Indirect Food Additives: Adhesives and Components of Coatings

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]

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