[Federal Register Volume 64, Number 213 (Thursday, November 4, 1999)]
[Rules and Regulations]
[Pages 60104-60106]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-28850]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 175
[Docket No. 91F-0431]
Indirect Food Additives: Resinous and Polymeric 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 2,2'-[(1-
methylethylidene)bis[4,1-phenyleneoxy[1-(butoxymethyl)-2,1-
ethanediyl]oxymethylene]]bisoxirane as a component of epoxy coatings
intended for use in contact with bulk dry foods. This action is in
response to a petition filed by Ciba-Geigy Corp.
DATES: This regulation is effective November 4, 1999; written
objections and requests for a hearing by December 6, 1999.
ADDRESS: 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 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 December 5, 1991
(56 FR 63737), FDA announced that a food additive petition (FAP 1B4278)
had been filed by Ciba-Geigy Corp., Seven Skyline Dr., Hawthorne, NY
10532-2188. The petition proposed to amend the food additive
regulations in Sec. 175.300 Resinous and polymeric coatings (21 CFR
175.300) to provide for the safe use of 2,2'-[(1-
methylethylidene)bis[4,1-phenyleneoxy[1-(butoxymethyl)-2,1-
ethanediyl]oxymethylene]]bisoxirane as a component of resinous and
polymeric coatings intended for use in contact with dry bulk foods.
In FDA's evaluation of the safety of this additive, 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
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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 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)).
III. Safety of the Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive, 2,2'-[(1-
methylethylidene)bis[4,1-phenyleneoxy[1-(butoxymethyl)-2,1-
ethanediyl]oxymethylene]]bisoxirane, will result in exposure no greater
than 4.4 parts per (pp) trillion of the additive in the daily diet (3
kilograms (kg)) or an estimated daily intake (EDI) of 13 nanograms per
person per day (ng/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, a carcinogenic chemical that
may be present as an impurity in the additive. The risk evaluation of
epichlorohydrin has two aspects: (1) Assessment of the 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
exposure to humans.
A. Epichlorohydrin
FDA has estimated the exposure to epichlorohydrin from the
petitioned use of the additive as a component of epoxy coatings to be
no more than 0.013 pp trillion of the daily diet (3 kg), or 39
picograms/person/day (pg/p/d) (Ref.3). The agency used data from a
carcinogenesis bioassay conducted on rats fed epichlorohydrin via their
drinking water (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 rats.
Based on the agency's estimate that exposure to epichlorohydrin
will not exceed 39 pg/p/d, FDA estimates that the upper-bound limit of
lifetime human risk from the petitioned use of the subject additive is
1.8 X 10-12, or 1.8 in one trillion (Ref. 5). 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 present as an
impurity in the food additive. The agency finds that specifications are
not necessary for the following reasons: (1) Because the low levels 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, 1.8 in a trillion.
IV. Conclusion
FDA has evaluated data in the petition and other relevant
material. The agency concludes that: (1) The proposed use of the
additive is safe, (2) the additive will achieve its intended technical
effect, and (3) the regulations in Sec. 175.300 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. Environmental Impact
The agency has determined under 21 CFR 25.32(j) that this action
is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment (EA) nor an environmental impact statement is
required.
VI. Paperwork Reduction Act of 1995
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.
VII. Objections
Any person who will be adversely affected by this regulation may
at any time on or before December 6, 1999, 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
[[Page 60106]]
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
(address above) 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 Division of Product Manufacture and Use,
Chemistry Review Team (HFS-246), to the Division of Petition Control
(HFS-215), entitled ``FAP 1B4278 (MATS #583, M2.2.1): Ciba-Geigy
Corp., Request from DHEE dated 12-16-97 for a revised exposure
estimate to Araldite XU GY 376, an epoxy resin for use as a repeat-
use coating component that will contact bulk grains and dry foods,''
dated February 27, 1998.
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in
Chemical Safety Regulation and Compliance, edited by F. Homburger
and J. K. Marquis, published by S. Karger, New York, NY, pp. 24 to
33, 1985.
3. Memorandum from the Chemistry Review Branch (HFS-247) to the
Indirect Additives Branch (HFS-216), entitled ``FAP-1B4278 (MATS
#583) Ciba-Geigy Corp., Submission dated 10-23-92. Araldite XU GY
376 as a component of food-contact coatings,'' dated May 12, 1993.
4. Konishi, Y. et al.,``Forestomach Tumors Induced by Orally
Administered Epichlorohydrin in Male Wistar Rats,'' Gann, 71: pp.
922 to 923, 1980.
5. Memorandum from the Indirect Additives Branch (HFS-216) to
the Executive Secretary, Quantitative Risk Assessment Committee
(QRAC) (HFS-308) entitled ``Estimation of the upper bound lifetime
risk from epichlorohydrin in 2,2'-[(1-methylethylidene)bis[4,1-
phenyleneoxy[1-(butoxymethyl)-2,1-ethanediyl]oxymethylene]]
bisoxirane, the subject of FAP 1B4278 (Ciba-Geigy Corp.),'' dated
November 22, 1993.
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, 21 CFR
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: Secs. 21 U.S.C. 321, 342, 348, 379e.
2. Section 175.300 is amended in paragraph (b)(3)(viii)(a) by
alphabetically adding an entry to read as follows:
Sec. 175.300 Resinous and polymeric coatings.
* * * * *
(b) * * *
(3) * * *
(viii) * * *
(a) * * *
* * * * *
2,2'-[(1-methylethylidene)bis[4,1-phenyleneoxy[1-(butoxymethyl)-
2,1-ethanediyl]oxymethylene]]bisoxirane, CAS Reg. No. 71033-08-4,
for use only in coatings intended for contact with bulk dry foods at
temperatures below 100 \1/2\F.
* * * * *
Dated: October 25, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-28850 Filed 11-3-99; 8:45 am]
BILLING CODE 4160-01-F