[Federal Register Volume 65, Number 34 (Friday, February 18, 2000)]
[Rules and Regulations]
[Pages 8272-8275]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-3805]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 175 and 176

[Docket No. 92F-0111]


Indirect Food Additives: Adhesives and Components of Coatings and 
Paper and Paperboard Components

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the food 
additive regulations to provide for the safe use of 2-acrylamido-2-
methyl-propanesulfonic acid, homopolymer, sodium salt in food-contact 
adhesives and as a component of paper and paperboard intended to 
contact food. This action is in response to three petitions filed by 
The Lubrizol Corp.

DATES: This rule is effective February 18, 2000; Written objections and 
requests for a hearing by March 20, 2000.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Edward J. Machuga, Center for Food 
Safety and Applied Nutrition (HFS-215), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3085.

SUPPLEMENTARY INFORMATION:

I. Background

    In a notice published in the Federal Register of April 8, 1992 (57 
FR 11958), FDA announced that three food additive petitions (FAP 
9B4133, 9B4131, and 9B4132) had been filed on behalf of The Lubrizol 
Corp., 29400 Lakeland Blvd., Wickliffe, OH 44092-2298. The petitions 
proposed, respectively, that the food additive regulations in 
Sec. 175.105 Adhesives (21 CFR 175.105), Sec. 176.170 Components of 
paper and paperboard in contact with aqueous and fatty foods (21 CFR 
176.170), and Sec. 176.180 Components of paper and paperboard in 
contact with dry food (21 CFR 176.180) be amended to provide for the 
safe use of poly(sodium 2-acrylamido-2-methylpropanesulfonate) in 
adhesives and as components of paper and paperboard intended to contact 
food.
    In the filing notice, FDA used the common name to identify the 
additive. However, in the final rule, the Chemical Abstract Service 
name, 2-acrylamido-2-methyl-propanesulfonic acid, homopolymer, sodium 
salt, is used because the structure of the food additive is more 
readily understood from this name. In addition, FDA believes that 
listing the additive under both Secs. 176.170 and 176.180 is redundant 
because Sec. 176.180(b)(1) (21 CFR 176.180(b)(1)) permits the use of 
those substances listed in Sec. 176.170 (21 CFR 176.170) as components 
of paper and paperboard in contact with dry food. Therefore, FDA is 
listing the proposed uses of the additive only under Secs. 176.170 and 
175.105.
    In FDA's evaluation of the safety of 2-acrylamido-2-methyl-
propanesulfonic acid, homopolymer, sodium salt, the agency reviewed the 
safety of the additive itself and the chemical impurities that may be 
present in the additive resulting from its manufacturing process. 
Although the additive itself has not been shown to cause cancer, it may 
contain minute amounts of acrylamide and acrylonitrile as impurities 
resulting from its manufacture. These chemicals have been shown to 
cause cancer in test animals. Residual amounts of impurities are 
commonly found as constituents of chemical products, including food 
additives.

II. Determination of Safety

    Under the general safety standard of the Federal Food, Drug, and 
Cosmetic Act (the act), (21 U.S.C. 348(c)(3)(A)), a food additive 
cannot be approved for a particular use unless a fair evaluation of the 
data available to FDA establishes that the additive is safe for that 
use. FDA's food additive regulations (21 CFR 170.3(i)) define safe as 
``a reasonable certainty in the minds of competent scientists that the 
substance is not harmful under the intended conditions of use.''
    The food additives anticancer, or Delaney, clause of the act (21 
U.S.C.

[[Page 8273]]

348(c)(3)(A)) provides that no food additive shall be deemed safe if it 
is found to induce cancer when ingested by man or animal. Importantly, 
however, the Delaney clause applies to the additive itself and not to 
impurities in the additive. That is, where an additive itself has not 
been shown to cause cancer, but contains a carcinogenic impurity, the 
additive is properly evaluated under the general safety standard using 
risk assessment procedures to determine whether there is a reasonable 
certainty that no harm will result from the intended use of the 
additive. Scott v. FDA, 728 F.2d 322 (6th Cir. 1984).

III. Safety of the Petitioned Uses of the Additive

    FDA estimates that the petitioned uses of the additive, 2-
acrylamido-2-methyl-propanesulfonic acid, homopolymer, sodium salt, 
will result in exposure to no greater than 100 parts per billion (ppb) 
of the additive in the daily diet (3 kilograms (kg)) or an estimated 
daily intake (EDI) of no more than 300 micrograms per person per day 
(g/p/d)(Ref. 1).
    FDA does not ordinarily consider chronic toxicological studies to 
be necessary to determine the safety of an additive whose use will 
result in such low exposure levels (Ref. 2), and the agency has not 
required such testing here. However, the agency has reviewed the 
available toxicological data on the additive and concludes that the 
estimated small dietary exposure resulting from the petitioned uses of 
this additive is safe.
    FDA has evaluated the safety of this additive under the general 
safety standard, considering all available data and using risk 
assessment procedures to estimate the upper-bound limit of lifetime 
human risk presented by acrylamide and acrylonitrile, the carcinogenic 
chemicals that may be present as impurities in the additive. The risk 
evaluation of acrylamide and acrylonitrile has two aspects: (1) 
Assessment of exposure to the impurities from the petitioned uses of 
the additive; and (2) extrapolation of the risk observed in the animal 
bioassays to the conditions of exposure to humans.

A. Acrylamide

    FDA has estimated the exposure to acrylamide from the petitioned 
uses of the additive as a component of adhesives and of paper and 
paperboard in contact with food to be no more than 0.15 part per 
trillion (ppt) in the daily diet (3 kg), or 0.45 nanogram per person 
per day (ng/p/d) (Ref. 3). The agency used published data from a long-
term rat bioassay on acrylamide conducted by Johnson et al. (Ref. 4), 
in addition to unpublished data from this bioassay contained in FAP 
9B4131, to estimate the upper-bound limit of lifetime human risk from 
exposure to this chemical resulting from the petitioned uses of the 
additive. The authors reported that the test material caused 
significantly increased incidences of thyroid follicular adenomas and 
testicular mesotheliomas in male rats, and mammary tumors (adenomas or 
adenocarcinomas; fibromas or fibroadenomas; adenocarcinomas alone), 
central nervous system tumors (brain astrocytomas, brain or spinal cord 
glial tumors) and uterine tumors in female rats.
    Based on the agency's estimate that exposure to acrylamide will not 
exceed 0.45 ng/p/d, FDA estimates that the upper-bound limit of 
lifetime human risk from the petitioned uses of the subject additive is 
5.4  x  10-9, or 5.4 in a billion (Refs. 5 and 6). Because 
of the numerous conservative assumptions used in calculating the 
exposure estimate, the actual lifetime-averaged individual exposure to 
acrylamide is likely to be substantially less than the estimated 
exposure, and therefore, the probable lifetime human risk would be less 
than the upper-bound limit of lifetime human risk. Thus, the agency 
concludes that there is reasonable certainty that no harm from exposure 
to acrylamide would result from the petitioned uses of the additive.

B. Acrylonitrile

    FDA has estimated the exposure to acrylonitrile from the petitioned 
uses of the additive as a component of adhesives and of paper and 
paperboard in contact with food to be no more than 0.3 ppt in the daily 
diet (3 kg), or 0.9 ng/p/d (Ref. 3). The agency used data from a long-
term rodent bioassay on acrylonitrile conducted by Quast et al. (Ref. 
7), to estimate the upper-bound limit of lifetime human risk from 
exposure to this chemical resulting from the petitioned uses of the 
additive. The authors reported that the test material caused 
astrocytomas of the nervous system, papillomas and carcinomas of the 
tongue, papillomas and carcinomas of the stomach, and Zymbal's gland 
carcinomas in male and female rats. The authors also reported 
carcinomas of the small intestine and the mammary gland in female rats.
    Based on the agency's estimate that exposure to acrylonitrile will 
not exceed 0.9 ng/p/d, FDA estimates that the upper-bound limit of 
lifetime human risk from the petitioned uses of the subject additive is 
1.6  x  10-9, or 1.6 in a billion (Refs. 8 and 9). Because 
of the numerous conservative assumptions used in calculating the 
exposure estimate, the actual lifetime-averaged individual exposure to 
acrylonitrile is likely to be substantially less than the estimated 
exposure, and therefore, the probable lifetime human risk would be less 
than the upper-bound limit of lifetime human risk. Thus, the agency 
concludes that there is reasonable certainty that no harm from exposure 
to acrylonitrile would result from the petitioned uses of the additive.

C. Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of acrylamide and acrylonitrile as impurities in 
the food additive. The agency finds that specifications are not 
necessary for the following reasons: (1) Because of the low levels at 
which acrylamide and acrylonitrile may be expected to remain as 
impurities following production of the additive, the agency would not 
expect these impurities to become components of food at other than 
extremely low levels; and (2) the upper-bound limits of lifetime human 
risk from exposure to acrylamide and acrylonitrile are very low, 5.4 in 
a billion and 1.6 in a billion, respectively.

IV. Conclusion

    FDA has evaluated data in the three petitions and other relevant 
material. Based on this information, the agency concludes that: (1) The 
proposed uses of the additive as a component of adhesives, and paper 
and paperboard in contact with food are safe, (2) the additive will 
achieve its intended technical effect, and therefore, (3) the 
regulations in Secs. 175.105 and 176.170 should be amended as set forth 
below.
    In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition 
and the documents that FDA considered and relied upon in reaching its 
decision to approve the petition are available for inspection at the 
Center for Food Safety and Applied Nutrition by appointment with the 
information contact person listed above. As provided in Sec. 171.1(h), 
the agency will delete from the documents any materials that are not 
available for public disclosure before making the documents available 
for inspection.

V. Environmental Impact

    The agency has determined under 21 CFR 25.32(i) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment

[[Page 8274]]

nor an environmental impact statement is required.

VI. Paperwork Reduction Act of 1995

    This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

VII. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before March 20, 2000 file with the Dockets Management 
Branch (address above) written objections thereto. Each objection shall 
be separately numbered, and each numbered objection shall specify with 
particularity the provisions of the regulation to which objection is 
made and the grounds for the objection. Each numbered objection on 
which a hearing is requested shall specifically so state. Failure to 
request a hearing for any particular objection shall constitute a 
waiver of the right to a hearing on that objection. Each numbered 
objection for which a hearing is requested shall include a detailed 
description and analysis of the specific factual information intended 
to be presented in support of the objection in the event that a hearing 
is held. Failure to include such a description and analysis for any 
particular objection shall constitute a waiver of the right to a 
hearing on the objection. Three copies of all documents shall be 
submitted and shall be identified with the docket number found in 
brackets in the heading of this document. Any objections received in 
response to the regulation may be seen in the Dockets Management Branch 
(address above) between 9 a.m. and 4 p.m., Monday through Friday.

VIII. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.

    1. Memorandum of an internal communication between A. B. Bailey, 
Chemistry and Environmental Review Team, K. Biddle and K. P. Misra, 
Division of Health Effects Evaluation, and D. N. Harrison, Division 
of Petition Control, dated October 6, 1998.
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' In 
Chemical Safety Regulation and Compliance, edited by F. Homburger, 
and J. K. Marquis, New York, NY, pp. 24-33, 1985.
    3. Memorandum dated June 15, 1998, from Chemistry and 
Environmental Review Team to the Division of Petition Control, ``Use 
of poly(sodium 2-acrylamido-2-methylpropanesulfonate) in Latex 
Emulsions for Adhesives and Coatings in Paper and Paperboard.''
    4. Johnson, K. A., Gorzinski, S. J., Bodner, K. M., Campbell, R. 
A., Wolf, C. H., Friedman, M. A., and Mast, R. W. ``Chronic Toxicity 
and Oncogenicity Study on Acrylamide Incorporated in the Drinking 
Water of Fischer 344 rats,'' Toxicology and Applied Pharmacology, 
85:154-168, 1986.
    5. Memorandum dated December 18, 1998, from the Division of 
Petition Control to the Quantitative Risk assessment Committee, 
``Estimation of Upper-Bound Lifetime Risk for 2-acrylamido-2-
methylpropanesulfonic acid, homopolymer, sodium salt, FAPS 9B4131, 
9B4132 and 9B4133.''
    6. Memorandum of Conference, Date: February 13, 1985; June 6, 
1985; May 31, 1996, Place: FDA, CFSAN, Washington, DC, Purpose: 
Cancer Assessment Committee Meeting, Subject: Acrylamide.
    7. Quast, J. F., Wade, C. E., Humiston, C. G., Carreon, R. M., 
Hermann, E. A., Park, C. N., Schwetz, B. A. ``A Two Year Toxicity 
and Oncogenicity Study with Acrylonitrile Incorporated in the 
Drinking Water of Rats,'' Toxicology Research Laboratory, Health and 
Environmental Sciences, Dow Chemical USA, Midland, MI 48640. Final 
report dated January 22, 1980. Corrections dated November 17, 1980.
    8. Memorandum dated September 4, 1998, from the Division of 
Health Effects Evaluation to the Division of Petition Control, 
``FAPs 9B4131, 9B4132, and 9B4133: Worst-Case Cancer Risk Assessment 
for Acrylonitrile,'' Correction to July 28, 1998, memorandum from 
the Division of Health Effects Evaluation to the Quantitative Risk 
Assessment Committee.
    9. Memorandum dated July 28, 1998, from the Division of Health 
Effects Evaluation to the Quantitative Risk Assessment Committee, 
``FAPs 9B4131, 9B4132, and 9B4133: Worst-Case Cancer Risk Assessment 
for Acrylonitrile'' and the April 15, 1999, Addendum.

List of Subjects

21 CFR Part 175

    Adhesives, Food additives, Food packaging.

21 CFR Part 176

    Food additives, Food packaging.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
175 and 176 are amended as follows:

PART 175--INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF 
COATINGS

    1. The authority citation for 21 CFR part 175 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 342, 348, 379e.

    2. Section 175.105 is amended in the table in paragraph (c)(5) by 
alphabetically adding a new entry under the heading ``Substances'' to 
read as follows:


Sec. 175.105  Adhesives.

* * * * *
    (c) * * *
    (5) * * *

 
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                 Substances                          Limitations
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  *                    *                    *                    *
                   *                    *                    *
2-Acrylamido-2-methyl-propanesulfonic acid,
 homopolymer, sodium salt (CAS Reg. No.
 35641-59-9).
  *                    *                    *                    *
                   *                    *                    *
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PART 176--INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS

    3. The authority citation for 21 CFR part 176 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 342, 346, 348, 379e.

    4. Section 176.170 is amended in the table in paragraph (b)(2) by 
alphabetically adding a new entry under the headings ``List of 
substances'' and ``Limitations'' to read as follows:


Sec. 176.170  Components of paper and paperboard in contact with 
aqueous and fatty foods.

* * * * *
    (b) * * *
    (2) * * *

[[Page 8275]]



 
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         List of Substances                      Limitations
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  *                    *                    *                    *
                   *                    *                    *
2-Acrylamido-2-methyl-               For use only in coatings at a level
 propanesulfonic acid, homopolymer,   not to exceed 0.01 mg/in2
 sodium salt (CAS Reg. No. 35641-59-
 9).
  *                    *                    *                    *
                   *                    *                    *
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* * * * *

    Dated: February 8, 2000.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-3805 Filed 2-17-00; 8:45 am]
BILLING CODE 4160-01-F