[Federal Register Volume 65, Number 90 (Tuesday, May 9, 2000)]
[Rules and Regulations]
[Pages 26744-26746]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-11478]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 177

[Docket No. 98F-1019]


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 polyurethane resins 
manufactured from diphenylmethane diisocyanate, 1,4-butanediol, and 
adipic acid as a component of cap liners used on bottles in contact 
with food. This action responds to a petition filed by BF Goodrich 
Specialty Chemicals.

DATES: This rule is effective May 9, 2000. Submit written objections 
and requests for a hearing by June 8, 2000.

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: Hortense S. Macon, Center for Food 
Safety and Applied Nutrition (HFS-205), Food and Drug Administration, 
200 C St., SW., Washington, DC 20204, 202-418-3086.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of November 30, 1998 (63 FR 65793), FDA announced that a food 
additive petition (FAP 8B4631) had been filed by BF Goodrich Specialty 
Chemicals, 9911 Brecksville Rd., Cleveland, OH 44141. The petition 
proposed to amend the food additive regulations in Sec. 177.1210 
Closures with sealing gaskets for food containers (21 CFR 177.1210) to 
provide for the safe use of polyurethane resins manufactured from 
diphenylmethane diisocyanate, 1,4-butanediol, and adipic acid as a 
component of cap liners used on bottles in contact with food.
    In its evaluation of the safety of these resins, 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 dianiline (MDA), which has been shown to cause cancer in test 
animals. MDA is produced when diphenylmethane diisocyanate (MDI), a 
starting material used in the manufacture of polyurethane resins, 
reacts with water. Residual amounts of reactants and manufacturing 
aids, such as MDA, 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 
(section 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

    The petitioner determined the levels of three migrants extracted 
from the additive, polyurethane resins manufactured from MDI, 1,4-
butanediol, and adipic acid. These three migrants were 1,4-butanediol, 
oligomers of the additive, and MDA (the hydrolysis product of MDI). FDA 
agrees that the determination of the levels of these three types of 
migrants are appropriate to evaluate the safe use of the additive. FDA 
estimates that the petitioned use of the additive will result in 
exposure to 1,4-butanediol of not more than 90 micrograms per person 
per day (<greek-m>g/p/d) while exposure to the other two migrants will 
be even lower (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 MDA, the carcinogenic chemical that may be 
present as an impurity in the additive. This risk evaluation of MDA 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 Dianiline

    FDA has estimated the exposure to MDA from the petitioned use of 
the additive in the manufacture of cap liners intended to contact food 
to be no more than 4.1 parts per trillion in the daily diet, or 0.012 
<greek-m>g/p/d (Refs. 1 and 5). The agency used data from a bioassay of 
MDA, sponsored by the National Toxicology Program, to estimate the 
upper-bound limit of lifetime human risk from exposure to MDA that may 
result from the proposed use of the additive (Ref. 3). The bioassay 
report showed that MDA ingestion produced tumors at multiple sites in 
both sexes of rats and mice.
    Based on the agency's estimate that exposure to MDA will not exceed 
0.012 <greek-m>g/p/d, FDA estimates that the upper-bound limit of 
lifetime human risk for MDA from the petitioned use of the subject 
additive is 1 x 10<SUP>-8</SUP> or 1 in 100 million (Ref. 4). Because 
of numerous conservative assumptions used in calculating the exposure 
estimate, the actual lifetime-averaged individual exposure to MDA 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 MDA 
would result from the petitioned use of the additive.

B. Need for Specifications

    The agency also has considered whether specifications are necessary 
to control the amount of MDA present as an impurity in the additive. 
The agency finds that the specifications are not necessary for the 
following reasons: (1)

[[Page 26745]]

Because of the low level at which MDA 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 MDA is very low, less than 1 in 100 million.

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 use of the additive as a component of cap liners for food-
contact articles is safe, that the food additive will achieve its 
intended technical effect, and that the regulations in Sec. 177.1210 
should be amended 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 
contact person listed above. As provided in Sec. 171.1(h), the agency 
will delete any materials from the documents that are not available for 
public disclosure before making the documents available for inspection.

IV. Environmental Impact

    The agency has previously considered the environmental effects of 
this rule as announced in the notice of filing for FAP 8B4631 (63 FR 
65793, November 30, 1998). No new information or comments have been 
received that would affect the agency's previous determination that 
there is no significant impact on the human environment and that an 
environmental impact statement is not required.

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 file with the Dockets Management Branch (address above) 
written objections by June 8, 2000. 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 are to be submitted and are to 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 to the file dated May 19, 1999, from the Petitions 
Contract Working Group (HFS-205), concerning FAP 8B4631.
    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. ``Carcinogenesis Studies of 4,4'''-Methylenedianiline 
Dihydrochloride) (CAS Reg. No. 13552-44-8) in F344/N Rats and 
B6C3F<INF>1</INF> Mice (Drinking Water Studies),'' National 
Toxicology Program Technical Report Series, No. 248, June 1983.
    4. Memorandum dated January 28, 1999, from the Regulatory Policy 
Branch (HFS-206), to Executive Secretary, Quantitative Risk 
Assessment Committee (QRAC) (HFS-308), entitled ``Estimation of the 
Upper-Bound Lifetime Risk for Methylene-4,4'''-Dianiline (MDA): 
Subject of Food Additive Petition 8B4631 (BF Goodrich Specialty 
Chemicals).''
    5. Memorandum dated May 13, 1999, from the Scientific Support 
Branch (HFS-207), entitled ``FAP 8B4631 (MATS #1041)--Keller & 
Heckman (K & H), on Behalf of BF Goodrich Specialty Chemicals. Risk 
Assessment for Methylene Dianiline (MDA).''

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 177.1210 is amended in table 1 in paragraph (b)(5) by 
alphabetically adding an entry to read as follows:


Sec. 177.1210  Closures with sealing gaskets for food containers.

* * * * *
    (b) * * *
    (5) * * *

                                 Table 1
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                                      Limitations (expressed as percent
         List of substances          by weight of closure-sealing gasket
                                                 composition)
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  *                    *                    *                    *
                   *                    *                    *
Polyurethane resins manufactured     For use only:
 from diphenylmethane diisocyanate,    No limitation on amount used, but
 1,4-butanediol, and adipic acid      for use only in closure gasket
 (CAS Reg. No. 26375-23-5).           compositions used in contact with
                                      food types VI-A and VI-C (up to 15
                                      percent alcohol) under conditions
                                      of use D, E, F, and G, as
                                      described in Sec.  176.170(c) of
                                      this chapter, tables 1 and 2,
                                      respectively.
  *                    *                    *                    *
                   *                    *                    *
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[[Page 26746]]

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    Dated: April 28, 2000.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-11478 Filed 5-8-00; 8:45 am]
BILLING CODE 4160-01-F