[Federal Register Volume 63, Number 132 (Friday, July 10, 1998)]
[Rules and Regulations]
[Pages 37246-37249]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-18406]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 175
[Docket No. 90F-0142]
Indirect Food Additives: Adhesives and Components of Coatings
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
derived from the reaction of toluene diisocyanate or 4,4'
methylenebis(cyclohexylisocyanate) with fumaric acid-modified
polypropylene glycol or fumaric acid-modified tripropylene glycol,
triethylamine, and ethylenediamine as a component of adhesives for
articles intended to contact food. This action responds to a petition
filed by Olin Corp.
DATES: The regulation is effective July 10, 1998. Submit written
objections and requests for a hearing by August 10, 1998.
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: Daniel N. Harrison, Center for Food
Safety and Applied Nutrition (HFS-215), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3084.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of May 10, 1990 (55
FR 19667), FDA announced that a food additive petition (FAP OB4201) had
been filed by Olin Corp., 120 Long Ridge Rd., Stamford, CT 06904. The
petition proposed to amend the food additive regulations in
Sec. 175.105 Adhesives (21 CFR 175.105) to provide for the safe use of
polyurethane resins derived from the reactions of toluene diisocyanate
or 4,4' methylenebis(cyclohexylisocyanate) with carboxylic acid-
modified polypropylene glycol and with triethylamine and
ethylenediamine as a component of adhesives for articles intended to
contact food. In a notice published in the Federal Register of
September 5, 1997 (62 FR 46979), FDA amended the May 10, 1990, notice
to state that upon further review of the petition, the petitioner
specifically requested the approval of the use of polyurethane resins
derived from the reaction of toluene diisocyanate or 4,4'
methylenebis(cyclohexylisocyanate) with fumaric acid-modified propylene
glycol or fumaric acid-modified tripropylene glycol, triethylamine, and
ethylenediamine.
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 may
contain minute amounts of toluenediamine (TDA), which is a carcinogenic
impurity resulting from the manufacture of the additive. Residual
amounts of impurities are commonly found as
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constituents of chemical products, including food additives.
II. 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 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)).
III. Safety of the Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive, polyurethane
resins derived from the reaction of toluene diisocyanate or 4,4'
methylenebis(cyclohexylisocyanate) with fumaric acid-modified
polypropylene glycol or fumaric acid-modified tripropylene glycol,
triethylamine, and ethylenediamine, will result in exposure to the
additive that would be virtually nil (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
``virtually nil'' 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 TDA, the carcinogenic chemical that may be
present as an impurity in the additive. The risk evaluation of TDA has
two aspects: (1) Assessment of 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 exposure to
humans.
A. Toluenediamine
FDA has estimated the cumulative exposure to TDA from all currently
regulated uses of the additives where TDA may be present as an impurity
and from the petitioned use of the additive in polyurethane adhesive
applications to be no more than 0.059 part per billion in the daily
diet (3 kilograms) or 0.18 microgram (g)/person/day (Ref. 3).
The agency used data from long-term rodent bioassays on 2,4'
toluenediamine conducted by the National Cancer Institute (Ref. 4) to
estimate the upper-bound limit of lifetime human risk from the
cumulative exposure to this chemical resulting from the currently
regulated food additive uses where TDA may be present as an impurity
and the proposed use of the additive. The authors reported that the
test material caused significant amounts of hepatocellular carcinomas
in both male and female rats and carcinomas of the mammary gland in
female rats. The test chemical was also carcinogenic for female mice,
causing hepatocellular carcinomas.
Based on the agency's estimate that exposure to TDA will not exceed
0.18 g/person/day, FDA estimates that the upper-bound limit of
lifetime human risk from all regulated uses of the additives where TDA
may be present as an impurity and from the proposed use of the subject
additive is 6.1 x 10-7, or 6 in 10 million (Ref. 5). Because
of the numerous conservative assumptions used in calculating the
exposure estimate, the actual lifetime-averaged individual exposure to
TDA 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 TDA
would result from the proposed use of the additive.
B. Need for Specifications
The agency has also considered whether specifications are necessary
to control the amount of TDA as an impurity in the food additive. The
agency finds that specifications are not necessary for the following
reasons: (1) Because of the low levels at which TDA 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
human risk from exposure to TDA is very low (6 in 10 million).
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 adhesives for articles intended to
contact food is safe, and that the additive will achieve its intended
technical effect. Therefore, the agency concludes that the regulations
in Sec. 175.105 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
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. 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. 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. No comments were received during the 30-day comment
period specified in the May 10, 1990, filing notice for comments on the
environmental assessment submitted with the petition.
VII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before August 10, 1998, file with the Dockets Management
Branch (address above) written objections thereto. Each objection shall
be separately numbered, and each
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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.
VIII. 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 Food and Color Additives Review Section
(HFF-415) to the Indirect Additives Branch (HFS-335) entitled ``FAP
0B4201--Olin Corporation: Polyurethane resins from carboxyl-modified
polyols as components of adhesives of coatings contacting foods:
submission of 3-12-90,'' dated July 18, 1990.
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. Memorandum from the Chemistry Review Branch (HFS-247) to the
Indirect Additives Branch (HFS-216) entitled ``FAP 0B4201 MATS#
471): Newly Revised Exposure Estimate for Tolenediamine (TDA) from
Polyurethane Adhesive Applications and Cumulative Exposure to TDA,''
dated March 2, 1993.
4. ``Bioassay of 2,4-Diaminotoluene for Possible
Carcinogenicity,'' National Cancer Institute. NCI-CG-TR-162, 1979.
5. Report of the Quantitative Risk Assessment Committee entitled
``FAP 0B4201: Upper Bound Lifetime Carcinogenic Risk from Exposure
to Toluenediamine (TDA) from Polyurethane Adhesive Applications and
Cumulative Exposure to TDA,'' dated June 14, 1996.
List of Subjects in 21 CFR Part 175
Adhesives, Food additives, Food packaging.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, part 175 is
amended as follows:
PART 175--INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF
COATINGS
1. The authority citation for 21 CFR part 175 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 379e.
2. Section 175.105 is amended in the table in paragraph (c)(5) by
revising the entry for ``Polyurethane resins * * *'' under the heading
``Substances'' to read as follows:
Sec. 175.105 Adhesives.
* * * * *
(c) * * *
(5) * * *
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Substances Limitations
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* * * * * *
*
Polyurethane resins produced by: (1) reacting
diisocyanates with one or more of the polyols or
polyesters named in this paragraph, or (2) reacting
the chloroformate derivatives of one or more of the
polyols or polyesters named in this paragraph with one
or more of the polyamines named in this paragraph, or
(3) reacting toluene diisocyanate or 4,4'
methylenebis(cyclohexylisocyanate) (CAS Reg. No. 5124-
30-1) with: (i) one or more of the polyols or
polyesters named in this paragraph and with either N-
methyldiethanolamine (CAS Reg. No. 105-59-9) and
dimethyl sulfate (CAS Reg. No. 77-78-1) or
dimethylolpropionic acid (CAS Reg. No. 4767-03-7) and
triethylamine (CAS Reg. No. 121-44-8), or (ii) a
fumaric acid-modified polypropylene glycol or fumaric
acid-modified tripropylene glycol), triethylamine (CAS
Reg. No. 107-15-3), and ethylenediamine (CAS Reg. No.
121-44-8), or (4) reacting meta-tetramethylxylene
diisocyanate (CAS Reg. No. 2778-42-9) with one or more
of the polyols and polyesters listed in this paragraph
and with dimethylolpropionic acid (CAS Reg. No. 4767-
03-7) and triethylamine (CAS Reg. No. 121-44-8), N-
methyldiethanolamine (CAS Reg. No. 105-59-9), 2-
dimethylaminoethanol (CAS Reg. No. 108-01-0), 2-
dimethylamino-2-methyl-1-propanol (CAS Reg. No. 7005-
47-2), and/or 2-amino-2-methyl-1-propanol (CAS Reg.
No. 124-68-5).
* * * * * *
*
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Dated: June 30, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-18406 Filed 7-9-98; 8:45 am]
BILLING CODE 4160-01-F