[Federal Register Volume 64, Number 96 (Wednesday, May 19, 1999)]
[Rules and Regulations]
[Pages 27177-27179]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-12531]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 177
[Docket No. 95F-0191]
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 polyestercarbonate
resins produced by the condensation of 4,4'-isopropylidenediphenol,
carbonyl chloride, terephthaloyl chloride, and isophthaloyl chloride.
The finished resins are composed of 45 to 85 mole percent ester, of
which up to 55 mole percent is the terephthaloyl isomer, as articles or
components of articles in contact with food. This action responds to a
petition filed by the General Electric Co.
DATES: This regulation is effective May 19, 1999; written objections
and requests for a hearing by June 18, 1999.
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: Julius Smith, Center for Food Safety
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204, 202-418-3091.
SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of July 31, 1995 (60 FR 39000), FDA announced that a food
additive petition (FAP 5B4470) had been filed by the General Electric
Co., 1 Lexan Lane, Mt. Vernon, IN 47620-9364. The petition proposed to
amend the food additive regulations in Sec. 177.1585 Polyestercarbonate
resins (21 CFR 177.1585) to provide for the safe use of
polyestercarbonate resins produced by the condensation of 4,4'-
isopropylidenediphenol, carbonyl chloride, terephthaloyl chloride, and
isophthaloyl chloride. The finished resins are composed of 45 to 85
percent ester, of which up to 55 percent is the terephthaloyl isomer,
as articles or components of articles in contact with food. (The agency
will subsequently use mole-percent to describe these resins because
this term better describes the resin composition.)
In its evaluation of the safety of this food additive, FDA has
reviewed the safety of the additive itself, the starting materials
used, 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
residual amounts of methylene chloride, which has been shown to cause
cancer in test animals. 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 general safety standard of section 409(c)(3)(A) 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
(409(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
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)).
II. Safety of Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive,
polyestercarbonate resins, as food packaging, will not significantly
increase the overall exposure to polyestercarbonate oligomers,
monomers, p-cumylphenol, and methylene chloride above the exposure from
the currently regulated uses of these polyestercarbonate resins (Ref.
1).
FDA does not ordinarily consider chronic toxicological studies to
be necessary to determine the safety of an additive use of which 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
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 methylene chloride, the carcinogenic chemical
that may be present as an impurity in the additive. This risk
evaluation of methylene chloride 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 bioassay to the
conditions of probable exposure to humans.
A. Methylene Chloride
FDA has estimated the exposure to methylene chloride from the
petitioned and regulated uses of polyestercarbonate resins as articles
intended to contact food to be no more than 4.9 parts per billion in
the daily diet (3 kilogram), or 15 micrograms per person per day (Ref.
1). The agency used data in the National Toxicology Program Report No.
306 (January 1986), on inhalation studies in F344/N rats and
B6C3F1 mice to estimate the upper-bound limit of lifetime
human risk from exposure to this chemical resulting from the petitioned
and regulated uses of the additive (Ref. 3). The authors reported that
the test material caused an increased incidence of liver cell neoplasms
and lung neoplasms in both male and female B6C3F1 mice.
Based on the agency's estimate that exposure to methylene chloride
will not exceed 15 micrograms/person/day, FDA estimates that the upper-
bound limit of lifetime human risk from the regulated and petitioned
uses of the polyestercarbonate resins is 1 x 10-7 or 1 in 10
million (Ref. 4). Because of 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 estimated exposure, and therefore, the probable lifetime
human risk would be less than the upper-bound limit of lifetime human
risk. Thus, the
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agency concludes that there is reasonable certainty that no harm from
exposure to methylene chloride 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 methylene chloride present as an impurity in
the additive. The agency finds that the specification currently in
Sec. 177.1585 is adequate to insure that the risk from methylene
chloride resulting from the petitioned use of the polyestercarbonate
resins in contact with food is insignificant and that use of the resins
is safe.
III. Conclusion on Safety
FDA has evaluated the data in the petition and other relevant
material. Based on this information, the agency concludes that the
proposed uses for the food additive in food-contact articles are safe,
that the food additive will achieve its intended technical effect, and
that the regulations in Sec. 177.1585 should be amended as set forth in
the codified of this document.
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 previously. As provided in
Sec. 171.1(h)(2), 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. 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.
VI. Objections
Any person who will be adversely affected by this regulation may at
any time on or before June 18, 1999, file with the Dockets Management
Branch (address above) written objections thereto and may make a
written request for a public hearing on the stated objections and the
grounds for the objection. Each objection shall be separately numbered,
and each numbered objection shall specify with particularity the
provision 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.
VII. 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 April 25, 1996, from the Chemistry Review
Branch (HFS-247), to the Indirect Additives Branch (HFS-216)
entitled ``FAP 5B4470 (MATS 825, M2.0 and 2.1--General
Electric Company (GE) Polyestercarbonate (PEC) resins. Submission
dated 6-1-95.''
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, NY, pp. 24-33, 1985.
3. ``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 (January 1986).
4. Memorandum, dated June 4, 1996, from the Indirect Additives
Branch, (HFS-216), to Executive Secretary, Quantitative Risk
Assessment Committee (QRAC), (HFS-308), entitled ``Estimation of
Upper-bound Lifetime Human Risk from Methylene Chloride in
Polyestercarbonate Resins, the Subject of FAP 5B4470 (General
Electric Co.).''
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 177.1585 is amended by revising paragraphs (a) and
(c)(1) to read as follows:
Sec. 177.1585 Polyestercarbonate resins.
* * * * *
(a) Polyestercarbonate resins (CAS Reg. No. 71519-80-7) are
produced by the condensation of 4,4'-isopropylidenediphenol, carbonyl
chloride, terephthaloyl chloride, and isophthaloyl chloride such that
the finished resins are composed of 45 to 85 molepercent ester, of
which up to 55 mole-percent is the terephthaloyl isomer. The resins are
manufactured using a phthaloyl chloride/carbonyl chloride mole ratio of
0.81 to 5.7/1 and isophthaloyl chloride/terephthaloyl chloride mole
ratio of 0.81/1 or greater. The resins are also properly identified by
CAS Reg. No. 114096-64-9 when produced with the use of greater than 2
but not greater than 5 weight percent p-cumylphenol (CAS Reg. No. 599-
64-4), as an optional adjuvant substance in accordance with paragraph
(b)(2) of this section.
* * * * *
(c) * * *
(1) Specifications. Polyestercarbonate resins identified in
paragraph (a) of this section can be identified by their characteristic
infrared spectrum. The resins shall comply with either or both of the
following specifications:
(i) The solution intrinsic viscosity of the polyestercarbonate
resins shall be a minimum of 0.44 deciliter per gram, as determined by
a method entitled ``Intrinsic Viscosity (IV) of Lexan
Polyestercarbonate Resin by a Single Point Method Using Dichloromethane
as the Solvent,'' developed by the General Electric Co., September 20,
1985, which is incorporated by reference in accordance with 5 U.S.C.
552(a) and 1 CFR part 51. Copies are available from the Office of
Premarket Approval, Center for Food Safety and Applied Nutrition (HFS-
215), Food and Drug
[[Page 27179]]
Administration, 200 C St. SW., Washington, DC 20204, or may be examined
at the Center for Food Safety and Applied Nutrition's Library, Food and
Drug Administration, 200 C St. SW., rm. 3321, Washington, DC, or at the
Office of the Federal Register, 800 North Capitol St. NW., suite 700,
Washington, DC; or
(ii) A minimum weight-average molecular weight of 27,000, as
determined by gel permeation chromatography using polystyrene
standards.
* * * * *
Dated: May 10, 1999.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 99-12531 Filed 5-18-99; 8:45 am]
BILLING CODE 4160-01-F
