[Federal Register Volume 61, Number 159 (Thursday, August 15, 1996)]
[Rules and Regulations]
[Pages 42379-42381]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-20852]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 177
[Docket No. 95F-0331]
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 polyaryletherketone
resins (i.e., poly(oxy-1,4-phenylenecarbonyl-1,4-phenyleneoxy-1,4-
phenylenecarbonyl-1,4-phenylenecarbonyl-1,4-phenylene) as a basic resin
for use in food-contact materials. This action is in response to a
petition filed by BASF Aktiengesellschaft.
DATES: Effective August 15, 1996; written objections and requests for
a hearing by September 16, 1996.
ADDRESSES: 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: Vir D. Anand, Center for Food Safety
and Applied Nutrition (HFS-216), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204, 202-418-3081.
SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of October 19, 1995 (60 FR 54076), FDA announced that a food
additive petition (FAP 5B4483) had been filed by BASF
Aktiengesellschaft, c/o Keller and Heckman, 1001 G St. NW., suite 500
West, Washington, DC 20001. The petition proposed to amend the food
additive regulations to provide for the safe use of polyaryletherketone
resins (i.e., poly(oxy-1,4-phenylenecarbonyl-1,4-pheneyleneoxy-1,4-
phenylenecarbonyl-1,4-phenylenecarbonyl-1,4-phenylene) as a basic resin
for use in food-contact materials, establishing a new food additive
regulation, Sec. 177.1556 Polyaryletherketone resins (21 CFR 177.1556).
Subsequently, the petition was amended to request approval only for the
use of the polyaryletherketone resins in repeated use food-contact
applications. This amendment is reflected in this final rule.
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 residual methylene chloride,
which is a carcinogenic impurity resulting from the manufacture of the
additive. Residual amounts of reactants and manufacturing aids, such as
methylene chloride, are commonly found as contaminants in chemical
products, including food additives.
I. Determination of Safety
Under the so-called ``general safety clause'' 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 the 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
clause using risk assessment procedures to determine whether there is a
reasonable certainty that no harm will result from the proposed use of
the additive, Scott v. FDA, 728 F.2d 322 (6th Cir. 1984).
II. Safety of the Petitioned Use of the Additive
FDA finds that migration of polyaryletherketone resins is unlikely
because of the insolubility of the
[[Page 42380]]
polymer itself. However, the potential dietary concentration of the
oligomers migrating from the additive into food would be no greater
than 6 parts per billion (ppb), which equates to an estimated daily
intake (EDI) of 18 micrograms per person per day (g/person/
day) (Ref. 1). The agency concludes, further, that the total
nonvolatile extractives (TNE's) are exclusively oligomers, and
therefore, the dietary exposure to the TNE's is also 6 ppb with an EDI
of 18 g/person/day.
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 toxicity data on the additive and concludes that the low
exposure to the oligomers and TNE's resulting from the proposed use of
the additive is safe.
FDA has evaluated the safety of the additive under the general
safety clause, considering all available data and using risk assessment
procedures to estimate the upper-bound limit of risk presented by
methylene chloride, a carcinogenic chemical that may be present as an
impurity in the additive. This risk evaluation of methylene chloride
has two aspects: (1) Assessment of the worst-case exposure to the
impurity from the proposed use of the additive; and (2) extrapolation
of the risk observed in the animal bioassay to the conditions of
probable exposure to humans.
A. Methylene chloride
FDA has estimated the hypothetical worst-case exposure to methylene
chloride from the petitioned use of the additive in repeat use food
processing articles to be 8 parts per trillion of the daily diet (3
kilograms), or 20 nanogram (ng)/person/day (Ref. 3). The agency used
data in a National Toxicity Program report (No. 306: 1986) on
inhalation studies in F344/N rats and B6C3F1 mice (Ref. 4) to
estimate the upper-bound limit of lifetime human risk from exposure to
this chemical resulting from the proposed use of the additive (Ref. 4).
The results of the bioassays demonstrated that the material was
carcinogenic in male and female B6C3F1 mice under the conditions
of the study. The test material caused an increased incidence of liver
cell neoplasms and lung neoplasms in male and female mice.
Based on the estimated worst-case exposure to methylene chloride of
20 ng/person/day, FDA estimates that the upper-bound limit of lifetime
human risk from the use of the subject additive is 1.5 x 10-10, or
1.5 in 10 trillion (Ref. 5). Because of the numerous conservative
assumptions used in calculating the exposure estimate, the actual
lifetime-averaged individual exposure to methylene chloride is likely
to be substantially less than the worst-case exposure, and therefore,
the upper-bound lifetime human risk would be less. Thus, the agency
concludes that there is a reasonable certainty that no harm from
exposure to methylene chloride would result from the proposed use of
the additive.
B. Need for Specifications
The agency has also considered whether a specification is necessary
to control the amount of methylene chloride present as an impurity in
the additive. The agency finds that a specification is not necessary
for the following reasons: (1) Because of the low level at which
methylene chloride 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 risk from exposure to this
impurity, even under worst-case assumptions, is very low, 1.5 in 10
trillion.
III. Conclusion
FDA has evaluated the data in the petition and other relevant
material and concludes that the proposed use of the additive in
repeated use food-contact articles is safe. Based on this information,
the agency has also concluded that the additive will have the intended
technical effect. Therefore, the agency has concluded that a new
Sec. 177.1556 Polyaryletherketone resins should be established 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.
IV. 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.
V. Objections
Any person who will be adversely affected by this regulation may at
any time on or before September 16, 1996, 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
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 from the Chemistry Review Branch (HFS-247) to the
Indirect Additives Branch (HFS-216), concerning FAP 5B4483.
Submissions of 2/13/96; BASF Aktiengesellschaft. Exposure to
oligomers and total nonvolatile extracts from the use of
polyaryletherketone resins in repeat use articles, April 11, 1996.
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,''
Chemical Safety Regulation and Compliance, edited by F. Homburger
and J. K. Marquis, S. Karger, New York, NY, pp. 24-33, 1985.
3. Memorandum from the Chemistry Review Branch (HFS-247) to the
Indirect Additives Branch (HFS-216), concerning
[[Page 42381]]
FAP 5B4483, BASF Aktiengesellschaft, concerning exposure to
methylene chloride from the use of polyaryletherketone resins,
February 14, 1996.
4. ``Toxicology and Carcinogenesis Studies of Dichloromethane
(methylene chloride) (CAS Reg. No. 75-09-2) in F344/N Rats and
B6C3F1 Mice'' (Inhalation Studies). National Toxicology Program
Technical Report Series, No. 306 (1986).
5. Memorandum from the Quantitative Risk Assessment Committee,
concerning estimation of upper-bound lifetime risk from methylene
chloride for uses requested in FAP 5B4483 (BASF Aktiengesellschaft),
February 20, 1996.-
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: Secs. 201, 402, 409, 721 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).
2. New Sec. 177.1556 is added to subpart B to read as follows:
Sec. 177.1556 Polyaryletherketone resins.
The poly(oxy-1,4-phenylenecarbonyl-1,4-phenyleneoxy-1,4-
phenylenecarbonyl-1,4-phenylenecarbonyl-1,4-phenylene) resins (CAS Reg.
No. 55088-54-5 and CAS Reg. No. 60015-05-6 and commonly referred to as
polyaryletherketone 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. Polyaryletherketone resins consist of basic resins
produced by reacting 4,4'-diphenoxy benzophenone and terephthaloyl
dichloride in such a way that the finished resins have a minimum weight
average molecular weight of 20,000 grams per mole, as determined by
light scattering measurements in sulfuric acid at room temperature.
(b) Optional adjuvant substances. The basic polyaryletherketone
resins identified in paragraph (a) of this section may contain optional
adjuvant substances required in the production of such basic resins.
These adjuvants may include substances used in accordance with
Sec. 174.5 of this chapter and the following:
(1) Benzoyl chloride, poly(tetrafluoro ethylene).
(2) [Reserved]
(c) Extractive limitations. The finished food-contact article
yields net total extractives in each extracting solvent not to exceed
0.052 milligram per square inch (corresponding to 0.008 milligram per
square centimeter) of food-contact surface, when extracted at reflux
temperature for 2 hours with the following solvents: Distilled water,
50 percent (by volume) ethyl alcohol in distilled water, 3 percent
acetic acid (by weight) in distilled water, and n-heptane.
(d) In testing the finished food-contact article made of
polyaryletherketone resin, use a separate test sample for each required
extracting solvent.
Dated: August 2, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-20852 Filed 8-14-96; 8:45 am]
BILLING CODE 4160-01-F