[Federal Register Volume 63, Number 79 (Friday, April 24, 1998)]
[Rules and Regulations]
[Pages 20313-20315]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-10969]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 177
[Docket No. 92F-0290]
Indirect Food Additives: Polymers
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 poly(p-oxyphenylene
p-oxyphenylene p-carboxyphenylene) resins as a component of food-
contact articles intended for repeated use. This action responds to a
petition filed by ICI Americas, Inc.
DATES: This regulation is effective April 24, 1998; written objections
and requests for a hearing by May 26, 1998.
ADDRESS: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Mark A. Hepp, Center for Food Safety
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204, 202-418-3098.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of August 27, 1992
(57 FR 38840), FDA announced that a food additive petition (FAP 2B4333)
had been filed by ICI Americas, Inc., Concord Pike and Murphy Rd.,
Wilmington, DE 19897 (now Victrex USA, Inc., 601 Willowbrook Lane, West
Chester, PA 19382). The petition proposed to amend the food additive
regulations to provide for the safe use of polyetheretherketone resins
as articles or components of articles intended to contact food.
Polyetheretherketone resins are also known by the chemical name poly(p-
oxyphenylene p-oxyphenylene p-carboxyphenylene). The petition stated
that the subject resins are intended only for repeated use in contact
with food.
In its evaluation of the safety of this additive, FDA has 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 has
been found to contain minute amounts of hydroquinone as a byproduct
impurity of its production. Hydroquinone has been shown to cause cancer
in test animals. Residual amounts of reactants and byproduct
impurities, such as hydroquinone, are commonly found as contaminants in
chemical products, including food additives.
II. Determination of Safety
Under section 409(c)(3)(A) of the Federal Food, Drug, and Cosmetic
Act (the act) (21 U.S.C. 348(c)(3)(A)), the so-called ``general safety
clause,'' a food additive cannot be approved for a particular use
unless a fair evaluation of the evidence 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 (section
409(c)(3)(A)) further of the act (21 U.S.C. 348(c)(3)(A)) further
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)).
[[Page 20314]]
III. Safety of Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive, poly(p-
oxyphenylene p-oxyphenylene p-carboxyphenylene), will result in
exposure to no greater than 0.75 parts per billion of oligomers derived
from the additive in the daily diet (3 kilograms) or an estimated daily
intake (EDI) of 2.3 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 dietary exposure resulting from the petitioned use 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 hydroquinone, the carcinogenic chemical that
may be present as an impurity in the additive. The risk evaluation of
hydroquinone 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. Hydroquinone
FDA has estimated the exposure to hydroquinone from the petitioned
use of the additive as a component of repeated-use articles intended to
contact food to be no more than 0.4 part per trillion in the daily
diet, or 1.2 nanograms (ng)/person/day (Ref. 1). The agency used data
from 1989 National Toxicology Program rodent bioassays on hydroquinone
(Ref. 3), and a 1991 publication by Shibata et al. summarizing results
of rodent bioassays on hydroquinone (Ref. 4), to estimate the upper-
bound limit of lifetime human risk from exposure to this chemical
resulting from the petitioned use of the additive. The agency has made
an assumption that the results of these studies demonstrate that
hydroquinone produced tumors in male and female rats and mice following
oral administration for 2 years.
Based on the agency's estimate that exposure to hydroquinone will
not exceed 1.2 ng/person/day, FDA estimates that the upper-bound limit
of lifetime human risk from the petitioned use of the subject additive
is 1x10-10, or 1 in 10 billion (Ref. 5). Because of the
numerous conservative assumptions used in calculating the exposure
estimate, the actual lifetime-averaged individual exposure to
hydroquinone 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 hydroquinone would result from the petitioned use of the additive.
B. Need for Specifications
The agency has also considered whether specifications are necessary
to control the amount of hydroquinone present as an impurity in the
additive. The agency finds that specifications are not necessary for
the following reasons: (1) Because of the low levels at which
hydroquinone may be expected to remain as an impurity following
production of the additive, the agency would not expect the 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 the
impurity is very low (1 in 10 billion).
IV. Conclusion
FDA has evaluated data in the petition and other relevant material.
Based on this information, the agency concludes that the proposed use
of the additive as a component of repeated-use articles intended for
contact with food is safe, and that it will achieve its intended
technical effect. The agency has also determined, with the petitioner's
concurrence, that the additive should be listed by the chemical name,
poly(p-oxyphenylene p-oxyphenylene p-carboxyphenylene). Therefore, the
agency concludes that a new Sec. 177.2415 (21 CFR 177.2415) should be
added to 21 CFR part 177 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 carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
VI. 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 dated January 30,1997, from the Chemistry and
Environmental Review Team (HFS-207) to the Indirect Additive Branch
(HFS-216) entitled ``FAP 2B4333 (MATS# 659, M2.5)--Victrex USA,
Inc., Polyetheretherketone (PEEK) as a component of food-contact
articles intended for repeat-use. Submission dated 8/9/96.''
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology'' in
Chemical Safety Regulation and Compliance, edited by F. Homburger,
J. K. Marquis, and S. Karger, New York, pp 24-33, 1985.
3. ``Toxicology and Carcinogenesis Studies of Hydroquinone (CAS
No. 123-31-9) in F344/N Rats and B6C3F1 Mice (Gavage
Studies)'' National Toxicology Program, Technical Report Series, No.
366.
4. Shibata, M. A., M. Hirose, H. Tanaka, E. Asakawa, T. Shirai,
and M. Ito, ``Induction of renal cell tumors in rats and mice, and
the enhancement of hepatocellular tumor development in mice after
long-term hydroquinone treatment'' Japanese Journal of Cancer
Research, 82:1211-1219, 1991.
5. Memorandum dated November 18, 1997, from Division of Health
Effects Evaluation (HFS-225), to the Chairman of the Quantitative
Risk Assessment Committee (HFS-308) entitled ``Worst-case cancer
risk assessment for hydroquinone.''
VII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before May 26, 1998, 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
[[Page 20315]]
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.
List of Subjects in 21 CFR Part 177
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
177 is amended as follows:
PART 177--INDIRECT FOOD ADDITIVES: POLYMERS
1. The authority citation for 21 CFR part 177 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 379e.
2. Section 177.2415 is added to subpart C to read as follows:
Sec. 177.2415 Poly(aryletherketone) resins.
Poly(aryletherketone) resins identified in paragraph (a) of this
section may be safely used as articles or components of articles
intended for repeated use in contact with food subject to the
provisions of this section.
(a) Identity. For the purposes of this section,
poly(aryletherketone) resins are poly(p-oxyphenylene p-oxyphenylene p-
carboxyphenylene) resins (CAS Reg. No. 29658-26-2) produced by the
polymerization of hydroquinone and 4,4'-difluorobenzophenone, and have
a minimum weight-average molecular weight of 12,000, as determined by
gel permeation chromatography in comparison with polystyrene standards,
and a minimum mid-point glass transition temperature of 142 deg.C, as
determined by differential scanning calorimetry.
(b) Optional adjuvant substances. The basic resins identified in
paragraph (a) may contain optional adjuvant substances used in their
production. These adjuvants may include substances described in
Sec. 174.5(d) of this chapter and the following:
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Substance Limitations
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Diphenyl sulfone Not to exceed 0.2 percent by weight as a residual
solvent in the finished basic resin.
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(c) Extractive limitations. The finished food contact article, when
extracted at reflux temperatures for 2 hours with the following four
solvents, yields in each extracting solvent net chloroform soluble
extractives not to exceed 0.05 milligrams per square inch of food
contact surface: Distilled water, 50 percent (by volume) ethanol in
distilled water, 3 percent acetic acid in distilled water, and n-
heptane. In testing the final food contact article, a separate test
sample shall be used for each extracting solvent.
Dated: April 16, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-10969 Filed 4-23-98; 8:45 am]
BILLING CODE 4160-01-F
