[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]


=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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<SUP>-10</SUP>, 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 B6C3F<INF>1</INF> 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:

                                                                                                                
----------------------------------------------------------------------------------------------------------------
                       Substance                                               Limitations                      
----------------------------------------------------------------------------------------------------------------
Diphenyl sulfone                                         Not to exceed 0.2 percent by weight as a residual      
                                                          solvent in the finished basic resin.                  
----------------------------------------------------------------------------------------------------------------

    (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