[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