[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