[Federal Register Volume 64, Number 240 (Wednesday, December 15, 1999)]
[Rules and Regulations]
[Pages 69898-69901]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-32427]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 99F-1423]


Indirect Food Additives: Paper and Paperboard Components

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 4,5-dichloro-1,2-
dithiol-3-one (also known as 4,5-dichloro-3H-1,2-dithiol-3-one) as a 
slimicide in the manufacture of food-contact paper and paperboard. This 
action is in response to a petition filed by Yoshitomi Fine Chemicals, 
Ltd.

DATES: The regulation is effective December 15, 1999. Submit written 
objections and requests for a hearing by January 14, 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: Mark A. Hepp, Center for Food Safety 
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3098.

SUPPLEMENTARY INFORMATION: In a notice published in the  Federal 
Register of May 27, 1999 (64 FR 28825), FDA announced that a food 
additive petition (FAP 9B4654) had been filed by Yoshitomi Fine 
Chemicals, Ltd., c/o SRS International Corp., suite 1000, 1625 K St. 
NW., Washington, DC 20006-1604. The petition proposed to amend the food 
additive regulations in Sec. 176.300 Slimicides (21 CFR 176.300) to 
provide for the safe use of 4,5-dichloro-1,2-dithiol-3-one as a 
slimicide in the manufacture of food-contact paper and paperboard.
     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 1,2-dichloroethane and 
tetrachloroethylene, carcinogenic impurities resulting from the 
manufacture of the additive.

[[Page 69899]]

 Residual amounts of reactants and manufacturing aids, such as 1,2-
dichloroethane and tetrachloroethylene, are commonly found as 
contaminants in chemical products, including food additives.

 I. 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)).

 II. Safety of Petitioned Use of the Additive

     FDA estimates that the petitioned use of the additive, 4,5-
dichloro-1,2-dithiol-3-one, will result in exposure to no greater than 
0.8 part per billion of the additive in the daily diet (3 kilogram 
(kg)) or an estimated daily intake of 2.4 micrograms per person per day 
(g/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 dietary exposure resulting from the petitioned use of the 
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 1,2-dichloroethane and tetrachloroethylene, the 
carcinogenic chemicals that may be present as impurities in the 
additive. This risk evaluation of 1,2-dichloroethane and 
tetrachloroethylene has two aspects: (1) Assessment of the exposure to 
the impurities 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. 1,2-Dichloroethane

     FDA has estimated the exposure to 1,2-dichloroethane from the 
petitioned use of the additive as a slimicide in the manufacture of 
food-contact paper and paperboard to be no more than 24 parts per 
trillion (ppt) in the daily diet (3 kg), or 72 nanograms(ng)/p/d (Ref. 
4). The agency used data from a carcinogenesis bioassay on 1,2-
dichloroethane, conducted by the National Cancer Institute (Ref. 3), 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 squamous cell carcinomas of the forestomach and 
hemangiosarcomas of the circulatory system in male rats and 
adenocarcinomas of the mammary gland in female rats.
     Based on the agency's estimate that exposure to 1,2-dichloroethane 
will not exceed 72 ng/p/d, FDA estimates that the upper-bound limit of 
lifetime human cancer risk from the petitioned use of the subject 
additive is 1.3 x 10-8, or 1.3 in 100 million (Ref. 4). 
Because of the numerous conservative assumptions used in calculating 
the exposure estimate, the actual lifetime-averaged individual exposure 
to 1,2-dichloroethane 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 1,2-dichloroethane would result from the petitioned 
use of the additive.

 B. Tetrachloroethylene

     FDA has estimated the exposure to tetrachloroethylene from the 
petitioned use of the additive as a slimicide in the manufacture of 
food-contact paper and paperboard to be no more than 2.4 ppt in the 
daily diet (3 kg), or 7.2 ng/p/d (Ref. 4). The agency used data from a 
carcinogenesis bioassay on tetrachloroethylene, conducted by the 
National Toxicology Program (Ref. 5), 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 hepatocellular 
adenomas and carcinomas in male mice and hepatocellular carcinomas in 
female mice.
     Based on the agency's estimate that exposure to 
tetrachloroethylene will not exceed 7.2 ng/p/d, FDA estimates that the 
upper-bound limit of lifetime human risk from the petitioned use of the 
subject additive is 3.6 x 10-10, or 3.6 in 10 billion (Ref. 
4). Because of the numerous conservative assumptions used in 
calculating the exposure estimate, the actual lifetime-averaged 
individual exposure to tetrachloroethylene 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 tetrachloroethylene 
would result from the petitioned use of the additive.

 C. Need for Specifications

     The agency also has considered whether specifications are 
necessary to control the amount of 1,2-dichloroethane and 
tetrachloroethylene as impurities in the additive. The agency finds 
that specifications are not necessary for the following reasons: (1) 
Because of the low level at which 1,2-dichloroethane and 
tetrachloroethylene may be expected to remain as impurities following 
production of the additive, the agency would not expect the impurities 
to become components of food at other than extremely small levels; and 
(2) the upper-bound limits of lifetime risk from exposure to 1,2-
dichloroethane, and tetrachloroethylene are very low, less than 1.3 in 
100 million, and 3.6 in 10 billion, respectively.

 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 is safe, that the additive will achieve 
its intended technical effect, and therefore, that the regulations in 
Sec. 176.300 should be amended as set forth below.
     The additive, 4,5-dichloro-1,2-dithiol-3-one, intended for use as 
a slimicide in the manufacture of food-contact paper and paperboard, is 
regulated under section 409 of the act (21 U.S.C. 348) as a food 
additive and not as a pesticide chemical under section 408 of the act

[[Page 69900]]

(21 U.S.C. 346a). However, this intended use of 4,5-dichloro-1,2-
dithiol-3-one may nevertheless be subject to regulation as a pesticide 
under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 
Therefore, manufacturers intending to use 4,5-dichloro-1,2-dithiol-3-
one as a slimicide in the manufacture of food-contact paper and 
paperboard should contact the Environmental Protection Agency to 
determine whether this use requires a pesticide registration under 
FIFRA.
     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 previously considered the environmental effects of 
this rule as announced in the notice of filing for FAP 9B4654 (64 FR 
28825). No new information or comments have been received that would 
affect the agency's previous determination that there is no significant 
impact on the human environment and that an environmental impact 
statement is not required.

 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. Objections

     Any person who will be adversely affected by this regulation may 
at any time on or before January 14, 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.

 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 from the Chemistry and Environmental Review Team, 
FDA, to the Division of Petition Control, FDA, ``FAP 9B4654 (MATS # 
1039)--SRS International Corp. (on behalf of Yoshitomi Fine 
Chemicals, Ltd.). 4,5-Dichloro-3H-1,2-Dithiol-3-One (RYH-86) as a 
Slimicide in the Manufacture of Paper and Paperboard. Division of 
Petition Control (DPC) E-Mail Request of 9-14-99,'' October 12, 
1999.
     2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' 
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. ``Bioassay of 1,2-Dichloroethane for Possible 
Carcinogenicity,'' National Cancer Institute, NCI-CG-TR-55, 1978.
     4. Memorandum from the Indirect Additives Branch, FDA, to the 
Executive Secretary, Quantitative Risk Assessment Committee, FDA, 
``Third Estimation of the Upper-Bound Lifetime Risk From 1,2-
Dichloroethane (DCE) and Tetrachloroethylene (TCE) in 4,5-Dichloro-
1,2-Dithiol-3-One for FAP 8B4654,'' October 13, 1999.
     5. ``Toxicology and Carcinogenisis Studies of 
Tetrachloroethylene (Perchloroethylene) in F344/N Rats and 
B6C3F1 Mice (Inhalation Studies),'' National Toxicology 
Program Technical Report Series No. 311, 1986.

 List of Subjects in 21 CFR Part 176

     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 176 is amended as follows:

 PART 176--INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS

     1. The authority citation for 21 CFR part 176 continues to read as 
follows:
     Authority: 21 U.S.C. 321, 342, 346, 348, 379e.
     2. Section 176.300 is amended in the table in paragraph (c) by 
alphabetically adding an entry under the headings ``Lists of 
substances'' and ``Limitations'' to read as follows:


Sec. 176.300   Slimicides.

* * * * *
     (c) * * *

 
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         List of substances                      Limitations
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  *                    *                    *                    *
                   *                    *                    *
4,5-dichloro-1, 2-dithiol-3-one       For use only at levels not to
 (CAS Reg. No. 1192-52-5).            exceed 10 milligrams per kilogram
                                      in the pulp slurry.
  *                    *                    *                    *
                   *                    *                    *
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[[Page 69901]]

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    Dated: December 7, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-32427 Filed 12-14-99; 8:45 am]
BILLING CODE 4160-01-F