[Federal Register Volume 64, Number 235 (Wednesday, December 8, 1999)]
[Rules and Regulations]
[Pages 68629-68631]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-31700]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 86F-0312]


Indirect Food Additives: 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 acrylamide polymer 
with sodium
2-acrylamido-2-methylpropanesulfonate as a component of paper and 
paperboard in contact with dry food. This action is in response to a 
petition filed by American Cyanamid Co. (currently Cytec Industries, 
Inc.).

.DATES: This regulation is effective December 8, 1999; Submit written 
objections and requests for a hearing by January 7, 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 (CFSAN) (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 August 19, 1986 
(51 FR 29612), FDA announced that a food additive petition (FAP 6B3940) 
had been filed on behalf of American Cyanamid Co., One Cyanamid Plaza, 
Wayne, NJ 07470 (currently Cytec Industries, Inc., Five Garret Mountain 
Plaza, West Paterson, NJ 07424). The petition proposed that the food 
additive regulations in 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 acrylamide polymer with sodium 2-acrylamido-2-

[[Page 68630]]

methylpropanesulfonate as a component of paper and paperboard in 
contact with dry food.
    In its evaluation of the safety of acrylamide polymer with sodium 
2-acrylamido-2-methylpropanesulfonate, FDA 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 as an impurity resulting from its 
manufacture. This chemical has 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. 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 Use of the Additive

    FDA estimates that the petitioned use of the additive, acrylamide 
polymer with sodium 2-acrylamido-2-methylpropanesulfonate, will result 
in exposure no greater than 50 parts per billion of the additive in the 
daily diet (3 kilograms (kg)) or an estimated daily intake of no more 
than 150 micrograms per person per day (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 use of 
the 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, the carcinogenic chemical that may 
be present as an impurity in the additive. The risk evaluation of 
acrylamide has two aspects: (1) Assessment of exposure to the impurity 
from the petitioned use 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 
use of the additive as a component of paper and paperboard in contact 
with dry food to be no more than 0.78 part per trillion in the daily 
diet (3 kg) or 2.3 nanograms per person per day (ng/p/d) (Ref. 3). The 
agency used data from a long-term rat bioassay on acrylamide, conducted 
by Johnson et al. (Refs. 4 and 5), to estimate the upper-bound limit of 
lifetime human risk from exposure to this chemical resulting from the 
petitioned use 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 2.3 ng/p/d, FDA estimates that the upper-bound limit of lifetime 
human risk from the petitioned use of the subject additive is 2.7 X 
10-8  or 2.7 in 100 million (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 use of the additive.

B. Need for Specifications

    The agency also has considered whether specifications are necessary 
to control the amount of acrylamide as an impurity 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 may be expected to remain as an impurity following 
production of the additive, the agency would not expect this impurity 
to become a component of food at other than extremely low levels; and 
(2) the upper-bound limit of lifetime human risk from exposure to 
acrylamide is very low, 2.7 in 100 million.

IV. Conclusion

    FDA has evaluated data in the petition and other relevant material. 
Based on this information, the agency concludes that: (1) The proposed 
use of the additive as a component of paper and paperboard in contact 
with dry food is safe, (2) the additive will achieve its intended 
technical effect, and therefore, (3) the regulations in Sec. 176.180 
should be amended as set forth below.
    In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petitions 
and the documents that FDA considered and relied upon in reaching its 
decision to approve the petitions 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 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 January 7, 2000, file with the Dockets Management 
Branch

[[Page 68631]]

(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 
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 from the Chemistry and Environmental Review Team, 
FDA, to the Division of Petition Control, FDA, ``DPC Request to 
Identify and Address Unresolved Issues in the Pending Acrylamide 
Petitions,'' August 7, 1997.
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' 
Chemical Safety Regulation and Compliance, edited by F. Homburger, 
and J. K. Marquis, New York, NY, pp. 24-33, 1985.
    3. Memorandum from the Chemistry and Environmental Review Team, 
FDA, to the Division of Petition Control, FDA, ``Exposure to 
Acrylamide From the Use of the Sodium Salt of Copolymers 2-
Acrylamido-2-Methylpropanesulfonic Acid and Acrylamide,'' February 
3, 1999.
    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 from the Division of Petition Control, FDA, to the 
Quantitative Risk Assessment Committee, FDA, ``Estimation of Upper-
Bound Risk for Acrylamide Exposure Resulting From the Use of 
Acrylamide Polymer with Sodium 2-Acrylamido-2-
Methylpropanesulfonate--FAP 6B3940,'' March 3, 1999.
    6. Memorandum of Conference, FDA, CFSAN, Washington, DC, Cancer 
Assessment Committee Meeting on Acrylamide, February 13 and June 6, 
1985, May 31, 1996.

List of Subjects in 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 part 
176 is amended as follows:

PART 176--INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS

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

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

    2. Section 176.180 is amended in the table in paragraph (b)(2) by 
alphabetically adding an entry under the headings ``List of 
substances'' and ``Limitations'' to read as follows:


Sec. 176.180  Components of paper and paperboard in contact with dry 
food.

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

 
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         List of substances                      Limitations
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Acrylamide polymer with sodium 2-    For use at a level not to exceed
 acrylamido-2-methylpropane-          0.015 weight percent of dry fiber.
 sulfonate (CAS Reg. No. 38193-60-
 1)
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    Dated: November 30, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-31700 Filed 12-7-99; 8:45 am]
BILLING CODE 4160-01-F