[Federal Register Volume 62, Number 10 (Wednesday, January 15, 1997)]
[Rules and Regulations]
[Pages 2011-2014]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-1021]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 175 and 178
[Docket No. 91F-0356]
Indirect Food Additives: Adhesives and Components of Coatings;
Adjuvants, Production Aids, and Sanitizers
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 2,2'-
ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphonite as an
antioxidant in adhesives and in the preparation of polymers intended
for contact with food. This action responds to a petition filed by
Ethyl Corp.
DATES: Effective January 15, 1997; written objections and requests for
a hearing by February 14, 1997.
ADDRESSES: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Daniel N. Harrison, Center for Food
Safety and Applied Nutrition (HFS-216), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3084.
SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of September 30, 1991 (56 FR 49484), FDA announced that a food
additive petition (FAP 1B4281) had been filed on behalf
[[Page 2012]]
of Ethyl Corp., c/o 1150 17th St. NW., Washington, DC 20036. The
petition proposed to amend the food additive regulations in
Sec. 175.105 Adhesives (21 CFR 175.105) and Sec. 178.2010 Antioxidants
and/or stabilizers for polymers (21 CFR 178.2010) to provide for the
safe use of 2,2'-ethylidenebis(4,6-di-tert-
butylphenyl)fluorophosphonite as an antioxidant in adhesives and in the
preparation of polymers intended for contact with food.
Subsequent to the filing of the petition, Ethyl Corp. was
reorganized to form Albemarle Corp., an independent corporation. As a
result of this reorganization, FDA was informed that Albemarle Corp.
(c/o Lowell Harmison, Gallery House, 2022 R St. NW., Washington, DC
20009) is now the petitioner of record for this food additive petition.
In FDA's evaluation of the safety of 2,2'-ethylidenebis(4,6-di-
tert-butylphenyl)fluorophosphonite (CAS Reg. No. 118337-09-0), the
agency reviewed the safety of the additive, including impurities that
might be present in the additive. Although the additive itself has not
been shown to cause cancer, it may contain minute amounts of methylene
chloride, which is a carcinogenic impurity resulting from the
manufacture of the additive. Residual amounts of reactants and
manufacturing aids, such as methylene chloride, are commonly found as
contaminants in chemical products, including food additives.
I. 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 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
clause using risk assessment procedures to determine whether there is a
reasonable certainty that no harm will result from the proposed use of
the additive, Scott v. FDA, 728 F.2d 322 (6th Cir. 1984).
II. Safety of the Petitioned Use of the Additive
FDA estimates that the petitioned uses of the additive, 2,2'-
ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphonite will result in
exposure to the additive of no greater than 0.70 parts per million in
the daily diet (3 kilograms) which corresponds to an estimated daily
intake of no greater than 2.1 milligrams per person per day (mg/person/
day) (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 studies. Based on its review of these studies
and the low level of exposure to the additive, the agency concludes
that there is an adequate margin of safety for the proposed use of the
additive.
FDA has evaluated the safety of this additive under the general
safety clause, considering all available data and using risk assessment
procedures to estimate the upper-bound limit of lifetime human risk
presented by the carcinogenic chemical, methylene chloride, that may be
present as an impurity in the additive. This risk evaluation of
methylene chloride has two aspects: (1) Assessment of the worst-case
exposure to this impurity from the proposed use of the additive, and
(2) extrapolation of the risk observed in the animal bioassays to the
condition of worst-case exposure to humans.
A. Methylene Chloride
FDA has estimated the hypothetical worst-case exposure to methylene
chloride from the petitioned uses of the additive to be no greater than
0.9 microgram (g)/person/day (Ref. 3). The agency used data
from the National Toxicology Program report (Ref. 4) of an inhalation
bioassay on methylene chloride to estimate the upper-bound limit of
lifetime human risk from exposure to this chemical resulting from the
proposed use of the petitioned additive. The results of the bioassay
demonstrated that methylene chloride was carcinogenic for mice under
the conditions of the study. The test material induced benign and
malignant neoplasms in both the liver and lung of both sexes.
The agency also evaluated data from a second study in mice of the
same strain as used in the inhalation study. In this study, in which
methylene chloride was administered in the drinking water of the mice
(Ref. 5), there was no significant increase in the incidence of
neoplasms at any site examined. However, assuming that methylene
chloride would induce neoplasia at a dose just above the highest level
tested in the drinking water study, a maximum potency can be estimated.
This estimate is approximately the same as the potency calculated from
the data of the inhalation study, providing confidence that using the
inhalation study for upper-bound risk assessment is not likely to
underestimate any potential risk due to ingested methylene chloride
(Ref. 6).
Based on the estimated worst-case exposure of 0.9 g/
person/day, FDA estimates that the upper-bound limit of lifetime human
risk from the uses of this additive is 6.6 x 10-9, or 6.6 in 1
billion (Ref. 7). Because of numerous conservative assumptions used in
calculating the exposure estimate, the actual lifetime-averaged
individual exposure to methylene chloride is likely to be substantially
less than the worse-case exposure, and therefore even the upper-bound
limit of lifetime human risk would be less. Thus, the agency concludes
that there is a reasonable certainty that no harm from exposure to
methylene chloride 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 methylene chloride present as an impurity in
the additive. The agency finds that specifications are not necessary
for the following reasons: (1) Because of the low levels at which
methylene chloride may be expected to remain as an impurity, 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 methylene chloride, even under worst-case
assumptions, is very low (less than 7 in 1 billion).
III. 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 an antioxidant used in adhesives and in the
preparation of polymers intended for contact with food is safe, and
that the additive will achieve its intended technical effect.
[[Page 2013]]
Therefore, the agency concludes that the regulations in Secs. 175.105
and 178.2010 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.
IV. 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.
V. Objections
Any person who will be adversely affected by this regulation may at
any time on or before February 14, 1997, file with the Dockets
Management Branch (address above) written objections thereto. 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 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.
VI. 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 R. M. Jenkins, Chemistry Review Branch, to D.
Harrison, Indirect Additives Branch, dated July 23, 1992.
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in
Chemical Safety Regulation and Compliance, edited by F. Hombuger, J.
K. Marquis, and S. Karger, New York, NY, pp. 24-33, 1985.
3. Memorandum from R. M. Jenkins, Chemistry Review Branch, to D.
Harrison, Indirect Additives Branch, dated March 22, 1993.
4. ``Toxicology and Carcinogenesis Studies of Dichloromethane
(Methylene Chloride) (CAS Reg. No. 75-09-2) in F344/N Rats and
B6C3F1 Mice (Inhalation Studies),'' NTP Technical Report 306,
National Institutes of Health, Publication No. 86-2562, 1986.
5. Memorandum from C. S. Lin, Food Additives Evaluation Branch,
to R. Lorentzen, Executive Secretary, Cancer Assessment Committee,
dated August 21, 1985.
6. Memorandum from the Quantitative Risk Assessment Committee to
W. G. Hamm, Director, Office of Toxicology, dated November 15, 1985.
7. Memorandum from D. N. Harrison, Indirect Additives Branch, to
S. H. Henry, Quantitative Risk Assessment Committee, dated November
8, 1993.
List of Subjects
21 CFR Part 175
Adhesives, Food additives, Food packaging.
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, 21 CFR parts
175 and 178 are 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: Secs. 201, 402, 409, 721 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).
2. Section 175.105 is amended in the table in paragraph (c)(5) by
alphabetically adding a new entry under the headings ``Substances'' and
``Limitations'' to read as follows:
Sec. 175.105 Adhesives.
* * * * *
(c) * * *
(5) * * *
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Substances Limitations
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2,2'-Ethylidenebis(4,6-di-tert- For use as an antioxidant
butylphenyl)fluorophosphonite (CAS Reg. and/or stabilizer only.
No. 118337-09-0).
* * * *
* * *
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PART 178--INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND
SANITIZERS
3. The authority citation for 21 CFR part 178 continues to read as
follows:
Authority: Secs. 201, 402, 409, 721 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).
4. Section 178.2010 is amended in the table in paragraph (b) by
alphabetically adding a new entry under the headings ``Substances'' and
``Limitations'' to read as follows:
Sec. 178.2010 Antioxidants and/or stabilizers for polymers.
* * * * *
[[Page 2014]]
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Substances Limitations
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2,2'-Ethylidenebis(4,6-di- For use only:
tert- 1. As provided in Sec. 175.105 of this
butylphenyl)fluorophosphonit chapter.
e (CAS Reg. No. 118337-09- 2. In all polymers used in contact with
0). food of types I, II, IV-B, VI-A, VI-B,
VII-B, and VIII, under conditions of use
B through H described in Tables 1 and 2
of Sec. 176.170(c) of this chapter at
levels not to exceed 0.25 percent by
weight of polymers.
3. In polypropylene complying with Sec.
177.1520(c) of this chapter, item 1.1,
in contact with food of types III, IV-A,
V, VII-A, and IX, under:
(a) Conditions of use B through H
described in Tables 1 and 2 of Sec.
176.170(c) of this chapter at levels not
to exceed 0.25 percent by weight of the
polymer; or
(b) Condition of use A, limited to levels
not to exceed 0.1 percent by weight of
the polymer; provided that the food-
contact surface has an average thickness
not exceeding 375 micrometers (0.015
inch).
4. In olefin copolymers complying with
Sec. 177.1520(c) of this chapter, items
3.1a or 3.2a, and containing not less
than 85 percent by weight of polymer
units derived from propylene, in contact
with food of types III, IV-A, V, VII-A,
and IX, and under:
(a) Conditions of use C through G,
described in Tables 1 and 2 of Sec.
176.170(c) of this chapter, limited to
levels no greater than 0.2 percent by
weight of the copolymers; or
(b) Conditions of use A, B, and H,
limited to levels no greater than 0.1
percent by weight of the olefin
copolymers; provided that the food-
contact surface has an average thickness
not exceeding 375 micrometers (0.015
inch).
5. In olefin polymers complying with Sec.
177.1520(c) of this chapter, items 1.2
or 1.3 in contact with food of types
III, IV-A, V, VII-A, and IX, under
conditions of use A through H, described
in Tables 1 and 2 of Sec. 176.170(c) of
this chapter at levels not to exceed 0.1
percent by weight of the polymers;
provided that the food-contact surface
has an average thickness not exceeding
375 micrometers (0.015 inch).
6. In polyethylene complying with Sec.
177.1520(c) of this chapter, items 2.1
or 2.2, having a density of not less
than 0.94, in contact with food of types
III, IV-A, V, VII-A, and IX, and under:
(a) Conditions of use B through H,
described in Tables 1 and 2 of Sec.
176.170(c) of this chapter limited to
levels not to exceed 0.2 percent by
weight of the polymers; or
(b) Condition of use A, described in
Tables 1 and 2 of Sec. 176.170(c) of
this chapter, limited to levels not to
exceed 0.1 percent by weight of the
polymer; provided that the food-contact
surface has an average thickness not
exceeding 125 micrometers (0.005 inch).
7. In olefin copolymers complying with
Sec. 177.1520(c) of this chapter, items
3.1a, 3.1b, 3.2a, or 3.2b, containing
not less than 85 percent by weight of
polymer units derived from ethylene and
having a density of not less than 0.94,
in contact with food of types III, IV-A,
V, VII-A, and IX, and under:
(a) Conditions of use C through G,
described in Tables 1 and 2 of Sec.
176.170(c) of this chapter limited to
levels not to exceed 0.2 percent by
weight of the copolymers; or
(b) Conditions of use A, B, and H,
limited to levels not to exceed 0.1
percent by weight of the copolymers;
provided that the food-contact surface
has an average thickness not exceeding
125 micrometers (0.005 inch).
8. In olefin polymers complying with Sec.
177.1520(c) of this chapter, items
3.1a, 3.1b, 3.2a, or 3.2b containing not
less than 85 percent by weight of
polymer units derived from ethylene, in
contact with food of types III, IV-A, V,
VII-A, and IX, under conditions of use A
through H, as described in Tables 1 and
2 of Sec. 176.170(c) of this chapter at
levels not to exceed 0.1 percent by
weight of the copolymer; provided that
the food-contact surface has an average
thickness not exceeding 75 micrometers
(0.003 inch).
9. In polyethylene phthalate polymers
complying with Sec. 177.1630 of this
chapter in contact with food of types
III, IV-A, V, VI-C, VII-A, and IX, and
under:
(a) Conditions of use B through H,
described in Tables 1 and 2 of Sec.
176.170(c) of this chapter, limited to
levels not to exceed 0.3 percent by
weight of the polymers; or
(b) Condition of use A with food of types
III, IV-A, V, VII-A, and IX, and limited
to levels not to exceed 0.1 percent by
weight of the polymers; provided that
the film thickness does not exceed 875
micrometers (0.035 inch).
* * * *
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Dated: January 6, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-1021 Filed 1-14-97; 8:45 am]
BILLING CODE 4160-01-F
