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MONSANTO
-IPANY
St. Louis, Missouri
DEV. DEPT. CALL REPORT NO.

103-69

Pood and Drue Administration
Washington, D. C.
Date of Call:

November 25, 1969

FORFDA
to. F.'Randolph
A. Holz
Krishna Misera
Higenbothem

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E. P. Eenzing
D. R. Dill
A. J. Lauck
J. P. Petrovich
J. G. Bergomi
A. H. Tiff t
K. A. Pollart
M. V. Merchant
R. E. Keller
W. H. Hunt
George Ingle - Washington
FDA

Resins, Wet Strength

FOR KOMSAirrO
P. Bonzlng
V. H. Hunt
R. E. Keller
I). L. Taylor
PURPOSE 07 CALL:

To review new RPC-1101 water extraction data
prior to submitting a new petition.

ACTION:

1)

Complete the RPC-1101 extraction study using the
other food simulating solvents,

2)

Characterize the chemistry of the water extraction
residue,

3)

Review completed data with'FDA.

4)

Initiate extraction studies vrith high pressure
EVC1 latices and review data with FDA.

SUMMARY:

The new data, shewing 20 to 90 times less RPC-1101
extracted by v;ater than reported in our now
withdrawn petition, puts us near the "nnn--evtrrotr.LJ c
.range.
FDA advised completion of the extraction
study and chemical characterization of the v:ator
extract prior to our considering any 90-day
feeding studies. V.'e should then seek an advisory
opinion from them. We learned two important points
regarding extraction data on unseated* paper:
1)

The FDA now defines the sample area extracted as cr.ly
one side of th? paper specimen even though it is
thoroughly sosked -- this doubles our previously
reported extras tabj Hty figures;

?)

The FDA no longer demands "extraction to c-quilibrj urn."
data on unseated paper -- 24 hour, 120° F. ‘data is
sufficient.
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FDAV Dev®Dept. Cal.
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Report No. 103-69

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3)

PB-702 is FDA approved for dry food contact under
regulation 121.257.1.

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Guidance on which latex .compositions to select for
extraction studies has been obtained.
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5)

-

Extraction studies made on coatings on inert substrates
will be acceptable.

DETAILS:
A week before the meeting we had sent Randolph the new data showing
1.1 x 10~Z*' mg/in of RPC-1101 extracted by water from paperboard
treated at 10 lb./ton. and 4.3 x 10-tJ mg/in from a 20 lb./ton treated
board.
Reduction frora the 90 x 10"^ mg/in reported in the original
petition resulted froa several refinements in our papermaking and
extraction techniques
as detailed in the attached table.
This table
was not shown to the FDA because they did not question the validity
of the new data.
• Randolph began his commentary by pointing out that our extraction
; data in terms of mg/in2 were low by a factor of tv/o.
We had been
counting both sides of the paper sample as extracted area because
a) the samples are entirely soaked through by the solvent; and
• b;
the FDA at one tirce recommended counting both sides.
Their
current view is that food contacts only one side of a paperboard
package or container but could extract material out of the entire
thickness of the paperboard.
Therefore where we had counted 100 in2
from eight 2£ inch squares, the FDA now counts only 50 in2.
This,
of course, doubles our reported weight per unit area extraction data.
Randolph mentioned that v/e may be penalizing ourselves by using the
“sandwich" extraction technique rather than the ASTM flat cell technique
where the sample is backed by a metal plate.
The sandwich method
as v/e have been running it (scrcen/paper/screon/paper, etc.) allcvrs
extractives to diffuse out of both surfaces of the paper, whereas
this is less likely in the cell method.
A post-meeting review of
the data in our petition shows that this may be so.
The residue
extracted (one-side basis) by the two methods from a waterleaf
board by 12(5^”F. water in 24" hours v;as:
a)

Cell method

(pg. B-40)

=

0.14

mg/in2

b)

Sandwich method

(pg. B-12)

=

0.32

mg/in2
%

We'll rccheck this point on paperboard made by the improved proce­
dures.
This tine we vrlll follovr exactly the car.dvrich method des­
cribed in Section 121.2525 of the Federal Regulations v.h ich .involves
back-to-back paper samples:screen/paper/paper/screen/paper/paper,
etc.
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0008908

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FDA - Dev. Dept. Call Report No. 108-69
Page 3
FDA says that our new extraction data puts RPC-1101 very near to the
"non-extractable" classification, with water as solvent.
Randolph
V
offered! that we definitely .should not begin expensive 90-day feeding
' studies before first completing the extraction work and seeking an
advisory opinion from FDA.
After scaling up our extraction results
by a factor of two, as discussed'above, FDA calculates that an
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aqueous food could absorb 0.02 ppm of RPC-1101 from paperboard
treated at 10 lb./ton and 0.09 ppm from paperboard treated at
20 lb./ton.
To place these figures in perspective, consider the
following::
a)

’■ The11 FDA Guidelines" of 19&6 say that 0.01 ppm
j] of a substance added to food by migration ~is not
‘ considered a^food additive.

b)

The FDA is currently considering raising this to
0.05 ppm as a result of discussions with industry at a
T§58"—FD.C sponsored conference.

c)

According to Randolph, industry representatives are
suggesting 0.5 ppm as being more realistic.

d)

Dr. J. P. Frawley ‘(chief toxicologist, Hercules)
proposed at the 1968 conference that food packaging
components contributing less than 0.1 ppm to the total
diet of man be considered as nonmigratory.

Thus our extraction data is near to demonstrating "non-extractability"
of RPC-1101, depending on how that term is defined.
For this reason
the FDA wants to see new extraction data with the other food simulating
solvents and a chemical characterization of the water extract before
offering an advisory opinion on whether we can justifiably petition
for RPC-1101 on the basis on non-extractability,
Randolph said that the new extractions need be run only for 2H
hours at 120° F in the case of uncoated paper.
This represents
a considerable easing on the "extraction to equilibrium" requirement
stated in the Guidelines.
The principal extraction data in our
petition was at 120 hours. Another point made by Randolph and Holtz
was that 8£ ethanol would be a more realistic solvent to use than the
50£ ethanol in the Guidelines.
The other solvents will be
acetic
acid and n-heptane.

3

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:Dept* Call Report No. 108-69
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To satisfy their request for more thorough chemical characterization
of the v/ater extract we will obtain 0.2 g of residue from untreated
and 1# RPC-rllOl treated paperboard by running 24-replicate extractions
of each.
This will provide enough material to determine C, H, N, Cl,
infra-red-spectra, average molecular weight, and vapor phase chromato­
graph.
If the latter shows unique peaks in the extract from the
treated board we may use the rapid scan mass spectrum technique to
further characterize these peaks.
Kith regard to the September 23 FDA request for acute oral toxicity
data on selected components of the amine raw material and for sub­
acute (90-day) feeding studies on the RPC-1101, Randolph said that
these requests no longer stand because they were based on the data
available at that time.
The new data will be judged on its own
merits.
Kisera said that if the new data still showed the need for
subacute feeding studies, the paper extract it'self is what should be
fed, not the resin solution.
We agreed that this was proper
however 1 pointed out that obtaining the large amounts of residue
needed would be a nearly impossible task.
Misera suggested that vie
could identify the residue chemically and then synthesize it.
I
feel that the possibility of doing this is quite remote.
Hopefully
the new.data will render this problem irrelevant.
PIGMENf BINDER
PB—702 is covei'ed for dry food contact under an existing regulation
121.2571 and no further work on our part is needed for such applica­
tions •
We explained that we would be interested in obtaining clearance
for latexes with the following composition ranges:
60 - 95#
vinylchloride, 5 - 40# ethylene, and .0 - 5£ acrylamide with the
acrylamide either intact or partially or completely hydrolyzed.
We asked for guidance as to vihat compositions to use for the
extraction studies.
FDA personnel felt they had enough experience
with ethylene and vinylchloride polymers to conclude that chsngj ng
ratios of these monomers in the proposed range v:as not critical to
toxicity.
Of greater concern vrould be the acrylamide problem and
what influence the hydrolysis step might have on amount and nature
of extractants.
The extraction study should be done on the polymer
containing the highest level of acrylamide that v/e want to get
approved and for hydrolyzed and unhydrolyzed polymer.
Ethylene end
vinylchloride contents at the level we are presently using will
be satisfactory.

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0008910

FDA - Dev. Dept. Call Report No. 108-69
Page 5
Polyacrylamide in the aaueous phase will be covered by the existing
regulation‘in 121.2512 (no molecular weight limitation<^0.acryl­
amide monomer)..
We indicated that v/e would like to obtain approval for pigment binder,
prime coating and barrier coating applications.
Randolph confirmed
that for the barrier application extraction requirements would be
more stringent and that if v/e could pass these, they could assume that
i/e would be OK for less severe applications.
II
FDA agreed: that if vre v/ould prepare our coatings on a non-pf-per
substrate/ e.g., glass or metal under the sane conditions ns paper
coatings ire could use them for extraction studies.
Holtz hacl reviewed the.1967 Monsanto internal extraction report by
R. E. Keller. He suggested that our petition include validation of
our analytical methods at the best achievable sensitivity levels.
It should also include a more complete description of our process
including the hydrolysis step.
There was considerable discussion
as to the best method to characterize extractable low molecular
weight material.
It was agreed that this v/ould depend on the
nature of the material.
In some cases N analys5.fi.-_ v/ould be best
in others Cl analysis and in still others a combination.
The
extraction data should be represented in tables showing the amounts
Of extract in mg/in *
Sample calculations should be shown.
Holtz suggested that after we reorganize our data in this
vre contact them again, for further comment.

/ds

/

E.

P. Benaring

D.

L.

manner

Taylor

Attachment

RSV

0008911

RPC-1101
PDA WATER

EXTRACTIONS

NITROGEN

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DATA

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Procedure3

1968 Data in
Petition 9B2371

Oct.,

Deionised
Wool Pelt
20
Deion., Diet.
120
1 or 2
Combustion

Deionized
Wool Pelt
10
Delon., Dist.
24
2
KJeldahl

Nitroren, /tp oer Extract
✓
Resin Added
Resin Added
Resin Added
Resin Added

Nov.f 1969
s

•

^

Papermaking Water
Pressing
Curing, min. at 120° C.
Extraction Water
Hours extracted at 120° F.
Replicate Extractions
Nitrogen Analysis

0;»
y/j
i'jj
2}j

1969

•
.

■

Net
206
278 _

-

(72)

Distilled
Blotters
10
' Redi3t.,over aci<
24
6
KJeldahl
Net-

99
97
104

-

•*

;-2)
: 5)

Net
15-2
16.1
18.6

,

-

Background from Water only
Background from Paper only
(by dlff.)

_

73

-

26

6.7

90# Confidence Limits

-

+30

+ 2.0

Conversion Factors

ppm in food

■

( 0.9)
| 3.4)

-

1
11
1
1

8.5

1

of N per extract)/80

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