26744 Federal Register / Vol. 65, No. 90 / Tuesday, May 9, 2000 / Rules and Regulations

[FR Doc. 00–11579 Filed 5–8–00; 8:45 am]

BILLING CODE 4910–13–M

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.

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 § 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 (μg/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 μg/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

μg/p/d, FDA estimates that the upperbound limit of lifetime human risk for

MDA from the petitioned use of the

subject additive is 1 x 10-8 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)

Federal Register / Vol. 65, No. 90 / Tuesday, May 9, 2000 / Rules and Regulations 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 § 177.1210 should be amended as set

forth below.

In accordance with § 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 § 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

B6C3F1 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 UpperBound 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:

§ 177.1210 Closures with sealing gaskets

for food containers.

* * * * *

(b) * * *

(5) * * *

TABLE 1

List of substances Limitations (expressed as percent by weight of closure-sealing gasket

composition)

*******

Polyurethane resins manufactured from diphenylmethane diisocyanate,

1,4-butanediol, and adipic acid (CAS Reg. No. 26375–23–5).

For use only:

No limitation on amount used, but for use only in closure gasket

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 § 176.170(c) of this chapter, tables 1 and 2, respectively.

*******

26746 Federal Register / Vol. 65, No. 90 / Tuesday, May 9, 2000 / Rules and Regulations

* * * * *

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

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 178

[Docket No. 99F–1910]

Indirect Food Additives: Adjuvants,

Production Aids, and Sanitizers

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 2-[4,6-bis(2,4-

dimethylphenyl)-1,3,5-triazin-2-yl]-5-

(octyloxy)phenol as a stabilizer for

olefin polymers intended for use in

contact with food. This action is in

response to a petition filed by Cytec

Industries, Inc.

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: Vir

D. Anand, Center for Food Safety and

Applied Nutrition (HFS–215), 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

June 22, 1999 (64 FR 33306), FDA

announced that a food additive petition

(FAP 9B4675) had been filed by Cytec

Industries, Inc., c/o Keller and Heckman

LLP, 1001 G St. NW., suite 500 West,

Washington DC 20001. The petition

proposed to amend the food additive

regulations in § 178.2010 Antioxidants

and/or stabilizers for polymers (21 CFR

178.2010) to provide for the safe use of

2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-

triazin-2-yl]-5-(octyloxy)phenol as a

stabilizer for olefin polymers intended

for use in contact with food.

FDA has evaluated the data in the

petition and other relevant material.

Based on this information, the agency

concludes that: (1) The proposed use of

the additive is safe, (2) the additive will

achieve its intended technical effect,

and therefore, (3) that the regulations in

§ 178.2010 should be amended as set

forth below.

In accordance with § 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 21 CFR

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.

The agency has previously considered

the environmental effects of this rule as

announced in the notice of filing for

FAP 9B4675. 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.

This final rule contains no collections

of information. Therefore, clearance by

the Office of Management and Budget

under the Paperwork Reduction Act of

1995 is not required.

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.

List of Subjects in 21 CFR Part 178

Food additives, Food packaging.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs and redelegated to

the Director, Center for Food Safety and

Applied Nutrition, 21 CFR part 178 is

amended as follows:

PART 178—INDIRECT FOOD

ADDITIVES: ADJUVANTS,

PRODUCTION AIDS, AND SANITIZERS

1. The authority citation for 21 CFR

part 178 continues to read as follows:

Authority: 21 U.S.C. 321, 342, 348, 379e.

2. Section 178.2010 is amended in the

table in paragraph (b) by alphabetically

adding an entry under the headings

‘‘Substances’’ and ‘‘Limitations’’ to read

as follows:

§ 178.2010 Antioxidants and/or stabilizers

for polymers.

* * * * *

(b) * * *