REC'D

LAW OFFICES

Kelleb and Heckntajst
JOSEPH E KELLEB

NOV 13 1969

iriS N STREET. N. W

JEHOME H. HECKMAN
CHARLES M

MEEHAN

WILLIAM H

BORGHE&AN1, JR,

WASHINGTON, D-C. £0036

TELEPHONE
20S

S06-S200

CABLE ADDRESS"KELMAN"

ROBERT R TIERNAN
WAYNE V BLACK
THOMAS J, HUGHES, JR
DAVID T, HILL
MARTIN W BERCOVICI

November 10,

1969

Mr. Robert M. Miller
Hercules Inc.
Delaware Trust Building
Wilmington. Delaware
Dear Bob:
Following up on our letter of last
week, I thouaht you and all of the members of
our Food, Drug and Cosmetic Packacrina Materials
Committee night be interested m seeincr the
coverage given the release of the NAS-NRC ^Toxi­
cological Insignificance' report by Lou Roths­
child, editor of Food Chemical News.
Thus, as
we have done m the oast, 1 have obtained Lou’s
permission to reproduce paces 14 throuch 17 of
this week's issue, and an enciosirc reproductions
of the same herewith.
I realize, of course, that many of
our Committee members receive Lou's excellent
trade paper but I know that sore do not.
In
any case, sending you this material should helo
to provide everyone with a further insight into
what is happening as regards the anticipated
proposal to revise Section 121.2500 of the Food
Additive Regulations.
While writing to bring this informa­
tion to your attention, let me also take this
opportunity to mention that I have noticed a
new series of articles on food additives beina
run in The New York Times as an aftermath of
1Cyclamania."
The first m this series, written
by a Miss Sandra Blakeslee, began on the first
page of yesterday's 'Times. '
I was particularly
interested in Miss Blakeslee's observations
about 'accidental or unintentional food additives.”

ASI-pr

°000686

Mr. Robert Millei
November 10, 1969
Page Two

Interestincrly
tbe -.at.
'As many experts
t.
been done to limit aru

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of unintentional add^tn
.
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i t
has
been done to control . r
;
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i
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r-at.f^r
this really amounts t.
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or
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observation.
It may it.
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m u.<,
of our Committee member. .■ . r. .
l
\
tr.e
Times' series, as v.t- u,.^. t
TVe shall da
informing you about trm.s l ...
have any questions ±n tr.e m.
not hesitate to let a, k,.. t .

cc

SPI Food,

Drug ana

-t:.

Materials Conm i t 11e

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Page 14
November 10, 1969

FOOD CHEMICAL NEWS

FDA noted U conducted during 1969 three studies "to determine the residues
of sulfa drugs In animal tissues resulting from feeding studies conducted according
to authorized use of such drugs. " The agency explained that "the results of this
study will provide assurance for BVM In reaching a decision as to the safety of
the continued use of these three registered sulfa drugs. "
Under study were: (1) sulfaquinoxaline residues in chicken tissues; (2) sulfathiazole residues in swine tissues; and (3) sulfamerazine residues in calf tissues.
Among FDA's objectives for the fiscal year 1969-1974 period is the develop­
ment of "new and better methods for detecting residues of antibiotic and non­
antibiotic drugs in meat and milk for 40 drugs for which tolerance levels have
not yet been established, " the report disclosed.
During 1969, FDA said, 12 analytical methods were validated, 8 of them for
drug residues in animal tissues and 4 for drug residues in animal feeds,
"The results of the validation studies provide BVM with the necessary infor­
mation in order to determine the safety of proposed uses of such drugs,"
FDA said.
Methods were validated for residues in animal tissues of: (1) ronidazole;
(2) zearalanol; (3) rofenaid; (4) chlormadinone acetate; (5) maretin; (6) medrol;
(7) 1-tetramlsole; and (8) decoquinoate. Methods were validated for residues
in feeds of: (1) ronidazole; (2) chlormadinone acetate; (3) cyzine; and (4) dimetrldazole.
FDA also said that during fiscal year 1969 it conducted a study designed to develop
a method for determination of the gramicidin and tyrocidin components of tyrothricin in milk. The study showed that such a method is "feasible," the agency
said.

NA5-NRC TOXICOLOGICAL INSIGNIFICANCE REPORT FINALLY PUBLISHED
The National Academy of S ciences-National Research Council's Food Protection
Committee has officially released its task force report on "Guidelines for Esti­
mating Toxicologically Insignificant Levels of Chemicals in Food," as expected
(See FOOD CHEMICAL NEWS, Sept. 29, Page 2).
»
The report was held up five months after it was informally transmitted to the
Food and Drug Administration and was reported in FCOD CHEMICAL NEWS
(See FOOD CHEMICAL NEWS , Feb. 3, Page 29). Despite the long delay in
publication of the 8-page pamphlet, only editorial changes were made in the
report. There were no substantive changes.
Net effect of the NAS-NRC delay was to officially release the report at the wrong
time — politically, that is. With the current furor over food additives, and
especially those exempted from clearance procedures, the official exclusion of
indirect additives from clearance: procedures at this time could subject both
FDA and industry to widespread criticism.
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November 10, 1969

Page 15
FOOD CHEMICAL NEWS

The task force report, and any adoption of the principle of "toxicological insigni­
ficance" by FDA, is scientifically acceptable, at any time. Politically, however,
it might be unpalatable right now.
FDA May Propose Regulations for Indirect Additives
Despite the political realities, FDA may forge ahead with its proposal to exclude
toxicologically insignificant indirect additives from clearance procedures. The
agency earlier distributed a "discussion draft" of its proposal (See FOOD
CHEMICAL NEWS, May 12, Page 3), and has received industry comments on it
(See FOOD CHEMICAL NEWS, Sept. 15, Page 3). The agency was waiting only
for formal publication of the NAS-NRC task force report.
Armed with the report, the agency is now seeking final comments from FDA-ers
on the proposal - - in the light of the task force report and industry comments.
Next step will be publication of a proposal in the Federal Register - - unless
politically sensitive officials in FDA's parent Health, Education and Welfare
Department decide to sit tight until the current food additive hysteria blows over.
Of long-range significance is the NAS-NRC acceptance of the principle of "toxi­
cological insignificance," with FDA acceptance of the idea apparently imminent.
Whereas the primary practical impact may be in the field of indirect additives,
there eventually could be a similar change in attitude towards many direct food
additives used at low levels.
On the one hand, the current furor over the "generally recognized as safe" list
of additives excluded from clearance procedures may make it difficult to imple­
ment the "toxicological insignificance" principle at this time. On the other hand,
however, problems of the status of some substances now considered GRAS could
ultimately be resolved by a finding that they are "toxicologically insignificant."
Copies of "Guidelines for Estimating Toxicologically Insignificant Levels of
Chemicals in Food" are available from NAS-NRC.
The report excludes from consideration for toxicological insignificance certain
impurities or contaminants of natural origin such as aflatoxin, certain essential
nutrients and hormones, certain heavy metals and their compounds, and certain
organic compounds employed for their biological activity. The FDA discussion
paper had similar exclusions.
The task force recommended that a chemical be considered toxicologically
insignificant if it has been in commercial production for five years or more,
"without evidence of toxicological hazard incident to its production or use, "
if it is used at a level that provides no more than 0.1 p.p. m. to the diet.
Substances used above 0.1 p. p. m. of the diet but at 1.0 p.p.m. or less would be
considered toxicologically insignificant if they are of known structure and purity,
they are structurally simple, they are readily handled through known m tabollc
pathways, and they are members of closely related groups of substances that are
low in toxicity.
o

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Page 16
November 10, 196 9

FOOD CHEMICAL NEWS

The report also discussed new substances where studies establish safe levels
of at least two analogous substances, where the acute or subacute' toxicity of the
new substance and the analogous substances is of the same nature and degree.
If the safe levels for all structurally analogous substances are "essentially
Identical, " the report said, 1/10 of the estimated safe level can be considered
toxicologically insignificant. If there is appreciable difference among the safe
levels of analogous substances, the insignificant level would be 1/20 of the esti­
mated safe level.
In contrast to the NAS-NRC recommendation on toxicological insignificance
based upon the amount of a substance in the total diet, FDA in its draft paper
proposed that a substance be considered toxicologically insignificant if it can
be present at not more than 0.05 p. p.m. in contacted food.
Although industry would prefer the NAS-NRC approach, involving amounts in the
total diet, it is apparent that it would go along with FDA's approach basing
toxicological insignificance on amounts in contacted foods. However, industry
spokesmen have urged a maximum amount of 0. 5 p. p. m. rather than 0. 05 p. p. m. ,
and there have been indications that FDA may raise the 0.05 p. p.m. figure.
FDA is not expected to go along with an industry proposal, first propounded by
Hercules' Dr. John Frawley, exempting from clearance procedures substances
used at less than 0.2% by weight of packaging material.
Another recommendation in the NAS-NRC report dealt with pesticide degradation
products. The report said, "If the safe level of the pesticide is 1 p. p. m. or above,
it appears to be a safe working guideline that dietary levels of degradable products
below 0.1 p.p.m. are insignificant and undeserving of laboratory investigation."
A portion of the FDA draft proposal which is non-controversial would exclude from
clearance procedures broad categories of substances which are not technically
"food additives. " These substances, although many are now cleared under Food
Additive Orders, do not actually get into food.
The Task Force included in its report a mildly-worded criticism of the Delaney
Clause of the Food Additive Law. Noting that the Delaney Clause bans use of a
substance "if a level in the feeding test that permits survival of at least some
of the animals for the duration of the test is found to produce cancer, " the report
said:
"An observation of any such serious condition makes it
prudent to consider the nature of the dose-response
relationship and the physiologic, metabolic, or pathologic
processes involved to insure against the possibility that
the same effect might occur in man. "
In the wake of the banning of cyclamates as a food ingredient, there has been
increased discussion about the possible revocation of the Delaney Clause.
How ver, it is apparent that repeal or even amendment of the provision will

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Page 17

No/ember 10, 1969

FOOD CHEMICAL NEWS

be politically difficult, until some common, needed food ingredients are shown
to be carcinogenic in animal tests. (See story, Page 3).
Under discussion outside of government circles is the possibility of amending
the Delaney Clause to bar substances found to be carcinogenic to laboratory
animals only if the tests are deemed by FDA to be applicable to human exposure.

NCA OPPOSES ASCORBIC ACID QUANTITY LABELING FOR PEACHES
The National Canners Association, which proposed an amendment to the food
standard for Canned Peaches to permit use of ascorbic acid and erythorbic
acid, wrote to the Food and Drug Administration recently to oppose a suggestion
that labels declare the minimum amount of ascorbic acid.
In a comment on the proposed amendment, University of California's (Berkeley)
Dr. George M. Briggs urged that the minimum quantity be declared (See FOOD
CHEMICAL NEWS, Oct. 13, Page 23). NCA said in its letter that "the declaration
of ascorbic acid as vitamin C would only serve to mislead the consumer into
believing that canned peaches might be intended as a proper source of vitamin C
in her diet. "
The Association said that the addition of nutrients to standardized foods for
fortification "is subject to a number of criteria relating to the suitability of
adding the particular nutrient to the food under consideration. " NCA 6aid its
proposal "makes no showing that these criteria are met with respect to the addi­
tion of ascorbic acid to canned peaches and NCA has no intention of demonstrating,
or ability to demonstrate, that the proposed addition would meet these criteria."
The Association explained:
"While Professor Briggs is entirely correct that ascorbic
acid has recognized nutritive values as vitamin C in addi­
tion to its color fixative properties, his comment misses
the mark. As proposed by NCA the only purpose of the
additive ascorbic acid is as a color fixative. While this
additive may have the incidental effect of providing some
vitamin C fortification for this product, this is not its
intent. Hence, the quantity added will vary according
to the technical requirements of the preservation of color
and may well vary so much that no meaningful or consistent
statement could be made of its incidental attributes."

IMITATION MILK OPTIONAL INGREDIENT REVISION ASKED
Central Soya last week asked the Food and Drug Administration to revise the
provision of the proposed food standard for Imitation Milk which covers optional
ingredients.

ASI-PR 0000691

LAW OFFICES

Kelleb and Heckman
JOSEPH E KELLER

1713 77 STEEET, N. W

JEROME H, HECKMAN
CHARLES M MEEHAN

WASHINGTON, DC. S0036

TELEPHONE

WILLIAM R. BORGHESANI, JR
eobebt r

SOS

396-3700

CABLE ADDEESS "EELMAN"

tiebnan

WAYNE V. BLACK
THOMAS J
DAVID

HUGHES, JR.

L. HILL

MARTIN W, HERCOVICI

November 6,

1969

Mr. Robert M. Miller
Hercules Inc.
Delaware Trust Building
Wilmington, Delaware
Dear Bob:
As you are aware, for quite some
time now we have been awaiting word that
the Food Protection Committee - Food and
Nutrition Board of the National Academy of
Sciences - National Research Council has
finally published the Food Protection Com­
mittee's report entitled 'Guidelines for
Estimating Toxicologically Insignificant
Levels of Chemicals in Food.1
Indeed, for
the past several weeks, we have been in­
formed by the Food and Drug Administration
that it, too, was awaiting receipt of the
formal document and would be delayincr action
on the proposal to amend Section 121,2500
of the Food Additive Peculations until this
report was official.
We are pleased to inform you that
this report has now been printed, copies
have been sent to FDA, and we have been able
to obtain a very small supply.
At our re­
quest, Mr. Paul Johnson of the National
Academy of Sciences is preparing an addi­
tional 150 copies so that we can transmit
one to each member of the SPI Food, Drug
and Cosmetic Packaging Materials Committee.
The reproduction effort by Mr. Johnson is
underway so we should have the copies for
everyone within the next week or so.
In
the meantime, one copy is enclosed herewith
for your information.

ASI-PR 0000692

Mr. Robert Miller
November 6, 1969
Page Two

Now that the ''Guidelines” are in
every sense 'official," we believe that the
FDA Staff will complete its work on the draft
revisions of Section 121.2500 and publish
the same as a "Notice of Proposed Rule Makinq”
in a forthcoming issue of the Federal Register.
Exactly when this will happen is difficult
to predict,, especially in iight of the Agency's
Dresent preoccupation with the aftermath of
its Cyclamates announcement.
’Cyclamania" is
the order of the day at the Food and Drucr Admini­
stration now so the publication of any oroposal to relax food additive control to any
degree is apt to be delayed for a more favor­
able time.
From all we have been able to gather
at this point, we doubt that FDA will oublish
anything more favorable than the Proposal pre­
viously submitted to us and considered in such
depth by the Inter-Industry Committee. In
other words, we are not too optimistic about
the possibility of the Agency’s raising the
.05 ppm extraction criterion.
In any case, there
is little we can do other than to wait for the
publication of the anticipated "Notice of Pro­
posed Rule Making.”
In keeping with some of
our previous discussions, I continue to feel
that the next meeting of our Committee should
be delayed until the "Notice of Proposed Rule
Making” is published.
As soon as we have the additional
copies of the Food Protection Committee's re­
port, we shall be writing to you and the other
members of the Committee again to transmit the
same.
At that time, I will also try to aive
you any further word we may have received

ASI-PR 0000693

Mr. Robert Miller
November 6
1969
Page Three

concerning action on the over-all incidental
additives problem.
If you have any Questions
before then, please do not hesitate to let
me know.

cc

SPI Food, Drug and Cosmetic Packacrinq
Materials Committee

ASI-PR 0000694