[Federal Register Volume 64, Number 231 (Thursday, December 2, 1999)]
[Rules and Regulations]
[Pages 67483-67486]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-31228]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 178
[Docket No. 95F-0150]
Indirect Food Additives: 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 7-oxa-3,20-
diazadispiro-[5.1.11.2]-heneicosan-21-one,2,2,4,4-tetramethyl-
,hydrochloride, reaction products with epichlorohydrin, hydrolyzed,
polymerized (CAS Reg. No. 202483-55-4) as an antioxidant and/or
stabilizer for polyolefins intended for contact with food. This action
is in response to a petition filed by Hoechst Aktiengesellschaft.
DATES: The regulation is effective December 2, 1999. Submit written
objections and requests for a hearing by January 3, 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: Vivian M. Gilliam, Center for Food
Safety and Applied Nutrition (HFS-215), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3094.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of July 12, 1995 (60
FR 35914), FDA announced that a food additive petition (FAP 5B4461) had
been filed by Hoechst Aktiengesellschaft, c/o 1001 G St. NW., suite 500
West, Washington, DC 20001. The petition proposed that the food
additive regulations in Sec. 178.2010 Antioxidants and/or stabilizers
for polymers (21 CFR 178.2010) be amended to provide for the safe use
of polymeric 2,2,4,4-tetramethyl-7-oxa-3,20-diaza-20-(2,3-epoxypropyl)-
dispiro-[5.1.11.2]-heneicosane-21-one (CAS Reg. No. 78301-43-6) as an
antioxidant and/or stabilizer for polyolefins intended for contact with
food.
Subsequent to the filing of the petition, Hoechst
Aktiengesellschaft sold its speciality business, including food
additive petition 5B4461, to
[[Page 67484]]
Clariant AG, Switzerland. The petitioner also obtained a new Chemical
Abstracts Service (CAS) Registry number for the additive under the
following name: 7-oxa-3,20-diazadispiro-[5.1.11.2]-heneicosan-21-
one,2,2,4,4-tetramethyl-,hydrochloride, reaction products with
epichlorohydrin, hydrolyzed, polymerized (CAS Reg. No. 202483-55-4).
In FDA's evaluation of the safety of 7-oxa-3,20-diazadispiro-
[5.1.11.2]-heneicosan-21-one,2,2,4,4-tetramethyl-,hydrochloride,
reaction products with epichlorohydrin, hydrolyzed, polymerized the
agency 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 has been found to contain minute amounts of
epichlorohydrin, a carcinogenic impurity resulting from the manufacture
of the additive. Residual amounts of impurities are commonly found as
constituents of chemical products, including food additives.
II. Determination of Safety
Under the general safety standard 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, 7-oxa-3,20-
diazadispiro-[5.1.11.2]-heneicosan-21-one,2,2,4,4-tetramethyl-
,hydrochloride, reaction products with epichlorohydrin, hydrolyzed,
polymerized, will result in exposure to no greater than 224 parts per
billion (ppb) of the additive in the daily diet (3 kilogram (kg)) or an
estimated daily intake of 0.67 milligram per person per day (mg/p/d)
(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 small 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 epichlorohydrin, the carcinogenic chemical that
may be present as an impurity in the additive. The risk evaluation of
epichlorohydrin 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 bioassays to the conditions of
exposure to humans.
A. Epichlorohydrin
FDA has estimated the exposure to epichlorohydrin from the
petitioned use of the additive as an antioxidant and/or stabilizer for
polyolefins to be no more than 0.011 ppb in the daily diet (3 kg) or 33
nanograms (ng)/p/d (Ref.1). The agency used data from a carcinogenesis
bioassay on epichlorohydrin conducted by Konishi et al. (Ref. 4), to
estimate the upper-bound limit of lifetime human risk from exposure to
this chemical resulting from the petitioned use of the additive. The
authors reported that the test material caused significantly increased
incidence of stomach papillomas and carcinomas in male rats.
Based on the agency's estimate that exposure to epichlorohydrin
will not exceed 33 ng/p/d, FDA estimates that the upper-bound limit of
lifetime human risk from the petitioned use of the subject additive is
1.5 x 10-9 or 1.5 in a billion (Ref. 3). Because of the
numerous conservative assumptions used in calculating the exposure
estimate, the actual lifetime-averaged individual exposure to
epichlorohydrin 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 epichlorohydrin would result from the petitioned use of the
additive.
B. Need for Specifications
The agency has also considered whether specifications are necessary
to control the amount of epichlorohydrin as an impurity in the
additive. The agency finds that specifications are not necessary for
the following reasons: (1) Because of the low level at which
epichlorohydrin 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
epichlorohydrin is very low, 1.5 in a billion.
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 an antioxidant and/or stabilizer for polyolefins
intended for contact with food is safe, and that the additive will
achieve its intended technical effect. Therefore, the agency concludes
that the regulations in Sec. 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.
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
[[Page 67485]]
in the Dockets Management Branch (address above) between 9 a.m. and 4
p.m., Monday through Friday.
VII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before January 3, 2000, 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.
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 A. B. Bailey, Chemistry and Environmental
Review Team, to D. Harrison, Division of Petition Control, dated
August 6, 1998.
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in
Chemical Safety Regulation and Compliance, edited by F. Homburger,
and J. K. Marquis, New York, NY, pp. 24-33, 1985.
3. Memo from Division of Petition Control (HFS-215) to Sara H.
Henry, Quantitative Risk Assessment Committee (HFS-308),
``Verification of upper bound risk calculation for epichlorohydrin
(ECH) for petition No. FAP 5B4461,'' dated February 10, 1998.
4. Konishi, Y. et al., ``Forestomach Tumors Induced by Orally
Administered Epichlorohydin in Male Wistar Rats,'' Gann, 71:922-923,
1980.
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, 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 a new entry under the headings ``Substances'' and
``Limitations'' to read as follows:
Sec. 178.2010 Antioxidants and/or stabilizers for polymers.
* * * * *
(b) * * *
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Substances Limitations
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7-Oxa-3,20-diazadispiro-[5.1.11.2]-heneicosan-21- For use only:
one,2,2,4,4-tetramethyl-,hydrochloride, reaction 1. At levels not to exceed 0.5 percent by weight of
products with epichlorohydrin, hydrolyzed, polymerized olefin polymers complying with Sec. 177.1520 of this
(CAS Reg. No. 202483-55-4). chapter, items 1.1, 3.1, and 3.2, where the copolymers
complying with items 3.1 and 3.2 contain not less than
85 weight percent of polymer units derived from
propylene; in contact with all types of food described
in Table 1 of Sec. 176.170 of this chapter, provided
that the finished food-contact article will have a
capacity of at least 18.9 liters (5 gallons) when in
contact with food of types III, IV-A, V, VII-A, and
IX, described in Table 1 of Sec. 176.170 of this
chapter.
2. At levels not to exceed 0.5 percent by weight of
olefin polymers complying with Sec. 177.1520 of this
chapter, items 2.1, 2.2, 3.1, and 3.2, having a
density of not less than 0.94 gram/milliliter, where
the copolymers complying with items 3.1 and 3.2
contain not less than 85 weight percent of polymer
units derived from ethylene; in contact with food only
under conditions of use C, D, E, F, and G, described
in Table 2 of Sec. 176.170 of this chapter, provided
that the finished food-contact article will have a
capacity of at least 18.9 liters (5 gallons) when in
contact with food of types III, IV-A, V, VII-A, and
IX, described in Table 1 of Sec. 176.170 of this
chapter.
3. At levels not to exceed 0.3 percent by weight of
olefin polymers complying with Sec. 177.1520 of this
chapter, items 2.1, 2.2, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6,
and 4.0, having a density of less than 0.94 gram/
milliliter, in contact with food only under conditions
of use D, E, F, and G, described in Table 2 of Sec.
176.170 of this chapter, provided that the finished
food-contact article will have a capacity of at least
18.9 liters (5 gallons) except that, films and molded
articles containing not more than 0.2 percent by
weight of the stabilizer may contact aqueous food of
types I, II, IV-B, VI, and VIII, described in Table 1
of Sec. 176.170 of this chapter with no restrictions
on the amount of food contacted.
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[[Page 67486]]
Dated: November 23, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-31228 Filed 12-1-99; 8:45 am]
BILLING CODE 4160-01-F