Federal Register: July 10, 1998 (Volume 63, Number 132)Rules and RegulationsPage 37246-37249From the Federal Register Online via GPO Access [wais.access.gpo.gov]

DOCID:fr10jy98-4

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 175

Docket No. 90F-0142Indirect Food Additives: Adhesives and Components of Coatings

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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 filedby 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 filedby 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

[Page 37247]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 (<greek-m>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 <greek-m>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<SUP>-7</SUP>, 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

[Page 37248]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) * * *

Substances

Limitations

*

*

*

*

*

*

*

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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[Page 37249]

Dated: June 30, 1998. William K. Hubbard, Associate Commissioner for Policy Coordination.

FR Doc. 98-18406Filed7-9-98; 8:45 amBILLING CODE 4160-01-F