[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

[[Page 60105]]

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