[Federal Register Volume 63, Number 212 (Tuesday, November 3, 1998)]
[Rules and Regulations]
[Pages 59213-59215]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29333]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 178

[Docket No. 96F-0214]


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 2,9-dichloro-5,12-
dihydroquinone[2,3-b]acridine-7,14-dione (C.I. Pigment Red 202) as a 
colorant for polymers used in contact with food. This action is in 
response to a petition filed by Ciba-Geigy Corp.

DATES: The regulation is effective November 3, 1998; submit written 
objections and requests for a hearing December 3, 1998.

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 July 5, 1996 (61 FR 35229), FDA announced that a food 
additive petition (FAP 6B4512) had been filed by Ciba-Geigy Corp., 335 
Water St., Newport, DE

[[Page 59214]]

19804 (currently, c/o Keller and Heckman, 1001 G St. NW., suite 500 
West, Washington, DC 20001). The petition proposed to amend the food 
additive regulations in Sec. 178.3297 Colorants for polymers (21 CFR 
178.3297) to provide for the safe use of 2,9-dichloro-5,12-
dihydroquinone[2,3-b]acridine-7,14-dione (C.I. Pigment Red 202) as a 
colorant in polymers used in contact with food.
    In its evaluation of the safety of this additive, FDA has 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 para-chloroaniline, a 
carcinogenic impurity resulting from the manufacture of the additive. 
Residual amounts of reactants and manufacturing aids, such as para-
chloroaniline, 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 additive anticancer, or Delaney, clause of the act further 
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 constituents of 
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 proposed use of the 
additive (Scott v. FDA, 728 F.2d 322 (6th Cir. 1984)).

II. Safety of Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, 2,9-
dichloro-5,12-dihydroquinone[2,3-b]acridine-7,14-dione, will result in 
exposure to no greater than 2.5 parts per billion of the additive in 
the daily diet (3 kilogram (kg)), or an estimated daily intake of 7.5 
microgram per person per 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 data on the additive and concludes that the 
estimated small dietary exposure resulting from the proposed use of 
this additive is safe.
    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 para-chloroaniline, the carcinogenic chemical that may be 
present as an impurity in the additive. The risk evaluation of para-
chloroaniline has two aspects: (1) Assessment of exposure to the 
impurity from the proposed use of the additive; and (2) extrapolation 
of the risk observed in the animal bioassay to the conditions of 
probable exposure to humans.

A. Para-Chloroaniline

    FDA has estimated the exposure to para-chloroaniline from the 
petitioned use of the additive as a colorant in polymers to be 20 parts 
per trillion in the daily diet (3 kg), or 60 nanograms per person per 
day (ng/p/d) (Ref. 1). The agency used data from a carcinogenicity 
study of para-chloroaniline conducted by the National Toxicology 
Program (NTP) (Ref. 3), to estimate the upper-bound limit of lifetime 
human risk from exposure to this chemical resulting from the proposed 
use of the additive. The results of the NTP carcinogenicity studies on 
this chemical demonstrated that administration of the test material to 
Fisher 344 rats by gavage caused increased incidence of splenic 
sarcomas in male rats.
    Based on the agency's estimated exposure to para-chloroaniline of 
60 ng/p/d, FDA estimates that the upper-bound limit of lifetime human 
risk from the proposed use of the subject additive is 1 x 
10-8, or 1 in 100 million (Ref. 4). Because of the numerous 
conservative assumptions used in calculating the exposure estimate, the 
actual lifetime-averaged individual exposure to para-chloroaniline 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 para-
chloroaniline 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 para-chloroaniline present 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 para-chloroaniline 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 the impurity is very low, less than 1 in 100 million.

III. Conclusion

    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 colorant in polymers in contact with 
food is safe, and that the additive will achieve its intended technical 
effect. Therefore, the agency concludes that the regulations in 
Sec. 178.3297 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 (address above) 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. Paperwork Reduction Act of 1995

    This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget

[[Page 59215]]

under the Paperwork Reduction Act of 1995 is not required.

VI. Objections

    Any person who will be adversely affected by this regulation may at 
anytime on or before December 3, 1998, file with the Dockets Management 
Branch (address above) written objection 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 
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 objection 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 dated August 29, 1996, from the Chemistry Review 
Branch (HFS-247), to the file concerning FAP 6B4512, dietary 
concentrations of the additive and the impurity (para-
chloroaniline).
    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. 24-33, 
1985.
    3. Chhabra, R. S., Toxicology and Carcinogenesis Studies of 
para-Chloroaniline Hydrochloride in F344/N Rats and B6C3F1 Mice 
(Gavage Studies), National Toxicology Program, Technical Report 
Series No. 351, July 1989.
    4. Report of the Quantitative Risk Assessment Committee, FDA, 
concerning ``Assessment of Carcinogenic upper-bound lifetime risk 
resulting from contamination by para-chloroaniline residues in C.I. 
Pigment Red 202 (Ciba-Geigy Corp.), FAP 6B4512, dates April 9, 1998.

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 178.3297 is amended in the table in paragraph (e) by 
alphabetically adding an entry under the headings ``Substances'' and 
``Limitations'' to read as follows:

Sec. 178.3297  Colorants for polymers.

* * * * *
    (e) * * *

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                       Substances                                              Limitations
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  *                    *                    *                    *                    *                    *
                                                             *
2,9-Dichloro-5,12-dihydroquinone[2,3-b]acridine-7,14-    For use at levels not to exceed 1.0 percent by weight
 dione (C.I. Pigment Red 202, CAS Reg. No. 3089-17-6).    of polymers.
  *                    *                    *                    *                    *                    *
                                                             *
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     Dated: October 26, 1998.
 William K. Hubbard,
 Associate Commissioner for Policy Coordination.
[FR Doc. 98-29333 Filed 11-2-98; 8:45 am]
BILLING CODE 4160-01-F