group
were 101.6 millions/ml, 82.9% alive, 70.4% motile and 33.4% abnormal, respectively.
Following a three month interval, asthenospermia, mobility and necrospermia had
improved in the exposed group, but teratospermia persisted. The authors concluded that
2,4-D at these exposure levels damaged the germinal epithelium resulting in altered
spermatogenesis.
The effects of T C D D on human, mouse and rat embryonic palatal shelves in organ
culture were studied by Abbott and Birnbaum (1991).

Palates were cultured in the

presence of various levels of T C D D to determine points at which cytotoxicity and altered
41

577
£) '-Q0(o

differentiation of medial palatal cells occurred. Cytotoxicity, as detected by transmission
electron microscopy, was observed at 10'10 M T C D D in mouse tissue, but at 10'7 M in rat
and human cultures. Similarly, itwas found that altered differentiation of medial palatal
cells occurred at 5 x 10'11 M T C D D in mouse, but at 10'8 M in rat and human preparations.
The data suggest that the sensitivity of humans to T C D D is similar to that of rats, and that
high levels of T C D D would be necessary to alter human palatal shelf differentiation. This
study also examined the effects of exposure to T C D D on EGF, TGF-/31,TGF-02 and TGFa receptors. At higher T C D D doses, medial epithelial levels of EGF were increased, nasal

epithelial levels of TGF-/31 and TGF-/32 were decreased and TGF-a was decreased in all
epithelial regions. TCDD-induced changes in growth factor expression may be at least
partially responsible for alterations in normal palatogenesis.

2. Animal studies
The effect of T C D D on rat testes was studied by Rune et a/. (1991). Rat testes
were injected with a single dose of T C D D (0.3-25 jug/kg body weight) and examined
seven days later by light and electron microscopy. Exposed testes exhibited decreased
intercellular contacts, sloughing of premature spermatids, and increase in necrotic germ
cells. Cytoplasmic vacuolization, with increases in lipid droplets and phagolysosomes
was also observed in exposed Sertoli cells. No spermatogenic stage-specific sensitivity
to T C D D was found.

T C D D produced a decrease in 3 /3- and 17 /3-hydroxysteroid

dehydrogenase activity at 1 jug/kg body weight, and morphological changes in the
germinal epithelium at 3 /ig/kg body weight.
Chahoud et al. (1991) examined whether paternal exposure to T C D D could
produce abnormalities in the progeny. Male rats were exposed to T C D D weekly for 10
weeks prior to mating, and 12 weeks during the actual mating period. No change was
noted in the number of implantations, the number of fetuses per litter, the resorption rate
or fetal weights. No gross abnormalities were observed. However, a slightly increased
rate of still births was discovered, and incomplete ossification of fingers and ossa
zygomatica was observed in the offspring. The authors concluded that the data do not
demonstrate any "biologically significant paternally-mediated developmental toxicity". On
42

578

the other hand, maternal exposure to T C D D (acute doses of 0.3 or 12 jug/kg by gavage
on gestation day 6) induced hydronephrosis in the offspring of C57BL/6N mice (CoutureHaws et al. 1991). Total incidence of the lesions was 69.50 ± 9.90% at the low, and
72.18 ± 6.11% at the high T C D D doses. Administration of the dioxin to lactating dams
led to essentially the same incidence of hydronephrosis in the nurselings (70.15 ± 7.77
and 64.70 ± 8.32%, respectively), and exacerbated the condition persisting from prior
exposure in utero, giving values of 79.52 ± 7.98 and 88.64 ± 5.30%, for the double
exposure at the high and low dosages, respectively.
The teratogenic effects of brominated dioxins (TBDD) and furans (TBDF) were
studied by Birnbaum etal. (1991). Pregnant mice were injected with 0-4,000 fjg/kg of the
individual T B D D or TBDF congeners. Maternal liver weight increased at all dose levels
without evidence of toxicity, and brominated dioxins and furans produced hydronephrosis
at doses below those at which they induced cleft palate. The incidence of cleft palate fit
a curve with a c o m m o n slope for all four brominated compounds and TCDD, indicating
that a c o m m o n mechanism of action was involved in all cases. Increased fetal mortality
was observed at 500 fjg TBDF/kg. The authors concluded that bromination decreased
the teratogenic activity of T B D D relative to T C D D but increased the potency of TBDF
relative to TCDF. Therefore, the brominated compounds produce the same teratogenic
alterations as their chlorinated congeners but with altered potency. Yasuda et al. (1991)
discovered that exencephalic mouse fetuses were resistant to cleft palate induction by
TCDD.

Pregnant mice were given one of two dosage regimens of CdCI2 in order to

produce exencephalic embryos. Dams were then given 40 jug TCDD/kg on Day 12.5,
and fetuses were examined on Day 18.5. At one dose regimen, 76 % of live fetuses were
exencephalic and did not develop cleft palate.
exencephaly had cleft palate.

All remaining live fetuses without

The other dose regimen produced similar results,

demonstrating resistance to TCDD-induced cleft palate in exencephalic mice.
Reproductive toxicity related to environmental exposure to T C D D was studied in
several different species.

Mink and otter populations were reduced relative to their

proximity to contaminated water sources in the Great Lakes region (Wren 1991). This
reduction was attributed to consumption of contaminated fish by mink and otters.
43

579

Additional research is needed to strengthen the association between chemicals and
reductions in these animal population. Bishop et al. (1991) studied the effects of dioxins,
furans, PCBs and other organochlorine pesticides on turtle eggs. Eggs were examined
for hatching success and the presence of deformities. The eggs obtained from highly
contaminated locales contained higher pesticide residues and were more poorly
developed than those obtained from less polluted areas. Additional controlled studies are
needed to confirm these observations.
The effects of Baltic herring oil and Icelandic cod liver oil on embryos of the
Japanese medaka were studied by Cooper etal. (1991). A commercial Icelandic cod liver
oil and fish oil derived from wild Baltic herring collected from the Gulf of Bothnia, Sweden,
were analyzed for specific dioxin and furan isomers. Both types of oil contained similar
isomers, but the herring oilcontained almost twice the concentration of dioxins and furans
as the Icelandic cod liver oil. This was attributed to the higher level of pollution in the Gulf
of Bothnia. The oils were tested for embryotoxicity in Japanese medaka using an embryo
larval assay. Oil derived from Baltic herring produced hemorrhage, cardiac effects, tissue
necrosis and lethality (30-90%) in exposed medaka. These lesions were not observed in
embryos exposed to the Icelandic cod liver oil or control corn oil. The author cautioned
that the use of contaminated fish oils in hatchery feed may be responsible for the poor
viability of Swedish hatchery salmon. This theory is supported by the presence of lesions
in hatchery-reared fish which resemble those observed in medaka following exposure to
dioxin/furan-contaminated oil.
Recent articles by Ames and Gold (1991) and Myers and Colborn (1991) may be
consulted for a review and discussion of the risk posed by dioxin with regard to
reproductive toxicity and teratology.

44

580

REFEREN CES

Abbott, B. and L. Bimbaum. (1991) TCDD exposure of human embryonic palatal shelves In organ
culture alters the differentiation of medial epithelial cells. Teratology 43(2): 119-132.
Ames, B.N. and L.S. Gold. (1991) Cancer prevention strategies greatly exaggerate risks. Chem.
Eng. News Jan 7: 28-32.
Bimbaum, L.S., R.E. Morrissey and M.W. Harris. (1991) Teratogenic effects of
2.3.7.8- tetrabromodibenzo-p-dioxin and threepolybrominated dibenzofurans inC57BL/6N
mice. Toxicol. Appl. Pharmacol. 107(1): 141-152.
Bishop, C., R. Brooks, J. Carey, P. Ng, R. Norstrom and D. Lean. (1991) The case for a
cause-effect linkage between environmental contamination and development in eggs of
the common snapping turtle (Chelydra serpentina) from Ontario, Canada. J. Toxicol.
Environ. Health 33(4): 521-547.
Chahoud, I., R. Krowke, G. Bochert, B. Burkle and D. Neubert. (1991) Reproductive toxicity and
toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Problem of paternally-mediated
abnormalities in the progeny of rat. Arch. Toxicol. 65(1): 27-31.
Cooper, K.R., H. Liu, P.-A. Bergqvist and C. Rappe. (1991) Evaluation of Baltic herring and
Icelandic cod liver oil for embryo toxicity, using the Japanese medaka (Oryzias latipes)
embryo larval assay. Environ. Toxicol. Chem. 10(6): 707-714.
Couture, L.A., B.D. Abbott and L.S. Bimbaum. (1990) A critical review of the developmental
toxicityand teratogenicity of2,3,7,8-tetrachlorodibenzo-p-dioxin: recent advances toward
understanding the mechanism. Teratology 42(6): 619-627.
Couture-Haws, L., M.W. Harris, A.C. Lockhart and L.S. Bimbaum. (1991) Evaluation of the
persistence of hydronephrosis induced in mice following in utero and/or lactational
exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 107(3): 402412.
Lerda, D. and R. Rizzi. (1991) Study of reproductive function in persons occupationally exposed
to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutat. Res. 262(1): 47-50.
Myers, J.P. and T. Colborn. (1991) Blundering questions, weak answers lead to poor pesticide
policies. Chem. Eng. News Jan 7: 40-43.
Rune, G.M., P. De Souza, R. Krowke, H.J. Merker and D. Neubert. (1991) Morphological and
histochemical pattern of response in rat testes after administration of
2.3.7.8- tetrachlorodibenzo-p-dioxin (TCDD). Histol. Histopathol. 6(4): 459-467.
Wren, C. (1991) Cause-effect linkages between chemicals and populations of mink (Mustela
vison) and otter (Lutra canadensis) in the Great Lakes basin. J. Toxicol. Environ. Health
33(4): 549-585.
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Yasuda, M., T.J. Sato and H. Sumida. (1991) Exencephalic mouse fetuses are resistant to cleft
palate induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Teratology 43(5): 445.

582

E.

Immunological Sequelae
There is a general consensus that 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD)

impacts on the functioning of the immune system.

Studies have consistently

demonstrated that low levels of T C D D affect various lymphocytic subsets. However, itis
difficult to compare directly the various study results due to the diversity of immunological
protocols employed.

Changes in specific study parameters may produce conflicting

results. These parameters include the species employed, age at the time of exposure,
presentation of the antigen relative to T C D D exposure (before, after, or simultaneous),
and the level and duration of exposure. Two reviews were published in 1991 which
discuss the role of T C D D in immunosuppression.

Holsapple ef al. (1991b) reviewed

alterations in the immune system produced by exposure to dioxin, including effects on
specific indicators of immune function, innate and acquired immunity, lymphocytic homing,
and immune function in exposed human populations. In a separate article, Holsapple et
al. (1991a) reviewed the potential mechanisms for TCDD-induced immunosuppression,

including the role of the Ah receptor, phosphorylation, calcium and hormones.

1. Human and Primate Studies
The 1987 Air Force Health Study (Roegner et al. 1991) found no clinically
significant alterations of immune status related to current or initial dioxin levels in Ranch
Hands. There was, however, a significant association between the initial dioxin level and
increased IgA levels in Ranch Hands. Also, in the current report, a composite skin-test
analysis did not demonstrate any dioxin-related effect on delayed hypersensitivity skin-test
responses (DHR). The authors speculated that the abnormal D H R results reported in the
initial analysis of the 1987 follow-up may have been unrelated to dioxin.
Neubert et al. (1991b) studied the effects of T C D D on lymphocytes isolated from
humans and from a non-human primate (Callithrix jacchus, marmoset monkey). When
lymphocytes from either species were cultured in the presence of T C D D and mitogen, a
pronounced decrease in the CD4 (helper/inducer) and CD20+ (B1) lymphocytic subsets
was observed. The percentage of C D 8 + (cytotoxic/suppressor) cells was increased in
most experiments, buttheCD4+CD45+ (suppressor/inducer) population was apparently
47

583 '

not significantly affected. This study is notable in that it describes the lowest T C D D
concentration, 2.5 fg/ml, yet reported to produce a biological effect. Similar results were
obtained in studies with human whole blood, but much higher concentrations of T C D D
(250 fg/ml) were required to produce an effect, and the suppressor/inducer population
was reduced. Similar results were reported by Neubert et al. (1991a) when monkeys
were treated in vivo with a single dose of TCDD. However, Neubert noted that a multiple
dose regimen produced conflicting results in the CD4 subset at high versus low exposure
levels. He cautioned that observations at higher doses should not be extrapolated to very
low exposures. Hong (1991) studied the effects of prolonged T C D D exposure on rhesus
monkeys and their offspring. A decrease in helper (C4+) cells and an increase in
cytotoxic cells were observed in the mothers, but lymphocytic populations were unaltered
in the offspring.

None of the animals exhibited any clinical evidence of immune

suppression.
Waithe et al. (1991) characterized a high-affinity Ah receptor in a human Blymphoblastoid cell line (BCR-5). A complete regulatory mechanism for the Ah-receptor mediated induction of cytochrome P450IA1 was demonstrated in this cell line. The
maximum concentration of Ah-receptor in the cytosol was 200 fmol/mg protein. This
concentration, which is greater than other studies have described for peripheral
leukocytes, may be correlated with the blastoid nature of this particular cell line. This
enhanced concentration of receptors in blastoid cells lends support to the theory that
dioxins primarily effect precursor or immature lymphocytes (Holsapple et al. 1991b).
Lorenzen and Okey (1991) described the presence of a functional Ah receptor in human
tonsils and suggested that tonsil might be an appropriate model for mechanistic studies
of aromatic hydrocarbon-induced immunotoxicity.
Two studies were published in 1991 that examined the potential association
between dioxins/furans and HIV infection. Schecter et al. (1991) examined the dioxin
levels in pooled blood samples from five groups of individuals. These groups included
male homosexual AIDS patients with opportunistic infections (n = 100), male homosexual
AIDS patients with Kaposi’s sarcoma (n = 100), asymptomatic HIV-1 positive male
homosexual patients (n = 100), asymptomatic HIV-1 positive intravenous drug users (n
48

584

= 50), and blood bank controls (n = 100). Toxicity equivalents (TEQ), a measure of the
total toxicity of various P C D D and P C D F congeners, were determined for each group
according to the International Dioxin Toxic Equivalent Factors method. The total TEQs
for HIV-1 positive asymptomatic intravenous drug users and for the Kaposi’s sarcoma
group did not differ significantly from the control group. The total T E Q for HIV-1 positive
asymptomatic homosexual patients (33.3) was significantly less than that of the control
group (42). However, AIDS patients with opportunistic infections had a total T E Q of 52.2,
a statistically significant elevation compared to the total T E Q of the control population.
The authors speculate that HIV-1 positive individuals with a higher dioxin body burden
may be more susceptible to opportunistic infections than those with low to normal dioxin
levels.

This increased susceptibility may be the result of TCDD-induced immune

suppression. Definitive studies of individual patients using age-, race- and sex-matched
controls are needed to confirm these preliminary findings. The role of T C D D as a
possible activator of HIV infection was studied by Pokrovsky et al. (1991). The effects of
10-150 N m T C D D on HIV reproduction in lymphoid cell cultures was examined. T C D D
did not produce toxic effects on MT-4 cells at this concentration. However, HIV viral
production, as evaluated by viral antigen determination and reverse transcriptase activity,
was increased in MT-4 cells after exposure to TCDD. The phenomenon may be related
to T C D D bound to the Ah receptor since removal of free T C D D did not alter the activation
of HIV. The authors speculate that T C D D may alter HIV regulatory gene expression. The
activation of viral production could also result from actions on transcription, processing,
R N A stability, translation or protein stability.

2. Animal Studies
Early immunotoxicity studies demonstrated that thymic involution occurred as a
consequence of T C D D exposure. The nature of thymic involution has been a source of
some controversy. Some investigators have suggested that T C D D directly affects thymic
lymphocytes, while others believe that it is the thymic epithelia which sustain damage.
Several 1991 studies addressed this issue.

49

585

Korte et al. (1991 b) injected pregnant rats with T C D D (0.3 pg/kg body weight) and
demonstrated that in utero exposure to T C D D caused thymic involution in offspring.
Andersson et al. (1991) studied the effects of coplanar polychlorinated biphenyls and
T C D D on thymus organ cultures from fetal mice. Lymphoid development was inhibited
in the presence of these compounds. These workers also found a decreased number
of lymphoid cells in thymuses isolated from chicks which had been injected with T C D D
in ovo.

Lundberg (1991) injected mice with 50 pg/kg body weight of T C D D and examined
the thymuses on days 1,2,4 and 8 after exposure. Cell proliferation within the thymus was
decreased by 50% and cell number by 20%, on the second day of exposure. Proliferation
increased on Day 3 but cell number continued to decrease throughout the 8-day
observation period.

Lymphocytic subpopulation analysis revealed that the immature

precursor lymphocytes CD4 + C D 8 + (double positive) and CD4-CD8- (double negative)
cells continued to decrease for twenty days after exposure, but mature helper/inducer
(CD4+) and suppressor/cytotoxic (CD8+) cells were only marginally affected by TCDD.
The author suggested that T C D D may induce thymic atrophy by inhibiting cell proliferation
and disturbing the lymphocytic selection/differentiation process. However, the author
believed that a direct action of T C D D on thymocytes is unlikely, since cell number did not
decrease immediately, and the C D 4 + and C D 8 + subsets were only marginally affected.
Additional evidence that T C D D inhibits normal thymocyte maturation was presented by
Holladay et al. (1991). Pregnant mice were treated with T C D D (1.5 or 3.0 jug/kg/day) on
gestational days 6-14. TCDD-exposed offspring exhibited severe thymic atrophy and
cellular depletion when examined pre- or post-natally. No change in cellular distribution
was found, but distinctive alterations in thymocyte subsets were discovered. Immature
thymocyte populations (CD4-8- and CD4-8+) were increased with TCDD-exposure, but
thymocytes further along the differentiation pathway (CD4 + 8+) were decreased in
number. Therefore, the authors suggest that T C D D interferes with normal thymocyte
differentiation.
Van Loveren et al. (1991) demonstrated the reversibility of TCDD-induced thymic
atrophy. Male rats were exposed to 50 fig of TCDD/kg body weight. The right thymus
50

586
p-4!

lobes from treated and control rats were transplanted to 9-week-old rats and the vascular
connections were restored. The left thymus lobes were used to determine the number
of lymphocytes present at the time of transplantation. The thymus tissue of untreated rats
exhibited “normal histology, but TCDD-treated animals had a severe depletion of cortical
elements. Recipient animals were sacrificed twenty days after transplantation and the
grafted thymus lobes were examined. A full restoration of thymic size and architecture
had occurred in the interim, and the grafts exhibited normal cellular subset composition.
The authors conclude that the epithelial component of the thymus sustained reversible
TCDD-induced damage, and restoration of normal morphology was accompanied by an
influx and expansion of new progenitor cells from the recipient’s bone marrow. These
three studies by Lundberg, Holladay and Van Loveren support the contention that T C D D
inhibits lymphocyte differentiation indirectly by altering the cellular microenvironment.
The mechanisms responsible for TCDD-induced thymic involution are unclear.
Morris et al. (1991d) designed a study to determine the role of the Ah receptor in thymic
involution. They compared Ah-high-responder (B6C3F1) and Ah-low responder (DBA/2)
strains of mice which were administered acute (4.2,14 or 42 /jg/kg by oral gavage) and
subchronic (0.3, 1.0, or 3.0 /jg/kg by oral gavage for 14 days) doses of TCDD. B6C3F1
mice exhibited an abrupt, dose-related decrease in thymus and spleen weights with acute
exposure, whereas DBA/2 mice exhibited a decrease in thymus and spleen weights only
at the highest acute dose of TCDD. This would tend to support an Ah-receptor-related
mechanism for thymic involution. However, conflicting results were obtained when the
subchronic dosage regimen was used. Wh e n both strains of mice were exposed to
T C D D over a 14-day period, thymic involution in the Ah-low responder strain was greater
than that exhibited by the Ah-high responder strain with either acute or subchronic dosing
(68% versus 56% decrease after a total dose of 42 /L/g/kg). This suggests that multiple
mechanisms may be involved in TCDD-induced thymic involution, and that the conditions
of exposure may alter the toxic effects.
The effects of T C D D on peripheral lymphocytes were also examined by several
investigators in 1991.

Analysis of subpopulations of lymphocytes following T C D D

exposure have produced a number of theories concerning the mechanism(s) responsible

51

for TCDD-induced immunosuppression. Several investigators have found a deficit in the
T-helper cell population as a consequence of T C D D exposure. Tomar and Kerkvliet
(1991) evaluated the role of T-helper cells in the TCDD-induced suppression of the
antibody response. Mice were primed with the T-cell-dependent antigen S R B C (sheep
red blood cells) and simultaneously exposed to TCDD. Whe n spleen cells from these
mice were cultured with a hapten-antigen (TNP-SRBC), a reduced anti-hapten response
was observed compared to controls. To confirm that T-helper cells were responsible for
the decreased antibody response, unexposed B cells were incubated with T cells primed
by simultaneous exposure to the carrier hapten and TCDD. The anti-hapten response
was profoundly suppressed, and removal of the suppressor cell population did not
increase this response. These results indicate a reduced T-helper activity inTCDD-primed
T cells as opposed to the generation of suppressor cells.
Lundberg et al. (1991) used the popliteal lymph node assay to study the effects
of T C D D on the immune response to the T-dependent antigen, ovalbumin. Ovalbumin
was injected into the hind foot pads of mice 4 days after T C D D exposure. Exposed
animals exhibited a decreased cell number in lymph nodes, a reduced population of
antigen-specific B cells, and an impairment of T cell function in the DTH (delayed type
hypersensitivity) assay. Isolated B cells retained the ability to produce antibody and their
proliferation was not affected in response to an in vivo secondary immunization. Antigenpresenting cells (APC) were also relatively unaffected. The results of this and the previous
study suggests that T C D D exposure alters T cell function which then leads to impaired
B cell activation. The popliteal lymph node assay was also used by Korte et al. (1991a)
to study TCDD-induced immunosuppression in rats. No immunosuppressive response
to human R B C antigen was demonstrable with T C D D exposures of up to 600 ng/kg body
weight. The authors suggested that this assay is not sensitive enough to detect small
immunotoxic effects and that itproduces a wide variability in the data. This conflicts with
the clear response described in the previous study by Lundberg et al. (1991). These two
studies differed, however, in several experimental parameters, such as the species used
(mice, rats), the time interval between antigen exposure and assay (4 days, 7 days), and
the level of exposure (50 /j g/kg vs. 0.06-600 ng/kg). Couture et al. (1990) reviewed

52

differences in sensitivity to T C D D with respect to developmental toxicity and pointed out
that rats are 200-fold less sensitive to the toxic effects of T C D D than mice. Perhaps a
differential species sensitivity to T C D D could account for the lack of response observed
in rats with this assay, and therefore for the disparate results between the two studies.
Morris and Holsapple (1991a) have also examined the TCDD-induced suppression
of the T-dependent antibody response to SRBC.

Their results suggest a mechanism

which differs from that proposed inthe previous studies, one involving the direct activation
by T C D D of resting B cells. Spleen-derived resting B cells, which had not been previously
exposed to antigen, were exposed to T C D D in vitro. An increase in total IgM occurred
on day 7, but itwas noted that only certain lots of serum could support this in vitro B cell
activation. In a comparable study, SRBC-sensitized and unsensitized mice were exposed
to T C D D for 5 days. Isolated splenic B cells from unsensitized mice again exhibited a
serum-dependent proliferation. SRBC-sensitized mice had a complete loss oftheir splenic
B cell population, indicating movement of these cells to the blastogenic stage. T-helper
cells were apparently not required, since B cells could be activated by T C D D without
antigen sensitization. The activation was dependent on the presence of serum in vitro,
and appeared to be intensified by the presence of antigen in vivo.

The evidence

implicates the direct activation of B cells by TCDD.
In an extension of this work, Morris and Holsapple (1991b) demonstrated that, in
the absence of serum, y-IFN (gamma interferon) could potentiate the proliferation of
resting B cells and IL-2 (interleukin 2) inhibited this co-stimulatory activity. TCDD, IL-2 and
y-IFN alone had no effect on B cell proliferation. These data demonstrate a direct
interaction of these compounds with B cells, and supports the role of cytokines in
modulating the immune response to TCDD. The modulation of B cell activation by serum
factors was examined in additional studies by Morris etal. (1991c). T C D D mirrored the
action of Staphylococcus aureus Cowan Strain I(SAC), a polyclonal B cell activator. Both
T C D D and S A C suppressed the T-dependent antibody response to S R B C in a serumdependent manner. In the absence of serum, T C D D and S A C produced an increase in
B cell activation. The authors postulated that T C D D produces an "activation-like" signal
for the B cell, and the presence or absence of serum indirectly modulates this action.

53

589

Davis and Safe (1991) published additional evidence for the existence of multiple
mechanisms in TCDD-induced immune suppression. a-Naphthoflavone is considered to
have moderate affinity for the Ah receptor and to have weak agonist activity. TCDD, a
strong Ah receptor agonist, and 1,3,7,8-TCDF (tetrachlorodibenzofuran), a weak Ah
receptor agonist, have comparable immunosuppressive potencies. Cotreatment ofmouse
spleen cultures with 20 M m T C D D and 10/jM a-naphthoflavone significantly inhibited the
immunosuppressive activity of TCDD. A similar inhibition of immunosuppressive activity
was observed by cotreatment of spleen cultures with 1,3,7,8-TCDF and a-naphthoflavone.
a-Naphthoflavone was equally effective in modifying the immunosuppressive activity of
both a strong (TCDD) and a weak (TCDF) Ah-receptor agonist. The evidence, therefore,
does not support a role for the Ah receptor in mediating the immunosuppressive action
of these compounds.
Morris et al. (1991d) and Holsappleetal. (1991c) have also recently published data
which support the operation of multiple mechanisms in the immune suppression induced
by dioxin. Ah-high-responder (B6C3F1) and low-responder (DBA/2) mice were treated
with either acute or subchronic doses of TCDD. Subchronic exposure to T C D D (0.1,0.3,
1.0, or 3.0 ¿/g/kg/day for 14 days) of Ah-low-responder mice increased the suppression
of humoral immunity 10-fold over that produced by acute exposures to the same
cumulative T C D D dose. Thymic involution in the Ah-low-responders was also enhanced
with subchronic exposure and exhibited a higher degree of atrophy than was observed
in the Ah-high-responder line. This evidence suggests that whereas the Ah receptor may
play a major role inthe immunosuppression produced by a single exposure to high doses
of TCDD, it plays only a minimal role in immunosuppression produced by subchronic
exposure to much lower doses. T C D D may suppress humoral immunity through multiple
mechanisms.
Clark et al. (1991) studied the role of tyrosine phosphorylation in TCDD-induced
immunosuppression.

Within minutes of T C D D exposure, an increase in membrane

phosphorylation was observed. Two major, previously-identified, tyrosine-specific kinases
(Mr 54,000 and 61,000 proteins) of murine B lymphocytes exhibited a TCDD-dosedependent increase in autophosphorylation. T C D D also increased the tyrosine-specific

54

590
j)- ¿ I ?

phosphorylation of two additional proteins (Mr 78,000 and 90,000). Phosphorylation also
occurred on tyrosine residues of a synthetic exogenous substrate as early as 5 minutes
after T C D D exposure. The protein synthesis inhibitors puromycin and cycloheximide
reduced tyrosine phosphorylation by 32 % and 90%, respectively, and the transcriptional
inhibitor actinomycin D inhibited the response by 98%.

This suggests that tyrosine

phosphorylation is mediated partially by transcriptional events, and that de novo synthesis
of new protein may occur. The authors demonstrated that the T C D D dose-response for
phosphorylation was identical to that for the inhibition of antibody synthesis. Tyrosine
kinase activity has been linked to lymphocyte maturation in several studies (Bombick et
al. 1987; 1988). The cloning of the hck gene, which apparently codes for a tyrosine

kinase associated with hematopoietic cell differentiation, supports the role of tyrosine
kinases in lymphocytic differentiation (Quintrell etal. 1987; Ziegler etal. 1987). Previous
reports have also linked T C D D to other activities which are associated with tyrosine
kinase activity, such as the down-regulation of EGF receptors and an early increase in
hepatic tyrosine-specific kinase activity.
In light of the complex findings of the studies described in this Section, continued
investigation of TCDD-induced immune suppression, with emphasis on the possible role
of multiple dose-dependent mechanisms, is certainly warranted.

In attempting to

extrapolate the findings in experimental animals to humans, several points must be
considered. First, the type of effects that predominate, which involve both B and T cell
function, as well as altered lymphocyte maturation, are likely to lead to generalized
immunosuppression rather than lesions in a specific function. Ranch Handers and other
exposed human populations should be followed up with this in mind. Second, there
appear to be major differences in species sensitivity to TCDD, and itis not yet clear which
animal model best approximates to humans. Finally, the apparent existence of different
mechanisms operating under conditions of acute and chronic exposure, may mean that
immune effects differ according to the type of exposure received. Chronic occupational
exposures may yield a different pattern or intensity of effects from that observed after an
acute episode such as the Seveso incident.

55

REFERENCES

Andersson, L., E. Nikolaidis, B. Brunstrom, A. Bergman and L. Dencker. (1991) Effects of
polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the
thymus and the bursa of Fabricius of chick embryos in ovo and in mouse thymus
anlagen in vitro. Toxicol. Appl. Pharmacol. 107(1): 183-188.
Bombick, D.W., J. Jankun, K. Tullis and F. Matsumura. (1988) 2,3,7,8-Tetrachlorodibenzo-p-dioxin causes increases in expression of C-erb-A and levels of protein-tyrosine
kinases in selected tissues of responsive mouse strains. Proc. Natl. Acad. Sci. USA 85:
4128-4132.
Bombick, D.W. and F. Matsumura. (1987) TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) causes
increases in protein kinase activities at an early stage of poisoning in vivo in rat
hepatocyte membranes. Life Sci 41: 429-436.
Clark, G.C., J.A. Blank, D.R. Germolec and M.l. Luster. (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulation of tyrosine phosphorylation in B lymphocytes: potential role
in immunosuppression. Mol. Pharmacol. 39(4): 495-501.
Couture, L.A., B.D. Abbott and L.S. Birnbaum. (1990) A critical review of the developmental
toxicityand teratogenicity of2,3,7,8-tetrachlorodibenzo-p-dioxin: recent advances toward
understanding the mechanism. Teratology 42(6): 619-627.
Davis, D. and S. Safe. (1991) Halogenated aryl hydrocarbon-induced suppression of the in vitro
plaque-forming cell response to sheep red blood cells is not dependent on the Ah
receptor. Immunopharmocology 21(3): 183-190.
Holladay, S.D., P. Lindstrom, B.L. Blaylock, C.E. Comment, D.R. Germolec, J.J. Heindell and M.l.
Luster. (1991) Perinatal thymocyte antigen expression and postnatal immune
development altered by gestational exposure to tetrachlorodibenzo-p-dioxin (TCDD).
Teratology 44(4): 385-393.
Holsapple, M., D. Morris, S. Wood and N. Snyder. (1991a) 2,3,7,8-Tetrachloro-dibenzo- pdioxin-induced changes in immunocompetence: possible mechanisms. Annu. Rev.
Pharmacol. Toxicol. 31: 73-100.
Holsapple, M., N. Snyder, S. Wood and D. Morris. (1991b) A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update. Toxicology
69(3): 219-255.
Holsapple, M.P., N.K. Snyder, V. Gokani, R.E. Blair and D.L. Morris. (1991c) Role of Ah-receptor
in suppression of in vivo antibody-response by 2,3,7,8-tetrachlorodibenzo-para-dioxin
(TCDD) is dependent on exposure conditions (Abstract). FASEB J. 5(4): 508.
Hong, R. (1991) Effects of environmental toxins on lymphocyte function: studies in rhesus and
man. Ann. Allergy 66(6): 474-480.
56

Korte, M., R. Stahlmann, M. Kubickamuranyi, E. Gleichmann and D. Neubert. (1991a)
Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune-system. 3. No
immunosuppressive effect of 2 ,3 ,7 ,8 -TCDD ¡n the popliteal lymph-node assay (PLNA) in
rats. Arch. Toxicol. 65(8): 656-660.
Korte, M., R. Stalhlmann, R. Thiel, T. Nagao, I. Chahoud, H. Van Loveren, J.G. Vos and D.
Neubert. (1991b) Resistance to Trichinella spiralis infection, induction of hepatic
monooxygenases, and concentrations inthymus and liver in rats after perinatal exposure
to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 23(11-12): 1845-1854.
Lorenzen, A. and A.B. Okey. (1991) Detection and characterization of Ah receptor in tissue and
cells from human tonsils. Toxicol. Appl. Pharmacol. 107(2): 203-214.
Lundberg, K. (1991) Dexamethasone and 2,3,7,8-tetrachiorodibenzo-p-dioxin can induce thymic
atrophy by different mechanisms in mice. Biochem. Biophys. Res. Commun. 178(1):
16-23.
Lundberg, K., K.O. Gronvik and L. Dencker. (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
induced suppression of the local immune response. Int. J. Immunopharmacol. 13(4):
357-368.
Morris, D.L. and M.P. Holsapple. (1991a) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
on humoral immunity: II. B cell activation. Immunopharmacology 21(3): 171-181.
Morris, D.L. and M.P. Holsapple. (1991b) G a m m a interferon G-IFN potentiates the activation and
proliferation ofdense resting B cellsby 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD. FASEB
5(5): 1206.
Morris, D.L., S.D. Jordan and M.P. Holsapple. (1991c) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: I.Similarities to Staphylococcus aureus
Cowan strain I (SAC) in the in vitro T-dependent antibody response.
Immunopharmacology 21(3): 159-169.
Morris, D.L., N.K. Snyder, V. Gokani, R.E. Blair and M.P. Holsapple. (1991d) Enhanced
suppression of humoral immunity in DBA/2 mice following subchronic exposure to
2.3.7.8- tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Appi. Pharmacol. 112(1): 128-132.
Neubert, R., H. Helge, R. Stahlmann and D. Neubert. (1991a) Some effects of 2,3,7,8tetrachlorodibenzo-para-dioxin (T4CDD) and of 2,3,4,7,8-pentachlorodibenzofuran
(P5CDF) on peripheral lymphocytes of primates in vivo and in vitro. Allergologie 14(9):
360-371.
Neubert, R., U. Jacob-Muller, H. Helge, R. Stahlmann and D. Neubert. (1991b) Polyhalogenated
dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In vitro effects of
2.3.7.8- tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man
and a non-human primate (Callithrix jacchus). Arch. Toxicol. 65(3): 213-219.

57

Pokrovsky, A.G., A.I. Cherykh, O.N. Yastrebova and I.B. Tsyrlov. (1991) 2,3,7,8tetrachlorodibenzo-p-dioxin as a possible activator of HIV infection. Biochem. Biophys.
Res. Commun. 179(1): 46-51.
Quintrell, N., R. Lebo, H. Varmus, J.M. Bishop, M.J. Pettenati, M. LeBeau, M.O. Diaz and J.D.
Rowley. (1987) Identification of a human gene (HCK) that encodes a protein-tyrosine
kinase and is expressed in hemopoietic cells. Mol. Cell Biol. 7: 2276-2285.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson. (1991) An
epidemiologic investigation of health effects in Air Force personnel following exposure to
herbicides. Introduction, background and conclusions. Air Force Health Study Chapters
1-5, 18, 19: 1-133.
Schecter, A.J., B.J. Poiesz, P.W. Brandt-Rauf, O. Papke and M. Ball. (1991) Dioxin levels in blood
of AIDS patients and controls. Med. Sci. Res. 19(9): 273-275.
Tomar, R.S. and N.l. Kerkvliet. (1991) Reduced T-helper cell function in mice exposed to 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Lett. 57: 55-64.
Van Loveren, H., H-J. Schuurman, J. Kampinga and J.G. Vos. (1991) Reversibility of thymic
atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and bis(tri-n-butyl)oxide
(TBTO). Int. J. Immunopharmacol. 13(4): 369-377.
Waithe, W., M. Michaud, P. Harper, A. Okey and A. Anderson. (1991) The Ah receptor,
cytochrome P450IA1 m R N A induction, and aryl hydrocarbon hydroxylase in a human
lymphoblastoid cell line. Biochem. Pharmacol. 41(1): 85-92.
Ziegler, S.F., J.D. Marth, D.B. Lewis and R.M. Permutler. (1987) Novel protein-tyrosine kinase
gene (hck) preferentially expressed in cells of hematopoietic origin. Mol. Cell Biol. 7:
2276-2285.

594

F.

Neurobehavioral Effects and Appetite Suppression
A limited amount of new data on the neurobehavioral effects of the subject

herbicides and T C D D became available during 1991.

Although some follow-up

information was published on Vietnam veterans and on the civilian group who suffered
Yucheng disease in Taiwan, most reports dealt with the problems of appetite suppression
and myotonia in animals.

1. Human Studies
The Air Force Health Study report by Roegner et al. (1991) sought to relate any
neurobehavioral changes in the Ranch Hand cohort to current and estimated initialT C D D
levels, on the basis of three models, details of which may be found in Section III A.
Neurological assessment of the veterans was based on physical examination of cranial
nerve function, peripheral neurologic status and central coordination processes.

In

contrast to earlier studies of Ranch Hand personnel, there was no evidence of any
association between dioxin and increased incidence of benign essential tremor. Also, no
significant findings were made with respect to peripheral neuropathies, although both
animal and human occupational data has established that heavy exposure to T C D D can
give rise to such disorders, as for example in the Seveso incident in Italy in 1976, when
T C D D was released in quantity (Bertazzi 1991). On the other hand, in agreement with
previous reports, there was a significant association between dioxin and the results of the
C N S index, a composite of coordination, tremor and gait, on the basis of model 3 (only
current dioxin levels in Ranch Handers and the cohort of comparisons). The adjusted
model 1 (initial dioxin estimated by first order kinetics, Ranch Handers only) data were
significant for the C N S index, and marginally significant for coordination alone; when the
maximal assumption was used (all Ranch Handers with T C D D levels > 5 ppt) the C N S
index results were only marginally significant.
Psychological assessment of the veterans relied on reported sleep disorders,
verified psychological disorders, and two clinical psychology tests: the Symptom Check
List-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory (MCMI). SCL-90-R
is a list of 90 physical and mental symptoms that provide a measure of health-related
59

595

concerns, anxiety, depression and emotional discomfort, while the MCMI supplements this
assessment in the areas of depression, anxiety and hypochondriasis, but in addition, also
provides a screen for personality patterns and disorders, and the major psychiatric
syndromes. The unadjusted SCL-90-R variables often were associated significantly with
dioxin, but when an adjustment for covariates was made they generally became non­
significant. This was particularly true of the education covariate, which was correlated
with dioxin levels because of the relationship of each with military rank and occupation;
as will be described in Section V, rank was correlated with dioxin. Of the 20 MCMI
results, 9 were significant under the minimal or maximal assumptions for initial T C D D
levels; schizoid, avoidant, dependent, schizotypal, somatoform, psychotic thinking and
psychotic depression scores showed a positive association, and histrionic and narcissistic
scores a negative. This association held for most variables using model 2 analysis of
Ranch Handers whose service in Vietnam had taken place more than 18.6 years before,
while for model 3, Ranch Handers in the high current dioxin group had higher mean
schizoid and schizotypal, and lower mean histrionic scores than Comparisons with
background TCDD.

Interpretation of these results is difficult because of the conflict

between the verified psychological disorder questionnaire and the SCL-90-R, with their
essentially negative findings, on the one hand, and the MCM I scores, with many
correlations, on the other. It is significant that dioxin correlated with the fewest MCMI
scores on the basis of model 3, which makes no assumptions about either initial levels
or the pharmacokinetics of TCDD, but only includes current levels of dioxin in the total
Ranch Hand and Comparison cohorts; this probably represents the most rigorous test
of any association. Furthermore, the authors of the report felt that substantial overlap in
the construction of the test scales might contribute to many of the M C M I findings. Overall
itwould not appear that there is convincing evidence of a significant psychological deficit
among veterans resulting from Vietnam-era exposure to dioxin.
In 1979, there was an episode of poisoning (Yucheng disease) involving over 2,OCX)
people in Taiwan, associated with the consumption between May and October of that
year of cooking oil contaminated with PCBs and their PCD F breakdown products. Further
details of this event, and of studies undertaken to monitor the exposed population, may
60

596

be found in Section V of this report, and in earlier volumes of the Review. Yu etal. (i9. ;
studied 128 children born to wome n involved in this episode, and who thus had been
exposed to the compounds either transplacentally or through contaminated breast rn'"K.
This survey was carried out in 1985, 6 years after the initial episode, and involvec
interviews with parents, neurological examinations for the categories of prewalkers and
walkers (Perinatal Collaborative Study criteria of the U.S. National Institute of Neurological
Diseases and Blindness), and standard cognitive tests. In order to remove the variability
created by comparing groups of children of differing ages and developmental status, the
developmental scores were adjusted by adding or subtracting to all scores of a given test,
a constant chosen so as bring the means of the control group, over all time points, to
100. This was done, for example, for the Bayley scores and the WISC full and StanfordBinet Iqs.

Exposed children reached 32 of the 33 items used as milestones in the

interviews with parents, at a later time than controls, with the differences reaching
statistical significance in 9 at p < 0.05 and in a further 6 at p < 0.1.

Neurologic

evaluations indicated that exposed children were uniformly delayed at milestones
occurring at 18 months of age or more, but not at earlier times. There was an overall
impression of developmental or psychomotor delay in 12% of the exposed versus 2 % of
the control children, and of speech problems in 7 % and 3 % in these groups, respectively.
Bayley mental development and psychomotor development indices were both delayed
significantly compared with controls (p < 0.05). On an individual basis, delays tended to
be more pronounced for physically smaller children, in those who had evidenced some
physical signs of intoxication, and in those with a history of problems with nail growth.
Those delayed at initial evaluation also tended to be delayed at the 6-, 12- and 18-month
follow-ups. Among the 36 children in w h o m PC B levels in the blood were determined,
children with detectable concentrations tended to have lower developmental scores.
Although they were not detected in the children, PCDFs which are more toxic, were
measured in adults, and might have played a role in delayed development.

6 1

597

£)'(oZ(°

2. Studies in Animals
Most of the studies carried out in animals have addressed the hypophagia and
wasting syndrome characteristic of acute T C D D intoxication. One other characteristic is
the extreme variation in sensitivity to dioxin, and Tuomisto and Pohjanvirta (1991a) have
reviewed their series of studies which employed two rat strains of widely different
sensitivity to study the regulation of food intake. Han/Wistar (H/W) rats tolerate doses
up to 3,OCX) yug/kg, whereas 20 /L/g/kg is lethal to Long-Evans (L-E) rats, yet the two
strains behave essentially similarly in terms of the pharmacokinetics of TCDD, Ah receptor
binding, induction of P450 and associated hepatic enzymes, and other endocrinologic and
biochemical changes.

Hepatocyte swelling and vacuole formation, appearance of

multinucleated cells, and infiltration of the liver by inflammatory cells, seen in L-E rats
given a lethal dose of TCDD, were probably related to increased lipid peroxidation, made
evident by the thiobarbituric acid method. With careful pair feeding, to correct for the
tendency for TCDD-treated rats to scatter their feed, both control L-E and H / W rats
exhibited similar signs of lipid peroxidation, and it was evident that the liver changes
reflected the effects of starvation rather than of TCDD. The main difference between the
strains was that after an initial period of anorexia following T C D D treatment, H / W rats
started to eat in 1 to 2 weeks, whereas L-E rats did not eat again before they died. The
data could reflect a biochemical lesion associated with gluconeogenesis, a topic which
will be discussed in Section VI. T C D D also was more toxic in terms of hypophagia, when
given by the intraventricular route, suggesting a central mediation of the effect. Although
they recovered and recommenced feeding, even at 2 months after T C D D treatment, H / W
rats displayed an absence of the 2-deoxyglucose feeding response, coupled with a
hypersensitive satiety response to glucose, and more pronouncedly, to fructose.
The same group has further characterized the satiety signals in male H / W rats
(Pohjanvirta etal. 1991). The animals received a high but non-lethal dose (1,000 //g/kg)
of TCDD, which led to a sustained inhibition of body weight gain throughout the
experiment. At various times between 2 and 90 days, feed intake was stimulated by
depriving the animals of food for a 24-hour period. When starved TCDD- treated rats
were allowed to drink 20% glucose or 0.25% saccharin solutions before access to feed,

62

598
£>-<.2.1

food consumption was reduced 50% in the glucose group. This effect was not seen in
controls.

Direct infusion of glucose solution into the stomach produced a longer

suppression of feed intake in TCDD-treated than in control rats. In contrast, TCDDtreated rats were not hyperresponsive to intraperitoneal administration of sterile 30%
glucose solution; earlier irreproducibility of the parenteral glucose effect was related to
problems with tonicity of the solution. T C D D failed to affect significantly the suppressive
effects of sulfated cholecystokinin octapeptide (CCK-8) or bombesin on feeding. Oral
administration of corn oil also reduced feed intake, but the effect was only slightly greater
in the TCDD-treated rats. These data indicate that some gastrointestinal factor(s) is
responsible for the T C D D effect. Interestingly, in these studies the TCDD-treated animals
consumed more saccharin than glucose solution, suggesting that an aversive response
to a sweet taste was not responsible for the phenomenon.

That such an aversive

response could operate is suggested in a study by Daly (1991), who fed rats a diet
supplemented with salmon from Lake Ontario which are significantly contaminated with
PCBs, dioxins and other chlorinated organics. The exposed group showed a much larger
contrast (depression) effect to offering a small food reward than did control animals, when
they were switched from receiving 15- to 1-pellet rewards for running down an alley.
Several studies attempted to relate T C D D anorexia to changes in humoral factors.
While they had shown earlierthat brain serotonin levels were elevated inTCDD-intoxicated
rats, Stahl et al. (1991) found that depletion of brain serotonin by up to 90%, as a result
of intracerebroventricular injection ofthe neurotoxin 5,7-dihydroxytryptamine, did not affect
the reductions in body weight and feed intake induced by TCDD.

Maintenance of

nutritional homeostasis has generally been ascribed to the hypothalamus, and Tuomisto
et al. (1991b) used HPLC techniques to measure histamine concentrations in ten

hypothalamic nuclei, the pineal and the cortex. The only region in which an effect of
T C D D was evident was the median eminence, where histamine levels were significantly
elevated (p < 0.01, f-test). Elevated histamine levels in the whole hypothalamus have
been associated with decreased feed intake by the same workers, but the extreme
localization of these findings in TCDD-treated rats makes itunlikely that they are involved
in producing the hypophagia. Another hypothalamic system that has been associated

63

will i down regulation of feeding behavior is that involved in /3-endorphin action. A single
dose of T C D D (50 £/g/kg, below the LDM of 60 /jg/kg) given to Sprague-Dawley rats,
induced hypophagia and weight loss, accompanied by values for hypothalamic 0 -

endorphin that were 166%, 39% and 49% of control on days 1, 2 and 3, respectively.
Total brain mu-receptor content rose from 53.3 ± 7.3 fmol/mg in control rats to 85.6 ±
3.5 fmol/mg at day 3 after T C D D treatment, an approximately 60% increase (p < 0.05);
the value for food restricted animals at 52.0 ± 5.3 fmol/mg was unaffected.

Also

unaffected in both T C D D and diet restricted rats was the binding affinity of mu-receptor
for 0 -endorphin. This serves as evidence that 0 -endorphin may play a role in T C D D
hypophagia.
A three-part study of the toxicity of 2,4-D and 2-methoxy-3,6-dichlorobenzoic acid
(dicamba) in dogs was reported from the veterinary group at the University of Illinois
(Arnold et al. 1991a; Arnold et al. 1991b; Beasley et al. 1991). The toxicity of 2,4-D in
dogs is generally considered to be moderate, with an acute oral LD^ of 100 mg/kg, and
gastrointestinal irritation, and muscular or neuromuscular weakness. The LD^ for most
mammals is in the range of 300 to 1,000 mg/kg, and the greater sensitivity of dogs may
reflect limited renal organic anion transport. A dose escalation study, in which doses
were spaced at least 1 month apart, showed that English Pointers given 2,4-D at 175 or
220 mg/kg developed both clinical and electromyographic (EMG) evidence of myotonia
or pseudomyotonia. Subclinical evidence of myotonia was detected with the E M G at
86.7, 43.7 and 8.8 mg/kg, but not at 1.3 or 1 mg/kg. Dicamba appeared to be more
toxic than 2,4-D, since 86.7 mg/kg of this herbicide gave both clinical and E M G changes
similar to those given by the highest dose of 2,4-D.

In a dog given 175 mg/kg of

encapsulated 2,4-D, mild sedation and excessive slowing of the electroencephalogram
(EEG) with loss of low voltage fast activity were seen at 24 hours, whereas at 220 mg/kg,
EEG changes suggestive of irritation and mild seizure activity appeared at 7 hours, with
return to normal by 24 hours. No EE G changes were seen at lower doses. In an attempt
to determine ifthese physiological changes could be induced when the dogs ran free for
1 or 7 days on 2,4-D-treated lawns, three outdoor grass-plot enclosures were used,
sprayed with the dimethylamine formulation of 2,4-D at maximum recommended, and 4-

64

600

times maximum recommended levels, or with the vehicle alone. There was no evidence
of electrocardiographic, EEG, EMG, clinical, hematologic or biochemical changes in the
exposed dogs, nor could any gross pathologic or histologic effects be seen postmortem.
However, at 24 hours, the measured serum levels of 2,4-D were within an order of
magnitude of those found in dogs given the herbicide orally and exhibiting signs of
myotonia.

65

601
£ > £ ,3 0

REFEREN CES

Arnold, E.K., V.R. Beasley, A.J. Parker and J.R. Stedelln. (1991a) 2,4-D toxicosis II:a pilot stud^
of clinical pathologic and electroencephalographic effects and residues of 2,4-D in orally
dosed dogs. Vet. Human Toxicol. 33(5): 446-449.
Arnold, E.K., R.A. Lovell, V.R. Beasley, A.J. Parker and J.R. Stedelin. (1991b) 2,4-D toxicosis III.
an attempt to produce 2,4,-D toxicosis in dogs on treated grass plots. Vet. Human
Toxicol. 33(5): 457-461.
Beasley, V.R., E.K. Arnold and R.A. Lovell. (1991) 2,4-D Toxicosis 1: a pilot study of 2,4dichlorophenoxyacetic acid- and dicamba-induced myotonia in experimental dogs. Vet.
Human Toxicol. 33(5): 435-440.
Bertazzi, P. (1991) Long-term effects of chemical disasters. Lessons and results from Seveso.
Sci. Total. Environ. 106(1-2): 5-20.
Daly, H. (1991) Reward reductions found more aversive by rats fed environmentally contaminated
salmon. Neurotoxicol. Teratol. 13(4): 449-453.
Pohjanvirta, R., M. Unkila and J. Tuomisto. (1991) Characterization of the enhanced
responsiveness to postingestive satiety signals in 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD)-treated Han/Wistar rats. Pharmacol. Toxicol. 69(6): 433-441.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson. (1991) An
epidemiologic investigation of health effects in Air Force personnel following exposure to
herbicides. Introduction, background and conclusions. Air Force Health Study Chapters
1-5, 18, 19: 1-133.
Stahl, B.U., R.H. Alper and K. Rozman. (1991) Depletion of brain serotonin does not alter
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced starvation syndrome in the rat.
Toxicol. Lett. 59(1-3): 65-72.
Tuomisto, J. and R. Pohjanvirta. (1991a) Do new hypotheses on the mechanism of action of
dioxins help in risk evaluation? Sci. Total Environ. 106(1-2): 21-31.
Tuomisto, J.T., M. Unkila, R. Pohjanvirta, M. Koulu and L. Tuomisto. (1991b) Effect of a single
dose of TCDD on the level of histamine in discrete nuclei in rat brain. Agents Actions
33(1-2): 154-156.
Yu, M., C. Hsu, B. Gladen and W. Rogan. (1991) In utero PCB/PCDF exposure: relation of
developmental delay to dysmorphology and dose. Neurotoxicol. Teratol. 13(2): 195-202.

66

602

G.

Other Toxic Effects
1. Chloracne and Other Cutaneous Toxicity
Chloracne has long been associated with T C D D exposure, and is generally

considered to be an indication of heavy exposure in occupational or environmental
situations. This has been discussed in earlier volumes of the Review. More recently, this
relationship has been put on a firmer footing by establishing correlations with serum
dioxin levels. Examples of this are the Seveso incident in which an industrial accident led
to widespread T C D D contamination, but chloracne occurred only in 10 subjects from the
most heavily exposed group with serum T C D D levels between 828 and 56,000 pg/g lipid
(Bertazzi 1991; Mocarelli et al. 1991), and a study in chemical workers, among w h o m
chloracne was associated with elevated serum levels of T C D D (Neuberger et al. 1991).
In the latter report, T C D D levels on the basis of serum lipid, ranged from 98 to 659 pg/g
in nine workers with a history of chloracne compared with 8 to 28 pg/g in factory
reference subjects without such a history, and 5 to 23 pg/g in external referents. The
exposed workers had been involved in the production of 2,4,5-T and its raw material
2,4,5-trichlorophenol in 1971-1972, had experienced chloracne in the period 1972-1973,
and had blood T C D D assays performed in 1990. The operation was closed down in
1973, extensive clean-up undertaken, and a new manufacturing process installed which
did not involve formation of T C D D as a byproduct.
Normal mice do not exhibit cutaneous lesions after exposure to TCDD, but in
hairless (hr/hr) mice a form of hyperkeratinization occurs, especially in the dermal
epithelial cysts, and this effect is exacerbated by maintaining the animals on a Vitamin Adeficient diet (Puhvel et al. 1991).

The interaction between T C D D and Vitamin A is

considered in more detail in Section VI.

2. Hepatotoxicity
Evidence of subclinical hepatic damage associated with higher serum levels of
T C D D has been described in the latest report of the Air Force Health Study (Roegner et
al. 1991). This included positive associations between dioxin and serum cholesterol, high

67

603

density lipoproteins and triglycerides, as well as serum alanine aminotransferase and yglutamyl transpeptidase activities.
A large number of reports became available during 1991 that described hepatic
changes in animals treated with TCDD.

Many of these changes represent normal

processes of enzyme induction, or other metabolic effects that are more appropriate
subjects for Section VI, which covers basic studies of the effects of dioxin. Some degree
of hepatomegaly relative to body weight has been ascribed to treatment of rodents with
T C D D (McKim et al. 1991; Shen et al. 1991) or 1,2,3,7,8-pentachlorodibenzo-p-dioxin
(Koga et al. 1991) in several reports. In male Wistar rats, increased liver mass was
accompanied by increased hepatic lipid content (McKim et al. 1991), but in mice strain
differences were seen with respect to lipid accumulation. In TCDD-sensitive C57BL/6J
mice, mild to moderate fat accumulation was seen in the absence of inflammatory or
necrotic changes after 3 jug/kg, and mild inflammatory and necrotic effects with marked
lipid infiltration occurred after 30 pg/kg of T C D D by the intraperitoneal route. In contrast,
D B A mice showed evidence of inflammation and cellular necrosis after 30 pg/kg, and only
slight fatty changes were seen when a dose of 600 pg/kg was reached (Shen ef al.
1991). Both In vivo and in vitro exposure of rat hepatocytes to T C D D led to increased
protein synthesis with the appearance of new protein bands on two-dimensional
electrophoresis (Aoki et al. 1991). A study with rat 5L hepatoma cells, a derivate of the
H4IIEC3 cell line, indicated that T C D D blocked the entry of the cells into S-phase without
affecting progression throughout the rest of the cell cycle. This effect was seen within 4
to 8 hours, and led to a marked increase in cell volume, presumably due to the
accumulation of cells in G, phase (Wiebel et al. 1991).

Finally, in 19-day-old chick

embryos, 2,4-D and more especially 2-methyl-4-chlorophenoxyacetic acid (MCPA),
induced a biliary stasis that may have led to changes in drug metabolizing enzymes
(Santagostino et al. 1991).

3. Other Toxicity
It has been known for several years that toxic doses of the chlorophenoxy
herbicides can cause hemorrhage in various organs of animals that have been tested.
68

604

It is interesting that these compounds present structural analogies to clofibrate (2-\pchlorophenoxy]-2-methylpropionic acid), an antihyperlipidemic drug that is known to
potentiate anticoagulant action by inhibiting platelet aggregation, and sulotroban, a
derivative of phenoxyacetic acid that is a thromboxane Aj, (TxAg) antagonist. Two papers
from a group in Kuopio, Finland, have described the inhibition of human platelet
aggregation by eight phenoxy herbicides (Elo et al. 1991; Ylitalo et al. 1991).

The

herbicides studied were: 2,4-D; 2,4,5-T; MCPA; 2-(2,4-dichlorophenoxy) propionic acid;
4-(2,4-dichlorophenoxy) butyric acid; 2-(2,4,5-trichlorophenoxy) propionic acid; 2-(4chloro-2-methylphenoxy)propionic acid; and 4-(4-chloro-2-methylphenoxy) propionic acid
(MCPB). Aggregation of the thrombocytes was induced by adrenalin, ADP, collagen, or
the TxAj, agonist U-46619 (Upjohn), and measured in a nine-channel spectrophotometer
at 620 nm.

A dose-dependent inhibition was demonstrated for these herbicides at

concentrations between 0.02 and 2 mg/ml. No structure-activity relationship could be
discerned since their activities were essentially similar. While this may appear to be a
high concentration, it should be noted that blood levels in humans and animals with
severe or fatal poisoning by these agents have been in the range of 0.4 to 1.0 mg/ml.
When rabbits were injected subcutaneously with 2,4-D or M C P A at 100-150 mg/kg, the
platelet-rich plasma prepared 2.5 hours later showed a 20-30% reduction in ADPstimulated platelet aggregation compared with plasma obtained before injection. This
inhibitory effect was lost in 20-23 hours. Inhibition by 2,4-D of aggregation induced by
U-46619 was characterized by competitive kinetics, suggesting that the inhibition involved
action at the TxA2 receptor. Furthermore, 2,4-D or M C P B inhibited the production of
T x B2,as measured by a radioimmunoassay, during aggregation induced by U-46619 or
by A D P and collagen, respectively. This suggests that the antiaggregation effect is
mediated through interaction with the thromboxane system.
An effect on platelet aggregation, and thus on potential risk of bleeding, may not
be unique to the phenoxy herbicides. In a study of T C D D levels in the breast milk of 14
Dutch mothers, Koppe et al. (1991) found that in the four infants with identified bleeding
problems (two cases with intracranial bleeding within 48 hours of birth, and two in the
fourth week), the mean concentration of T C D D in their mothers’breast milk (range 7.44
69

to 16.82 ng/kg milk fat) was significantly higher (p = 0.02 Wilcoxon test) than for the
other ten. This relationship was not evident for 2,3,4,7,8- pentachlorodibenzofuran.
In a well-executed cross-sectional medical study of chronic respiratory conditions,
281 workers who had been exposed to T C D D more than 15 years earlier, while employed
at firms producing trichlorophenol and 2,4,5-T in Newark, N e w Jersey and Verona,
Missouri, were compared with 260 unexposed referents matched from within the individual
neighborhoods by age, sex and ethnic group. Medical histories, physical examinations,
serum T C D D assays, spirometric tests, and interviews regarding subjects’lifestyles and
occupational histories were the bases for the study. Personnel involved in obtaining the
information were blinded. Mean lipid-adjusted serum level of T C D D was 220 ppt for the
study group compared with 7 ppt for the controls.

Logistic and linear regression

analyses, allowing for T C D D levels, were used to control for confounders that included
past and current smoking and drinking status, height, other lung diseases, and dust
exposure. No significant differences could be determined between the two groups with
respect to risks for chronic bronchitis and chronic obstructive pulmonary disease. In
addition, there was no association between exposure to T C D D and the spirometric
parameters of lung function (Calvert et al. 1991).
Administration of T C D D to rats produces a hypergastrinemia that serves to protect
the gastrointestinal mucosa against the atrophy that is produced in the hypophagic state.
Since the antral mucosa is the source of much gastrin production, the response of this
tissue to T C D D was studied in male Sprague-Dawley rats (Theobald et al. 1991).
Fourteen days after an oral dose of T C D D (100 fjg/kg), there were significant increases
in antral wet weight and mucosal height, whereas pair-fed rats that experienced similar
weight loss had antral atrophy. Antral G-cells (the gastrin-containing cells) showed no
hyperplasia, however. A 7- to 10-fold increase in the serum gastrin concentrations, as
determined by radioimmunoassay, was seen at this time, although not before, but levels
of this hormone were unchanged in the controls. In contrast, antral concentrations both
of gastrin and somatostatin decreased significantly about 1 week before hypergastrinemia
was evident. Because of this difference in timing, the absence of G-cell proliferation, and
the fact that the E D ^ values for the decrease in antral hormone levels were in the range

of 19-29 jug/kg, compared with 46 jug/kg for hypergastrinemia, itis unlikely that the latter
results from the changes in antral hormone levels.

607

REFERENCES

Aoki, Y., E.K. Silbergeld, S.R. Max and B.A. Fowler. (1991) Alterations in protein synthesis in rat
liver cells by in vitro and in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Biochem. Pharmacol. 42(6): 1195-1201.
Bertazzi, P. (1991) Long-term effects of chemical disasters. Lessons and results from Seveso.
Sci. Total. Environ. 106(1-2): 5-20.
Calvert, G.M., M.H. Sweeney, J.A. Morris, M.A. Fingerhut, R.W. Hornung and W.E. Halperin.
(1991) Evaluation of chronic bronchitis, chronic obstructive pulmonary disease, and
ventilatory function among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Am.
Rev. Respir. Dis. 144(6): 1302-1306.
Elo, H.A., T. Luoma and P. Ylitalo. (1991) Inhibition of human and rabbit platelet aggregation by
chlorophenoxyacid herbicides. Arch. Toxicol. 65(2): 140-144.
Koga, N., J. Kuroki, H. Nakashima, Y. Hokama-Kuroki, H. Yoshimura, H. Kuroki and Y. Masuda.
(1991) Acute toxicity, inductive effects of liver enzymes and distribution in the liver of
1,2,3,7,8-pentachlorodibenzo-p-dioxin in rats. Fukuoka Igaku Zasshi 82(5): 197-206.
Koppe, J.G., H.J. Pluim, K. Olie and J. van Wijnen. (1991) Breast milk, dioxins and the possible
effects on the health of newborn infants. Sci. Total Environ. 106(1-2): 33-41.
McKim, J.J., K. Marien, H. Schaup and D. Selivonchick. (1991) Alterations of hepatic acetyl-CoA
carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Lipids 26(7): 521-525.
Mocarelli, P., L.L. Needham, A. Marocchi, D.G. Patterson Jr, P. Brambilla, P.M. Gerthoux, L.
Meazza and V. Carreri. (1991) Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. J. Toxicol.
Environ. Health 32(4): 357-366.
Neuberger, M., W. Landvoigt and F. Derntl. (1991) Blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chemical workers after chloracne and in comparison groups. Int.
Arch. Occup. Environ. Health 63(5): 325-327.
Puhvel, S.M., M.J. Connor and M. Sakamoto. (1991) Vitamin A deficiency and the induction of
cutaneous toxicity in murine skin by TCDD. Toxicol. Appl. Pharmacol. 107(1): 106-116.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson. (1991) An
epidemiologic investigation of health effects in Air Force personnel following exposure to
herbicides. Introduction, background and conclusions. Air Force Health Study Chapters
1-5, 18, 19: 1-133.
Santagostino, A., M. Leone, R. Maci, A. Casale and L. Marabinl. (1991) Effects of phenoxyacetic
acid herbicides on chicken embryo liverdrug metabolizing enzymes. Pharmacol. Toxicol.
68(2): 110-114.
72

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Shen, E.S., S.l. Gutman and J.R. Olson. (1991) Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated hepatotoxicity in C57BL/6J and DBA/2J mice. J. Toxicol.
Environ. Health 32(4): 367-381.
Theobald, H.M., G.B. Ingall, T.A. Mably and R.E. Peterson. (1991) Response of the antral
mucosa of the rat stomach to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl.
Pharmacol. 108(1): 167-179.
Wiebel, F.J., U. Klose and F. Kiefer. (1991) Toxicity of2,3,7,8-tetrachlorodibenzo-p-dioxin invitro:
H4IIEC3-derived 5L hepatoma cells as a model system. Toxicol. Lett. 55(2): 161-169.
Ylitalo, P., H. Ylihakola, H.A. Elo, H.-M. Koponen, E. Seppalo and H. Vapaatalo. (1991) Inhibition
of platelet aggregation and thromboxane A2 Production by chlorophenoxy acid
herbicides. Arch. Toxicol. Suppl. 14: 174-178.

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• JP -63^

IV. HEALTH E F F E C T S O F O TH ER H ERBICID A L A CTIVE IN GREDIEN TS

A.

Picloram
Picloram (4-amino-3,5,6-trichloropicolinic acid) was a major component of Agent

White, one of the herbicides used in Vietnam, whose activity was due to a mixture of the
triisopropylamine salts of picloram and 2,4-D. It is still commonly used on broadleaved
plants, most frequently in association with 2,4-D as various formulations of Tordon. The
compound has not been studied intensively, but reviews of earlier toxicologic studies may
be found in Volumes I, III, V, VII, IX and XVII of the Review that were compiled between
1981 and 1990. The overall picture presented is of a mildly hepatotoxic compound, for
which carcinogenicity and teratogenicity studies have yielded no conclusive results. Itis
absorbed readily from the gastrointestinal tract or through intact skin, but also is very
rapidly excreted in the urine, essentially without metabolism or significant retention in the
body. Two new studies involving picloram have appeared during 1991. In addition, a
review and analysis by Ashby and Tennant (1991), listed picloram as an equivocal
carcinogen in rats.
Adams et al. (1991) reported a study that involved exposure of female CD-1 mice
to Tordon 202c, a commercial mixture containing 12 g of picloram and 200 g of 2,4-D per
liter, at concentrations between 0 and 0.3% in the drinking water for 15 weeks. After 3
weeks of treatment, urethan (1.5 mg/g) was administered intraperitoneally, and the
formation of pulmonary adenomas evaluated 12 weeks later. Tordon did not produce any
visible signs of clinical toxicity, nor did it affect significantly measured weight gains or
water consumption.

It did, however, produce a dose-dependent increase in the

multiplicity, but not the size of lung tumors. Since Tordon caused a decrease in urethaninduced sleeping time, itwas concluded that the enhanced tumorigenesis did not result
from impaired metabolism or excretion of urethan, but rather from suppression of
immunological surveillance. No data were reported for the effects of each component of
Tordon alone, but since the two herbicides were used in combination in Vietnam, this is
not a significant defect for the purposes of this report.

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Channel catfish (Ictalurus punctatus) were exposed over the course of 10 days to
picloram (2,5 mg/liter of aquarium water, corresponding to 25% of the 96-hour LC^
concentration) and three concentrations of 2,4-D (22.5,7.5 and 2.25 mg/l, corresponding
to 25, 8.3 and 2.5% of the 96-hour LCgo concentration), alone or in admixture.

Fish

developed decreased serum chloride concentrations and liver/body weight ratios,
accompanied by increased ethoxyresorufin O-deethylase (EROD) in the liver, but only
when exposed to a mixture of herbicides. Picloram, alone or with 2,4-D, produced an
approximately 50% fall in hepatic lauroyl C o A oxidase (Gallagher and DiGiulio 1991).
Since the rise in E R O D was only 2.5-fold, it is likely that enzyme activation was
responsible rather than induction, which typically results in a 15-fold or greater increase.
The lauroyl C o A oxidase data indicated that picloram is not an inducer of peroxisomes.
This research is compatible with previous observations of picloram’s mild hepatotoxicity.

B.

Cacodylic Acid
The limited available information on the toxicology of this agent has been presented

in prior volumes of the Review.

In summary, this substance produces a spectrum of

acute toxic symptoms that includes gastrointestinal disorders, eye irritation and dermatitis.
Studies in experimental systems have indicated that ithas the potential for mutagenicity,
clastogenicity and teratogenicity. Carcinogenicity has not been tested adequately, but it
should be noted that this activity has been associated with other arsenic compounds.
Only one abstract in a primary journal on cacodylic acid was identified in the literature that
became available during 1991. Itreported mitotic arrest and sister chromatid exchanges
in V 79 Chinese hamster cells exposed to this compound (Kuroda et a/. 1991).

■p-ifo

REFERENCES

Adams, S.L., S.T. Horvat, A.E. Irwin, R.W. Junkin, N.M. Koreman and B.R. Blakley. (1991) The
effects of Tordon 202c exposure on urethan-induced lung adenoma formation in female
CD-1 mice. Vet. Hum. Toxicol. 33(3): 209-211.
Ashby, J. and R.W. Tennant. (1991) Definitive relationships among chemical structure,
carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res.
257(3): 229-306.
Gallagher, E. and R. DiGiulio. (1991) Effects of 2,4-dichlorophenoxyacetic acid and picloram on
biotransformation, peroxisomal and serum enzyme activities in channel catfish (Ictalurus
punctatus). Toxicol. Lett. 57(1): 65-72.
Kuroda, K., A. Okamoto, G. Endo, S. Horiguchi and Y.S. Yoo. (1991) Colchicine-like effects of
cacodylic acid. Mutat. Res. 252(1): 95.

76

V.

T IS S U E R ES ID U ES AND PH ARM ACOKIN ETICS OF CHLORINATED
DIBENZO-p-DIOXINS AND R ELA T ED COM POUNDS

The polychlorinated dioxins (PCDDs) and related compounds are of a highly
lipophilic nature, and therefore tend to become sequestrated into body fat depots from
which they are released only very slowly. As a result, levels of these compounds in
adipose tissue can serve to indicate the history of past exposure.

For example,

detectable levels of dioxins have been found in many individuals heavily exposed more
than 20 years previously, and in one case, T C D D and greater amounts of its tetrabromoanalog, were measured by mass spectroscopic methods in the blood lipid fraction of a
chemist exposed 34 years earlier while synthesizing these compounds (Schecter and
Ryan 1991c). It has been shown that at least for the lower polychlorinated PCDDs and
PCDFs such as TCDD, plasma or blood lipid levels are similar to those measured in
adipose tissue lipids (Schecter et at. 1991b). Thus, blood is an appropriate source of
samples for dioxin assays, one that is more accessible than adipose tissue. The extreme
sensitivity of available analytical techniques permits detection of dioxins in the fg/g to
pg/g, that is the parts per trillion (ppt) range. These techniques are being applied to
various groups of exposed populations, to experimental animals, and to the study of the
pharmacokinetics of these agents. It is probable that the linking of toxicologic findings
to actual measurements of dioxin body burdens and kinetics will not only provide more
meaningful interspecies comparisons, but also will help achieve much better risk
assessment based on no-adverse-effect-concentrations (Neubert 1991).

A.

Studies of Vietnam Veterans
Previous volumes of this Review have presented evidence from studies of adipose

tissue and serum levels of the major dioxin contaminant of Agent Orange, TCDD, which
supported the conclusion that Vietnam veterans who had experienced the greatest
exposure to Agent Orange had elevated serum levels of T C D D 15-20 years later. Other
Vietnam veterans without such documented high exposure, generally had blood and
tissue levels comparable to those in the general population or in non-Vietnam veterans.
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This correlation was seen, for example, in 888 serum samples from the Ranch Hand
cohort of veterans who had participated in the U.S. Air Force’s Operation Ranch Hand,
and thus were associated with the actual aerial application of the herbicide. Flying and
non-flying enlisted personnel exhibited much higher serum levels, 17.2 and 23.6 ppt,
respectively, than did nonflying officers, pilots and navigators (range of 6.6 to 9.3 ppt).
Matched control veterans (856 samples) not associated with Operation Ranch Hand, had
low serum levels of T C D D (range of 3.9 to 4.7 ppt) that were not correlated with rank
(Wolfe et al. 1990). A recent report (Roegner et al. 1991) has covered the serum dioxin
levels and long-term health effects in personnel exposed to herbicides for the 1987
examination cycle under the Air Force Health Study. For the total group of 866 Ranch
Hand personnel, the median T C D D level was 12.8 ppt serum lipid weight. Values for the
median serum levels, and ranges for the three ranks of officer, enlisted flyer and enlisted
groundcrew were, respectively: 7.8 ppt (0-42.6); 18.1 ppt (0-195.5); and 24.0 ppt (0617.8). In the comparison group of 804 personnel, median serum levels were 4.2 ppt
(range 0-54.8), with the breakdown by rank as follows: officer 4.7 ppt (0-18.5); enlisted
flyer 4.0 ppt (0-12.8); and enlisted groundcrew 4.0 ppt (0-54.8).
Kang etal. (1991) addressed the question of whether Vietnam veterans, in general,
received substantial exposure to dioxins while serving in Vietnam. This was a relatively
small study that used adipose tissue samples obtained from the U.S. Environmental
Protection Agency’s archival collection of 8,000 specimens. T C D D levels were determined
by

high resolution gas

chromatography coupled with double-focussing mass

spectrometry. Samples from 36 Vietnam veterans were compared with groups of 79 nonVietnam veterans and 80 civilians, matched for age and year of sample collection.
Arithmetic mean levels and standard deviations for the three groups, respectively, were
13.4 ± 7.4, 12.5 ± 7.2, and 15.8 ± 14.5 pg/g total extractable lipid. These means did
not differ significantly, and furthermore, there was no significant correlation between dioxin
levels and four surrogate measures of exposure to Agent Orange, namely military branch,
military occupation specialty code, military region, and time and distance from recorded
herbicide spraying, apart from slight rises in levels in those who had been in combat
status or within 3 days/2 k m of sprayed areas.

Since T C D D was the predominant

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polychlorinated dioxin contaminant of Agent Orange, the finding that there were no group
differences in relative tissue levels of other polychlorinated congeners, suggests that
sources other than Agent Orange, such as subsequent environmental or occupational
exposure, may have contributed to the Vietnam veterans’overall T O D D levels. The higher
levels of T C D D found in this study compared to others reported recently, were most likely
due to the relatively earlier years of sample collection, with a mean of 1978 compared with
the mid 80’s or later for most other reports.
Reliance on blood or tissue levels, in samples collected 15-20 years or more after
service in Vietnam, as a definitive indicator of whether or not veterans experienced highlevel exposure to TCDD, is a logical step, based on the available data. This was certainly
the conclusion of the Centers for Disease Control Veterans Health Studies (Centers for
Disease Control 1988). However, there are questions about its validity. Albanese has
raised concerns about the single compartment pharmacokinetic model used to estimate
prior exposure, the neglect of weight gain (mainly in the form of lipid) and of tissue
binding of TCDD, and possible selection bias (Albanese 1991). There is an approximate
doubling of body fat in moving from the 20-24 to the 40-49 year-old age group, which
would tend to lower serum T C D D levels by providing a larger depot storage compartment.
He calculated that with time this would lead to a steady increase in the estimated half-life
for T C D D as a result of altered body composition. Binding to specific or non-specific sites
within tissues also will increase the apparent half-life of TCDD, and the relative importance
of this factor will increase with time as body stores of unbound T C D D are depleted. The
use of data derived only from subjects with unusually high levels, as in the report of Pirkle
et al. (1989) which generated the commonly-used value of 7.1 years for the half-life of

TCDD, introduces selection bias, since the sampling may have favored not only those
heavily exposed, with resulting high initial levels, but also those who cleared body dioxin
loads unusually slowly. Albanese concluded that the net result will be that extrapolation
back to the time of exposure, using a probably overestimated half-life, derived from a
single compartment model based on two measurements made 5 years apart, will lead to
an underestimate of the exposures experienced 15-20 years before. These are powerful
arguments, to which might be added the fact that it is on a pharmacokinetic basis
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37-6 H

questionable to infer single compartment kinetics from only two measurements made at
extremely late times, with no information about the initial dose of T C D D received.
This issue calls for better definition of the pharmacokinetic pattern of T C D D in
humans, but it is difficult to see how use of data from veterans of the group exhibiting
lower levels of T C D D will help in this, considering the problems, both of relatively greater
background noise in analytic procedures at low levels, and of the confounding effect of
any possible subsequent chronic environmental exposures to TCDD, which would tend
to produce a steady-state situation for dioxin body loads (Phillips 1989).

Albanese

recommended the use of a multi-compartment model instead of one based on a single
compartment (Albanese 1991), and such a model for humans, involving seven body
compartments, has been proposed by Kissel and Roberge (1988). However, lack of a
range of sampled tissues, the paucity and limited collection times of those samples that
are available, and low concentrations of TCDD, make itimpossible to apply such complex
models to data from Vietnam veterans. It is in any case questionable whether they are
needed. Webster and Connett (1991) devised a new physiologically-based model with
a system of nine simultaneous differential equations (compared with 11 in that of Kissel
and Roberge). Using the same Ranch Hand data, a half-life of 7.9 years was arrived at,
very close to the 7.1 years derived by Pirkle et al. (1989). They found that the system
approximated a monophasic one (equivalent to a single compartment situation) after a
few early transients. This reflects the predominant role of depot fat in determining the
volume of distribution, the two orders of magnitude greater half-life of equilibration for this
compartment, and the limited metabolism and low fecal excretion of TCDD.
Another concern has been addressed in a recent report from the ongoing Air Force
Health Study, which focussed on the variability of T C D D half-life as a function of percent
body fat (Michalek et al. 1992). Based on a repeated measures linear model, these
authors found a marginally significant (p = 0.09) relationship between half-life and
percentage body fat, but no significant (p = 0.60) change in half-life with relative changes
in the percent body fat between 1982 and 1987.
In summary, studies reported during 1991 have generally supported earlier
conclusions that blood and adipose tissue levels of T C D D can serve to indicate heavy
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616

exposure to Agent Orange, but lesser degrees of exposure may not be reflected in
increased levels.

B.

Studies of Other Exposed Populations
Levels of PCDDs and PCDFs have been determined in a number of populations

that were exposed to these agents occupationally, as a result of an episode of poisoning
consequent to an industrial accident, or through environmental exposure.
A study of 281 chemical workers at plants in Newark, Ne w Jersey, and Verona,
Missouri, was undertaken to relate chronic bronchial disorders with exposure to dioxins.
This study group, which had been exposed to T C D D over an approximately 2-year period
15 years earlier, while employed in the production of trichlorophenol and 2,4,5-T, was
compared with 260 unexposed referents. The mean lipid-adjusted serum concentration
of T C D D in the study group was 220 ppt compared with 7 ppt in the controls. The halflife-extrapolated mean initial serum levels were estimated as 1,896 ppt (range 2-32,400)
for the exposed and 6 ppt (2-20) for the control populations (Calvert et al. 1991).
In a report from Austria, serum levels of T C D D were measured in nine production
workers with a history of developing chloracne after exposure to P C D D ’s during the
period 1971-1973. Serum levels were in the range of 98 to 659 pg/g blood lipid in 1990,
compared with 8 to 28 pg/g for a group of 4 workers from the same plant without a
history of T C D D exposure or chloracne, and 5 to 23 pg/g in 17 external referents
(Neuberger et al. 1991). Schecterand Ryan (1991c) found 20 ppt of T C D D and 1100 ppt
of the 2,3,7,8-tetrabromo- congener in the serum lipid of a chemist who was engaged in
synthesis of these compounds 34 years earlier. In a study from Ne w Zealand of 548
professional pesticide applicators who had utilized 2,4,5-T, Smith etal. (1992) measured
blood serum levels of T C D D in 11 men, identified as having the greatest number of years
and of months per year of pesticide application experience. They were matched with
controls of similar ages who had no occupational exposure. Average levels of T C D D
were 53.3 ± 16.1 and 5.6 ±1.1 ppt in the applicators and controls, respectively. Serum
levels of 6 other chlorinated dioxins and 9 chlorinated dibenzofurans were no higher in
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the study group than in the controls.

Variations in T C D D levels between individual

applicators was correlated (r = 0.72, p = 0.03) with duration of working exposure to
2,4,5-T. Since the level of the T C D D contaminant in the 2,4,5-T used in N e w Zealand fell
200-fold, from approximately 1 p p m to 5 ppb between 1971 and 1985, much of the serum
dioxin is probably attributable to exposure many years previously. Knopp (1991) has
monitored urinary excretion of 2,4-D by workers involved in spraying this herbicide. The
highest urinary concentration recorded in a morning urine sample was 2.5 ppm, clearance
half-life was 12 to 22 hours, and the calculated uptakes were 5.7 and 84.9 pg/kg.
There have been three major incidents of P C D D and PC D F poisoning that still
generated research reports in 1991. These were the contamination of an area near
Seveso, Italy, with 1.3 kg of T C D D in 1976, and the consumption of rice oil contaminated
with PCDFs and PCBs in Japan (Yusho) in 1968, and in Taiwan (Yucheng disease) in
1979. Data from the Seveso incident are of particular value in that they include serum
concentrations of T C D D measured within weeks of exposure, together with a 9-year
clinical follow-up. In the study by Mocarelli et al. (1991), detectable levels of T C D D were
only found in 20 serum samples, of which 19 were from those who stayed for any period
of time in the most contaminated A zone, in which soil T C D D levels were in the range of
956 to 1,185 pg / m 2. The serum levels in zone A subjects varied from 828 to 56,000 ppt
(lipid adjusted); none had undetectable levels. Of 10 subjects not associated with any of
the three contaminated zones, only one was positive for serum T C D D with a value of 137
ppt. Chloracne types 3 and 4 developed only in 10 of the heavily contaminated subjects;
in 3 of these, serum T C D D levels were at the lowest end of the range, but these
individuals had experienced direct contact with TCDD, leading to a reaction similar to
contact dermatitis. Clinical findings apart from the chloracne were unremarkable, with
only slight or transient changes in laboratory tests. Continued clinical monitoring for
cancer development is ongoing, but the findings to date do not support any firm
conclusions (Bertazzi 1991).
Three reports concerned work related to the Yusho incident. In a comparison of
7 Yusho patients with 8 normal controls, levels of PCBs, PCDFs and PCDDs were
measured in subcutaneous adipose tissue by high resolution gas chromatography and

mass spectrometry in ion monitoring mode. Average values in T C D D equivalents were
17, 491 and 24 ppt for coplanar PCBs, PCDFs and PCDDs, respectively (Hirakawa etal.
1991). In scoring the total clinical findings over the period 1972 to 1988, and relating these
scores to the coincident values for adipose tissue and blood levels of PCDFs, a strong
correlation was seen for females (r = 0.9885). There were not enough male patients for
statistical evaluation (Nakagawa and Takahashi 1991).

An interesting study was

performed in six Yusho patients who received the anion exchanger cholestyramine at a
dose of 4 g three times daily for 6 months, leading to enhanced fecal excretion of various
classes of polychlorinated compounds (lida et al. 1991).

This may represent

sequestration of material excreted through the intestinal epithelium and/or secreted in the
bile, making it unavailable for reabsorption.
Yu et al. (1991) reported on 128 children born to exposed w o m e n in Taiwan after
the contaminated oil had been removed from the market; developmental delays were
seen in many of these children. Measurable blood levels of PCBs were found in 34 of 74
mothers, and 20 of 36 children tested; no PCDFs were detected. P CB levels in children
were: 4.5 ppb in breast-fed exposed, 0.53 ppb in breast-fed controls, 0.44 ppb in bottlefed exposed and 0 in bottle-fed controls.

Another study carried out on 3 exposed

subjects between 1980 and 1989, however, found relatively high levels of penta-, hexaand hepta- chlorodibenzofurans (initially at 15.4, 37.7 and 4.8 ppb), with half-lives of 2.14,
2.56 and 2.32 years, respectively. High blood concentrations of 8 PC B congeners were
also documented; half-lives of those retained in the body were about twice as long as
those of the P C D F congeners (Masuda et al. 1991). Human placentas from 5 exposed
w o m e n were collected, beginning in 1983, four years after the incident (Lucier 1991).
PCDFs were found in the Yucheng but not in the control placental samples; mean levels
of the penta- and hexa-chlorinated derivatives were about 100 and 400 ppt, respectively.
Control placentas had measurable levels of PCBs, evidence for the widespread
environmental distribution of these compounds, but those in the exposed samples were
between 5 and 96 times greater.
Although the organochlorine compounds

are widespread throughout the

environment, the overall contributions from all sources must vary, since a survey of the
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levels of these compounds In human adipose tissue samples from throughout the U.S.
shows marked regional variations (Phillips and Birchard 1991). For P C D D s and PCDFs
the highest ranked area was the East North Central, followed by the Mid Atlantic and East
South Central.

Polychlorinated compounds, including dioxins, enter humans when

released through accidents, burning of materials, paper pulp processing, or when present
as contaminants of herbicides; the most important route is the food chain. Through the
food chain contaminants pass from soil or water to human populations.

Fish, for

example, are well known sources of these polychlorinated compounds, due to the
prevalence of contamination in certain bodies of water. A recent report documented the
levels of PCDDs and PCDFs in individuals eating fish from the Baltic Sea (Svensson et al.
1991). Ten dibenzofurans and 7 dioxins were assayed in plasma samples from three
groups of Swedish men, one with high, almost daily fish intake (n = 11), a second with
moderate intake (about once a week, n = 9), and a third with no fish intake (n = 9).
Median levels of T C D D were 8.0 pg/g (range 2-13) for the high, 2.6 pg/g (range 1.2-4.2)
for moderate, and 1.8 pg/g (range 1.0-2.5) for non-consuming groups, based on plasma
lipid content.
Since dioxins are so closely associated with carcinogenesis, itis not surprising that
attempts have been made to determine the levels of these compounds in patients with
cancer. Muto et al. (1991) studied the distribution of PCDDs in the lung, liver, kidney,
pancreas, spleen, gonads, gallbladder and muscle from each of 11 patients who had died
of cancer. None of the PCDDs were at levels outside the ranges of those associated with
unexposed populations in other studies reported in the literature. The dioxin present at
the highest levels in alltissues examined was octachlorodibenzo-p-dioxin (39.9-344 pg/g),
followed by the heptachloro- congener. T C D D was present at its highest level (0.8-3.2
pg/g) in the gonads.
Craig and Grzonka (1991) have developed an idealized, linear reaction kinetic
model for T C D D body burden which takes as its primary parameters the T C D D transfer
factor from soil to the human body, the background intake, the soil concentration and the
body and soil elimination half-times. Values for the transfer factor were estimated from
data derived from the Seveso incident in Italy (described above) and the Missouri incident
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in the U.S.A., which resulted from spraying horse arenas with TCDD-contaminated oil to
control dust. The model determines a time scale over which the body burden acquired
from a highly contaminated environmental exposure may exceed the levels due to other
ubiquitous sources, and provides perspectives that permit decision making on source
removal in connection with guidelines. It could be applied to mixed contamination with
PCDDs and PCDFs, using T C D D equivalents.

C.

Studies of Dioxins in Milk
Absorption of polychlorinated organic compounds and their subsequent excretion

in milk is an easily studied process, and one which could have profound impact on the
health of human infants, exposed at a particularly vulnerable period in their development.
This area continues to generate levels of research activity, both in humans and in animal
systems, similar to those recorded in Volume XVII of the Review. A large international
study documented the levels of a range of dioxins and dibenzofurans in human milk and
blood in Cambodia, Germany, Thailand, the U.S.A., the former U.S.S.R., and Vietnam
(Schecter et al. 1991a). In general, levels of the compounds studied were lower in milk
than in blood, as measured on a lipid basis. As regards blood, these levels were lower
in samples from Hanoi and other less industrialized countries.

However, among the

Vietnamese samples, T C D D concentrations were much higher in samples from Dong Nai
Province (mean 12 ppt) where Agent Orange had been used, than in those from Hanoi
(2.4 ppt, the detection limit) or Ho Chi Minh City (3.4 ppt). Milk samples also reflected
industrialization, with dioxin levels highest in German samples, followed by those from the
U.S., while samples from South Vietnam, where spraying with contaminated herbicides
had occurred, were higher than those from North Vietnam; milk from relatively nonindustrialized areas in Siberia and Cambodia had the lowest levels. In contrast, relatively
high levels of DDT and its derivates were found in the milk samples from all regions of
Vietnam, and also from Cambodia, Siberia and Thailand, reflecting widespread use of
D D T in mosquito control operations. A Dutch study also has underlined the variations
between breast milk samples collected from different countries (Koppe et al. 1991). In
14 Dutch mothers, milk levels in ng/kg milk fat ranged from 5.35 to 17.0 for T C D D and
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21.43 to 70.0 for 2,3,4,7,8-pentachlorodibenzofuran. The corresponding values for 5
Polish mothers were 2.58 to 4.59 for T C D D and 13.2 to 18.15 for the dibenzofuran,
reflecting lower levels of environmental dioxins and related compounds in Poland.
A PCB fire in Quebec, Canada, in August 1988, presented the opportunity to study
the levels of PCDDs and PCDFs in the milk of lactating wom e n within the first three days
of exposure; values were compared with those measured in samples from the general
population of Quebec (Dewailly et al. 1991). Mean total levels of the two classes of
compounds were 318 pg/g on a fat basis in the samples from the exposed women,
compared with 243 pg/g for the control group. These values, and the contents of the
major component (octr.chlorodibenzo-p-dioxin) and the hexachloro- and heptachlorodibenzofurans, were significantly different (p < 0.05). Mean levels of T C D D were 2.59
and 2.33 pg/g lipid in the exposed and control samples, respectively. The authors point
out that the mean level of polychlorinated compounds in human milk in Quebec translates
to 13.3 ng/kg, when expressed in Toxic Equivalency Factors (TEFs; toxicity expressed
relative to TCDD, see Barnes (1991)), which is much lower than those reported for other
areas such as the U.K. (29.5 and 36.9) or Germany (26.9), but comparable with figures
for the U.S.A. (Los Angeles, 16.6; Tennessee, 16.6). The report of Yu ef al. (1991) on the
Taiwanese children exposed in útero to PCB and P C D F contaminated oil, discussed in
Section V B above, also draws attention to the role of breast milk as a source of
accidentally-derived organochlorine compounds for infants. In that study, only the breast
fed exposed infants had significant levels of PCBs (4.5 ppb versus 0.44 ppb in exposed
bottle-fed infants).
Measures have been taken in a number of countries to restrict the use of
organochlorine compounds so as to reduce environmental pollution. Noren and Lunden
(1991) have followed the levels of PCDDs and PCDFs in human milk in the Stockholm
region over the period 1972-1989, which marked the implementation of Swedish control
measures. There was a continuous fall in PCB, P C D D and P C D F levels in milk samples
from 4.5 to about 1.8 pg/g T C D D equivalents over the period 1972-1985, with PCBs as
the major components, and T C D D as a very minor contributor. However, this decline
now seems to have ceased, since values for 1989 were at or above the 1985 figures. It
86

is possible that the 1989 values represent an anomaly due to factors such as a slightly
higher age group, a smaller population of nursing mothers as a donor pool, and new
restrictions applied to which wom e n could serve as donors.
Sullivan etal. (1991) have modified an earlier pharmacokinetic model that describes
the exposure of infants nursing from mothers who consume contaminated fish at the 25
ppt level of the FDA fish advisory. This model was validated by a study carried out in
rhesus monkeys dosed with 0.13 mg/kg/day of dioxin for 16 months before parturition,
and then throughout the period of lactation. The authors concluded that the intake of
T C D D by the infant as a result of successive lipid partitioning was sufficient to
approximately double the lifetime carcinogenic risk to the infant.
A number of studies have examined organochlorine compounds in the milk of
different animal species. In a toxicokinetic study in 4 cows, the animals received R e ­
labeled PCDDs and PCDFs dissolved in olive oil by the intraruminal route under light
sedation. The fate of the labeled compounds was studied by gas chromatography-mass
spectrometric assays of milk samples, adipose tissue biopsies, and tissues samples
collected when the animals were slaughtered on day 93. Milk levels were maximal 1 day
after dosing (about 200 pg/g for TCDD) falling to means around 2 pg/g by day 93. The
initial rapid drop in milk fat levels occurred during the first 5 or 6 days, and was
succeeded by a slow elimination phase that followed first order kinetics from days 27 to
93 for six of the eight congeners studied, including TCDD. The mean elimination half life
of T C D D (dose received 3.7 ng/kg) was calculated as 40.3 ± 7.7 days, and its
bioavailability as 29.5 ± 5.9 percent. The subcutaneous fat/milk fat ratio for T C D D was
relatively stable at 1.0-1.5 between days 6 and 93 (Oiling et al. 1991).
Several articles dealt with the transfer of organochlorine compounds both across
the placenta and into the milk. Using pregnant marmoset monkeys (Callithrix jacchus),
injected subcutaneously with a defined mixture of PCDDs and PCDFs 11 weeks before
delivery, Hagenmaier et al. (1990) studied the transfer of these compounds via the
placenta and through consumption of milk. Concentrations were measured in newborn
(1 day) infants and after 33 days lactation. Fetal, infant, and maternal P C D D and PCDF
tissue levels were measured and compared with those of other adults. Fetal liver levels,
87

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S ) -{-$*-

especially of PCDFs, were very low, but in suckling Infants, hepatic levels of TCDD, the
corresponding dlbenzofuran, and 1,2,3,7,8-pentachlorodlbenzo-p-dioxln were 2 to 4 times
higher than maternal levels; in contrast, O C D D levels were only 10 % of those in the
mothers. Adipose tissue and thymus levels of 2,3,7,8-substltuted congeners were high.
The data testified to the efficiency of transfer of T C D D in the milk as well as through the
placenta. Although no assays of milk concentrations of T C D D were performed, two
reports by Couture-Haws etal. (1991a; 1991b) demonstrated that the amounts of TCDD
present in the milk from treated rats were sufficient to Induce hydronephrosis in nursing
pups, and were equally effective toxicologlcally to treatments received while the animals
were in utero.

D.

Pharmacokinetic Studies in Animals
There have been several reported studies of the pharmacokinetics of T C D D In

animals. For example, Banks and Birnbaum (1991) studied the percutaneous absorption
of T C D D in 10-week-old male Fischer 344 rats. Absorption across the interscapular area
was a first-order process with an absorption rate constant for tritiated T C D D of 0.005 per
hour. Absorption reached 82 pmol (26 ng) in 120 hours, and the percentage of the dose
that could be detected In the blood never exceeded 0.3%. In a second study from the
same laboratory, Kedderls et al. (1991b) measured the distribution and excretion of the
tetrabromo- analog (TBDD) of T C D D given Intravenously at 0.001 or 0.1 pmol/kg to
Fischer 344 rats. Both fecal (major route) and urinary excretion were nonlinear with
respect to dose, although the terminal whole-body half-life calculated from fecal excretion
In both dosage groups was 18 days. At 56 days, there was a disproportionate elevation
in the ratio of the concentration in liver relative to adipose tissue at the high dose, 2.6
compared with 0.2 for the low dose. This may reflect to some extent the effects of
binding to specific hepatic Ah receptors. Terminal excretion half-life from adipose tissue
was about 60 days. The data were similar to earlier reports on TCDD. The same group
of investigators in further reports (Kedderis etal. 1991a; 1991c) compared the distribution
and excretion of tritiated T C D D and TBDD.

Biliary excretion of T C D D (1 nmol/kg

Intravenously) over an 8-hour period was somewhat greater than that of TBDD, 10%
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versus 7 % in 5 hours, all in the form of metabolites. Pretreatment of the rats with a single
dose (100 nmol/kg) of unlabeled T C D D or T B D D 3 days before tracer did not alter biliary
excretion, but did cause a doubling of hepatic radioactivity.

It was apparent that

autoinduction of the metabolism of T C D D and T B D D did not occur, despite demonstrable
induction of CYPIA1 and CYPIA2. Furthermore, induction of the latter did not appear to
account for all the dose-related increase in the ratio of liver to adipose tissue dioxin
concentrations. This dose-dependence was evident on comparing T B D D at 1 and 100
nmol/kg, when at 56 days, liver/adipose tissue ratios were 0.2 and 2.6, respectively.
Fecal excretion also showed some dose-dependence, reaching 50 and 7 0% of the
administered dose, for the low and high doses, respectively, at 56 days. The terminal
whole-body half-life was about 18 days at both dosage levels, but for excretion from the
adipose tissue compartment itwas about 60 days.
Some limited information on tissue levels of 2,4-D in dogs was published during
1991.

Maximal serum concentrations measured in dogs given encapsulated oral

formulations of 2,4-D were 1,075 pp m at 5 hours after 220 mg/kg, 718 p pm at 2 hours
after 175 mg/kg and 121 p p m at 4 hours after 43.7 mg/kg in English Pointer dogs.
Levels in the urine that were as high as 1,792 ppm, 2 hours after administration, were
indicative of very rapid excretion (Arnold et al. 1991a). When the same breed of dogs
were permitted to run on grass-plot enclosures sprayed with 2,4-D, serum concentrations
of 2,4-D ranged from 0.02 to 26.4 pp m (Arnold et al. 1991b).

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whole blood, blood plasma and adipose tissue. Chemosphere 23(11-12): 1913-1919.
Schecter, A. and J.J. Ryan. (1991c) Brominated and chlorinated dioxin blood levels in a chemist
34 years after exposure to 2,3,7,8-tetrachlorodibenzodioxin and 2,3,7,8-tetrabromodibenzodioxin. Chemosphere 23(11-12): 1921-1924.
Smith, A.H., D.G. Patterson, M.L. Warner, R. MacKenzie and L.L. Needham. (1992) Serum
2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their
implication for cancer hypotheses. J. Natl. Cancer Inst. 84(2): 104-108.
Sullivan, M.J., S.R. Custance and C.J. Miller. (1991) Infant exposure to dioxin in mother’s milk
resulting from maternal ingestion of contaminated fish. Chemosphere 23(8-10):
1387-1396.
Svensson, B.G., A. Nilsson, M. Hansson, C. Rappe, B. Akesson and S. Skerfving. (1991)
Exposure to dioxins and dibenzofurans through the consumption of fish. N. Engl. J.
Med. 324(1): 8-12.
Webster, T. and P. Connett. (1991) Estimating bioconcentration factors and half-lives in humans
using physiologically based pharmacokinetic modelling: 2,3,7,8-TCDD. Chemosphere
23(11-12): 1763-1768.
Wolfe, W.H., J.E. Michalek, J.C. Miner, A. Rahe, J. Silva, T. W.F., W.D. Grubbs, M.B. Lustik, T.G.
Karrison, R.H. Roegner and D.E. Williams. (1990) Health status of air force veterans
occupationally exposed to herbicides in Vietnam. 1. Physical health. JAMA 264(14):
1824-1831.
Yu, M., C. Hsu, B. Gladen and W. Rogan. (1991) In utero PCB/PCDF exposure: relation of
developmental delay to dysmorphology and dose. Neurotoxicol. Teratol. 13(2): 195-202.

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VI. BA SIC STU D IES RELEV A N T TO HEALTH E F F E C T S

A.

Introduction
Recent volumes of the Review have documented a steady increase in the

proportion of the literature on phenoxy herbicides and their dioxin contaminants that is
devoted to basic research on mechanisms of action.

This trend has continued

throughout 1991. Indeed, during this year the basic research area has received particular
attention as the major source of controversy regarding human

health hazard

assessments, and possible réévaluation of the Environmental Protection Agency’s (EPA)
regulations governing the dioxins, as can be seen for example in the article by Barnes
(1991). This is due, at least in part, to differing opinions on what the wider implications
of a mechanism of action that is based on interaction with receptors might be. Receptor-.
based mechanisms, which are common to most pharmaceutical agents for example, are
usually associated with sigmoidal dose-response curves, and exhibit definitive threshold
concentrations below which biological activity is negligible or nonexistent. In contrast,
regulatory agencies such as the EPA and the Food and Drug Administration, use a more
conservative model for hazard assessment of environmental dioxins that is based on
extrapolating dose-response curves linearly down to zero, the linearized multistage model.
This model assumes the worst case, that dioxins are complete carcinogens, for which it
has generally not been possible to define threshold levels, since a single molecular
interaction with D N A can in theory cause a mutational event that starts the process of
carcinogenesis. A recent review discusses many of these environmental issues (Safe
1991). In view of their relevance both to interpreting the findings from toxicologic studies
in experimental animals, and to making health hazard assessments in humans, itis only
fitting that recent studies of the mechanism of action of dioxins and related compounds
be considered in depth.
The major thrust of basic research over the past decade has established that most
biological effects of T C D D and related compounds are exerted through a mechanism that
involves interaction with an intracellular receptor. The steps involved have been concisely
summarized in recent reviews by Denison (Denison 1991) and by Landers and Bunce
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(1991a). The receptor for T C D D occurs in the cytosol fraction of a wide range of tissues
and organisms. It also appears to be involved in the action of a number of complex
aromatic compounds. Because of the aromatic character of the ligands that interact with
it, and the prototypical biochemical result of exposure to them, namely the induction of
the hepatic enzyme aryl hydrocarbon hydroxylase (AHH), the receptor with which they
interact was termed the aromatic hydrocarbon responsiveness (Ah) receptor. After T C D D
binds to the Ah receptor, the complex undergoes a process of transformation, the details
of which still remain to be completely elucidated, that enables it to translocate to the
nucleus and interact with special sites on DNA, the dioxin-responsive elements (DRE).
This interaction allows dioxins to modulate the activities of a battery of genes, most
notably CYPIA1 and CYPIA2, which are the structural genes responsible for the synthesis
of cytochromes P450IA1 and P450IA2. The increased levels of these cytochromes and
other enzymes which result, bring about the metabolism of the ligands that initiated the
process (and more especially of other compounds) to products which might include either
detoxified materials that are excreted, or activated intermediates that can damage critical
targets within the cell. Although most studies have concentrated on the CYPIA1 gene and
its associated DRE, it is likely that there are analogous dioxin-responsive sites flanking
other genes, and that altered expression of the latter may in part underlie the species and
tissue variations in T C D D toxicity. These variations lead to interspecies LD^ levels that
range from 0.6-2.5 /jg/kg in guinea pigs to 1,157-5,051 /vg/kg in hamsters (World Health
Organization 1989).

Even two strains of a single species may show a difference in

sensitivity of a similar order of magnitude. Han/Wistar rats, for example, can tolerate up
to 3,000 /ug/kg, while Long-Evans rats are killed by 20 [ig/kg of T C D D (Tuomisto and
Pohjanvirta 1991).

At present there is insufficient information available to determine

exactly where humans fit on the scale of species sensitivity.
In the sections that follow, we will consider recent work on the Ah receptor itself
first, and then relate this to the various modulations in gene expression and other events
that may stem from it.

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£)-&£> O

B.

The Ah Receptor
The Ah receptor is a member of the erb-A family which also includes the receptors

for steroid and thyroid hormones and retinoic acid.
compounds,

such

It binds a variety of aromatic

as the polycyclic hydrocarbons,

heterocyclic amines,

and

polychlorinated aromatics that include dioxins, dibenzofurans and biphenyls, and is able
to mediate many of their biological actions. Some of these compounds, such as the
polycyclic hydrocarbons, do not act exclusively through the Ah receptor but also interact
with other receptors. No endogenous ligand for the Ah receptor has yet been identified,
and indeed, itis possible that itsfunction relates exclusively to exogenous agents that are
continually entering living organisms, and must be eliminated in order to maintain the
internal cellular milieu. Previous volumes of the Review have presented the literature in
which the interaction of dioxins with the Ah receptor was initially demonstrated. Most
current research is concerned with the nature and properties of the receptor, and the
kinetics, mechanism and biological implications of this interaction.
Studies of the role of the Ah receptor in dioxin action continue, as in the past, to
utilize for the most part, mammalian (usually rodent) liver or hepatoma tissue as the
experimental system of choice. However, the receptor is widely distributed, and recent
reports suggest that other systems may offer advantages in specific situations. One
species that might be of relevance to questions that are of environmental concern, is the
rainbow trout. The RTG-2 cell line which is derived from the embryonic gonad cells of this
teleost fish, contains a 145 kDa Ah receptor protein, that is larger than the mammalian
receptor, but shows an order of affinity for agonists that is similar to the latter for a range
of ligands (Swanson and Perdew 1991). In another study, it was found that primary
hepatocyte cell cultures from this fish are closely analogous to rodent liver, in terms of a
dose-dependent increase in the activity of ethoxyresorufin O-deethylase (EROD) activity
and levels of P450IA1 determined immunologically, on exposure to T C D D and pnaphthoflavone. This effect was especially long-lived for T C D D (Pesonen et al. 1991;
Pesonen and Andersson 1992).
Closer to the purview of this Review, in an extension of earlier findings, the Ah
receptor was characterized in human tonsillar tissue. The receptor, present at levels of
96

100-300 fmol/ m g cytosol, could transform to a nuclear binding form sedimenting at 6 S
(Lorenzen and Okey 1991). The human B lymphoblastoid cell line BCR-5 has also served
as a source of a characterized human Ah receptor (Waithe et al. 1991). This receptor
was present at levels of about 200 fmol/mg of protein as a 9 S peak that bound labeled
TCDD, had an apparent binding affinity (KD) of about 5nM, and was extracted from the
nuclei as a complex with T C D D that sedimented at 5 S. These two systems offer the
opportunity to study the mechanism of action of T C D D in a surgically-available human
tissue and a standard cell line, respectively, which may be especially appropriate for
approaching mechanistic questions regarding the potential human immunotoxicity of
dioxins. Other potential sources of human material appear to be the Mz-Hep-1 human
liver cell line described by Roberts et al. (1991), human placenta (Lucier 1991), and the
human colon adenocarcinoma cell line LS 180 (Harper et al. 1991a).

Levels of the

receptor in the latter cells were as high as 500 fmol/mg protein, similar to those in mouse
hepatoma cells. The cytosolic form corresponded to a multimer of molecular weight 285
Kda, compared to 175 Kda for the nuclear TCDD-bound form that sedimented at 6.2 S.
The smallest ligand-binding subunit was a 110-Kda fragment. It is apparent from the
reported characteristics of these human Ah receptor preparations that they are similar in
their general properties to the rodent materials.
Nevertheless, there are sufficient interspecies variations in the properties of the
various Ah receptors, especially in terms of ligand affinities, to justify the study of a range
of systems. For example, tritiated T C D D and 7-(125l)iodo-2,3-dibenzo-p-dioxin as highaffinity ligands were used to photoaffinity label nuclear Ah receptor from rodent (H-4-II E
and Hepa 1c1c7) and human (Hep G2) cells. Yields of photoaffinity-labeled nuclear Ah
receptor were much lower (0.5-2.5%) from mouse cells compared to human (>15%),
suggesting a difference in stability of the two complexes. In experiments using photolyzed
or unphotolyzed complexes of the photoaffinity-labeled nuclear Ah receptor with synthetic
DRE, gel mobilities of the rodent and human complexes were found to differ, and the
binding ofthe human receptor complex underwent significant (27%) photolysis, in contrast
to the rodent material (Wang et al. 1991). In the human colon carcinoma LS180, the
affinity of the Ah receptor for T C D D (Kdvalue about 5 Nm, also for 3-methylcholanthrene)

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and sensitivity of the cells to A H H induction were an order of magnitude lower than in the
murine system (Harper etal. 1991a). Finally, a striking difference has been observed in
the effect of sodium molybdate on human Ah receptor as contrasted with that from other
species (Harper etal. 1991c). Molybdate at 20 N m added before or during ligand binding
by human receptor completely prevented formation of receptor-DNA complexes, whereas
rodent preparations showed no such sensitivity. Itappeared that molybdate stabilized the
multimeric 9 S form of the receptor. This observation has practical consequences in
studies of the Ah receptor, since molybdate has been used to help stabilize the receptor
during manipulation, especially in the case of the human preparation, which appears to
be more labile than that from rodents. Whether such differences underlie the extreme
variations in species and strain sensitivity to dioxins that have been documented is at
present unclear.
Mouse liver Ah receptor has been purified more than 150,000-fold from C57BL/6J
mice to yield a 95 Kda protein with an N-terminal peptide sequence determined as:
ala/asp-ser-Arg-Lys-arg-Lys-Pro-Val-GIn-Lys-Thr-Val-Lys-Pro-lle-Pro-Ala-Glu-Gly-lle-Lysser-Asn-Pro-ser-Lys-(the use of lowercase for certain residues indicates some uncertainty
in their characterization)(Bradfield et al. 1991). However, itis known that more than one
form of the receptor occurs, even within the same tissue, and modulation of these
different forms may constitute a normal in vivo function. Using a combination of DNASepharose chromatographic fractionation, SDS-polyacrylamide gel electrophoresis and
photoaffinity labeling techniques with rat liver cytosols, it has been shown (Gasiewicz et
al. 1991a) that the DNA-binding form of the Ah receptor is a multimer consisting of at

least two components, of which the 100-kDa protein binds TCDD, whereas the 110-kDa
peak does not. The 100-kDa monomer, bound to ligand, must interact with the 110-kDa
protein to generate the 200-kDa form of the receptor that binds with high affinity to the
dioxin-responsive elements (DRE), such as the D N A recognition motifs upstream of
CYPRIA1 and other possible sites that are less well established, thus regulating gene
expression. Landers et al. (1991b) have described an inducible Ah receptor-like protein
in rat liver that was detectable after cotreatment with T C D D and 2 ,2 ’,4 ,4 \5 ,5 ’-hexachlorobiphenyl.

This protein was essentially indistinguishable from the constitutive
98

receptor interms of chromatographic behavior and molecular weight (about 150 Kda), but
was kinetically distinct, being more stable thermally, but with a first order rate constant for
dissociation from T C D D of 0.55 versus <0.0024 min'1 for the normal Ah receptor.
Like the steroid receptors, the Ah receptor is known to occur normally as an
inactive complex with the heat shock protein hsp 90, sedimenting at 9-10 S. In Hepa
1c1 c7 cells, for example, all the cytosolic Ah receptor is in the bound form, whereas in
the nucleus there is also a 6 S form without hsp 90, which has a more basic pi and
enhanced ability to specifically bind ATP (Perdew 1991). The cytosolic complex cannot
bind to target D N A sequences until itis dissociated from this complex. Itis of interest that
apart from mild heating, which would be expected, given the nature of hsp 90,
physiological levels of ATP also appear to stimulate the conversion of the complexed Ah
receptor to its DNA-binding form (Cary and Dougherty 1991a; Cary et al. 1991b).
However, this point is not entirely clear, since Perdew’s data (Perdew 1991) would
suggest that interaction with ATP occurs only after the Ah receptor has translocated to
the nucleus. The availability of a cell-free system that exhibits dioxin-induced activation
of latent Ah receptor to the form which binds D N A (Cuthill et al. 1991) may help elucidate
the complete details of the transformation process. In this system, the presence of ligand
alone was sufficient to activate the cytosolic receptor to a DNA-binding form. The order
of ligand effectiveness in inducing activation in this system was closely correlated with
relative affinity for the receptor and ability to lead to gene transcription in vivo. Prokipcak
and Okey (1991) have studied the short-term fate of the Ah receptor in mouse hepatoma
cells (Hepa-1) exposed to tritiated TCDD. During the first 2 hours, there was translocation
of cytoplasmic Ah receptor with a rise in the nuclear form, but by 5 hours the latter had
fallen to about 50% of maximal concentrations. This process was not accompanied by
regeneration of the cytosolic form, or by recycling into that compartment of the nuclear
receptor, so that by 6 hours the total cellular level of receptor was only 15-20% of the
initial value.

It could not be determined whether this short-term effect was due to

reversible loss of ligand-binding capacity, resulting from some molecular modification, or
to loss of receptor protein itself.

635

The transformation of cytosolic receptor-TCDD complex to the active nuclear form
may represent a possible site for differences in inherent sensitivity to dioxins. In a study
of two classes of mutant strains of mouse hepatoma (Hepa 1c1c7) cells, class I was
found to have low levels of both cytosolic and nuclear receptor, whereas in class II, levels
of T C D D receptor in the cytosol were comparable to those in the wild strain, but the
nuclear complex was significantly reduced. Since incubation of ligand-bound cytosol from
class II cells with cytosol from class I cells transformed the ligand-bound receptor to
active DNA-binding material, itwas suggested that failure of class II cells to respond to
T C D D was due, at least in part, to a defect in the factors responsible for transformation
(Piskorska-Pliszczynska et al. 1991b).
There is increasing evidence for the existence of other factors which also may
modulate the Ah receptor. By pretreating rat hepatic cytosol with activated charcoal
before adding tritiated T C D D as the tracer ligand, transformation of receptor to the D N A
binding form was inhibited. However, cytosol from either DBA/2J mice, which as was
mentioned above shows negligible affinity for TCDD, or from rats where the Ah receptor
had been prebound and thus saturated with unlabeled TCDD, stimulated the
transformation (Henry and Gasiewicz 1991b). This implies the existence of a cytosolic
transforming factor which is independent of ligand binding, that can be adsorbed or
inactivated by charcoal. Gel retardation studies of the partially-purified untransformed
receptor suggested that the factor is a heat-labile, trypsin-sensitive protein of molecular
weight somewhat greater than 50 kDa, which associates with the monomeric TCDDbound subunit to enable itto bind to the DRE that constitute the target D N A sequences.
In the need for this additional factor(s) in order to interact with DNA, the Ah receptor
differs from the steroid receptors, but resembles those for thyroid hormone and 1,25dihydroxyvitamin D3.

Studies from Oliver Hankinson’s group also have provided

information about an additional factor required in the transformation process. The cDNA
and part of the gene were cloned for a protein required in the translocation of the TCDDbound subunit from the cytosol to the nucleus. This 87-kDa protein has certain features
in its sequence that relate to the basic helix-loop-helix D N A binding-proteins, while others
resemble two Drosophila proteins, Per and Sim (Hoffman et al. 1991).
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C.

M echanism of Ah Receptor Interaction with TCDD
The mechanism whereby T C D D interacts with the Ah receptor and modulates gene

expression is becoming better understood as an increasing variety of techniques is
applied to the problem. Studies with inhibitors are frequently very fruitful in providing
information about the underlying mechanism of action of imperfectly understood
processes like the dioxin interaction. In the case of TCDD, such studies are providing
information about other factors that may be involved in the basic interaction. Inhibitory
effects of two different enzymes on TCDD-receptor function have been described. In one
case, the specific DNA-binding ability of the TCDD-Ah receptor complex was reduced or
abolished by incubating with acid phosphatase, an effect that was in its turn inhibited by
sodium phosphate (Pongratz et al. 1991).

These findings suggest that as in other

transcriptional processes, the function of the dioxin receptor may be regulated by
phosphorylation.
Acting at a somewhat earlier step in the process, ribonuclease A decreased the
affinity of TCDD-Ah receptor complex for DNA, and inhibited transformation of the TCDDbound receptor to the DNA-binding form, without altering the number of potential binding
sites, or affecting the preformed TCDD-receptor complex (Henry et al. 1991a). This
introduces the possibility that, as in the case of the steroid hormone receptors, R N A plays
some as yet undefined role in Ah receptor transformation. A different mechanism is
indicated for the inhibitory effect of a-naphthoflavone (Gasiewicz and Rucci 1991b). This
compound apparently functions as an antagonist of TCDD, competing for binding to the
Ah receptor, and blocking the ability of T C D D to transform the receptor to a form able to
bind to DRE.

In a similar fashion, 6-125l-methyl-8-iodo-1,3-dichlorodibenzofuran, an

antagonist of TCDD, was found to act by competition between the ligand-receptor
complexes for nuclear binding (Piskorska-Pliszczynska et al. 1991a). Chlorinated trans
stilbenes also compete with T C D D for receptor binding, and act as antagonists of
monooxygenase induction by TCDD, while themselves functioning as weak agonists for
enzyme induction (Bunceetal. 1990). Finally, administration of the tumor promoter 12-0tetradecanoylphorbol-13 acetate to C57BL/6 mice at the same time as TCDD, abolished
the accumulation of the nuclear dioxin receptor observed on treatment with T C D D alone,
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637

thereby inhibiting transcriptional activation of the CYPIA1 and CYPIA2 genes (Okino and
Tukey 1991). It is possible that this also represents a competitive action.
With respect to the molecular details of the interaction with specific D N A
sequences, a gel retardation study undertaken with rat hepatic cytosol (Denison and Yao
1991) indicated that there is a protein factor(s) which binds to D R E in a manner that is
TCDD-inducible, and dependent on sequence, time and temperature. This factor has Ah
receptor ligand specificity. The affinity of the complex for D R E was more than 3800 times
stronger than for non-specific D N A sequences. The total concentration of transformed
receptor was estimated as 56.1 fmole/mg protein, and a chelatable divalent cation
appeared to play a role in the transformation. In rat liver, the two D R E sites located about
1 kb upstream of the cytochrome P 450IA1 gene (CYPIA1) exist prior to ligand induction^
a process which does not affect their Dnase l-hypersensitivity. A constitutive, labilefactor, ^
which is

distinct from the Ah receptor recognizes and binds to the D R E in vitro.:

However, there is another Dnase l-hypersenitive site that is responsive to xenobiotics =
.
located near the transcription initiation region. This differs from the D R E sites in that its<j
DNase sensitivity markedly increases after induction by p-naphthoflavone (Hapgood ef;:;
al. 1991).

Attention has been given to structure-activity relationships in Ah receptor s
interactions. While some studies have determined the actual amount of bound ligand, e
others have used some surrogate measure of receptor interaction, such as enzyme
induction. The Computer-Automated Structure Evaluation Program, automatically selects 5
descriptors for structure-activity relationships. It was applied to Ah receptor binding by k
223 compounds, using data taken from the literature. These compounds included
polycyclic aromatic hydrocarbons (PAH), substituted dibenzo-p-dioxins, dibenzofurans.u
biphenyls, nitro-PAH, halo-PAH and A/-heterocyclics, from two databases, one comprising
136 compounds studied by sucrose density gradient techniques, and the other of 87 compounds that were subjected to electrofocussing assays (Rannug etal. 1991). Among
the PAH and heterocyclic compounds, those fragments with the classical "bay" region, •
previously related to carcinogenesis, were the most strongly correlated with T C D D
receptor binding.

On the other hand, in the case of the dioxins and benzofurans,
10 2

receptor binding affinitywas associated with the presence of halogens in lateral positions;
longitudinal substitutions decreased receptor affinity. The absence of com m o n biophores
between these two classes of compounds, both of which have high affinity for the Ah
receptor, suggests that there may be two different recognition sites involved in receptor
interaction.
Another study by Kobayashi et al. (1991) that examined structure-activity
relationships, correlated biological activity with calculations of the energy difference
between the homo and the lowest unoccupied molecular orbitals.

The order of

decreasing energy difference from molecular orbital considerations was TCDD, followed
by the 1,2,3,7,8-penta-chloro-, 1,2,3,7,8,9-hexachloro-, 2,3,7-trichloro- and 2,8-dichloroanalogs; this was consistent with the biological toxicity and AHH-inducing capacity of the
compounds.
In an assessment of the biological activities of mixtures of various polychlorinated
dioxins, as measured by the induction of E R O D activity in primary rat hepatocyte cultures
and the hepatoma H4I1E cell line, activity was found to reflect the additive effects of the
2.3.7.8- substituted components (Schrenk etal. 1991b). A similar relationship was evident
in a comparison of the efficacy for hepatic A H H induction in C57 and DB A mice of TCDD,
2.3.4.7.8- pentachlorodibenzofuran,and3-methyl-sulfonyl-4,5,3’,4’-tetrachlorobiphenyl,as
compared with 7,8-benzoflavone and methylcholanthrene (Nagayama etal. 1991). Koga
etal. (1991) found T C D D and 1,2,3,7,8-pentachlorodibenzo-p-dioxin to be similarly potent

in enzyme induction in rat liver, but the pentachloro- derivative persisted in the animal for
a longer period of time. Studies in which the inductive potency of T C D D has been
compared with its tetrabromo-analog, TBDD, or mixed halogenated congeners, in terms
of E R O D activity, have shown them to be essentially equipotent (Kedderis et al. 1991;
Schulz-Schalge etal. 1991).
It is possible that differences in the properties of Ah receptor with respect to its
interaction with T C D D might affect an organism’s inherent sensitivity to this agent. Thus,
in a comparison of hepatic cytosols from C57BL/6J mice, which are responsive to TCDD,
in terms of the induction of cytochrome P450 and aryl hydrocarbon hydroxylase (AHH)
on exposure to this dioxin, and the nonresponsive strains DBA2J, AKR/J and SWR/J,

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rP-6,4, S'

Harper and coworkers had shown in 1989 that the amount of Ah receptor and its affinity
for T C D D were both much lower in the latter strains. When the study was extended to
embryonic cells, this distinction still existed, but was found to be less pronounced, with
a two-fold rather than a ten-fold difference in affinity for T C D D (Harper et al. 1991b). At
present there is no obvious explanation for the difference between adult and embryonic
tissues. Strain differences in the distribution pattern of the Ahd and Ah^3 alleles of the
mouse Ah receptor gene have been described recently by Poland and Glover (1991).
W e will next turn to the biochemical implications of Ah receptor interactions, many
of which can be understood best in terms of a battery of six Ah-related genes (Nebert ef
al. 1989a; 1989b). In the conventional terminology used for drug metabolism, there are

two Phase Igenes, CYPIA1 and CYPIA2, which encode for cytochrome P450 forms, and:
four Phase IIgenes encoding for: NAD(P)H:quinone oxidoreductase (NQ01, alternatively
termed N M 0 1 for menadione as the natural quinone); aldehyde dehydrogenase (ALDH-3)
associated with tumor; UDP-glucuronyl transferase (UGT-1); and glutathione transferase:
(GT-1). T C D D induces all members of this battery.
•

D.

t-

Induction of Cytochrome P450
The recent reports of receptor interactions outlined above have continued to stress

the resultant induction of one form of cytochrome P450, cytochrome P450IA1. Indeed,:
so characteristic is the induction of this cytochrome by polychlorinated dibenzo-p-dioxins1
and dibenzofurans, that Schrenk et al. (1991a) have suggested that the presence of the >
hepatic microsomal enzyme EROD, which is a functional parameter of P450IA1,is a useful:
bioindicator of exposure of feral animal populations to these agents. Anderson and her:
coworkers (1991) have demonstrated that P450IA1 and E R O D activities, once induced,:
may persist at high levels for prolonged periods.

In adult male Swiss mice, both:

parameters were still elevated in the liver one month after a single low dose (5 nmole/kg)
of TCDD, while in the lung, E R O D activity was even more pronounced, being elevated 10fold at 12 weeks. These authors considered that such extreme persistence in the lung,
which was even more pronounced in animals treated with Aroclor 1254, would be ;
sufficient for tumor promotion, ifP450IA1 induction was indeed a factor in tumorigenesis.

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Studies by Jones et al. (1991), in which transgenic mice were created by using a D N A
fragment containing the CYPIA1 enhancer elements and promoter, coupled with the
chloramphenicol acetyltransferase reporter (CAT) gene, have indicated that this region
functions as a strongly-inducible promoter in vivo, and that there are gender-specific
differences in response to induction. Even in a fish such as the rainbow trout, induction
of P450IA1, together with M R N A for the responsible CYPIA1 gene, can readily be
demonstrated (Pesonen and Andersson 1992). The central role played by the P450 family
of cytochromes in the oxidation of drugs, toxins and various exogenous compounds is
well known; a recent review has covered aspects most relevant to the metabolism of
toxins and carcinogens (Guengerich and Shimada 1991).
The molecular regulation of gene expression for the P450IA family has received
recent attention. Nemoto et al. (1991) have stressed that regulation of aryl hydrocarbon
hydroxylase (AHH) induction in primary hepatocyte cultures from T C D D responsive
(C57BL/6) and nonresponsive (DBA/2) mice is qualitatively similar but quantitatively
different.

Thomsen and her colleagues (1991) have continued studies in human breast

carcinoma cell lines of differing responsiveness to TCCD, by employing an expression
vector containing the functional 5’-regulatory region of human CYPIA1 fused to the
reporter gene C A T for chloramphenicol acetyltransferase. Lines highly responsive to
TCDD, in terms of the amount of CYPIA1 m R N A induced, were also highly responsive to
T C D D in the chloramphenicol acetyltransferase assay.

These responsive cell lines

expressed a nuclear protein that binds the DRE. A similar correlation between induction
of CYPIA1 m R N A and of acetyltransferase held for the poorly or nonresponsive lines, and
the authors concluded that poor response reflected altered trans-acting factors. In the
case of one of these poorly-responsive lines (CAMA-1), an Ah receptor constitutively
bound to the Ah responsive element was postulated, leading to high basal activity
coupled with low induction. Studies using pyridine as the inducer have demonstrated an
interesting difference between cytochrome P450 subfamilies. Induction of both P450IA1
and P450IA2 is associated with increased m R N A levels through either transcription or
stabilization, a known outcome of earlier work, reviewed by Lusska etal. (1991), whereas

105

in contrast, induction of P450IIE1 which belongs to a different cytochrome P450 subfamily,
appears to result from the increased efficiency with which itis translated (Kim etal. 1991 ).
Immunological techniques have been used with success to demonstrate the
localization of P450 induction. In rats, low doses of both T C D D and Aroclor 1254 induced
P450IA1 primarily in the acinar zone 3 of the liver, whereas after high doses there was no
zonal pattern of induction, as determined by polyclonal antibodies raised against this
cytochrome (Bars and Elcombe 1991). It is of interest that similar immunologic probes,
in addition to E R O D activity, have been used to establish the induction of p450IA1 and
other cytochromes in a human colon cell line; this system may be relevant to colon
carcinogenesis (White et al. 1991). An analogous immunohistochemical technique has
been adapted to demonstrate the localization of P450IA1 induced in the liver and other
tissues of the teleost fish (Stenotomus chrysops) by chlorinated benzofuran and biphenyl
derivatives (Smolowitz et al. 1991; Stegeman et al. 1991).
Among other Ah-dependent enzymatic effects that have been observed is the
bilirubin-degrading system induced in rat liver microsomes by TCDD, which, like the wellcorrelated induction of E R O D activity, is inhibited by a monoclonal antibody raised against
cytochrome P450IA1 (DeMatteis et al. 1991). Another interesting effect of this type isthe
superinduction of the Phase II enzyme aldehyde dehydrogenase in rat hepatoma cells,
whereby cotreatment with the protein synthesis inhibitors puromycin or cycloheximide
caused a 10-fold greater accumulation of the ALDH-3 m R N A than the induction produced
by T C D D alone. Transcription rates for the ALDH-3 gene were increased 4- to 5-fold,
consistent with the existence of a labile protein factor for gene transcription that
modulates the action of T C D D (Takimoto et al. 1991).
While nearly all the literature on induction of P450 and the hepatic microsomal
system associated with it has been concerned with T C D D and its congeners, a few
reports have examined 2,4-D. Thus, in the channel catfish, Ictalurus punctatus, a 10-day
exposure to a mixture of 2,4-D and picloram led to increased serum levels of EROD.
However, this change was not seen on exposure to either compound alone (Gallagher
and DiGiulio 1991). In mice treated with various combinations of pesticides that included
2,4-D (Chaturvedi et al. 1991), induction of the hepatic microsomal mixed-function
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oxygenase system was clearly associated only with combinations containing toxaphene.
In chicken embryo liver, 2,4-D (1, 2 or 4 mg/egg) raised the levels of hepatic postmicrosomal glutathione-S-transferase and E R O D activities, but not of other hepatic mixedfunction oxygenases (Santagostino etal. 1991). Thus, the overall conclusion isthat 2,4-D
alone does not appear to be an effective inducer of the mixed-function oxygenase system,
but can contribute to such an effect when it is administered as a component of the
appropriate combinations.

E.

Interaction of TCD D with Other Receptors and Effects on Expression of Other
G enes
Apart from its primary interaction with the Ah receptor, T C D D also intervenes in

other receptor-mediated processes, albeit in most cases through processes that are Ahdependent; however, some immunologic studies have suggested an Ah-independent
mechanism. This has been discussed at some length in earlier volumes of the Review.
Two recent examples of such interactions come from research by Goldstein’s group at
the National Institute of Environmental Health Sciences. In the first study, a single oral
dose of T C D D in an Ah-responsive (Ahb/b) strain of C57BL/6J mice led to a 30% decrease
in the binding capacities of both hepatic glucocorticoid and estrogen receptors, and a 50fold induction of E R O D activity which is specifically associated with the P450IA subfamily
of cytochromes. Ah-nonresponsive (Ahd/d) mice showed a 10-fold lower level of enzyme
induction, and a statistically-significant difference in the sensitivity of the estrogen
receptor. However, there was a similar degree of reduction in binding capacity of the
glucocorticoid receptor, and of tyrosine aminotransferase activity which is mediated by
this receptor, in both responsive and nonresponsive strains (Lin et al. 1991b). This
suggests that while the Ah receptor may mediate the effects of T C D D on the estrogen
receptor, this mechanism does not apply to the glucocorticoid receptor. In females of the
same responsive and nonresponsive mouse strains, T C D D caused an 80-90% decrease
in the maximum binding capacity of the epidermal growth factor (EGF) receptor, but the
EDgo for this effect was 10-fold higher in the Ahd/d compared with the Ahb/b strain. Since
T C D D did not affect total hepatic contents of the m R N A transcripts of either the EGF
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receptor (both the 10 and 6 kb transcripts) or transforming growth factor alpha (TGF-a),
while markedly increasing m R N A for cytochrome P450IA1 with the same 10-fold difference
in ED«, for the two strains, it is most probable that the effects of T C D D on the EGF
receptor are mediated by the Ah receptor (Lin et al. 1991a).
There have been a number of reports describing effects of T C D D on the
expression of genes other than CYPIA1. Aoki et al. (1991) examined rat liver after both
in vivo and in vitro exposure to TCDD. They identified induced P450IA1 and P450IA2 with

specific antibodies, but also noted increased amounts of five other proteins with molecular
weights of 26 (2 proteins), 36 and 39 (2 proteins) kD after in vivo treatment, and
reductions in three additional proteins (24, 25 and 29 kD) when liver parenchymal cells
were exposed to TCDD. No identity or functional role was ascribed to any of these new
proteins, but some induction effects noted in the literature could have significant biological
repercussions.
When cultures of human keratinocytes (SCC-12F) were exposed to T C D D on a
continuing basis, TGF-a was released into the medium at a rate of about 30 fmol/ml/day,
accompanied by a 3- to 6-fold increase in the expression of m R N A for this factor. The
process appeared to be mediated through the Ah receptor (Choi etal. 1991). This may
be a tissue- or species-dependent effect, since as described above, Lin et al. (1991a)
failed to show an effect on TGF-a m R N A in mouse liver. It is interesting that treatment
of C57BL/6J(Ahb/b) mice with T C D D (10-500 /L/g/kg) produced up to a 48-fold increase
in the release of another biologically-active polypeptide, tumor necrosis factor-a, when the
animals were challenged with endotoxin. A much smaller effect was seen in the (Ahd/d)
strain which is Ah-receptor deficient. Thus this effect is mediated through the Ah receptor
system (Clark et al. 1991a).

Whether it plays any role in the wasting syndrome

characteristic of T C D D intoxication is unknown.
The SCC-12F keratinocyte line also has been the source of five TCDD-responsive
complementary clones from which c D N A libraries were prepared (Sutter et al. 1991). Of
these four clones, one was found to encode plasminogen activator inhibitor-2 (which
modulates proteolysis of extracellular matrix thus influencing growth and differentiation),
and another encoded interleukin-1 p, permitting T C D D to affect both differentiation and
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inflammation. NAD(P)H:quinone oxidoreductase (NQ01), which isidentical to diaphorase
4, is a flavoprotein which catalyzes the reduction of various quinones, and which is
believed to protect against their toxicity and carcinogenicity. This enzyme is induced by
TCDD, with an accompanying 3-fold increase in transcription of the N Q 0 1 gene in human
hepatoblastoma (Hep-G2) cells. The human gene for N Q 0 1 has been cloned and
partially sequenced, and the cDNA transfected into COS-1 monkey cells in which the
enzyme was expressed (Jaiswal 1991; Shaw et al. 1991). Among the findings from
sequence analysis was a copy of G C G T G

at position 740 that resembled the

xenobiotic/dioxin response elements in CYPIA1. It is interesting that TCDD, which has
a number of antiestrogenic actions, decreased constitutive levels of c-fos m R N A in the rat
uterus, and markedly inhibited the stimulatory effect of 17 /3-estradiol on this parameter
when administered at the same time as the hormone (Astroff et al. 1991). W e shall
consider some of the interrelationships of T C D D with steroid hormones in the next
Section. There was a report in 1988 (Burt and Thorgeirsson 1988) that T C D D increased
rodent liver levels of m R N A transcribed from both multidrug resistance (MDR) and CYPIA2
genes.

Recent attempts to repeat these observations, studying CYPIA1, NQO-1 and

MDR1, -2, and -3 have been unsuccessful, however (Teeter et al. 1991).
In a study with potential relevance to immunotoxicity, it was found that T C D D
increases the phosphorylation of membrane protein in B lymphocytes, an action at least
in part attributable to stimulation of tyrosine-specific phosphorylation (Clark etal. 1991b).
This effect was observed within minutes, exhibited a dose-response curve identical to that
for inhibition of antibody synthesis, and appeared to be unrelated to protein kinase C.
The protein synthesis inhibitors, puromycin and cycloheximide, and an inhibitor of
transcription, actinomycin D, partially prevented the increase, suggesting that new protein
synthesis is required.

This study confirms and extends earlier work in B cells and

thymocytes. Holsapple etal. (1991) have reviewed the evidence for phosphorylation as
an action of T C D D that might be independent of mediation by the Ah receptor, although
such independence would be hard to establish ifAh receptor action itself involves some
type of phosphorylation as the evidence discussed above would suggest.

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Finally, with regard to the enzymes of Phase II drug metabolism, a recent review
has discussed the possible role played by phenol UDP-glucuronyl transferase, an isozyme
induced by TCDD, as a control for proximate carcinogens, and a contributor to the
persistently altered enzyme pattern in premalignant stages of cancer development (Bock
1991).

F.

General Metabolic Effects of Dioxins
The polychlorinated dioxins and biphenyls are capable of a wide range of biological

actions.

In the case of the polychlorinated biphenyls (PCBs), a recent review has

attempted to attribute their effects to an Ah-mediated production of P C B metabolites
which intervene in endocrine and Vitamin A metabolism (Brouwer 1991). T C D D shares
at least some of the characteristics of PCBs, including interaction with the Ah receptor
and intervention in endocrine systems, for which reason it has been termed an
"environmental hormone" (Schmidt 1992).

1.

Effects on Endocrine Systems

A number of studies have examined the question of modulation of steroid hormone
function by TCDD, which has been shown to exert both antiestrogenic and antiandrogenic
actions.

The antiestrogenic character of T C D D and related compounds has been

reviewed recently by Safe et al. (1991). Actions falling into this category include inhibition
of 17 ¿8-estradiol-induced increases in uterine weight, estrogen and progestin receptor
levels, EGF receptor binding, c-fos- and EGF m R N A levels, and peroxidase activity. The
structure-activity relationships for T C D D and similar compounds as antiestrogens closely
parallels their affinities for the Ah receptor, and the effects of T C D D are inhibited by both
actinomycin D and cycloheximide. In wild-type Hepa 1c1c7 cells, T C D D produced as
much as a 74% decrease in immunodetectable cytosolic and nuclear estrogen receptor
protein, but only ifthe cells were pretreated with T C D D for 1 to 42 hours before addition
of labeled estradiol (Zacharewski et al. 1991). Mutant lines with defects in Ah receptor
levels or in formation of transcriptionally-active receptor complexes, showed minimal or
no response to TCDD. Reduction of receptor protein must also form the basis for other

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646

recently-observed effects, such as inhibition ofthe estradiol-induced stimulation of glucose
to lactate conversion in MCF-7 human breast cancer cells (Narasimhan etal. 1991). This
N M R study of 1-13C-glucose metabolism, demonstrated an inhibitory effect within 1 hour,
in contrast to induced monooxygenase activity, which was not seen before 3 hours.
The antiandrogenic effects of T C D D appear to arise by a quite different
mechanism, one that involves luteinizing hormone (LH). T C D D has long been known to
cause ultrastructural changes in the testis, with impaired spermatogenesis in the rat,
associated with reduced plasma concentrations of testosterone and its 5 a-dihydroderivative. Lowered androgen levels were associated with decreased levels of testicular
cytochrome P45017a, 17 a-hydroxylase and C 17.20 lyase activities. Although earlier data
had suggested that levels of LH were unaffected, itnow appears that the plasma level of
this hormone is indeed reduced by 4 0 % within one day. Treatment of rats with human
chorionic gonadotropin (hCG) prevented the inhibition of these androgenic parameters
(Ruangwises etal. 1991). Additional information has been obtained in this area by Moore
et at. (1991) whose results suggested that T C D D inhibits the LH-dependent mobilization

of cholesterol to the cytochrome P450.*,. system responsible for pregnenolone synthesis,
by acting at a step subsequent to the formation of cAMP.
Another endocrine system that has been reported to be sensitive to the action of
T C D D is melatonin synthesis or secretion. In order to clarify this effect, Linden et al.
(1991) studied the most TCDD-resistant strain of rats (Han/Wistar) from 6 hours to 28
days after exposure to the dioxin. A single intraperitoneal injection of T C D D (50 /ug/kg)
lowered serum melatonin by 50% within a day, and kept it at this level for the total
observation period. However, even after a dose as high as 1,000 jug/kg, there was no
light or electron microscopic evidence of histopathology in the pineal gland 3 days after
injection of TCDD. There is as yet no information regarding the mechanism involved.

2.

Effects on Vitamin A Homeostasis

The ability of T C D D to interfere with Vitamin A metabolism figured prominently in
the 1990 literature reviewed in Volume XVII of the Review. The analogies between the Ah
and the retinoid receptors, and the superficial similarities in many of the symptoms
ill

resulting from Vitamin A deficiency and exposure to TCDD, namely hypophagia, weight
loss, cutaneous morphologic changes, elevated renal levels of retinoids and diminished
hepatic Vitamin A levels, make it plausible to consider that the same underlying
mechanism is at work. To date, however, no studies have approached this problem at
the molecular level which should provide the most definitive data, although work further
documenting the interrelationship of Vitamin A and T C D D in whole animals has appeared
recently.
Two reports from the Karolinska Institute dealt with this topic. In a study that
included male Hartley guinea pigs, Sprague-Dawley rats, C57BL/6 and DBA/2 mice, and
Golden Syrian hamsters, the animals were given intraperitoneal injections of isotoxic
doses of T C D D (in the range 0.5 to 400 /ug/kg), and sacrificed after 1, 7, 14, 28, 56 and
112 days. The time-related increase in hepatic storage of Vitamin A was inhibited by
TCDD, but only the guinea pig, which is especially sensitive to dioxin, failed to have
increased levels of the vitamin at the end of the experiment. Only in the rat could there
be seen a marked increase in renal, and a slight increase in serum, levels of the vitamin.
Pulmonary Vitamin A fell in all except C57BL/6 mice (Hakansson etal. 1991a). The same
group supplemented the diets of rats given single oral doses of T C D D with Vitamin A at
2,000, 5,000, 8,000 or 21,000 IU per kg, and obtained data which suggested that low
levels of dietary Vitamin A were associated with impaired abilityto tolerate the lethal action
of TCDD. Loss of total body or testicular weight, or liver enlargement, were more severe
at low levels of dietary Vitamin A, but loss in thymus weight was equally severe in all
groups. Except for the kidney, where there was an increase, levels of Vitamin A fell in
most tissues examined (Hakansson etal. 1991b).
In hairless (hr/hr) mice, Vitamin A deficiency caused the keratinization of dermal
epithelial cysts (structures derived from the involution of hair follicles), and enhanced the
hyperkeratinization induced by topical treatment with TCDD; body weight and thymus
gland atrophy were unaffected by Vitamin A status. No cutaneous changes were seen
in the congenic haired mice. T C D D treatment did not affect the cutaneous levels of
Vitamin A, but significant reductions in those in the liver occurred in both hairless (48%
after 0.6 /jg over 2 weeks) and haired (70% after 6 fjg over 2 weeks) mice. The authors

ii2

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suggested that the data are not consistent with the concept that T C D D toxicity is
mediated via an induced Vitamin A deficiency state (Puhvel et al. 1991). Infant male
Sprague-Dawley rats exposed to T C D D derived from their mothers’ milk exhibited
induction of E R O D activity, reduction in liver and lung Vitamin A content, and rises in the
levels of this vitamin in the kidney and serum. These changes were seen at doses of
T C D D that did not affect significantly the food consumption, growth or organ weights of
the dams, although liver, kidney and serum, but not lung Vitamin A levels, and hepatic
E R O D activities, showed similar changes to those seen in the nurselings (Waern et al.
1991).
Modulation ofTCDD- or phenobarbital-induced promotion of hepatocarcinogenesis
by manipulation of dietary Vitamin A has been studied in Sprague-Dawley rats (Flodstrom
etal. 1991). Carcinogenesis was initiated with 30 mg/kg of nitrosodiethylamine, followed

by the promoters at 0.07 or 0,7 fig per week by subcutaneous injection for TCDD, or 500
p p m in the drinking water in the case of phénobarbital, for a total of 16 weeks.

The

incidence of y-glutamyltranspeptidase-positive altered hepatic foci (AHF) was used as a
surrogate marker of hepatocarcinogenesis. Both T C D D and phénobarbital stimulated the
development of AHF. Vitamin A deficiency also led to an increase in A H F by itself, and
furthermore, enhanced the induction of foci by T C D D but not by phénobarbital. Vitamin
A deficiency also tended to increase other toxic effects of TCDD. Feeding the animals
a cereal diet rather than a purified diet based on casein, led to greater formation of AHF
in groups treated with TCDD.

Finally, both T C D D and phénobarbital lowered hepatic

levels of Vitamin A, but plasma retinol concentrations were only affected by T C D D in rats
on the purified diet. These data do not support the concept that a TCDD-induced vitamin
A deficiency is the primary mechanism for hepatic tumor promotion by TCDD, but are
compatible with a modulating role for this deficiency in concert with some other
mechanism.

3.

Effects on Intermediary Metabolism

The acute toxicity of T C D D is characterized by wasting which is believed to be
associated primarily with food refusal, although it is possible that there might also be a
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D-

contribution from other effects, such as the release of tumor necrosis factor (TNF-a), or
the changes in hypothalamic histamine and /0-endorphin discussed earlier. Whatever the
mechanism, the resultant hypoglycemia is a well established effect of T C D D in rats, which
is accompanied by early alterations in the release of C 0 2 from administered labeled
glucose, and evidence of a reduced rate of gluconeogenesis. Two recent reports (Weber
et at. 1991 a; 1991 b) have ascribed this reduction to significant dose-dependent decreases

in the activities of phosphoenol-pyruvate carboxykinase (PEPCK) and pyruvate
carboxylase, enzymes generally considered to be rate-limiting steps in gluconeogenesis,
and a trend toward reduction in glucose-6-phosphatase.

These losses in enzyme

activities were significant within 2 days, and maximal at 5 0 % or more, 8 days after dosing
with T C D D at 5-125 jug/kg. It appeared that the primary effect was exerted on PEPCK,
which was affected earlier and more strongly; the other enzyme changes followed. Itis
entirely plausible that the inhibition of PEP C K results in early accumulation of tryptophan,
a gluconeogenic substrate, and a precursor of the appetite suppressant neurotransmitter
serotonin. Thus an increased serotonin turnover may occur with resulting food refusal.
Impairment of the D-glucose transport system and Na +/K+ ATPase in the plasma
membranes of human skin fibroblasts has been reported to occur after exposure to 2,4-D
(Cascorbi and Foret 1991). Using various xenobiotics, a correlation emerged between
this action and lipophilicity of the compound. Itis not known whether T C D D has a similar
action, and if it does, whether this effect is related to the changes in glucose utilization
noted above.
Several reports were devoted to the interaction of T C D D with lipid metabolism. A
single dose of 20 /ug/kg of T C D D produced in rats a marked mobilization of depot fat,
giving within 3 days up to a 2.8-fold increase in plasma free fatty acids. Significant
inhibition of hepatic oleate oxidation occurred, together with even more marked (85 and
69%, respectively) stimulation of ketogenesis from oleate and octanoate. Ketogenesis
from glycerol, and its oxidation to C 0 2,were both inhibited. The authors suggested that
T C D D inhibited complete oxidation of lipids via the tricarboxylic acid cycle, and the
formation of acetyl CoA from glycerol, while diverting acetyl C o A derived from fatty acids
to ketogenesis (Lakshman etal. 1991). Even ifthere is reduced oxidation of lipids via the
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V -vn

tricarboxylic acid cycle, however, there remains the possibility that peroxisomal oxidation
is able to sustain adequate levels of lipid oxidation. Two reports relevant to this question,
described the induction of peroxisomal fatty acid oxidation in rat liver by T C D D (Al-Bayati
and Stohs 1991) and by a number of chlorinated phenoxyacetic and phenoxypropionic
acid derivatives, including 2,4,5-T (Kozuka etal. 1991). The study with T C D D suggested
that phospholipase-A,, lipoxygenase and hydrogen peroxide were involved in the
microsomal peroxidation induced by 40 /jg/kg of TCDD.

On the other hand, another

report (Sanner et al. 1991) concluded that there was no induction of this system in Syrian
hamster cells exposed to 2,4-D or 2,4,5-T. McKim et al. (1991) showed that the TCDDinduced accumulation of free fatty acids in rats produced, by allosteric interaction, a 65%
inhibition of hepatic acetyl CoA carboxylase, a key enzyme in fatty acid synthesis. This
mobilization of fat is consistent with observations of changes in respiratory quotients
made in the chick embryo (Lentnek et al. 1991), which demonstrated that exposure to
T C D D increased dependence on fats as a fuel source. In the same study, experiments
in which fatty acid oxidation was inhibited by aminocarnitine, gave results consistent with
the suggestion that the reliance upon fatty acids resulted from impaired production, but
not utilization, of carbohydrate.

For such studies of respiratory quotients, the chick

embryo system presents advantages over the use of adults of this or any other species,
because it obviates the problems of compensating for both the energy entailed in
movements by the animals, and the effect of hypophagia resulting from any T C D D
toxicity.
When Chinese hamster ovary (CHO) cells were exposed to 2,4-D the synthesis of
protein and D N A was inhibited, and the cells were arrested at the G1/S interphase.
These effects appear to be related to alterations in polyamine metabolism, specifically an
inhibition of ornithine decarboxylase activity, and reduction in intracellular levels of
spermine and spermidine, without significant effects on putrescine (Rivarola and Balegno
1991a; 1991b).

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G.

Summary and Conclusions
Recent studies have further documented the central role of the Ah receptor system

in the mechanism of TCDD-induced toxicity, and have provided additional information on
the molecular nature of the interaction between ligand and receptor.

This primary

interaction serves as the basis for effects on other systems, most notably xenobiotic
metabolism, steroidogenesis and lipid metabolism. However, the possibility of other
mechanisms has not been excluded, and indeed, some evidence has been published
during 1991 which favors such additional sites of action. Although T C D D induces a
vitamin A-deficient state, this does not appear to be a primary mechanism of T C D D
toxicity. The increasing use of a broader range of study systems affords the opportunity
to define more clearly the mechanistic basis for differences in tissue and species
sensitivity to TCDD.

This is particularly true for human tissues, since the position of

humans in the wide spectrum of species sensitivity to dioxin remains uncertain. Such
understanding isessential for definitive assessment of the human health hazard presented
by dioxins and related compounds.

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Poland, A. and E. Glover. (1991) Characterization and strain distribution pattern of the murine Ah
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Ruangwises, S., L. Bestervelt, D. Piper, C. Nolan and W. Piper. (1991) Human chorionic
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and serum testosterone concentrations in2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.
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COS-1 cells is identical to diaphorase 4. Eur. J. Biochem. 195(1): 171-176.

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Smolowitz, R., M. Hahn and J. Stegeman. (1991) Immunohistochemical localizatlortllP
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Drug Metab. Dispos. 19(1): 113-123.
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environmentally induced cytochrome P450IA1 in multiple organs of the marine
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s'M
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,
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r,
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VVeber, L.W.D., B.U. Stahl, M. Lebofsky, R.H. Alper, L. Kerecsen and K. Rozman. (1991b)
Inhibition of phosphoenolpyruvate carboxykinase activity appears to be the key
biochemical lesion in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats.
Chemosphere 23(11-12): 1957-1962.
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cytochromes P450 involved in carcinogen activation in a human colon cell line. Mol. Cell.
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dibenzo-para-dioxins and dibenzofurans.

Polychlorinated

Zacharewski, T., M. Harris and S. Safe. (1991) Evidence for the mechanism of action of the
2,3,7,8-tetrachlorodibenzo-p-dioxin-mediateddecrease ofnuclearestrogen receptor levels
in wild-type and mutant mouse Hepa 1c1c7 cells. Biochem. Pharmacol. 41(12):
1931-1939.

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662

V A Contract Number: V101(93)P-1333

R EVIEW O F LITER A TU R E ON H ER B IC ID ES,
INCLUDING PHENOXY H ER B IC ID ES
AND A SSO CIA TED DIOXINS
Volume XX: Annotated Bibliography
of Recent Literature on Health Effects
Published in 1991

Prepared for:
Lawrence B. Hobson, M.D., Ph.D.
Director and
Contracting Officer’s Technical Representative
Environmental Agents Service
Veterans Health Administration
Department of Veterans Affairs
810 Vermont Avenue, N.W.
Washington, D.C. 20420

Submitted by:
Information Ventures, Incorporated
1500 Locust Street, Suite 3216
Philadelphia, Pennsylvania 19102

June 1992

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Abbott, B. and L. Birnbaum (1991) T C D D exposure of human embryonic palatal shelve
s in organ culture alters the differentiation of medial epithelial cells. Teratology
43(2): 119-132.
Key Terms: teratologic effects, acute toxicity, experimental exposure, dioxins, in
vitro, journal article
See pages 41 and 42.
Abenhaim, L., S. Cordier, D.D. Le, D. Bard, D.C. Hoang, B. Larouze and M.F. Gonnord
(1991) Consequences of Agent Orange on health -the INSERM study in Vietnam.
Arch. Environ. Health 46(2): 119.
Key Terms: cancer, reproductive toxicity, chronic toxicity, environmental exposure,
military exposure, dioxins, human, abstract
See page 24.
Adams, S.L., S.T. Horvat, A.E. Irwin, R.W. Junkin, N.M. Koreman and B.R. Blakley (1991)
The effects of Tordon 202c exposure on urethan-induced lung adenoma formation
in female CD-1 mice. Vet. Hum. Toxicol. 33(3): 209-211.
Key Terms:
article

cancer, subchronic toxicity, oral, 2,4-D, picloram, mouse, journal

See pages 33 and 74.
Al-Bayati, Z.A.F. and S.J. Stohs (1991) The possible role of phospholipase A2 in hepatic
microsomal lipid peroxidation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in
rats. Arch. Environ. Contam. Toxicol. 20(3): 361-365.
Key Terms: hepatotoxicity, enzyme induction or inhibition, oral, dioxin, rat, journal
article
See page 115.
Albanese, R.A. (1991) The chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin and U.S. Army
Vietnam-era veterans. Chemosphere 22(5-6): 597-604.
Key Terms: Tissue residues, military exposure, dioxins, human, model
See pages 27, 79 and 80.
Ames, B.N. (1991) Natural carcinogens and dioxin. Sci. Total Environ. 104(1-2): 159-166.

1

665

Key Terms: cancer, chronic toxicity, genetic toxicity, dioxins, unspecified route or v
exposure, human, other species, in vitro, commentary or opinion
The author states that studies of the toxicology of high doses of synthetic
chemicals must be viewed in the context of the world of natural chemicals to which
humans are exposed. When tested at near toxic doses, where cell killing o c c u rs ,;
about one half of allsynthetic or natural compounds are carcinogens, one third are
teratogens and one half are clastogens. At the very low doses of most human i '
exposures, such synthetic chemicals do not kill cells and the health hazards are §
very low or zero; dioxin is used as an example.
Ames, B.N. and L.S. Gold (1991) Cancer prevention strategies greatly exaggerate riskalP
Chem. Eng. News Jan 7: 28-32.
'

A*.

Key Terms: cancer, chronic toxicity, genetic toxicity, teratologic effects, oral,
dioxins, human, commentary or opinion
v

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See page 44.

Anderson, L., L. Beebe, S. Fox, H. Issaq and R. Kovatch (1991) Promotion of mouse lung 4
tumors by bioaccumulated polychlorinated aromatic hydrocarbons. Exp. Lung'1/
Res. 17(2): 455-471.
-1/

%

Key Terms: cancer, subchronic toxicity, enzyme induction or inhibition, gavage, ^
dioxins, mouse, journal article
^

See pa ge K M .

^

Andersson, L., E. Nikolaidis, B. Brunstrom, A. Bergman and L. Dencker (1991) Effects of ,
polychlorinated biphenyls with Ah receptor affinity on lymphoid development inthe#'
thymus and the bursa of Fabricius of chick embryos in ovo and in mouse thymus ^
anlagen in vitro. Toxicol. Appl. Pharmacol. 107(1): 183-188.
Key Terms: immunotoxicity, acute toxicity, other route of exposure, PCB, bird,
journal article
O

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V^vldiA.

See page 50.

Aoki, Y., E.K. Silbergeld, S.R. Max and B.A. Fowler (1991) Alterations in protein synthesis
in rat liver cells by in vitro and in vivo exposure to 2 ,3 ,7 ,8 -tetrachlorodibenzo-p-dioxin. Biochem. Pharmacol. 42(6): 1195-1201.
Key Terms: hepatotoxicity, other toxic effects, mechanism of action, experimental,^
dioxins, in vitro, journal article

2
666!

See pages 68 and 108.
Arnold, E.K., V.R. Beasley, A.J. Parker and J.R. Stedelin (1991) 2,4-D toxicosis II: a pilot
study of clinical pathologic and electroencephalographic effects and residues of
2,4-D in orally dosed dogs. Vet. Human Toxicol. 33(5): .446-449.
Key Terms: neurobehavioral effects, acute toxicity, oral, 2,4-D, dog, journal article
See pages 64, 65 and 89.
Arnold, E.K., R.A. Lovell, V.R. Beasley, A.J. Parker and J.R. Stedelin (1991) 2,4-D
toxicosis III: an attempt to produce 2,4,-D toxicosis in dogs on treated grass plots.
Vet. Human Toxicol. 33(5): 457-461.
Key Terms:
neurobehavioral effects, other toxic effects, acute toxicity,
environmental exposure, 2,4-D, dog, journal article
See pages 64, 65 and 89.
Ashby, J. and R.W. Tennant (1991) Definitive relationships among chemical structure,
carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat.
Res. 257(3): 229-306.
Key Terms: cancer, genetic toxicity, experimental, dioxins, picloram, rodent, in
vitro, review
See pages 30 and 74.
Astroff, B., B. Eldridge and S. Safe (1991) Inhibition of the 17beta-estradiol-induced and
constitutive expression of the cellular proto-oncogene c-fos by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the female rat uterus. Toxicol. Appl. Pharmacol.
56(305-315.
Key Terms: alterations in sex hormones, other toxic effects, acute toxicity,
mechanism of action, injection, dioxins, rat, journal article
See page 109.
Astroff, B. and S. Safe (1991) 6-Alkyl-1,3,8-trichlorodibenzofurans as antiestrogens in
female Sprague-Dawley rats. Toxicology 69(2): 187-197.
Key Terms: alteration in sex hormones, acute toxicity, experimental, furans, rat,
journal article

3

667

Treatment of rats with 17 p -estradiol at 0.33 /jmol/kg x 2 increased uterine wet
weight, EGF, estrogen and progesterone receptor levels, and EGF receptor mRNA.
6-Methyl-1,3,8-trichlorodibenzofuran and its6-t-butyl analog, which have moderate
Ah receptor affinity, decreased the estradiol and constitutive response at a dose
of 100 /vmol/kg, whereas the low-affinity 6-cyclohexyl congener had no effect
These furans have low toxicity that may make them useful antiestrogens.
Bailar, J.C., 3d (1991) H o w dangerous is dioxin? [Editorial; comment]. N. Engl. J. Med
324(4): 260-262.
Key Terms:
commentary

cancer, chronic toxicity, occupational exposure, dioxin, human,

This editorial accompanied the Fingerhut report on the NIOSH study of cancer In
workers at 12 sites exposed to dioxin contamination. While admitting that the latter
study did not disclose an overwhelming increase in overall cancer mortality, and
that itinvolved few cancer deaths, he considered that itshould be taken as a flag
of a probable human risk. The estimated risk of soft tissue sarcoma of about 2 per
1,000 greatly exceeds acceptable public lifetime risks of 1 per 100,000 or 1 per
million.
Banks, Y. and L. Birnbaum (1991) Absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxIn
(TCDD) after low dose dermal exposure. Toxicol. Appl. Pharmacol. 107(2):
302-310.
V^v
Key Terms: pharmacokinetics, tissue residues, dermal, dioxins, rat, journal article
See page 88.

^

Barnes, D.G. (1991) Toxicity equivalents and EP A ’s risk assessment of 2,3,7,8-TCDD. Sci. Total Environ. 104(1-2): 73-86.
Key Terms: miscellaneous study, dioxins, human, journal article
See pages 86 and 94.
Bars, R.G. and C.R. Elcombe (1991) Dose-dependent acinar induction of cytochromes
P450 in rat liver. Evidence for a differential mechanism of induction of P450IA1 by <
/?-naphthoflavone and dioxin. Biochem. J. 277(Pt 2): 577-580.
Key Terms: enzyme induction or inhibition, injection, dioxin, rat, journal article
See page 106.

668

?

Beasley, V.R., E.K. Arnold and R.A. Lovell (1991) 2,4-D Toxicosis 1: a pilot study of
2,4-dichlorophenoxyacetic acid- and dicamba-induced myotonia in experimental
dogs. Vet. Human Toxicol. 33(5): 435-440.

Key Terms: neurobehavioral effects, acute toxicity, oral, 2,4-D, dog, journal article
See pages 64 and 65.
Becker, M., T. Phillips and S. Safe (1991) Polychlorinated diphenyl ethers - a review.
Toxicological and Environmental Chemistry 33(3-4): 189-200.

Key Terms: dioxins, fish, furans, rat, review, tissue residues
This is a review of the toxicity, measurement, metabolism, tissue retention,
excretion and environmental/toxicologic implications of polychlorinated diphenyl
ethers. Research data from rats and fish are examined.
Becker, M.C. (1991) Toxicity of polychlorinated diphenyl ethers in Hydra attenuata and
in rat whole embryo culture (Thesis). 1-97.
Key Terms: teratologic effects, acute toxicity, experimental exposure, dioxins, rat,
thesis
This thesis includes a review of the toxicity and environmental issues regarding
these compounds, and the wide range of species and habitats in which they have
been detected. N e w studies reported in the thesis include work that demonstrated
in both the Coelenterate, Hydra, and in rat embryos, that these compounds,
including TCDD, are neither embryotoxic nor teratogenic.
Beebe, L.E., S.D. Fox, H.J. Issaq and L.M. Anderson (1991) Biological and biochemical
effects of retained polyhalogenated hydrocarbons. Environmental Toxicology and
Chemistry 10(6): 757-763.
Key Terms: cancer, enzyme induction or inhibition, dioxins, furans, rat, mouse,
review
In this review, both new data and the literature were used to examine the long term
effects of persistent body burdens of these compounds, in terms of tumor
formation and cytochrome P450-associated mixed function oxidase induction.
Effects of specific congeners on lung tumor formation initiated by Nnitrosodimethylamine, their retention by tissues, and the induction of enzymes such
as aminopyrine demethylase, are consistent with activation of the Ah receptor
being integral to tumor promotion by these compounds.

5

Bertazzi, P. (1991) Long-term effects of chemical disasters. Lessons and results from
Seveso. Sci. Total. Environ. 106(1-2): 5-20.
Key Terms: chloracne, neurobehavioral effects, cardiovascular toxicity, cancer
hepatotoxicity, chronic toxicity, other route of exposure, dioxins, human, journal
article
See pages 28, 29, 59, 67 and 82.
Bestervelt, L.L., C.J. Nolan, Y. Cai, P. Maimansomsuk, C.A. Mousigian and W.N. Piper
(1991) Tetrachlorodibenzo-p-dioxin alters rat hypothalamic endorphin and m u
opioid receptors. Neurotoxicol. Teratol. 13(1-6): 495-497.
Key Terms: neurobehavioral effects, acute toxicity, oral, dioxins, rat, journal article
After acute oral dosage with T C D D (50jug/kg), hypophagia and weight loss
occurred in rats, accompanied by initial increase in hypothalamic beta-endorphin
to 166% of control on day 1. By days 2 and 3, levels of beta-endorphin had fallen
to 39% and 49% control, respectively. Brain mu-opioid receptor number was
increased 60% in TCDD-treated rats on day 3. These effects were not seen in
food-restricted rats, implicating involvement of changes in these receptors in
hypophagia.
Birnbaum, L.S., R.E. Morrissey and H. M.W. (1991) Teratogenic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin and three polybrominated dibenzofurans in C57BL/6N
mice. Toxicol. Appl. Pharmacol. 107(1): 141-152.
Key Terms: teratologic effects, acute toxicity, gavage, dioxins, mouse, journal
article

,,:0-: :

See page 43.
Bishop, C., R. Brooks, J. Carey, P. Ng, R. Norstrom and D. Lean (1991) The case for a ■
cause-effect linkage between environmental contamination and development in
eggs of the c o m m o n snapping turtle (Chelydra S.serpentina) from Ontario,
Canada. J. Toxicol. Environ. Health 33(4): 521-547.
Key Terms: reproductive toxicity, chronic toxicity, environmental, dioxins, furans,
turtle, journal article
See page 44.
Bjeldanes, L., J. Kim, K. Grose, J. Bartholomew and C. Bradfield (1991) Aromatic
hydrocarbon responsiveness-receptor agonists generated from indole-3 -carbinol

6

;67a

in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. pr0c.
Natl. Acad. Sci. U.S.A. 88(21): 9543-9547.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
This study compared the binding by Ah receptor of the carbazole metabolite of the
dietary carcinogenesis modulator, indole-3-carbinol, with that of TCDD. The role
of this binding in different carcinogenic and anticarcinogenic actions of indole-3carbinol was discussed.
Blevins, R. (1991) 2,3,7,8 Tetrachlorodibenzodioxin infish from the Pigeon River of eastern
Tennessee, USA: itstoxicity and mutagenicity as revealed by the Ames Salmonella
assay. Arch. Environ. Contam. Toxicol. 20(3): 366-370.
Key Terms: genetic toxicity, tissue residues, environmental, dioxins, fish, journal
article
See page 38.
Bock, K. (1991) Roles of UDP-glucuronosyltransferases in chemical carcinogenesis. Crit.
Rev. Biochem. Mol. Biol. 26(2): 129-150.
Key Terms: cancer, mechanism of action, experimental, dioxins, in vitro, review

See page 110.
Bock, K.W. (1991) Dioxin carcinogenicity. Dtsch. Med. Wochenschr. 116(24): 959.
Key Terms: cancer, dioxins, human, commentary or opinion, in German
Bradfield, C.A., E. Glover and A. Poland (1991) Purification and N-terminal amino acid
sequence of the Ah receptor from the C57BL/6J mouse. Mol. Pharmacol. 39(1):
13-19.
Key Terms: mechanism of action, experimental, dioxins, mouse, journal article
See page 98.
Brouwer, A. (1991) The role of enzymes in regulating the toxicity of xenobiotics. Biochem
Soc (London) 19(3): 731-737.

7

671

Key Terms: enzyme induction or inhibition, mechanism of action, environmental
exposure, other route of exposure, dioxins, PCBs, review
See page 110.
Buchta, M. and B. Dolezal (1991) Problems of polychlorinated dibenzo-p-dioxins and
dibenzofurans. Chem. Listy 85(2): 158-170.
Key Terms: dioxins, furans, review
This is an analysis of the problems that are associated with the particular chemical
and biological properties of the dioxins and furans.
-Hr?
Calvert, G.M., M.H. Sweeney, J.A. Morris, M.A. Fingerhut, R.W. Hornung and W.E.
Halperin (1991) Evaluation of chronic bronchitis, chronic obstructive pulmonary
disease, and ventilatory function among workers exposed to 2,3,7,8-tetrachloro*
dibenzo-p-dioxin. Am. Rev. Respir. Dis. 144(6): 1302-1306.
Key Terms: other organic toxicity, chronic toxicity, occupational exposure, dioxins,
human, journal article
See pages 70 and 81.
Campt, D.D., J.V. Roelofs and J. Richards (1991) Pesticide regulation is sound, protective,
and steadily improving. Chem. Eng. News Jan 7: 44-47.
Key Terms: cancer, other toxic effects, chronic toxicity, oral, environmental, other
route of exposure, pesticide, human, commentary or opinion
^

:V08

As participants in a C & EN News forum, the authors defend current regulatory
practices, but stress that many chemicals registered years before lack the basis
of scientific studies that is now required. This gap is being attended to. There te?
special need for knowledge of long-term, low-level exposure effects. The need for
ensuring public trust is also stressed.
4
::

Carlo, G.L., K.G. Sund, R.W. Morgan, L. Hardell, M. Erikkson, O. Axelson, LR. Goldman,
D. Hayward, D.M. Siegel, R.D. Stephens et al. (1991) Dioxin and m ortality from
cancer [Letter]. N. Engl. J. Med. 324(25): 1809-1812.
Key Terms: cancer, chronic toxicity, occupational exposure, dioxins, human,
commentary or opinion
See page 25.

8
672

V -

7t><

Carpenter, W.D. (1991) Insignificant risks must be balanced against great benefits.
Chem. Eng. News Jan 7: 37-39.
Key Terms: cancer, oral, pesticides, commentary or opinion
As a participant in a C & EN News forum, the author discusses the benefits
provided by agricultural chemicals. He stresses that the Delaney clause is not
compatible with today’s highly sensitive assay technology, which can detect
substances in the parts per billion or trillion range, at which levels there are no
discernable risks.
Cary, A.J., P.A. Martin and J.J. Dougherty (1991) ATP promotes the appearance of two
DNA-binding forms of the Ah receptor. Arch. Biochem. Biophys. 288(1): 287-292.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 99.
Cary, A.J. and J.J. Dougherty (1991) Nucleoside triphosphates promote the trans­
formation of Ah receptor to its D N A form. Biochem. J. 274(Mar): 401-404.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 99.
Cascorbi, I. and M. Foret (1991) Interaction of xenobiotics on the glucose-transport
system and the Na+/K(+)-ATPase of human skin fibroblasts. Ecotoxicol. Environ.
Safety 21(1): 38-46.
Key Terms: enzyme induction or inhibition, mechanism of action, experimental
exposure, 2,4-D, in vitro, journal article
See page 114.
Chahoud, I., R. Krowke, G. Bochert, B. Burkle and D. Neubert (1991) Reproductive
toxicity and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Problem of
paternally-mediated abnormalities in the progeny of rat. Arch. Toxicol. 65(1):
27-31.
Key Terms: reproductive toxicity, teratologic effects, dioxins, rats, journal article
See page 42.

9

673

Chaturvedi, A., D. Kuntz and N. Rao (1991) Metabolic aspects of the toxicology of
mixtures of parathion, toxaphene and/o r 2,4-D in mice. J. Appl. Toxicol. 11(4)245-251.
Key Terms: mechanism of action, oral, 2,4-D, mouse, journal article
See pages 106 and 107.
Choi, E., D. Toscano, J. Ryan, N. Riedel and W.J. Toscano (1991) Dioxin induces trans­
forming growth factor-alpha in human keratinocytes. J. Biol. Chem. 266(15)*
9591-9597.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 108.
Cikryt, P. (1991) Ah-receptor, A R N T (Ah-receptor nuclear translocation) protein and
toxicity of dioxins. Chemie in Unserer Zeit 25(4): 176.
Key Terms: mechanism of action, dioxins, experimental, journal article
Cikryt, P. (1991) Endangering mankind - dioxin and related compounds. Nachr. Chem.,
Tech. Lab. 39(6): 650-656.
Key Terms: chronic toxicity, environmental exposure, dioxins, human, review
Clapp, R.W., L.A. Cupples, T. Colton and D.M. Ozonoff (1991) Cancer surveillance of
veterans in Massachusetts, USA, 1982-1988. Int. J. Epidemiol. 20(1): 7-12.
Key Terms: cancer, military exposure, phenoxy herbicides, human, journal article
See page 21.
Clark, G.C., J.A. Blank, D.R. Germolec and M.l. Luster (1991) 2 ,3 ,7 ,8 -Tetrachlorodibenzo-p-dioxin stimulation oftyrosine phosphorylation in B lymphocytes: potential
role in immunosuppression. Mol. Pharmacol. 39(4): 495-501.
Key Terms: immunotoxicity, mechanism of action, experimental, dioxins, journal
article
See pages 54, 55 and 109.
Clark, G.C., M.J. Taylor, A.M. Tritscher and G.W. Lucier (1991) Tumor-necrosis factor
involvement in 2,3,7,8-tetrachlorodibenzo-para-dioxin-mediated endotoxin hyper-

674
P-7Q3

sensitivity in C57BL/6J mice congenic at the Ah locus. Toxicol. Appl. Pharmacol.
111(3): 422-431.
Key Terms: toxicity, mechanism of action, dioxins, mouse, journal article
Clark, G., A. Tritscher, G. Lucier and M. Taylor (1991) Dose-dependent increase in tumor
necrosis factor-alpha production in T C D D exposed mice is Ah dependent.
Chemosphere 23(11-12): 1817-1823.
Key Terms: mechanism of action, unspecified route of exposure, dioxins, mouse,
journal article
See page 108.
Coggon, D., B. Pannett and P. Winter (1991) Mortality and incidence of cancer at four
factories making phenoxy herbicides. Br. J. Ind. Med. 48(3): 173-178.
Key Terms: cancer, chronic toxicity, occupational exposure, phenoxy herbicide
formulations, human, journal article
See page 26.
Collins, J.J., J.F. Acquavella and B.R. Friedlander (1992) Reconciling old and new findings
on dioxin. Epidemiology 3(1): 65-69.
Key Terms: cancer, chloracne, chronic toxicity, occupational exposure, dioxins,
human, commentary or opinion
See page 29.
Cooper, K.R., H. Liu, P.-A. Bergqvist and C. Rappe (1991) Evaluation of Baltic herring and
Icelandic cod liver oil for embryo toxicity, using the Japanese medaka (Oryzias
latipes) embryo larval assay. Environ. Toxicol. Chem. 10(6): 707-714.
Key Terms: reproductive toxicity, chronic toxicity, environmental exposure, dioxins,
furans, fish, journal article
See page 44.
Couture-Haws, L., M.W. Harris, A.C. Lockhart and L.S. Birnbaum (1991) Evaluation of the
persistence of hydronephrosis induced in mice following in utero and/or lactational
exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 107(3):
402-412.

675

Key Terms: other toxic effects, acute toxicity, oral, dioxin, mouse, journal article
See pages 43 and 88.
Couture-Haws, L., M.W. Harris, M.M. McDonald, A.C. Lockhart and L.S. Birnbaum (1991)
Hydronephrosis in mice exposed to TCDD-contaminated breast milk: identification
of the peak period of sensitivity and assessment of potential recovery. Toxicol.
Appl. Pharmacol. 107(3): 413-428.
Key Terms: other toxic effects, acute toxicity, oral, dioxin, mouse, journal article
See page 88.
Craig, T.O. and R.B. Grzonka (1991) A time-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin
body-burden model. Arch. Environ. Contam. Toxicol. 21(3): 438-446.
Key Terms: pharmacokinetics, environmental exposure, dioxins, human, journal
article
See pages 84 and 85.
Cuthill, S., A. Wilhelmsson and L. Poellinger (1991) Role of the ligand in intracellular
receptor function: receptor affinity determines activation in vitro of the latent dioxin
receptor to a DNA-binding form. Mol. Cell Biol. 11(1): 401-411.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
See page 99.
Dalager, N.A., H.K. Kang, V.L. Burt and L. Weatherbee (1991) Non-Hodgkin’s lymphoma
among Vietnam veterans. J. Occup. Med. 33(7): 774-779.
Key Terms: cancer, chronic toxicity, military exposure, 2,4-D, 2,4,5-T, human,
journal article
See page 22.
Daly, H. (1991) Reward reductions found more aversive by rats fed environmentally
contaminated salmon. Neurotoxicol. Teratol. 13(4): 449-453.
Key Terms: neurobehavioral effects, acute toxicity, oral, fish, rat, environmental
exposure, journal article

12

676
J>-7’
o5'

See page 63.
Davis, D. and S. Safe (1991) Halogenated aryl hydrocarbon-induced suppression of the
in vitro plaque-forming cell response to sheep red blood cells is not dependent on
the Ah receptor. Immunopharmocology 21(3): 183-190.
Key Terms: immunotoxicity, acute toxicity, experimental, dioxins, mechanism of
action, in vitro, journal article
See page 54.
Dearman, R.J. and I. Kimber (1991) Immunotoxicity and allergy - opportunities for in vitro
analysis. Toxicology In Vitro 5(5-6): 519-524.
Key Terms: immunotoxicity, in vitro, journal article
DeFerrari, M., M. Artuso, S. Bonassi, S. Bonatti, Z. Cavalieri, D. Pescatore, E. Marchini,
V. Pisano and A. Abbondandolo (1991) Cytogenetic biomonitoring of an Italian
population exposed to pesticides: chromosome aberration and sister-chromatid
exchange analysis in peripheral blood lymphocytes. Mutat. Res. 260(1): 105-113.
Key Terms: cancer, genetic toxicity, occupational exposure, 2,4-D, phenoxy
herbicides, human, journal article
See page 38.
DeMatteis, F., S. Dawson, A. Boobis and A. Comoglio (1991) Inducible bilirubin-degrading
system of rat liver microsomes: role of cytochrome P450IA1. Mol. Pharmacol.
40(5): 686-691.
Key Terms: hepatotoxicity, mechanism of action, enzyme induction or inhibition,
injection, dioxins, rat, journal article
See page 106.
Denison, M.S. (1991) The molecular mechanism of action of 2,3,7,8-tetrachlorodibenzop-dioxin and related halogenated aromatic hydrocarbons. Chemosphere 23
(11-12): 1825-1830.
Key Terms: enzyme induction or inhibition, mechanism of action, unspecified route
of exposure, dioxins, review
See pages 94 and 95.

JMoCo

Denison, M.S. and Y. E.F. (1991) Characterization of the interaction of transformed rat
hepatic cytosolic Ah receptor with a dioxin responsive transcriptional enhancer
Arch. Biochem. Biophys. 284(1): 158-166.
Key Terms: mechanism of action, dioxins, experimental, in vitro, journal article
See page 102.
Dewailly, E., J.P. Weber, S. Gingras and C. Laliberte (1991) Coplanar P C B ’s in human
milk in the province of Quebec, Canada - are they more toxic than dioxin for breast
fed infants. Bull. Environ. Contam. Toxicol. 47(4): 491-498.
Key Terms: tissue residues, oral, dioxins, human, journal article
The levels of various coplanar PCB congeners were measured in human milk.
Non-ortho coplanar congeners were found at ppt levels, and mono-ortho coplanar
congeners were present at ppb levels. The authors conclude that in this study,
PCBs represented a higher risk than PCDFs or PCDDs.
Dewailly, E., H. Tremblay-Rousseau, G. Carrier, S. Grouix, S. Gingras, K. Boffess, J.
Stanley and J.P. Weber (1991) PCDDs, PCDFs and PCBs in human milk of women
exposed to a PCB fire and of wom e n from the general population of the province
of Quebec - Canada. Chemosphere 23(11-12): 1831-1835.
Key Terms: tissue residues, other route of exposure, dioxins, furans, human,
journal article
See page 86.
Dobkin, P., M. Dongier, D. Cooper and J.M. Hill (1991) Screening for alcoholism in a
psychiatric-hospital. Can. J. Psychiatry 36(1): 39-45.
Key Terms: other toxic effects, military exposure, dioxins, human, journal article
This study investigated the correlation between alcoholism and various parameters,
including military exposure to dioxins. No positive association with dioxin exposure
was found.
Dragan, Y.P., T. Rizvi, Y.-H. Xu, J.R. Hully, N. Bawa, H.A. Campbell, R.R. Maronpotand
H.C. Pitot (1991) An initiation-promotion assay in rat liver as a potential
complement to the 2-year carcinogenesis bioassay. Fundam. Appl. Toxicol. 16:
525-547.

14

678

V'jor

Key Terms: cancer, enzyme induction or inhibition, experimental, dioxins, in vitro,
journal article
See page 32.
Eisen, S.A., J. Goldberg, W.R. True and W.G. Henderson (1991) A co-twin control study
of the effects of the Vietnam war on the self-reported physical health of veterans.
A m J Epidemiol 134(1): 49-58.
Key Terms: cancer, other cutaneous effects, miscellaneous study, military
exposure, phenoxy herbicide formulations, human, journal article
See page 17.
El Bahri, L. and S.B. Romdane (1991) Arsenic poisoning in livestock. Vet. Hum. Toxicol.
33(3): 259-264.
Key Terms: pharmacokinetics, oral, arsenic, cow, chicken, sheep, review
This article reviewed arsenic poisoning in cows, sheep and chickens by various
arsenic-containing compounds, including cacodylic acid.
Elo, H.A., T. Luoma and P. Ylitalo (1991) Inhibition of human and rabbit platelet
aggregation by chlorophenoxyacid herbicides. Arch. Toxicol. 65(2): 140-144.
Key Terms: hematologic effects, acute toxicity, injection, 2,4-D, 2,4,5-T, rabbit,
journal article
See page 69.
Elsenhans, B., W. Forth and E. Richter (1991) Increased copper concentrations in rat
tissues after acute intoxication with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch.
Toxicol. 65(5): 429-432.
Key Terms: hepatotoxicity, acute toxicity, injection, dioxins, rat, journal article
When rats received 125 /jg/kg of TCDD, and tissue metal contents determined by
atomic emission spectrometry, there were increases in liver (> 2-fold) and kidney
(> 4-fold) Cu relative to pair-fed controls. The effect was ascribed to impaired
biliary excretion of Cu due to TCDD.
Eriksson, M. and L. Hardell (1991) Ne w experiences strengthen the connection between
dioxins, phenoxy acids and malignant tumors. Lakartidningen 88(24): 2210-2211.

15

679
D7o«'

Key Terms: cancer, dioxins, phenoxy herbicides, human, journal article
This is a review in Swedish of the association of dioxins with non-Hodgkin’s
lymphoma and soft tissue sarcoma.
Fagan, J.B., F. Saatcioglu, D.J. Perry, M.E. Richardson and D.S. Pasco (1991) XF1 and
XF2 act through xenobiotic response elements to modulate transcriptional
activation of the cytochrome P450IA1 gene by the dioxin Ah receptor. J. Cell
Biochem. Suppl. 15 Part B): 269.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, abstract
Two hepatic nuclear fractions, XF1 and XF2 were purified and characterized.
These factors compete with the dioxin receptor for binding sites on the xenobiotic
response elements, and may modulate the transcriptional regulatory function ofthe
receptor.
Fahrig, R. (1991) Genetic effects of dioxin. Environ. Mol. Mutagen Suppl. 19): 24-25.
Key Terms:
abstract

cancer, genetic toxicity, experimental exposure, dioxins, mouse,

See page 38.
Fanelli, R. and S. Garattini (1991) Human exposure to dioxin. Prog. Clin. Biol. Res. 372:
167-177.
Key Terms: chronic toxicity, tissue residues, environmental exposure, occupational
exposure, dioxins, human, review
This review covers the relative LD,*, values for T C D D compared with natural toxins,
the sources of human exposure to dioxin, toxicology and dosimetry, and human
serum levels in the NIOSH and Seveso studies.
Fingerhut, M.A., W.E. Halperin, D.A. Marlow, L.A. Piacitelli, P.A. Honchar, M.H. Sweeney,
A.L. Greife, P.A. Dill, K. Steenland and A.J. Suruda (1991) Cancer mortality in
workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N. Engl. J. Med. 324(4):
212-218.
Key Terms: cancer, chronic toxicity, lethality, tissue residues, occupational
exposure, dioxins, human, journal article
See pages 24 and 25.

16

680

Fingerhut, M.A., K. Steenland, M.H. Sweeney, W.E. Halperin, L.A. Piacitelli and D.A.
Marlow (1992) Old and new reflections on dioxin. Epidemiology 3(1): 69-72.
Key Terms: cancer, chronic toxicity, occupational exposure, dioxins, human,
commentary
See page 29.
Flodstrom, S., L. Busk, T. Kronevi and U. Ahlborg (1991) Modulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin
and
phenobarbital-induced
promotion
of
hepatocarcinogenesis in rats by the type of diet and vitamin A deficiency. Fundam.
Appl. Toxicol. 16(2): 375-391.
Key Terms: cancer, subchronic toxicity, mechanism of action, oral, dioxins, rat
journal article
See page 113.
Fokin, A.V., Y.A. Borisov, V.G. Enchev, N.l. Raevskii and N.P. Borob’eva (1991) Electron
structure and geometry of the dioxin-type xenobiotics and their ecotoxicity. Dokl.
Akad. Nauk. S.S.S.R. 316(5): 1165-1168.
Key Terms: toxicity, dioxins, mechanism of action, journal article
The toxicity of dioxins was analyzed in terms of their electronic structure and
molecular configuration. The text is in Russian.
Forum (1991) Risk assessment of pesticides. Chem. Eng. News Jan. 7: 27-55.
Key Terms: cancer, chronic toxicity, unspecified route of exposure, dioxins,
human, commentary or opinion
This is a compilation of several diverse views concerning pesticides and the risks
which they pose to humans and the environment.
Gallagher, E. and R. DiGiulio (1991) Effects of 2,4-dichlorophenoxyacetic acid and
picloram on biotransformation, peroxisomal and serum enzyme activities in channel
catfish (Ictalurus punctatus). Toxicol. Lett. 57(1): 65-72.
Key Terms: other toxic effects, enzyme induction or inhibition, other route of
exposure, 2,4-D, picloram, fish, journal article
See pages 75 and 106.

17

681

V'Jlo

Gasiewicz, T.A. and G. Rucci (1991) a-Naphthoflavone Acts as an antagonist of 2,3,7,8tetrachlorodibenzo-p-dioxin by forming an inactive complex with the Ah receptor
Mol. Pharmacol. 40(5): 607-612.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 101.
Gasiewicz, T., C. Elferink and E. Henry (1991) Characterization of multiple forms of the
Ah receptor: recognition of a dioxin-responsive enhancer involves heteromer
formation. Biochemistry 30(11): 2909-2916.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
See page 98.
Gawkrodger, D.J. (1991) Chloracne: causation, diagnosis and treatment. J. Dermatol.
Treat. 2(2): 73-76.
Key Terms: chloracne, occupational exposure, dioxins, human, review
The author review the causes and clinical features of chloracne, stressing the
principle signs (comedones) and the relative resistance to conventional acne
treatments. Topical, but not systemic tretinoin may be of benefit, as is light cautery
of comedones.
Gaylor, D.W. (1991) Biologically-based empirical dose-response model for cleft palate
utilizing fetal weight reduction. Teratology 43(5): 436.
Key Terms: acute toxicity, experimental exposure, 2,4,5-T, mouse, abstract
Gebhardt, D.O.E., A.J. Moolenaar and A. M o h a m m e d (1991) Distribution of lipophilic
xenobiotics among plasma lipoproteins. Arch. Toxicol. 65(5): 436.
Key Terms: pharmacokinetics, dioxins, human, rat, commentary or opinion
This comment on the possible effect of hypertriglyceridemia on dioxin distribution
among plasma lipoproteins is accompanied by a reply from A. Mohammed.
Gilman, A. and R. Newhook (1991) An updated assessment of the exposure of Canadians
to dioxins and furans. Chemosphere 23(8-10): 1161-1167.

682

Key Terms: oral, environmental exposure, dioxins, furans, human, journal article
Goldman, L.R., D. Hayward, D.M. Siegel and R.D. Stephens (1991) Dioxin and mortality
from cancer (Letter). N. Engl. J. Med. 324(25): 1811.
Key Terms: cancer, tissue residues, occupational exposure, dioxins, human,
commentary or opinion
See page 25.
Gordon, G.B. (1991) Induction of NAD(P)H:quinone reductase in human peripheral blood
lymphocytes. Carcinogenesis 12(12): 2393-2396.
Key Terms: enzyme induction or inhibition, experimental, dioxins, in vitro, journal
article
The authors describe a simple microtiter plate assay for quinone reductase activity.
T C D D is among the compounds that induce this enzyme.
Gottlicher, M. and F.J. Wiebel (1991) 2,3,7,8-Tetrachlorodibenzo-para-dioxin causes
unbalanced growth in 5L hepatoma-cells. Toxicol. Appl. Pharmacol. 111(3):
496-503.
Key Terms: other toxic effects, acute toxicity, experimental, dioxins, in vitro, journal
article
Gough, M. (1991) Agent Orange: exposure and policy [Editorial]. Am. J. Public Health
81(3): 289-90.
Key Terms: cancer, other toxic effects, chronic toxicity, military exposure, dioxins,
human, commentary or opinion
See page 13.
Gough, M. (1991) Human health effects: what the data indicate. Sci. Total Environ.
104(1-2): 129-158.
Key Terms: cancer, chloracne, chronic toxicity, acute toxicity, occupational
exposure, dioxins, human, review
See page 29.
Green, L.M. (1991) A cohort mortality study of forestry workers exposed to phenoxy acid
herbicides. Br. J. Ind. Med. 48(4): 234-238.
19

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p -7 /5 -

Key Terms: chronic toxicity, occupational exposure, phenoxy herbicides, human,
journal article
Guengerich, F.P. and T. Shimada (1991) Oxidation of toxic and carcinogenic chemicals
by human cytochrome P-450 enzymes. Chem. Res. Tox. 4(4): 391-407.
Key Terms:
review

cancer, enzyme induction or inhibition, polycyclic hydrocarbons,

See page 105.
Hakansson, H., E. Manzoor and U. Ahlborg (1991) Interaction between dietary vitamin A
and single oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the
TCDD-induced toxicity and on the vitamin A status in the rat. J. Nutr. Sci.
Vitaminol. (Tokyo) 37(3): 239-255.
Key Terms: other toxic effects, acute toxicity, oral, dioxins, rat, journal article
See page 112.
Hakansson, H., L. Johansson, E. Manzoor and U. Ahlborg (1991) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the vitamin A status of Hartley guinea pigs,
Sprague-Dawley rats, C57BI/6 mice, DBA/2 mice, and Golden Syrian hamsters.
J. Nutr. Sci. Vitaminol. (Tokyo) 37(2): 117-138.
Key Terms: other toxic effects, subchronic toxicity, injection, dioxins, guinea pig,
rat, mouse, hamster, journal article
See page 112.
Hall, T.A. (1991) The basis for measuring human exposure to dioxins, PCBs and their
congeners. J. Occup. Med. 33(4): 538.
Key Terms: dioxins, PCBs, human, method, journal article
Hankinson, O., B. Brooks, K. Weir-Brown, E. Hoffman, B. Johnson, J. Nanthur, H. Reyes
and A.J. Watson (1991) Genetic and molecular analysis of the Ah receptor and of
Cyplal gene expression. Biochimie 73(1): 61-6.
Key Terms: dioxin, mechanism of action, experimental, journal article
Hanson, D. (1991) EPA to take another hard look at dioxin health risk. Chemical and
Engineering News 69(17): 13-14.

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JP-7i3

Key Terms: cancer, environmental exposure, dioxins, human, news report
This news report provides a concise, simply-written, overall view of developments
in the areas of mechanism of action of dioxin, historical background to current
controversy, the Ranch Hand Study, measurements of T C D D levels in special
groups and the general population, antiestrogenic actions, and environmental
findings. It deals with the effect of these factors on regulatory standards of the
EPA.
Hanson, D.J. (1991) Dioxin toxicity: new studies prompt debate, regulatory action.
Chem. Eng. News 69(32): 7-14.
Key Terms: chronic toxicity, acute toxicity, mechanism of action, dioxins, human,
news report
Hapgood, J., S. Cuthill, P. Soderkvist, A. Wilhelmsson, I.Pongratz, R. Tukey, E. Johnson,
J. Gustafsson and L. Poellinger (1991) Liver cells contain constitutive DNase
l-hypersensitive sites at the xenobiotic response elements 1 and 2 (XRE1 and -2)
of the rat cytochrome P-450IA1 gene and a constitutive, nuclear XRE-binding factor
that is distinct from the dioxin receptor. Mol. Cell Biol. 11(9): 4314-4323.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 102.
Harden, L, M. Eriksson, O. Axelson and M. Fredriksson (1991) Increased risk of soft
tissue sarcoma in persons exposed to dioxin. Lakartidningen 88(47): 4005-4006.
Key Terms: cancer, chronic toxicity, environmental exposure, occupational
exposure, dioxins, human, journal article
See page 26.
Harper, P.A., C.L. Golas and A.B. Okey (1991) Ah receptor in mice genetically
"nonresponsive" for cytochrome P4501A1 induction: cytosolic Ah receptor,
transformation to the nuclear binding state, and induction of aryl hydrocarbon
hydroxylase by halogenated and nonhalogenated aromatic hydrocarbons in
embryonic tissues and cells. Mol. Pharmacol. 40(5): 818-826.
Key Terms: mechanism of action, enzyme induction or inhibition, experimental,
dioxins, in vitro, journal article
See pages 103 and 104.

21

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Harper, P., R. Prokipcak, L. Bush, C. Golas and A. Okey (1991) Detection and
characterization of the Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the
human colon adenocarcinoma cell line LS180. Arch. Biochem. Biophys. 290(1)27-36.
Key Terms: cancer, mechanism of action, experimental exposure, dioxins, in vitro,
journal article
See page 98.
Harper, P.A., A.B. Okey and M.S. Denison (1991) Transformation of human Ah receptor
to a form binding to a dioxin responsive element inhibition by sodium molybdate.
J. Cell Biochem. Suppl. 15(Part B): 244.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, abstract
See page 98.
Haugland, R., U. Sangodkar, P. Sferra and A. Chakrabarty (1991) Cloning and characteri­
zation of a chromosomal D N A region required for growth on 2,4,5-T by Pseudo­
monas cepacia AC1100. Gene 100: 65-73.
Key Terms: 2,4,5-T, in vitro, bacteria, mechanism of action, experimental, journal
article
Hayes, H.M., R.E. Tarone, K.P. Cantor, C.R. Jessen, D.M. McCurnin and R.C. Richardson
(1991) Case-control study of canine malignant lymphoma: positive association
with dog owner’s use of 2,4-dichlorophenoxyacetic acid herbicides. JNCI 83(17):
1226-1231.
Key Terms: cancer, chronic toxicity, environmental exposure, 2,4-D, dog, journal
article
See pages 32 and 33.
Health, N.I.F.O.S.A. (1991) Occupational Safety and Health for Fiscal Year 1988 under
Public Law 91-596. 1-43.
Key Terms: chronic toxicity, occupational exposure, dioxins, human, governm ent
report
Helferich, W.G. and M.S. Denison (1991) Ultraviolet photoproducts of tryptophan can act
as dioxin antagonists. 40(5): 674-678.

22

686

Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
This article suggests that UV-light induced tryptophan photoproducts may
specifically bind to the Ah receptor, thereby inducing aryl hydrocarbon hydroxylase
activity.
Henry, E.C. and T.A. Gasiewicz (1991) Inhibition and reconstitution of Ah receptor
transformation in vitro: role and partial characterization of a cytosolic factor(s).
Arch. Biochem. Biophys. 288(1): 149-156.
. Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 100.
Henry, E., K. Hayden, P. Bauman and T. Gasiewicz (1991) Ribonuclease inhibits Ah
receptor transformation in vitro. Biochem. J. 279(3): 689-294.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
See page 101.
Hirakawa, H., T. Matsueda, T. lida, K. Fukamachi, K. Takahashi, J. Nagayama and T.
Nagata (1991) Coplanar PCBs, PCDFs and PCDDs in the subcutaneous adipose
tissue of Yusho patients and normal controls. Fukuoka Igaku Zasshi 82(5):
274-279.
Key Terms: tissue residues, other route of exposure, furans, dioxins, human,
journal exposure
See pages 82 and 83.
Hirano, S., C. Tohyama, F. Mitsumori, H. Ito and K. Suzuki (1991) Identification of
metabolites of 2-chlorodibenzofuran in the rat. Arch. Environ. Contam. Toxicol.
20(1): 67-72.
Key Terms: miscellaneous study, furans, method, injection, rat, tissue residue
journal article
Hirose, R., M. Hori, H. Toyoshima, T. Shukuwa, M. Udono and H. Yoshida (1991) A study
of epidermal alterations induced by PCD F on experimental carcinogenesis.
Fukuoka Igaku Zasshi 82(5): 240-245.
Key Terms: cancer, acute toxicity, dermal, furans, mouse, journal article
23

687
I7-7/C.

Hoffman, E.C., H. Reyes, F.F. Chu, F. Sander, L.H. Conley, B.A. Brooks and O. Hankinson (1991) Cloning of a factor required for activity of the Ah (dioxin) receptor.
Science 252(5008): 954-958.
Key Terms: mechanism of action, dioxins, in vitro, journal article
See page 100.
Holladay, S.D., P. Lindstrom, B.L. Blaylock, C.E. Comment, D.R. Germolec, J.J. Heindell
and M.l. Luster (1991) Perinatal thymocyte antigen expression and postnatal
immune development altered by gestational exposure to tetrachlorodibenzo-pdioxin (TCDD). Teratology 44(4): 385-393.
Key Terms: immunotoxicity, acute toxicity, oral, dioxins, mouse, journal article
See page 50.
Holsapple, M., N. Snyder, S. W o o d and D. Morris (1991) A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update.
Toxicology 69(3): 219-255.
Key Terms: immunotoxicity, dioxins, review
See pages 47 and 48.
Holsapple, M., D. Morris, S. W o o d and N. Snyder (1991) 2,3,7,8-tetrachlorodibenzo-pdioxin-induced changes in immunocompetence: possible mechanisms. Annu. Rev.
Pharmacol. Toxicol. 31: 73-100.
Key Terms: immunotoxicity, mechanism of action, dioxins, human, review
See pages 47 and 109.
Holsapple, M.P., N.K. Snyder, V. Gokani, R.E. Blair and D.L. Morris (1991) Role of
Ah-receptor in suppression of in vivo antibody-response by 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is dependent on exposure conditions (Abstract).
FASEB J. 5(4): 508.
Key Terms: immunotoxicity, acute toxicity, subchronic toxicity, experimental
exposure, dioxins, mouse, abstract
See page 54.

24

688

P -W

Hong, R. (1991) Effects of environmental toxins on lymphocyte function: studies in rhesus
and man. Ann. Allergy 66(6): 474-480.
Key Terms: immunotoxicity, chronic toxicity, oral, dioxins, monkey, journal article
See page 48.
Hori, M., M. Udono, H. Toyoshima, R. Hirose and H. Yoshida (1991) Influences of
polychlorinated dibenzofuran on pUC18 plasmid DNA. Fukuoka Igaku Zasshi
82(5): 228-231.
Key Terms: genetic toxicity, experimental exposure, furans, plasmid, journal article
Huang, L., B. Eitzer, C. Moore, S. M c G o w n and K. Tomer (1991) The application of hybrid
mass spectrometry/mass spectrometry and high-resolution mass spectrometry to
the analysis of fish samples for polychlorinated dibenzo-p-dioxins and
dibenzofurans. Biol. Mass Spectrom. 20(4): 161-168.
Key Terms: analytical method, dioxins, journal article
Huang, S.W. and G.G. Gibson (1991) Differential induction of cytochromes-P450 and
cytochrome-P450-dependent arachidonic-acid metabolism by 3,4,5,3’,4’-pentachlorobiphenyl in the rat and the guinea-pig. Toxicol. Appl. Pharmacol. 108(1):
86-95.
Key Terms: enzyme induction or inhibition, rat, guinea pig, journal article
Huang, L.Q. (1991) The application of hybrid mass spectrometry/mass spectrometry and
high resolution mass spectrometry to the analysis of fish samples for
polychlorinated dibenzo-p-dioxins and dibenzofurans. Chemosphere 23(8-10):
1043-1053.
Key Terms: method, fish, dioxins, journal article
Huff, J.E. and J.K. Haseman (1991) Exposure to certain pesticides may pose real carcino­
genic risk. Chem. Eng. News Jan 7: 33-37.
Key Terms:
cancer, chronic toxicity, experimental, dioxins, 2,4-D, rodent,
commentary or opinion
As invited participants in a C & EN News forum, the authors defend the value of
current animal carcinogenesis studies, stressing that exposure at high levels is
essential for thorough exploration of the risk that such compounds pose. Itis the
inherent insensitivity of a bioassay that prevents relatively small increases in tumor

25

689

incidence from being apparent at lower doses. They stress that carcinogenicity is
not always associated with toxicity.
Huff, J., A. Salmon, N. Hooper and L. Zeise (1991) Long-term carcinogenesis studies on
2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins. Cell Biol.
Toxicol. 7(1): 67-94.
Key Terms: cancer, chronic toxicity, dioxins, review
See page 30.
Huff, J., J. Cirvello, J. Haseman and J. Bucher (1991) Chemicals associated with
site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory
rodents. Environ. Health Perspect. 93: 247-270.
Key Terms: cancer, chronic toxicity, experimental, dioxins, rodents, journal article
See pages 30 and 38.
lida, T., H. Hirakawa, T. Matsueda, R. Nakagawa, S. Takenaka, K. Morita, Y. Narazaki,
K. Fukamachi, H. Tokiwa, K. Takahashi et al. (1991) Therapeutic trialfor promotion
of fecal excretion of PCDFs and PCBs by the administration of cholestyramine in
Yusho patients. Fukuoka Igaku Zasshi 82(5): 317-325.
Key Terms: chronic toxicity, pharmacokinetics, other route of exposure, furans,
human, journal article
See page 213.
lida, J., T. Takeda, T. Takasuga, J. Moncur, P. Ireland and B. Wright (1991) Approaches
to dioxin analysis by H R G C - H R M S and hybrid HRGC-MS-MS. J. High Resolut.
Chromatogr. 14(2): 103-109.
Key Terms: method, dioxins, journal article
Jacobi, H. and I. Witte (1991) Synergistic effects of U46 D fluid (dimethylammonium salt
of 2,4-D) and CuCI2 on cytotoxicity and D N A repair in human fibroblasts. Toxicol.
Lett. 58(2): 159-167.
Key Terms: other toxic effects, acute toxicity, experimental, 2,4-D, in vitro, journal
article
The cytotoxicity of U46 D fluid, as manifested by inhibition of cell growth and D N A
synthesis in human fibroblast cultures, was enhanced by CuCI2;CuCI2 alone had

26

690

no effect. Preincubation with CuCI2) followed by exposure to U46 D fluid, induced
D N A repair, as measured by unscheduled synthesis. Neither agent alone exhibited
this effect.
Jaiswal, A.K. (1991) Human NAD(P)H:quinone oxidoreductase (NQO,) gene structure and
induction by dioxin. Biochemistry 30(44): 10647-10653.
Key Terms: mechanism of action, injection, dioxins, in vitro, journal article
See page 109.
Janz, D.M. and C.D. Metcalfe (1991) Nonadditive interactions of mixtures of 2,3,7,8-TCDD
and 3,3’,4,4’-tetrachlorobiphenyl on aryl-hydrocarbon hydroxylase induction in
rainbow-trout (Oncorhynchus mykiss). Chemosphere 23(4): 467-472.
Key Terms: enzyme induction or inhibition, experimental exposure, dioxins, fish,
journal article
Janz, D.M. and C.D. Metcalfe (1991) Relative induction of aryl-hydrocarbon hydroxylase
by 2,3,7,8-TCDD and 2 coplanar PCBs in rainbow-trout (Oncorhynchus-mykiss).
Environmental Toxicology and Chemistry 10(7): 917-923.
Key Terms: enzyme induction or inhibition, dioxins, fish, journal article
Jappinen, P. and E. Pukkala (1991) Cancer incidence among pulp and paper workers
exposed to organic chlorinated compounds formed during chlorine pulp bleaching.
Scand. J. Work Environ. Health 17(5): 356-359.
Key Terms: cancer, chronic exposure, occupational exposure, dioxins, human,
journal article
Johnson, E. (1991) A partnership between the dioxin receptor and a basic helix-loop-helix
protein. Science 252(5008): 924-925.
Key Terms: mechanism of action, dioxins, review
Jones, S.N., P.G. Jones, H. Ibarguen, C.T. Caskey and W.J. Craigen (1991) Induction of
the CYP1A-1 dioxin-responsive enhancer in transgenic mice. Nucleic Acids Res.
19(23): 6547-6551.
Key Terms:
enzyme induction or inhibition, injection, mouse, 3-methylcholanthrene, journal article
See page 105.
27

691
P-72-0

Karnrin, M. and L. Fischer (1991) Workshop on human health impacts of halogenated
biphenyls and related compounds. Environ. Health Perspect. 91: 157-164.
Key Terms: acute toxicity, chronic toxicity, dioxins, human, other species, meeting
report
Kanetoshi, A., A.M. Ward and A.B. Rifkin (1991) Immunochemical separation of cyto­
chrome P-450S metabolizing arachidonic acid A A in 2,3,7,8-tetrachlorodibenzop-dioxin T C D D and phénobarbital PB induced livers. FASEB 5(6): 1570.
Key Terms: enzyme induction or inhibition, experimental exposure, dioxins, in
vitro, abstract
Kang, H.K., K.K. Watan.^be, J. Breen, J. Remmers, M.G. Conomos, J. Stanley and M.
Flicker (1991) Dioxins and dibenzofurans in adipose tissue of US Vietnam veterans
and controls. Am. J. Public Health 81(3): 344-349.
Key Terms: tissue residues, military exposure, dioxins, human, journal article
See pages 78 and 79.
Karch, N.J. (1991) The toxicological basis for predicting the human health risk from
exposures in dioxins, PCBs and their congeners. J. Occup. Med. 33(4): 538.
Key Terms: acute toxicity, chronic toxicity, dioxins, PCBs, human, abstract
Kedderis, L.B., J.J. Diliberto and L.S. Birnbaum (1991) Disposition and excretion of
intravenous 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) in rats. Toxicol. Appl.
Pharmacol. 108(3): 397-406.
Key Terms: pharmacokinetics, injection, dioxins, rat, journal article
See page 88.
Kedderis, L.B., J.J. Diliberto, P. Linko, J.A. Goldstein and L.S. Birnbaum (1991)
Disposition of 2,3,7,8-tetrabromodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat: biliary excretion and induction of cytochromes CYP1A2
and CYP1A2. Toxicol. Appl. Pharmacol. 111(1): 163-172.
Key Terms: pharmacokinetics, oral, dioxins, rat, journal article
See pages 88, 89 and 103.

28

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P - V p ./

Kedderis, L.B., J.J. Diliberto and L.S. Birnbaum (1991) Disposition and excretion of
intravenous 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) in rats. Toxicol. Appl.
Pharmacol. 108(3): 397-406.
Key Terms: pharmacokinetics, injection, dioxins, rat, journal article
See pages 88 and 89.
Keenan, R., D. Paustenbach, R. Wenning and A. Parsons (1991) Pathology réévaluation
of the Kociba et al. (1978) bioassay of 2,3,7,8-TCDD: implications for risk
assessment. J. Toxicol. Environ. Health 34(3): 279-296.
Key Terms: cancer, chronic toxicity, experimental, dioxins, rat, journal article
See page 31.
Kim, S.G., S.L. Reddy, J.C. States and R.F. Novak (1991) Pyridine effects on expression
and molecular regulation of the cytochrome P450IA gene subfamily. Mol.
Pharmacol. 40(1): 52-57.
Key Terms: enzyme induction or inhibition, in vitro, journal article
See page 106.
Kimbrough, R.D. (1991) Uncertainties in risk assessment. Appl. Occup. Environ. Hyg.
6(9): 759-763.
Key Terms: cancer, other toxic effects, chronic toxicity, unspecified route of
exposure, dioxins, human, commentary or opinion
This is the text of the 1991 Herbert E. Stokinger Lecture, in which the author
reviews the extrapolation of animal data to set standards for contaminants in the
workplace and general environment. Predictions are made about potential adverse
effects in humans based on the toxicity observed in animals ifhuman data do not
exist. Ifchemicals cause cancer in animals at doses at which pronounced damage
occurs to the target organ, there would be a less than linear response, or no
tumors at all, at lower doses where no tissue damage took place. The major
chronic diseases are multifactorial in origin, and the contribution from trace
amounts of environmental contaminants is likely to be minimal. Recent work on
T C D D is cited which shows that the potential human health risks have been
exaggerated.

29
693

p

-755-

Kamrin, M. and L. Fiscly
biphenyls and re'%.

(1991) In vitro effects of L-ascorbic-acid
oxylase-activity in hepatic microsomes of

> Q.

Key Terms: ar

report

a,

%

%®.
Kanetoshi, A., A

%

¿ V

chrome r
p-dioxir
Key ^
vhr
Kang, Y %

dioxins, mouse, journal article

w .

lorophenoxyacetic acid-exposed
Occup. Environ. Health 63(5):

-y

\

.,ietics, occupational exposure, 2,4-D,
^

.,A. Tanaka and S. Tobinaga (1991) Relationship between
„y of polychlorinated dibenzo-para-dioxins and their electronic
.narm. Bull. 39(8): 2100-2105.
.is: mechanism of action, dioxins, model
page 103.
.\oga, N., J. Kuroki, H. Nakashima, Y. Hokama-Kuroki, H. Yoshimura, H. Kuroki and Y.
Masuda (1991) Acute toxicity, inductive effects of liver enzymes and distribution in
the liver of 1,2,3,7,8-pentachlorodibenzo-p-dioxin in rats. Fukuoka Igaku Zasshi
82(5): 197-206.
Key Terms: hepatotoxicity, enzyme induction or inhibition, acute toxicity, chronic
toxicity, unspecified route of exposure, dioxins, rat, journal article
See pages 68 and 103.
Kononen, D.W. and R.C. Schwing (1991) Comments on "background exposure to chemi­
cals: What is the risk?". Risk Anal. 11(3): 375.
Key Terms:
opinion

cancer, environmental exposure, dioxins, human, commentary or

Koppe, J.G., H.J. Pluim, K. Olie and J. van Wijnen (1991) Breast milk, dioxins and the
possible effects on the health of newborn infants. Sci. Total Environ. 106(1-2):
33-41.

30

694
P - 7 ^3

Key Terms: hematologic effects, enzyme induction or inhibition, oral, dioxins,
human, journal article
See pages 69 and 70.
Koppe, J., H. Pluim, K. Olie and J. van Wijnen (1991) Breast feeding, PCBs and dioxins.
Tijdschr. Kindergeneeskd 59(1): 9-15.
Key Terms:
article

hematologic effects, tissue residues, oral, dioxins, furans, journal

See pages 85 and 86.
Korte, M., R. Stahlmann, M. Kubickamuranyi, E. Gleichmann and D. Neubert (1991)
Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune-system.
3. No immunosuppressive effect of 2,3,7,8-TCDD inthe popliteal lymph-node assay
(PLNA) in rats. Arch. Toxicol. 65(8): 656-660.
Key Terms: immunotoxicity, acute toxicity, injection, dioxins, furans, rat, journal
article
See page 52.
Korte, M., R. Stalhlmann, R. Thiel, T. Nagao, I. Chahoud, H. Van Loveren, J.G. Vos and
D. Neubert (1991) Resistance to Trichinella spiralis infection, induction of hepatic
monooxygenases, and concentrations in thymus and liver in rats after perinatal
exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Chemosphere 23(11-12):
1845-1854.
Key Terms: immunotoxicity, enzyme induction or inhibition, tissue residues,
injection, dioxins, rat, journal article
See page 50.
Kozuka, H., J. Yamada, S. Horie, T. Watanabe, T. Suga and T. Ikeda (1991) Character­
istics of induction of peroxisomal fatty acid oxidation-related enzymes in rat liver by
drugs. Relationships between structure and inducing activity. Biochem. Pharmacol.
41(4): 617-623.
Key Terms: enzyme induction or inhibition, oral, 2,4-D, 2,4,5-T, rat, journal article
See page 115.

31

Kruger, N., H. Helge and D. Neubert (1991) Significance of PCDD/PCDF (dioxins) in
pediatrics. Monatsschr. Kinderheilkd. 139(8): 434-441.
Key Terms: enzyme induction or inhibition, oral, dioxins, human, journal article
The authors suggested that a breath test to determine induction of
monooxygenase activity by T C D D should be administered to human breast-fed
newborns and infants. This would facilitate the study of possible biologic effects
of T C D D in breast-fed children.
Kuroda, K., A. Okamoto, G. Endo, S. Horiguchi and Y.S. Yoo (1991) Colchicine-like ef­
fects of cacodylic acid. Mutat. Res. 252(1): 95.
Key Terms: cacodylic acid, genetic toxicity, experimental exposure, hamster,
journal article
See page 75.
Lakshman, M.R., P. Ghosh and S*J. Chirtel (1991) Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin on intermediary metabolism in the rat. J. Pharmacol. Exp.
Ther. 258(1): 317-319.
Key Terms: hepatotoxicity, mechanism of action, dioxins, rat, journal article
See page 114.
Lamm, S.H. (1991) The epidemiological basis for assessing human risk from exposures
in dioxin. 33(4): 538.
Key Terms: cancer, chronic toxicity, occupational exposure, military exposure,
dioxins, human, abstract
Landers, J. and N. Bunce (1991) The Ah receptor and the mechanism of dioxin toxicity.
Biochem. J. 276(2): 273-287.
Key Terms: mechanism of action, enzyme induction or inhibition, dioxins, human,
rodents, review
See pages 94 and 95.
Landers, J., M. Winhall, T. McCready, D. Sanders, D. Rasper, J. Nakai and N. Bunce
(1991) Characterization of an inducible aryl hydrocarbon receptor-like protein in rat
liver. J. Biol. Chem. 266(15): 9471-9480.

32

V '1 * S

Key Terms: hepatotoxicity, mechanism of action, dioxins, rat, journal article
See pages 98 and 99.
LeBel, G.L., D.T. Williams, F.M. Benoit and M. Goddard (1991) Polychlorinated dibenzodioxins and dibenzofurans in human adipose tissue samples from five Ontario
municipalities. Chemosphere 21(12): 1465-1475.
Key Terms:
article

tissue residues, environmental exposure, dioxins, human, journal

Lentnek, M., O.W. Griffith and A.B. Rifkind (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin
increases reliance on fats as a fuel source independently of diet: evidence that
diminished carbohydrate supply contributes to dioxin lethality. Biochem. Biophys.
Res. Commun. 174(3): 1267-1271.
Key Terms: other toxic effects, mechanism of action, dioxins, bird, journal article
See page 115.
Lerda, D. and R. Rizzi (1991) Study of reproductive function in persons occupationally
exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutat. Res. 262(1): 47-50.
Key Terms: reproductive toxicity, chronic toxicity, occupational exposure, 2,4-D,
human, journal article
See page 41.
Lin, F.H., S.J. Stohs, L.S. Birnbaum, G. Clark, G.W. Lucier and J.A. Goldstein (1991) The
effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hepatic estrogen and
glucocorticoid receptors in congenic strains of Ah responsive and Ah
nonresponsive C57BL/6J mice. Toxicol. Appl. Pharmacol. 108(1): 129-139.
Key Terms: alteration in sex hormones, mechanism of action, oral, dioxins,
mouse, journal article
See page 107.
Lin, F.H., G. Clark, L.S. Birnbaum, G.W. Lucier and G. J.A. (1991) Influence of the Ah
locus on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic epidermal
growth factor receptor. Mol. Pharmacol. 39(3): 307-313.
Key Terms: other toxic effects, mechanism of action, experimental, dioxins,
mouse, journal article
33

697

See pages 107 and 108.
Linden, J., R. Pohjanvirta, T. Rahko and J. Tuomisto (1991) T C D D decreases rapidly and
persistently serum melatonin concentration without morphologically affecting the
pineal gland in TCDD-resistant Han/Wistar rats. Pharmacol. Toxicol. 69(6):
427-432.
Key Terms: other toxic effects, acute toxicity, injection, dioxins, rat, journal article
See page 111.
Lloyd, O.L., M.M. Lloyd, F.L.R. Williams, A. McKenzie and A. Hay (1991) Toxicity from
ragwort and fat cow syndrome, or from industrial chemicals - the value of
epidemiologic analysis for interpreting clinicopathological findings. Sci. Total
Environ. 106(1-2): 83-96.
Key Terms: other toxic effects, chronic toxicity, environmental exposure, dioxins,
cow, journal article
Lorenzen, A. and A.B. Okey (1991) Detection and characterization of Ah receptor in tissue
and cells from human tonsils. Toxicol. Appl. Pharmacol. 107(2): 203-214.
Key Terms: immunotoxicity, mechanism of action, experimental, dioxin, human,
journal article
See pages 48, 96 and 97.
Lucier, G.W. (1991) Humans are a sensitive species to some of the biochemical effects
of structural analogs of dioxin. Environmental Toxicology and Chemistry 10(6):
727-735.
Key Terms: cancer, enzyme induction or inhibition, tissue residues, experimental,
dioxins, human, rat, journal article
See pages 83 and 97.
Lucier, G.W., A. Tritscher, T. Goldsworthy, J. Foley, G. Clark, J. Goldstein and R.
Maronpot (1991) Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxinmediated increases in cell proliferation and preneoplastic foci in a two-stage model
for rat hepatocarcinogenesis. Cancer Res. 51(5): 1391-1397.
Key Terms: cancer, steroid hormones, mechanism of action, oral, dioxins, rat,
model, journal article

34

D-72-7

See page 32.
Lundberg, K., K.O. Gronvik and L. Dencker (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin
(TCDD) induced suppression of the local immune response. Int. J. Immunopharmacol. 13(4): 357-368.
Key Terms: immunotoxicity, acute toxicity, injection, dioxins, mouse, journal article
See page 52.
Lundberg, K. (1991) Dexamethasone and 2,3,7,8-tetrachlorodibenzo-p-dioxin can induce
thymic atrophy by different mechanisms in mice. Biochem. Biophys. Res.
Commun. 178(1): 16-23.
Key Terms: immunotoxicity, acute toxicity, dioxins, mouse, journal article
See page 50.
Lundgren, K., C. Rappe and H.-R. Buser (1991) Detection of alkylated polychlorodibenzofurans and alkylated polychlorodibenzo-p-dioxins by tandem mass
spectrometry for the analysis of crustacean samples. Chemosphere 23(8-10):
1591-1604.
Key Terms: method, dioxins, journal article
Luotamo, M. (1991) Congener specific assessment of human exposure to polychlorinated
biphenyls. Chemosphere 23(11-12): 1685-1698.
Key Terms: tissue residues, occupational exposure, environmental exposure, other
route of exposure, PCBs, human, journal article
Lusska, A., K. Jones, C. Elferink, L. Wu, E. Shen, L. W e n and J.J. Whitlock (1991) 2,3,7,8Tetrachlorodibenzo-p-dioxin induces cytochrome P450IA1 enzyme activity by
activating transcription of the corresponding gene. Adv. Enzyme Regul. 31:
307-317.
Key Terms: mechanism of action, enzyme induction or inhibition, experimental
exposure, dioxins, in vitro, journal article
See page 105.
Manz, A., J. Berger, J.H. Dwyer, D. Flesch-Janys, S. Nagel and H. Waltsgott (1991)
Cancer mortality among workers in chemical plant contaminated with dioxin.
Lancet 338(8773): 959-964.
35

699

Q - Ir t

Key Terms: cancer, chronic toxicity, occupational exposure, dioxins, human,
journal article
See pages 26 and 27
Massa, T., A. Esmaeili, B. Schlatterer, H. Hagenmaier and P. Chandra (1991) Carcino­
genic and co-carcinogenic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a
host-mediated in vivo/in vitro assay. Chemosphere 23(11-12): 1855-1868.
Key Terms: cancer, other toxic effects, acute toxicity, injection, dioxins, mouse, in
vitro, journal article
See pages 31 and 32.
Masuda, Y., H. Kuroki, K. Haraguchi, J. Ryan and S. Shu (1991) Elimination of PCD F and
PCB congeners in the blood of patients with PCB poisoning in Taiwan. Fukuoka
Igaku Zasshi 82(5): 262-268.
Key Terms: tissue residues, chronic toxicity, other route of exposure, furans,
human, journal article
See page 83.
Masuda, Y. (1991) Toxic evaluation of chlorinated aromatic-hydrocarbons in human
environments. Daiichi Coll. Pharmaceut. Sci. 7(5-6): 137-141.
Key Terms: chronic toxicity, environmental exposure, chlorinated hydrocarbons,
human, journal article
Matsuoka, K., S. Nonaka, T. Ohgami, H. Yoshida and F. Murayama (1991) In vitro ana­
lysis of polychlorinated biphenyls (PCBs) and 2,3,4,7,8-pentachlorodibenzofurar,
(PCDF) cellular toxicity in PLC/PRF/5 cell proliferation - the effect of ursodeoxy­
cholic acid, inchin-gorei-san and shou-saiko-to on cell toxicity. Fukuoka Igaku
Zasshi 82(5): 232-239.
Key Terms: other toxic effects, furans, in vitro, journal article
Mattina, M.J.I. (1991) Determination ofchlorophenoxy acids using high-performance liquic
chromatography-particle beam mass spectrometry. J. Chromatogr. 542(385-395.
Key Terms: miscellaneous study, method, 2,4-D, 2,4,5-T, journal article
Using an isocratic mobile phase of methanol containing phenoxyacetic acid-dilute
acetic acid (70:30), the author achieved good HPLC separation of phenox\
36

700

herbicides. The eluate was introduced into a mass spectrometer using methaneenhanced electron-capture negative ionization conditions through the particle beam
interface. Detection limits were in the low pg/liter range.
McConnell, E.E., J.E. Huff, M. Hejtmancik, A.C. Peters and R. Persing (1991) Toxicology
and carcinogenesis studies of 2 grades of pentachlorophenol in B6C3F1-mice.
Fundam. Appl. Toxicol. 17(3): 519-532.
Key Terms: cancer, dioxins, mouse, journal article
McGregor, D.B., A.G. Brown, S. Howgate, D. McBride, C. Riach and W.J. Caspary (1991)
Responses of the L5178Y mouse lymphoma cell forward mutation assay. V: 27
coded chemicals. Environmental and Molecular Mutagenesis 17(3): 196-219.
Key Terms: genetic toxicity, experimental exposure, dioxins, in vitro, journal article
See page 38.
McKim, J.J., K. Marien, H. Schaup and D. Selivonchick (1991) Alterations of hepatic
acetyl-CoA carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Lipids 26(7):
521-525.
Key Terms: enzyme induction or inhibition, injection, dioxins, rat, journal article
See pages 68 and 115.
Mehta, S., T. Mazzonati and R. Kurl (1991) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin
on human T cell proliferation. Proc. Am. Assoc. Cancer Res. Annu. Meet. 32: 273.
Key Terms: immunotoxicity, dioxins, human, abstract
Michalek, J.E., R.C. Tripathi, S.P. Caudill and J.L. Pirkle (1992) Investigation of T C D D
half-life heterogeneity in veterans of Operation Ranch Hand. J. Toxicol. Environ.
Health 35: 29-38.
Key Terms: tissue residues, military exposure, dioxins, human, journal article
See page 80.
Mirvish, S.S., J. Nickols, D.D. Weisenburger, D. Johnson, S.S. Joshi, P. Kaplan, M. Gross
and H.Y. Tong (1991) Effects of 2,4,5-trichlorophenoxyacetic acid, pentachloro­
phenol, methylprednisolone, and Freund adjuvant on 2-hydroxyethylnitrosourea
carcinogenesis in MRC-Wistar rats. J. Toxicol. Environ. Health 32(1): 59-74.

37

701
£>- 13b

Key Terms:
article

cancer, subchronic toxicity, injection, dioxins, 2,4,5-T, rat, journal

See page 33.
Mocarelli, P., L.L. Needham, A. Marocchi, D.G. Patterson Jr, P. Brambilla, P.M. Gerthoux,
L. Meazza and V. Carreri (1991) Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. J.
Toxicol. Environ. Health 32(4): 357-366.
Key Terms: chloracne, tissue residues, other route of exposure, dioxins, human,
journal article
See pages 67 and 82.
Moody, D.E., B.A. Narloch, L.R. Shull and B.D. Hammock (1991) The effect of structurally
divergent herbicides on mouse-liver xenobiotic-metabolizing enzymes (P-450dependent mono-oxygenases, epoxide hydrolases and glutathione S-transferases)
and carnitine acetyltransferase. Toxicol. Lett. 59(1-3): 175-185.
Key Terms: cancer, enzyme induction or inhibition, experimental, 2,4-DP, mouse,
journal article
Moore, R., C. Jefcoate and R. Peterson (1991) 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits
steroidogenesis in the rat testis by inhibiting the mobilization of cholesterol to
cytochrome P450scc. Toxicol. Appl. Pharmacol. 109(1): 85-97.
Key Terms: alteration in sex hormones, mechanism of action, dioxin, rat, journal
article
See page 111.
Morgan, R.W. (1991) Dioxin and mortality from cancer (Letter). Environ. Health Strategies
324(25): 1810.
Key Terms: cancer, chronic toxicity, occupational exposure, dioxins, human,
commentary or opinion

Morita, M. (1991) Dioxins, their chemistry and toxic effects. Kami Pa Gikyoshi 45(8):
887-901.
Key Terms: toxicity, dioxins, review

38

702

V- 73'

Morris, D.L., S.D. Jordan and M.P. Holsapple (1991) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: I. Similarities to Staphylococcus
aureus Cowan strain I (SAC) in the in vitro T-dependent antibody response.
Immunopharmacology 21(3): 159-169.
Key Terms: immunotoxicity, acute toxicity, experimental, dioxins, in vitro, journal
article
See page 53.
Morris, D.L. and M.P. Holsapple (1991) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) on humoral immunity: II. B cell activation. Immunopharmacology 21(3):
171-181.
Key Terms: immunotoxicity, acute toxicity, experimental, dioxins, in vitro, journal
article
See page 53.
Morris, D.L. and M.P. Holsapple (1991) G a m m a interferon (G-IFN) potentiates the
activation and proliferation of dense resting B cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD. FASEB 5(5): 1206.
Key Terms: immunotoxicity, acute toxicity, experimental exposure, dioxins, in vitro,
mouse, abstract
See page 53.
Morris, D.L., N.K. Snyder, V. Gokani, R.E. Blair and M.P. Holsapple (1991) Enhanced
suppression of humoral immunity in DBA/2 mice following subchronic exposure
to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Appi. Pharmacol. 112(1):
128-132.
Key Terms: immunotoxicity, subchronic toxicity, gavage, dioxins, mouse, journal
article
See pages 51 and 54.
Mueller, H.E. (1991) Rational and irrational danger of dioxins. Dtsch. Med. Wochenschr.
116(20): 786-793.
Key Terms: chloracne, environmental exposure, dioxins, human, review

39

703

Mussalorauhamaa, H. (1991) Partitioning and levels of neutral organochlorine compounds
in human serum, blood-cells, and adipose and liver-tissue. Sci. Total Environ.
103(2-3): 159-175.
Key Terms: tissue residues, environmental exposure, furans, human, journal article
Muto, H., M. Shinada, T. Abe and Y. Takizawa (1991) The tissue distribution of 2,3,7,8chlorine substituted dibenzo-p-dioxins in humans who died of cancer. Life Sci.
48(17): 1645-1657.
Key Terms: cancer, tissue residues, environmental, dioxins, human, journal article
See page 84.
Myers, J.P. and T. Colborn (1991) Blundering questions, weak answers lead to poor
pesticide policies. Chem. Eng. News Jan 7: 40-43.
Key Terms: cancer, teratologic effects, other toxic effects, oral, environmental,
other route of exposure, pesticides, bird, dog, human, commentary or opinion
See page 44.
Nagayama, J., K. Wada, K. Haraguchi, Y. Masuda and S. Handa (1991) Effects of 3methylsulphonyl-4,5,3’,4’-tetrachlorobiphenyl and 7,8-benzoflavone on aryl hydro­
carbon hydroxylase activity in Ah responsive and Ah nonresponsive strains of
mice. Fukuoka Igaku Zasshi 82(5): 207-214.
Key Terms: enzyme induction or inhibition, experimental exposure, furans, dioxins,
mouse, journal article
See page 103.
Nagayama, J., M. Nagayama, K. Wada, T. lida, H. Hirakawa, T. Matsueda and Y. Masuda
(1991) The effect of organochlorine compounds on the induction of sister
chromatid exchanges in cultured human lymphocytes. Fukuoka Igaku Zasshi
82(5): 221-227.
Key Terms: genetic toxicity, immunotoxicity, experimental, furans, in vitro, journal
article
Nakagawa, R. and K. Takahashi (1991) Studies on the application of residual PCBs,
PCQs and PCDFs concentrations to Yusho diagnosis. Fukuoka Igaku Zasshi
82(5): 280-294.

704
V -1 3 3

Key Terms: other toxic effects, tissue residues, other route of exposure, furans,
human, journal article
See page 83.
Nam, K.S., S. Kapila, A.F. Yanders and R.K. Puri (1991) A multiple sample extraction and
on-line system for the analysis of chlorinated compounds. Chemosphere 23(8-10):
1109-1116.
Key Terms: method, dioxins, journal article
Narasimhan, T.R., S. Safe, H.J. Williams and A.I. Scott (1991) Effects of 2,3,7,8tetrachlorodibenzo-p-dioxin on 17/3-estradiol-induced glucose metabolism in MCF-7
human breast cancer cells: 13C nuclear magnetic resonance spectroscopy studies.
Mol. Pharmacol. 40: 1029-1035.
Key Terms: alteration in sex hormones, other toxic effects, mechanism of action,
acute toxicity, experimental exposure, dioxins, human, journal article
See pages 110 and 111.
Nemoto, N., J. Sakurai, A. Tazawa and T. Ishikawa (1991) Regulation of mouse P(1)450
gene expression in monolayer-cultured hepatocytes from responsive and
non-responsive strains. Carcinogenesis 12(4): 623-629.
Key Terms: enzyme induction or inhibition, mechanism of action, experimental
exposure, dioxins, in vitro, journal article
See page 105.
Nemoto, N. and J. Sakurai (1991) Proline is required for transcriptional control of the
aromatic hydrocarbon-inducible Pt450 gene in C57BI/6 mouse monolayer-cultured
hepatocytes. Jpn. J. Cancer Res. 82(8): 901-908.
Key Terms: enzyme induction or inhibition, mechanism of action, mouse, aryl
hydrocarbon hydroxylase, journal article
Induction of A H H by polycyclic aromatic hydrocarbons is dependent on a prolinerelated metabolism which influences transcription of the P ^ O gene.
Neuberger, M., W. Landvoigt and F. Derntl (1991) Blood levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chemical workers after chloracne and in comparison groups.
Int. Arch. Occup. Environ. Health 63(5): 325-327.

705

V-1H

Key Terms: chloracne, tissue residues, occupational exposure, dioxins, human,
journal article
See pages 67 and 81.
Neubert, R., U. Jacob-Müller, H. Helge, R. Stahlmann and D. Neubert (1991) Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 2. In
vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of
venous blood from man and a non-human primate (Callithrix jacchus). Arch.
Toxicol. 65(3): 213-219.
Key Terms: immunotoxicity, acute toxicity, experimental, dioxins, furans, in vitro,
journal article
See page 47 and 48.
Neubert, R., H. Helge, R. Stahlmann and D. Neubert (1991) Some effects of 2,3,7,8tetrachlorodibenzo-para-dioxin (T4CDD) and of 2,3,4,7,8-pentachlorodibenzofuran
(P5CDF) on peripheral lymphocytes of primates in vivo and in vitro. Allergologie
14(9): 360-371.
Key Terms: immunotoxicity, injection, experimental exposure, dioxins, furans,
primate, in vitro, journal article
See page 48.
Neubert, D. and H. Helge (1991) Problems with xenobiotics - especially ‘dioxins’ - in
human milk. Arch. Gynecol. Obstet. 250(1-4): 853-858.
Key Terms: tissue residues, oral, dioxins, furans, human, journal article
Neubert, D. (1991) Peculiarities of the toxicity of polyhalogenated dibenzo-p-dioxins and
dibenzofurans in animals and man. Chemosphere 23(11-12): 1869-1893.
Key Terms: cancer, immunotoxicity, mechanism of action, pharmacokinetics,
dioxins, furans, rat, in vitro, human, review
See page 77.
Nishizumi, M. (1991) Carcinogenicity of
2,3,4,7,8-pentachlorodibenzofuran and
1,2,3,4,7,8-hexachlorodibenzofuran when given by gavage to rats. Fukuoka Igaku
Zasshi 82(5): 246-250.
Key Terms: cancer, acute toxicity, oral, furans, mouse, journal article
42

706 „

1P-7Ä5

Noren, K. and A. Lunden (1991) Trend studies of polychlorinated biphenyls, dibenzo-pdioxins and dibenzofurans in human milk. Chemosphere 23(11-12): 1895-1901.
Key Terms: pharmacokinetics, tissue residues, environmental, dioxins, furans,
human, journal article
See pages 86 and 87.
O ’Brien, T.R., P. Decoufle, 2nd and C.A. Boyle (1991) Non-Hodgkin’s lymphoma in a
cohort of Vietnam veterans. Am. J. Public Health 81(6): 758-760.
Key Terms: cancer, chronic toxicity, military exposure, dioxins, human, journal
article
See pages 21 and 22.
Okino, S.T. and R.H. Tukey (1991) Phorbol ester treatment to mice inhibits D N A binding
of the T C D D inducible nuclear dioxin receptor to CYPIA1 enhancer elements.
FASEB J. 5(5): 1162.
Key Terms: enzyme induction or inhibition, mechanism of action, experimental
exposure, dioxins, mouse, abstract
See pages 101 and 102.
Oiling, M., H.J.G.M. Derks, P.L.M. Berende, A.K.D. Liem and A.P.J.M. De Jong (1991)
Toxicokinetics of eight 13C-labelled polychlorinated dibenzo-p-dioxins and -furans
in lactating cows. Chemosphere 23(8-10): 1377-1385.
Key Terms: pharmacokinetics, oral, dioxins, cows, journal article
See page 87.
Overby, L.H., G.T. Carver and R.M. Philpot (1991) Localization of messenger R N A for
cytochrome P-450IA1 in lungs of rabbits treated with 2,3,7,8-tetrachlorodibenzop-dioxin TCDD. Am. Rev. Respir. Dis. 143(4 Part 2): 135.
Key Terms: enzyme induction or inhibition, injection, dioxins, rabbit, abstract
Paulino, C.A. and J. Palermoneto (1991) Effects of acute 2,4-dichlorophenoxyacetic acid
intoxication on some rat serum components and enzyme-activities. Braz. J. Med.
Biol. Res. 24(2): 195-198.

707

Key Terms: acute toxicity, enzyme induction or inhibition, 2,4-D, rat, journal article

Paustenbach, D.J., M.W. Layard, R.J. Wenning and R.E. Keenan (1991) Risk assessment
of 2,3,7,8-TCDD using a biologically based cancer model: a réévaluation of the
Kociba et al. bioassay using a 1978 and 1990 histopathology criteria. J. Toxicol.
Environ. Health 34(1): 11-26.
Key Terms: cancer, chronic toxicity, dioxins, rat, model
See page 31.
Pavlica, M., D. Papes and B. Nagy (1991) 2,4-Dichlorophenoxyacetic acid causes
chromatin and chromosome abnormalities in plant cells and mutation in cultured
mammalian cells. Mutât. Res. 263(2): 77-81.
Key Terms: genetic toxicity, acute toxicity, experimental, 2,4-D, in vitro, journal
article
See pages 38 and 39.
Perdew, G. (1991) Comparison of the nuclear and cytosolic forms of the Ah receptor from
Hepa 1c1c7 cells: charge heterogeneity and ATP binding properties. Arch.
Biochem. Biophys. 291(2): 284-290.
Key Terms: mechanism of action, experimental, dioxin, in vitro, journal article
See page 99.
Pesonen, M. and T. Andersson (1991) Characterization and induction of xenobiotic
metabolizing enzyme activities in a primary culture of rainbow trout hepatocytes.
Xenobiotica 21(4): 461-471.
Key Terms: enzyme induction or inhibition, experimental exposure, dioxin, fish,
journal article
See page 96.
Pesonen, M., A. Gokoyr and T. Andersson (1992) Expression of P450IA1 in a primary
culture of rainbow trout hepatocytes exposed to /3-naphthoflavone or
2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch. Biochem. Biophys. 292(1): 228-233.
Key Terms: mechanism of action, enzyme induction or inhibition, experimental,
dioxins, in vitro, journal article
44

708

See pages 96 and 105.
Peto, R. (1991) Occupational exposure to chlorophenoxy herbicides and chlorophenols
[Letter], Lancet 338(8779): 1392.
Key Terms: cancer, chronic toxicity, military exposure, dioxins, phenoxyherbicides,
human, commentary or opinion
See pages 25 and 26.
Pettit, K., R.S. Brown and P.W. Jones (1991) The DB5 capillary column: the search for
sensitivity. Chemosphere 23(8-10): 1117-1123.
Key Terms: method, dioxins, journal article
Phillips, L. and G. Birchard (1991) Regional variations in human toxics exposure in the
USA: an analysis based on the National Human Adipose Tissue Survey. Arch.
Environ. Contam. Toxicol. 21(2): 159-168.
Key Terms:
article

tissue residues, environmental exposure, dioxins, human, journal

See pages 83 and 84.
Piskorska-Pliszczynska, J., B. Astroff, T. Zacharewski, M. Harris, R. Rosengren, V.
Morrison, L. Safe and S. Safe (1991) Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonists: characterization of 6-[125l]methyl-8-iodo-1,3dichlorodibenzofuran-Ah receptor complexes. Arch. Biochem. Biophys. 284(1):
193-200.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 101.
Piskorska-Pliszczynska, J., V. Morrison, T. Zacharewski and S. Safe (1991) D N A binding
properties of the Ah receptor in wild-type and variant mouse hepatoma cells. Arch.
Biochem. Biophys. 290(2): 362-368.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
See page 100.

45

Pohjanvirta, R., M. Unkila and J. Tuomisto (1991) Characterization of the enhanced
responsiveness to postingestive satiety signals in 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD)-treated Han/Wistar rats. Pharmacol. Toxicol. 69(6): 433-441.
Key Terms: neurobehavioral effects, subchronic toxicity, injection, dioxins, rat,
journal article
See pages 62 and 63.
Pokrovsky, A.G., A.I. Cherykh, O.N. Yastrebova and I.B. Tsyrlov (1991) 2,3,7,8-tetrachlorodibenzo-p-dioxin as a possible activator of HIV infection. Biochem. Biophys.
Res. Commun. 179(1): 46-51.
Key Terms: immunotoxicity, other toxic effects, acute toxicity, experimental,
dioxins, in vitro, journal article
See page 49.
Poland, A. and E. Glover (1991) Characterization and strain distribution pattern of the
murine Ah receptor specified by the Ahd and Ahb'3 alleles. Mol. Pharmacol. 38:
306-312.
Key Terms: mechanism of action, murine, journal article
See page 104.
Poland, A., E. Glover and C.A. Bradfield (1991) Characterization of polyclonal antibodies
to the Ah receptor prepared by immunization with a synthetic peptide hapten
[published erratum appears in Mol Pharmacol 1991 Apr. 39(4):435]. Mol.
Pharmacol. 39(1): 20-26.
Key Terms: mechanism of action, dioxins, journal article
The authors describe the use of a synthetic peptide based on the N-terminal
sequence of the Ah receptor from C57BL/6J mice, coupled with a keyhole limpet
hemocyanin, to produce polyclonal antiserum to Ah receptor in rabbits. Sensitivity
for Ah detection on a blot is 60-120 pg/200 m g protein/gel lane.
Politzer, P. and J.S. Murray (1991) Electrostatic potential analysis of dibenzo-p-dioxins and
structurally similar systems in relation to their biological activities. Theor. Biochem.
Mol. Biophys. 2: 165-191.
Key Terms: other toxic effects, mechanism of action, dioxins, journal article

46

Pongratz, I., P.-E. Stromstedt, G.G.F. Mason and L. Poellinger (1991) Inhibition of the
specific D N A binding activity of the dioxin receptor by phosphatase treatment. J.
Biol. Chem. 266(25): 16813-16817.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
See page 101.
Precht, C. (1991) Dioxins (Letter). Dtsch. Med. Wochenschr. 116(35): 1332-1333.
Key Terms: environmental exposure, dioxins, human, journal article
This letter in German mentions dioxins, furans, and the anticarcinogens in broccoli
as they relate to the Ah receptor.
Prokipcak, R.D. and A.B. Okey (1991) Down-regulation of the Ah receptor in mouse
hepatoma-cells treated in culture with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Can. J.
Physiol. Pharmacol. 69(8): 1204-1210.
Key Terms: enzyme induction or inhibition, mechanism of action, experimental
exposure, dioxins, in vitro, journal article
See page 99.
Puhvel, S.M., M.J. Connor and M. Sakamoto (1991) Vitamin A deficiency and the induc­
tion of cutaneous toxicity in murine skin by TCDD. Toxicol. Appl. Pharmacol.
107(1): 106-116.
Key Terms: other cutaneous effects, acute toxicity, dermal, dioxins, mouse, journal
article
See pages 67 and 113.
Purchase, R. (1991) Meeting report - Dioxins revisited. Food Chem. Toxicol. 29(12):
863-864.
Key Terms: tissue levels, environmental, dioxins, furans, human, meeting report
Raha, A., V. Reddy, L. Xu, W. Houser and E. Bresnick (1991) Presence of the 4 S poly­
cyclic hydrocarbon-binding protein in H4-II-E cells. Toxicology 66(2): 175-186.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article

47

711

Rannug, U., M. Sjogren, A. Rannug, M. Gillner, R. Toftgard, J.-A. Gustafsson, H. Rosen­
kranz and G. Klopman (1991) Use of artificial intelligence in structure-affinity
correlations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor ligands.
Carcinogenesis 12(11): 2007-2015.
Key Terms: mechanism of action, dioxins, model
See page 102.
Ray, P.K., K.P. Singh, Raiduddin and A.K. Prasad (1991) Immunological responses to
aflatoxins and other chemical carcinogens. J. Toxicol. - Toxin Reviews 10(1):
63-85.
Key Terms: immunotoxicity, dioxins, human, review
Rivarola, V.A. and H.F. Balegno (1991) Effects of 2,4-dichlorophenoxyacetic acid on
polyamine synthesis in Chinese hamster ovary cells. Toxicol. Lett. 56(1-2):
151-157.
Key Terms: enzyme induction or inhibition, mechanism of action, experimental,
2,4-D, in vitro, journal article
See page 115.
Rivarola, V. and H. Balegno (1991) 2,4-Dichlorophenoxyacetic acid effects on polyamine
biosynthesis. Toxicology 68(2): 109-119.
Key Terms: mechanism of action, experimental, 2,4-D, in vitro, journal article
See page 115.
Roberts, E.A., K.C. Johnson and W.G. Dippold (1991) Ah receptor mediating induction
of cytochrome P450IA1 in a novel continuous human liver cell line (Mz-Hep-1).
Detection by binding with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin and relationship
to the activity of aryl hydrocarbon hydroxylase. Biochem. Pharmacol. 42(3):
521-528.
Key Terms: hepatotoxicity, mechanism of action, experimental, dioxins, in vitro,
journal article
See page 97.
Roberts, L. (1991) Dioxin risks revisited [News]. Science 251(4994): 624-626.

48
-A

Key Terms: mechanism of action, dioxins, human, news report
This news report discusses the controversial suggestion that the risk assessment
of dioxin should reflect its molecular mechanism of action. Itdiscusses the merits
of the linear multistage model versus the receptor/threshold model relative to
setting acceptable exposure limits for dioxin.
Rodriguez, E. and R. Lombardo (1991) Acute toxicity of parathion and 2,4 D to estuarine
adult crabs. Bull. Environ. Contam. Toxicol. 46(4): 576-582.
Key Terms: acute toxicity, environmental exposure, 2,4-D, crab, journal article
The time- and concentration-dependence curves for the toxicity of 2,4-D and
parathion were determined in two species of crabs. Parathion was 2,500- and
6,000-fold more toxic than 2,4-D in these two species.
Rodriguez-Pichardo, A., F. Camacho, C. Rappe, M. Hansson, A.G. Smith and I.B. Greig
(1991) Chloracne caused by ingestion of olive oil contaminated with PVDDs and
PCDFs. Human and Experimental Toxicology 10(5): 311-322.
Key Terms: chloracne, oral, dioxins, furans, human, journal article
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson (1991) An
epidemiologic investigation of health effects in air force personnel following
exposure to herbicides. Air Force Health Study 1-9(Mar)
Key Terms: cancer, other toxic effects, pharmacokinetics, chronic toxicity, tissue
residues, military exposure, dioxins, human, government report
See page 21.
Roegner, R.H., W.D. Grubbs, M.B. Lustik, A.S. Brockman and S.C. Henderson (1991) An
epidemiologic investigation of health effects in Air Force personnel following
exposure to herbicides. Introduction, background and conclusions. Air Force
Health Study Chapters 1-5, 18, 19(1-133).
Key Terms: chronic toxicity, military exposure, phenoxy herbicides, dioxins,
human, government report
See pages 14, 15, 16, 47, 59, 67, 68 and 78.
Rozman, K., B. Pfeifer, L. Kerecsen and R.H. Alper (1991) Is a serotoninergic mechanism
involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced
appetite
suppression in the Sprague-Dawley rat. Arch. Toxicol. 65(2): 124-128.
49

Key Terms: neurobehavioral effects, acute toxicity, injection, other route of
exposure, dioxins, rat, journal article
This study investigated the role of serotonin in TCDD-induced appetite
suppression. Transfusion experiments demonstrated that TCDD-treated rats were
not satiated, but that their hunger was inhibited. Tryptophan in plasma and
hypothalamus, and 5-HT and 5-HIAA in the hypothalamus, increased progressively
in TCDD-treated rats. This indicates that a serotoninergic mechanism may be
involved in TCDD-induced appetite suppression.
Rozman, K. (1991) ED50 for E R O D induction and ED50 for PFCs/spleen [letter;
comment], Toxicol. Appl. Pharmacol. 108(3): 568-569.
Key Terms: enzyme induction or inhibition, mechanism of action, dioxins,
commentary or opinion
This letter discussing the findings of Howie et al. in Toxicol. Appl. Pharmacol. 105:
254-263 (1990), points out that the two potent isomers of hexaCDE have about the
same chance of being in a TCDD-like configuration, whereas the medium potency
isomer has only half this chance and the low potency isomer does not enter a
TCDD-like configuration. This is accompanied by a letter from S.H. Safe in reply.
Ruangwises, S., L. Bestervelt, D. Piper, C. Nolan and W. Piper (1991) Human chorionic
gonadotropin treatment prevents depressed 17 alpha-hydroxylase/C 17-20 lyase
activities and serum testosterone concentrations in 2,3,7,8-tetrachlorodibenzop-dioxin-treated rats. Biol. Reprod. 45(1): 143-150.
Key Terms: alteration in sex hormones, enzyme induction or inhibition, oral,
dioxins, rat, journal article
See page 111.
Rune, G., P. deSouza, R. Krowke, H. Merker and D. Neubert (1991) Morphological and
histochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on marmoset
(Callithrix jacchus) testes. Arch. Androl. 26(3): 143-154.
Key Terms: reproductive toxicity, acute toxicity, experimental exposure, dioxins,
marmoset, journal article
Rune, G.M., P. De Souza, R. Krowke, H.J. Merker and D. Neubert (1991) Morphological
and histochemical pattern of response in rat testes after administration of
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Histol. Histopathol. 6(4): 459-467.

50

Key Terms: reproductive toxicity, alteration in sex hormones, injection, dioxins, rat,
journal article
See page 42.
Safe, S., B. Astroff, M. Haris, T. Zacharewski, R. Dickerson, M. Romkes and L. Biegel
(1991) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds as
antioestrogens: characterization and mechanism of action. Pharmacol. Toxicol.
69(6): 400-409.
Key Terms: alteration in sex hormones, acute toxicity, experimental exposure,
dioxins, in vitro, review
See page 110.
Safe, S. (1991) Polychlorinated dibenzo-p-dioxins and related compounds: sources,
environmental distribution and risk assessment. Environ. Carcino. Ecotox. Revs.
C9(2): 261-302.
Key Terms: cancer, other toxic effects, mechanism of action, occupational,
environmental, other route of exposure, dioxins, human, review
See page 94.
Sanders, V.M., B.A. Fuchs, S.B. Pruett, N.l. Kerkvliet and N.E. Kaminski (1991)
Symposium on indirect mechanisms of immune modulation. Fundam. Appl.
Toxicol. 17(4): 641-650.
Key Terms: immunotoxicity, mechanism of action, experimental, dioxins, mouse,
journal article
Sanner, T., S. Mikalsen and E. Rivedal (1991) Hepatic peroxisome proliferators induce
morphologic transformation of Syrian hamster embryo cells, but not peroxisomal
beta oxidation. Prog. Clin. Biol. Res. 369: 77-89.
Key Terms: cell transformation, experimental exposure, 2,4-D, 2,4,5-T, in vitro,
journal article
See page 115.
Santagostino, A., M. Leone, R. Maci, A. Casale and L. Marabini (1991) Effects of
phenoxyacetic acid herbicides on chicken embryo liverdrug metabolizing enzymes.
Pharmacol. Toxicol. 68(2): 110-114.

51

Qt'I'H-

Key Terms: hepatotoxicity, enzyme induction or inhibition, injection, 2,4-D, bird,
journal article
See page 68 and 107.
Saracci, R., M. Kogevinas, P.-A. Bertazzi, B.H. Bueno de Mesquita, D. Coggon, L.M.
Green, T. Kauppinen et al. (1991) Cancer mortality in workers exposed to
chlorophenoxy herbicides and chlorophenols. Lancet 338(8774): 1027-1032.
Key Terms: cancer, chronic toxicity, occupational exposure, phenoxy herbicide
formulations, dioxins, human, journal article
See page 25.
Schecter, A.J., R. Malkin, O. Papke, M. Ball and P.W. Brandt-Rauf (1991) Dioxin levels in
blood of municipal incinerator workers. Med. Sci. Res. 19(11): 331-332.
Key Terms: tissue residues, occupational exposure, dioxins, human, journal article
Schecter, A.J., B.J. Poiesz, P.W. Brandt-Rauf, O. Papke and M. Ball (1991) Dioxin levels
in blood of AIDS patients and controls. Med. Sci. Res. 19(9): 273-275.
Key Terms: immunotoxicity, environmental exposure, dioxins, furans, human,
journal article
See pages 48 and 49.
Schecter, A., P. Furst, C. Furst, O. Papke, M. Ball, L.C. Dai, H.T. Quynh, N.T.N. Phoung,
A. Beim, B. Vlasov, V. Chongchet, J.D. Constable and K. Charles (1991) Dioxins,
dibenzofurans and selected chlorinated organic compounds in human milk and
blood from Cambodia, Germany, Thailand, the U.S.A., the U.S.S.R., and Vietnam.
Chemosphere 23(11-12): 1903-1912.
Key Terms: tissue residues, environmental exposure, occupational exposure,
military exposure, dioxins, furans, human, journal article
See page 85.
Schecter, A., O. Papke, M. Ball and J.J. Ryan (1991) Partitioning of dioxins and dibenzo­
furans: whole blood, blood plasma and adipose tissue. Chemosphere 23(11-12):
1913-1919.
Key Terms: pharmacokinetics, tissue levels, environmental exposure, dioxins,
furans, human, journal article
52

See page 77.
Schecter, A. and J.J. Ryan (1991) Brominated and chlorinated dioxin blood levels in a
chemist 34 years after exposure to 2,3,7,8-tetrachlorodibenzodioxin and 2,3,7,8tetrabromodibenzodioxin. Chemosphere 23(11-12): 1921-1924.
Key Terms:
article

tissue residues, other route of exposure, dioxins, human, journal

See pages 77 and 81.
Schmidt, K.F. (1992) Dioxin’s other face. Science News 141: 24.
Key Terms: cancer, other toxic effects, chronic toxicity, dioxins, news report
See page 110.
Schrenk, D., H.-P. Lipp, T. Wiesmuller, H. Hagenmaier and K.W. Bock (1991) Assessment
of biological activities of mixtures of polychlorinated dibenzo-p-dioxins: comparison
between defined mixtures and their constituents. Arch. Toxicol. 65(2): 114-118.
Key Terms: enzyme induction or inhibition, experimental, dioxins, in vitro, journal
article
See page 103.
Schrenk, D., H.-P. Lipp, H. Brunner, T. Wiesmuller, H. Hagenmaier and K.W. Bock (1991)
Induction of hepatic P450-dependent monooxygenase in feral mice from a
PCDD/PCDF-contaminated area. Chemosphere 22(11): 1011-1018.
Key Terms: hepatotoxicity, enzyme induction or inhibition, environmental, dioxins,
mouse, journal article
See page 104.
Schroder, C., E. Kruger and J. Abel (1991) Acute poisoning caused by the herbicide
dichlorprop (preparation SYS 67 PROP). Kinderarztl Prax. 59(3): 81-84.
Key Terms: hematologic effects, other toxic effects, environmental exposure,
2,4-D, human, journal article
This case report discussed the acute poisoning of a 5-year-old boy by dichlorprop.
Toxic effects were observed in almost all organs, but the predominant effect was
hemolytic anemia. Pathology was reversed by symptomatic treatment.
53

717
V -1^

Schulz-Schalge, T., E. Koch, G. Golor, T. Wiesmuller, H. Hagenmaier and D. Neubert
(1991) Comparison of the induction of cytochrome P450 and ethoxyresorufin
O-deethylase by a single subcutaneous administration of T C D D in livermicrosomes
of marmoset monkeys (Callithrix jacchus) and rats. Chemosphere 23(11-12):
1933-1939.
Key Terms: enzyme induction or inhibition, injection, dioxins, monkey, rat, journal
article
Schulz-Schalge, T., E. Koch, K.-H. Schwind, O. Hutzinger and D. Neubert (1991) Inductive
potency of T C D D and three 2,3,7,8-mixed-halogenated dioxins in liver microsomes
of male rats, enzyme kinetic considerations. Chemosphere 23(11-12): 1925-1931.
Key Terms: enzyme induction or inhibition, acute toxicity, injection, dioxins, rat,
journal article
See page 103.
Seegal, R.F., B. Bush and W. Shain (1991) Neurotoxicology of ortho-substituted poly­
chlorinated biphenyls. Chemosphere 23(11-12): 1941-1949.
Key Terms: neurobehavioral effects, mechanism of action, experimental, PCBs,
dioxins, in vitro, journal article
Shaub, W.M., Editor (1991) Dioxins. Chemistry and Health Effects. Sci. Total Environ.
104(1-2): 1-166.
Key Terms:

toxicity, dioxins, book

Shaw, P., A. Reiss, M. Adesnik, D. Nebert, J. Schembri and A. Jaiswal (1991) The human
dioxin-inducible NAD(P)H: quinone oxidoreductase cDNA-encoded protein
expressed in COS-1 cells is identical to diaphorase 4. Eur. J. Biochem. 195(1):
171-176.
Key Terms: mechanism of action, enzyme induction or inhibition, in vitro, journal
article
See page 109.
Shen, E.S., S.l. Gutman and J.R. Olson (1991) Comparison of 2,3,7,8-tetrachlorodibenzop-dioxin-mediated hepatotoxicity in C57BL/6J and DBA/2J mice. J. Toxicol.
Environ. Health 32(4): 367-381.

54

718
D-Wt

Key Terms: hepatotoxicity, acute toxicity, mechanism of action, injection, dioxins,
mouse, journal article
See page 68.
Silbergeld, E.K. (1991) Carcinogenicity of dioxins [Editorial]. JNCI 83(17): 1198-1199.
Key Terms: cancer, chronic toxicity, dioxins, commentary or opinion
See page 32.
Smith, E.A. and F.W. Oehme (1991) A review of selected herbicides and their toxicities.
Vet. Hum. Toxicol. 33(6): 596-608.
Key Terms: acute toxicity, unspecified route of exposure, arsenic, 2,4-D, 2,4,5-T,
human, review
Smith, A.H., D.G. Patterson, M.L. Warner, R. MacKenzie and L.L. Needham (1992) Serum
2.3.7.8- tetrachlorodibenzo-p-dioxin levels of N e w Zealand pesticide applicators and
their implication for cancer hypotheses. J. Natl. Cancer Inst. 84(2): 104-108.
Key Terms: cancer, tissue residues, occupational exposure, 2,4,5-T, dioxins,
human, journal article
Smolowitz, R., M. Hahn and J. Stegeman (1991) Immunohistochemical localization of
cytochrome P-450IA1 induced by 3,3’,4,4’-tetrachlorobiphenyl and by 2,3,7,8-tetrachlorodibenzofuran in liver and extrahepatic tissues of the teleost Stenotomus
chrysops (Scup). Drug Metab. Dispos. 19(1): 113-123.
Key Terms: mechanism of action, injection, furans, fish, journal article
See page 106.
Spitsbergen, J.M., M.K. Walker, J.R. Olson and R.E. Peterson (1991) Pathological
alterations in early life stages of lake trout, Salvelinus namaycush, exposed to
2.3.7.8- tetrachlorodibenzo-para-dioxin as fertilized-eggs. Aquatic Toxicology 19(1)
41-71.
Key Terms: acute toxicity, lethality, experimental exposure, dioxins, fish, journal
article
Stahl, B.U., R.H. Alper and K. Rozman (1991) Depletion of brain serotonin does not alter
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced starvation syndrome inthe rat.
Toxicol. Lett. 59(1-3): 65-72.
55

71 9

Key Terms: neurobehavioral effects, acute toxicity, dioxins, rat, journal article
See page 63.
Stanley, J.S., P.H. Cramer, K.R. Thornburg, J.C. Remmers, J.J. Breen and S. J. (1991)
Mass spectral confirmation of chlorinated and brominated diphenylethers in human
adipose tissues. Chemosphere 23(8-10): 1185-1195.
Key Terms: tissue residues, method, dioxins, human, journal article
Stegeman, J., R. Smolowitz and M. Hahn (1991) Immunohistochemical localization of
environmentally induced cytochrome P450IA1 in multiple organs of the marine
teleost Stenotomus chrysops (Scup). Toxicol. Appl. Pharmacol. 110(3): 486-504.
Key Terms: miscellaneous study, method, environmental exposure, furans, fish,
journal article
See page 106.
Stohs, S., N. Alsharif, M. Shara, Z. al-Bayati and Z. Wahba (1991) Evidence for the
induction of an oxidative stress in rat hepatic mitochondria by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Adv. Exp. Med. Biol. 283: 827-831.
Key Terms: other toxic effects, mechanism of action, dioxins, rat, journal article
Strubel, V., H.J. Knackmuss and K.H. Engesser (1991) Metabolism of dibenzofuran and
dibenzodioxin as model for2,3,7,8-tetrachlorodibenzodioxin degradation. Biochem.
Eng. Proc. Int. Symp.(2): 421-424.
Key Terms: dioxins, furans, model, journal article
Sullivan, M.J., S.R. Custance and C.J. Miller (1991) Infant exposure to dioxin in mother’s
milk resulting from maternal ingestion of contaminated fish. Chemosphere
23(8-10): 1387-1396.
Key Terms: pharmacokinetics, oral, dioxins, human, model, journal article
See page 87.
Sutter, T.R., K. Guzman, K.M. Dold and W.F. Greenlee (1991) Targets for dioxin: genes
for plasminogen activator inhibitor-2 and interleukin-1/3. Science 254(5030):
415-418.
Key Terms: other toxic effects, mechanism of action, experimental, dioxins, in
vitro, journal article
56

720

See pages 108 and 109.
Svensson, B.G., A. Nilsson, M. Hansson, C. Rappe, B. Akesson and S. Skerfving (1991)
Exposure to dioxins and dibenzofurans through the consumption of fish. N. Engl.
J. Med. 324(1): 8-12.
Key Terms: tissue residues, oral, dioxins, human, journal article
See page 84.
Swain, W.R. (1991) Effects of organochlorine chemicals on the reproductive outcome of
humans who consumed contaminated Great-Lakes fish - an epidemiologic
consideration. J. Toxicol. Environ. Health 33(4): 587-639.
Key Terms: reproductive toxicity, oral, PCB, human, journal article
Swanson, H. and G. Perdew (1991) Detection of the Ah receptor in rainbow trout: use of
2-azido-3-[125l]iodo-7,8-dibromodibenzo-p-dioxin in cell culture. Toxicol. Lett.
58(1): 85-95.
Key Terms: mechanism of action, experimental exposure, dioxins, in vitro, journal
article
See page 96.
Takayama, K., H. Miyata, O. Aozasa, M. Miumra and T. Kashimoto (1991) Dietary-intake
of dioxin-related compounds through food in Japan. Journal of the Food Hygienic
Society of Japan 32(6): 525-532.
Key Terms: oral, dioxins, human, journal article
Takayama, K., H. Miyata, M. Mimura, S. Ohta and T. Kashimoto (1991) Evaluation of
biological effects of polychlorinated compounds found in contaminated cooking oil
responsible for the disease Yusho. Chemosphere 22(5-6): 537-546.
Key Terms: enzyme induction or inhibition, oral, dioxins, furans, human, journal
article
Takemori, H., K. Koga and Y. Masuda (1991) Effects of 2,3,7,8-tetrachlorodibenzo-pdioxin and related compounds on "the somatic recombination and repair systems
of Drosophila-melanogaster. Mutat. Res. 252(1): 111-112.
Key Terms:
genetic toxicity,
melanogaster, journal article

experimental exposure,

dioxins,

Drosophila

57

721
¡>750

Takimoto, K., R. Lindahl and H. Pitot (1991) Superinduction of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase by the inhibition
of protein synthesis. Biochem. Biophys. Res. Commun. 180(2): 953-959.
Key Terms: mechanism of action, enzyme induction or inhibition, experimental
exposure, dioxins, in vitro, journal article
See page 106.
Tarone, R.E., H.M. Hayes, R.N. Hoover, J.F. Rosenthal, L.M. Brown, L.M. Pottern, N.
Javadpour, K.J. O ’Connell and R.E. Stutzman (1991) Service in Vietnam and risk
of testicular cancer (brief communication). JNCI 83(20): 1497-1499.
Key Terms: cancer, chronic toxicity, military exposure (possible), human, journal
article
See page 123.
Teeter, L.D., D.D. Petersen, D.W. Nebert and M.T. Kuo (1991) Murine mdr-1, mdr-2, and
mdr-3 gene expression: no coinduction with the Cypla-1 and Nmo-1 genes in liver
by 2,3,7,8-tetrachlorodibenzo-p-dioxin. D N A Cell Biol. 10(6): 433-441.
Key Terms: other toxic effects, mechanism of action, dioxins, rat, mouse, journal
article
See page 109.
Theelen, R., A. Knaap and B. Sangster (1991) Dioxin; standards recommended by the
World Health Organization. Ned. Tijdschr. Geneeskd. 135(20): 875-877.
Key Terms: dioxins, journal article
This article discusses variations in the standards based on the no-effect-observed
level established by different countries. Text is in Dutch.
Theobald, H.M., G.B. Ingall, T.A. Mably and R.E. Peterson (1991) Response of the antral
mucosa of the rat stomach to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl.
Pharmacol. 108(1): 167-179.
Key Terms: other toxic effects, acute toxicity, miscellaneous study, dioxins, rat,
journal article
See pages 70 and 71.

58

722

Thomas, T.L., H.K. Kang and N.A. Dalager (1991) Mortality among women Vietnam
veterans, 1973-1987. Am. J. Epidemiol. 134(9): 973-980.
Key Terms: cancer, cardiovascular toxicity, chronic toxicity, military exposure
(possible), human, journal article
See pages 13 and 21.
Thompson, T., T. Kolic and K. MacPherson (1991) Dual-column high-performance liquid
chromatographic cleanup procedure for the determination of polychlorinated
dibenzo-p-dioxins and dibenzofurans in fish tissue. J. Chromatogr. 543(1): 49-58.
Key Terms: analytical method, dioxins, journal article
Thomsen, J., L. Nissen, S. Stacey, R. Hines and H. Autrup (1991) Differences in
2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible CYPIA1 expression in human breast
carcinoma cell lines involve altered trans-acting factors. Eur. J. Biochem. 197(3):
577-582.
Key Terms: mechanism of action, enzyme induction or inhibition, experimental
exposure, dioxin, in vitro, journal article
See page 105.
Tillitt, D., G. Ankley, D. Verbrugge, J. Giesy, J. Ludwig and T. Kubiak (1991) H4IIE rat
hepatoma cell bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in
colonial fish-eating waterbird eggs from the Great Lakes. Arch. Environ. Contam.
Toxicol. 21(1): 91-101.
Key Terms: enzyme induction or inhibition, environmental exposure, dioxins, bird,
journal article
Tillitt, D.E., J.P. Giesy and G.T. Ankley (1991) Characterization of the H4IIE rat
hepatoma-cell bioassay as a tool for assessing toxic potency of planar halogenated
hydrocarbons in environmental-samples. Environmental Science and Technology
25(1): 87-92.
Key Terms: enzyme induction or inhibition, experimental exposure, dioxins, furans,
in vitro, journal article
bioassay method
Tollefson, L. (1991) Use of epidemiology data to assess the cancer risk of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Regul. Toxicol. Pharmacol. 13(2): 150-169.
59

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Key Terms: cancer, chronic toxicity, dioxins, human, review
See page 29.
Tomar, R.S. and N.l. Kerkvliet (1991) Reduced T-helper cell function in mice exposed to
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Lett. 57(1): 55-64.
Key Terms: immunotoxicity, acute toxicity, experimental, dioxins, mouse, in vitro,
journal article
See page 52.
Trakayama, K., H. Miyata, M. Mimura, S. Ohta and T. Kashimoto (1991) Evaluation of
biological effects polychlorinated compounds found in contaminated cooking oil
responsible for the disease Yusho. Chemosphere 22(5-6): 537-546.
Key Terms: acute toxicity, chronic toxicity, oral, dioxins, furans, PCBs, human,
journal article
Travis, C.C. and H.A. Hattemer-Frey (1991) Human exposure to dioxin.
Environ. 104(1-2): 97-127.

Sci. Total

Key Terms: miscellaneous study, environmental exposure, occupational exposure,
dioxins, human, review
The authors evaluated critical issues regarding the extent of background
contamination by TCDD, the potential for human exposure via the food chain, the
magnitude of various emissions of T C D D in the U.S., and the relationship of these
factors to setting appropriate standards.
Triebig, G. (1991) Is dioxin carcinogenic? Lancet 338(8752): 1592.
Key Terms: cancer, chronic toxicity, occupational exposure, dioxins, human,
commentary or opinion
See page 27.
Tsukazaki, N., S. Nonaka, T. Ohgami, H. Irifune, K. Tanaka, M. Yano and H. Yoshida
(1991) The synergistic effect of chlorinated chemicals (trichlorosalicylanilid,
4-chloro-m-cresol, trichlorophenoxyacetic acid, trichloroethanol, trichloromethiazide,
trichlorofon and trichloroacetaldehyde) and low concentrations of griseofulvin on
porphyrin metabolism. Fukuoka Igaku Zasshi 82(5): 215-220.

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Key Terms: hepatotoxicity, mechanism of action, oral, 2,4,5-T, phenoxyacetic acid,
mouse, journal article
Tuomisto, J. and R. Pohjanvirta (1991) Do new hypotheses on the mechanism of action
of dioxins help in risk evaluation? Sci. Total Environ. 106(1-2): 21-31.
Key Terms: lethality, neurobehavioral effects, other toxic effects, dioxins, rat,
journal article
See pages 62 and 95.
Tuomisto, J.T., M. Unkila, R. Pohjanvirta, M. Koulu and L. Tuomisto (1991) Effect of a
single dose of T C D D on the level of histamine in discrete nuclei in rat brain.
Agents Actions 33(1-2): 154-156.
Key Terms: neurobehavioral effects, acute toxicity, injection, dioxins, rat, journal
article
See pages 63 and 64.

(

Van den Berg, K.J., J.A.G.M. Van Raaij, P.C. Bragt and W.R.F. Notten (1991) Interactions
of halogenated industrial chemicals with transthyretin and effects on thyroid
hormone levels in vivo. Arch. Toxicol. 65(1): 15-19.
Key Terms: thyroid effects, chronic toxicity, occupational exposure, phenoxy
herbicides, human, journal article

Van der Heijden, C. (1991) H o w toxic are dioxins for man?
135(40): 1860-1865.
Key Terms:
article

Ned. Tijdschr. Geneeskd

chronic toxicity, other route of exposure, dioxins, human, journal

This article deals with the way in which dioxins become contaminants in chemicals,
incidents of environmental contamination, and the toxic sequelae and mechanism
of action of dioxin. Text is in Dutch.
Van Loveren, H.K., H.-J. Schuurman, J. Kampinga and J.G. Vos (1991) Reversibility of
thymic atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
bis(tri-n-butyltin)oxide (TBTO). Int. J. Immunopharmac. 13(4): 369-377.
Key Terms: immunotoxicity, acute toxicity, oral, dioxins, rat, journal article

See pages 50 and 51.
Vineis, P., F. Faggiano, M. Tedeschi and G. Ciccone (1991) Incidence rates of
lymphomas and soft-tissue sarcomas and environmental measurements of
phenoxy herbicides. J. Natl. Cancer Inst. 83(5): 362-363.
Key Terms: cancer, chronic toxicity, environmental exposure, phenoxy herbicide
formulations, 2,4-D, 2,4,5-T, human, journal article
See pages 27 and 28.
Waern, F., S. Flodstrom, L. Busk, T. Kronevi, I. Nordgren and U.G. Ahlborg (1991)
Relative liver tumor promoting activity and toxicity of some polychlorinated
dibenzo-p-dioxin- and dibenzofuran-congeners in female Sprague-Dawley rats.
Pharmacol. Toxicol. 69(6): 450-458.
Key Terms: cancer, acute toxicity, injection, furans, dioxins, rat, journal article
See page 32.
Waern, F., E. Manzoor, U.G. Ahlborg and H. Hakansson (1991) Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the lactating rat on maternal and neonatal
vitamin A status and hepatic enzyme induction: a dose-response study.
Chemosphere 23(11-12): 1951-1956.
Key Terms: other toxic effects, enzyme induction or inhibition, oral, dioxins, rat,
journal article
See page 113.
Waithe, W., M. Michaud, P. Harper, A. Okey and A. Anderson (1991) The Ah receptor,
cytochrome P450IA1 m R N A induction, and aryl hydrocarbon hydroxylase in a
human lymphoblastoid cell line. Biochem. Pharmacol. 41(1): 85-92.
Key Terms: immunotoxicity, mechanism of action, enzyme induction or inhibition,
dioxins, in vitro, journal article
See pages 48 and 97.
Wang, W., T.R. Narasimhan, V. Morrison and S. Safe (1991) In situ and in vitro
photoaffinity labeling of the nuclear aryl hydrocarbon receptor from transformed
rodent and human cell lines. Arch. Biochem. Biophys. 287(1): 186-194.
Key Terms: mechanism of action, experimental, dioxins, in vitro, journal article
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See page 97.
Watanabe, K.K., H.K. Kang and T.L. Thomas (1991) Mortality among Vietnam veterans:
with methodological considerations. J. Occup. Med. 33(7): 780-785.
Key Terms: cancer, other toxic effects, military exposure, phenoxy herbicide
formulations, human, journal article
See pages 13 and 21.
Weber, L.W.D., M. Lebofsky, H. Greim and K. Rozman (1991) Key enzymes of gluconeogenesis are dose-dependently reduced in 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD)- treated rats. Arch. Toxicol. 65(2): 119-123.
Key Terms: enzyme induction or inhibition, injection, dioxins, rat, journal article
See page 114.
Weber, L.W.D., M. Lebofsky, B.U. Stahl, J.R. Gorski, G. Muzi and K. Rozman (1991)
Reduced activities of key enzymes of gluconeogenesis as possible cause of acute
toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats. Toxicology 66(2):
133-144.
Key Terms: lethality, neurobehavioral effects, enzyme induction or inhibition,
injection, dioxins, rat, journal article
Weber, L, A. Zesch and K. Rozman (1991) Penetration, distribution and kinetics of
2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro. Arch. Toxicol. 65(5):
421-428.
Key Terms: pharmacokinetics, dermal, dioxins, human, journal article
Weber, L.W.D., B.U. Stahl, M. Lebofsky, R.H. Alper, L. Kerecsen and K. Rozman (1991)
Inhibition of phosphoenolpyruvate carboxykinase activity appears to be the key
biochemical lesion in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in
rats. Chemosphere 23(11-12): 1957-1962.
Key Terms: neurobehavioral effects, enzyme induction or inhibition, acute toxicity,
injection, dioxins, rat, journal article
See page 114.

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Webster, T. and P. Connett (1991) Estimating bioconcentration factors and half-lives in
humans using physiologically based pharmacokinetic modelling: 2,3,7,8-TCDD.
Chemosphere 23(11-12): 1763-1768.
Key Terms:
model

pharmacokinetic, unspecified route of exposure, dioxins, human,

See page 80.
Weinstein, I.B. (1991) Mitogenesis is only one factor in carcinogenesis.
251(4992): 387-388.

Science

Key Terms: cancer, dioxins, human, commentary or opinion
This article discusses various aspects of carcinogenesis, in addition to
mitogenesis, which should be considered when assessing the risk associated with
a potential carcinogen.
White, T.B., D.K. Hammond, H. Vasquez and H.W. Strobel (1991) Expression of two
cytochromes P450 involved in carcinogen activation in a human colon cell line.
Mol. Cell. Biochem. 102(1): 61-69.
Key Terms: cancer, enzyme induction or inhibition, in vitro, journal article
See page 106.
Wiebel, F.J., U. Klose and F. Kiefer (1991) Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
in vitro: H4IIEC3-derived 5L hepatoma cells as a model system. Toxicol. Lett.
55(2): 161-169.
Key Terms: other toxic effects, mechanism of action, experimental exposure,
dioxins, in vitro, model, journal article
See page 68.
Williams, F.L.R. (1991) Is dioxin carcinogenic? Lancet 338(8752): 1592.
Key Terms: immunotoxicity, cancer, mechanism of action, unspecified route of
exposure, dioxins, commentary or opinion
Wren, C. (1991) Cause-effect linkages between chemicals and populations of mink
(Mustela vison) and otter (Lutra canadensis) in the Great Lakes basin. J. Toxicol.
Environ. Health 33(4): 549-585.

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Key Terms: reproductive toxicity, chronic toxicity, environmental exposure, dioxins,
mink, otter, journal article
See page 43.
Yasuda, M., T.J. Sato and H. Sumida (1991) Exencephalic mouse fetuses are resistant
to cleft palate induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Teratology 43(5): 445.
Key Terms: neurobehavioral effects, other toxic effects, injection, dioxins, mouse,
abstract
See page 43.
Ylitalo, P., H. Ylihakola, H.A. Elo, H.-M. Koponen, E. Seppalo and H. Vapaatalo (1991)
Inhibition of platelet aggregation and thromboxane A2 Production by chlorophenoxy acid herbicides. Arch. Toxicol. Suppl. 14: 174-178.
Key Terms: hematologic effects, acute toxicity, experimental, 2,4-D, human, journal
article
See page 69.
Yu, M., C. Hsu, B. Gladen and W. Rogan (1991) In utero PCB/PCDF exposure: relation
of developmental delay to dysmorphology and dose. Neurotoxicol. Teratol. 13(2):
195-202.
Key Terms: neurobehavioral effects, chronic toxicity, other route of exposure,
furans, human, journal article
See pages 61, 83 and 86.
Zacharewski, T., M. Harris and S. Safe (1991) Evidence for the mechanism of action of
the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decrease of nuclear estrogen
receptor levels in wild-type and mutant mouse Hepa 1c1c7 cells. Biochem.
Pharmacol. 41(12): 1931-1939.
Key Terms: alteration in sex hormones, mechanism of action, experimental
exposure, dioxins, in vitro, journal article
See page 110.

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Zhamsaranova, S.D., R.A. Ayushinova and T.N. Baglaev (1991) Peculiarities of pesticide
actions on the native cytotoxicity of mouse spleen cells in dependence of animal
age. Gig. Sanit. 8: 59-60.
Key Terms: immunotoxicity, phenoxy herbicides, mouse, journal article

*U.S. GOVERNMENT PRINTINGOFFICE: 19 92 -3 13 -11 V76 102

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