[Federal Register Volume 62, Number 142 (Thursday, July 24, 1997)]
[Rules and Regulations]
[Pages 39770-39773]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-19428]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 93F-0428]


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 -
(dinonylphenyl)--hydroxy-poly(oxy-1,2-ethanediyl), containing 
7 to 24 moles of ethylene oxide per mole of dinonylphenol, as a 
component of defoaming agents used in styrene-butadiene coatings for 
paper and paperboard intended to contact food. This action is in 
response to a food additive petition filed by PPG Industries, Inc.

DATES: Effective July 24, 1997; written objections and requests for a 
hearing by August 25, 1997.
ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Andrew J. Zajac, Center for Food 
Safety and Applied Nutrition (HFS-215), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3095.

SUPPLEMENTARY INFORMATION:

I. Background

    In a notice published in the Federal Register of January 5, 1994 
(59 FR 590), FDA announced that a food additive petition (FAP 3B4363) 
had been filed by PPG Industries, Inc., One PPG Pl., Pittsburgh, PA 
15272 (formerly 440 College Park Dr., Monroeville, PA 15146). The 
petition proposed to amend the food additive regulations in 
Sec. 176.200 Defoaming agents used in coatings (21 CFR 176.200) and 
Sec. 176.210 Defoaming agents used in the manufacture of paper and 
paperboard (21 CFR 176.210) to provide for the use of -
(dinonylphenyl)--hydroxy-poly(oxy-1,2-ethanediyl), containing 
7 to 24 moles of ethylene oxide per mole of dinonylphenol, as a 
defoaming agent used in the production of paper and paperboard and 
coatings for paper and paperboard intended to contact food. The 
petitioner has subsequently withdrawn the request for approval of the 
use of the additive in the production of paper and paperboard and has 
requested that approval of the additive be limited to use in styrene-
butadiene polymer coatings for paper and paperboard intended to contact 
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 unreacted ethylene oxide and 
minute amounts of 1,4-dioxane as impurities resulting from its 
manufacture. These chemicals have been shown to cause cancer in test 
animals. Residual amounts of impurities are commonly found as 
constitutents of chemical products, including food additives.

[[Page 39771]]

II. 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 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 
clause 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 Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, -
(dinonylphenyl)--hydroxy-poly(oxy-1,2-ethanediyl), containing 
7 to 24 moles of ethylene oxide per mole of dinonylphenol, will result 
in exposure to no greater than 25 parts per billion (ppb) of the 
additive in the daily diet (3 kilogram (kg)) or an estimated daily 
intake (EDI) of 75 micrograms per person per day (g/person/
day) (Refs. 1 and 2).
    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. 3), 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 clause, considering all available data and using risk assessment 
procedures to estimate the upper-bound limit of lifetime human risk 
presented by ethylene oxide and 1,4-dioxane, the carcinogenic chemicals 
that may be present as impurities in the additive. The risk evaluation 
of ethylene oxide and 1,4-dioxane has two aspects: (1) Assessment of 
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. Ethylene oxide

    FDA has estimated the exposure to ethylene oxide from the 
petitioned use of the additive as a component of defoaming agents used 
in styrene-butadiene coatings for paper and paperboard to be no more 
than 0.25 part per trillion (pptr) in the daily diet (3 kg), or 0.75 
nanogram (ng)/person/day (Refs. 1 and 2). The agency used data from a 
long-term rodent bioassay on ethylene oxide conducted for the Institute 
of Hygiene, University of Mainz, Germany (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 author reported 
that the test material caused significantly increased incidence of 
squamous cell carcinomas in situ of the forestomach and carcinoma in 
situ of the glandular stomach in female rats.
    Based on the agency's estimate that exposure to ethylene oxide will 
not exceed 0.75 ng/person/day, 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. 5). Because of the 
numerous conservative assumptions used in calculating the exposure 
estimate, the actual lifetime-averaged individual exposure to ethylene 
oxide 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 
ethylene oxide would result from the petitioned use of the additive.

B. 1,4-Dioxane

    FDA has estimated the exposure to 1,4-dioxane from the petitioned 
use of the additive as a component of defoaming agents used in styrene-
butadiene coatings for paper and paperboard to be no more than 0.13 
pptr of the daily diet (3 kg), or 0.39 ng/person/day (Refs. 1 and 2). 
The agency used data from a long-term rodent bioassay on 1,4-dioxane 
conducted by the National Cancer Institute (Ref. 6), 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 in male and female rats and hepatocellular 
tumors in female rats and male and female mice.
    Based on the agency's estimate that exposure to 1,4-dioxane will 
not exceed 0.39 ng/person/day, FDA estimates that the upper-bound limit 
of lifetime human risk from the petitioned use of the subject additive 
is 1.4 x 10-11, or 14 in a trillion (Ref. 5). Because of the 
numerous conservative assumptions used in calculating the exposure 
estimate, the actual lifetime-averaged individual exposure to 1,4-
dioxane 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 1,4-
dioxane would result from the petitioned use of the additive.

C. Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of ethylene oxide and 1,4-dioxane present as 
impurities in the additive. The agency finds that specifications are 
not necessary for the following reasons: (1) Because of the low levels 
at which ethylene oxide and 1,4-dioxane 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 low levels; and (2) the upper-bound limits of lifetime human 
risk from exposure to the impurities, even under worst-case 
assumptions, are very low (less than 1.5 in 1 billion).

IV. 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 component of defoaming agents used in 
styrene-butadiene coatings for paper and paperboard 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. 176.200 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

[[Page 39772]]

documents any materials that are not available for public disclosure 
before making the documents available for inspection.

V. 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. No comments were received during the 30-day comment 
period specified in the filing notice for comments on the environmental 
assessment submitted with the petition.

VI. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before August 25, 1997, 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 dated June 19, 1995, from the Chemistry Review 
Branch (HFS-247), to the Indirect Additives Branch (HFS-216) 
entitled ``FAP 3B4363 (MATS No. 695; M 2.3 and M 2.4)-PPG 
Industries, Inc. Dinonylphenol-ethylene oxide adduct for use as a 
component of defoaming agents used in paper coatings and in the 
manufacture of paper and paperboard. Submissions dated 7-12-94, 10-
4-94, and 11-1-94.''
    2. Memorandum dated July 11, 1996, from the Chemistry Review 
Branch (HFS-247), to the Indirect Additives Branch (HFS-216) 
entitled ``FAP 3B4363 (MATS No. 695; M 2.4.1)-PPG Industries, Inc. 
Dinonylphenol-ethylene oxide adduct for use as a component of 
defoaming agents used in paper coatings. Telefax submissions dated 
9-22-95 and 3-7-96.''
    3. Kokoski, C. J., ``Regulatory Food Additive Toxicology'' in 
Chemical Safety Regulation and Compliance, edited by F. Homburger, 
J. K. Marquis, and S. Karger, New York, NY, pp. 24-33, 1985.
    4. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
Propylene Oxide Upon Intragastric Administration to Rats,'' British 
Journal of Cancer, 46:924, 1982.
    5. Memorandum dated July 24, 1996, from Indirect Additives 
Branch (HFS-216), to Sara H. Henry, Executive Secretary, 
Quantitative Risk Assessment Committee (HFS-308), entitled 
``Estimation of the upper-bound lifetime risk from ethylene oxide 
and 1,4-dioxane - FAP 3B4363.''
    6. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,'' 
National Cancer Institute, NCI-CG-TR-80, 1978.

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: Secs. 201, 402, 406, 409, 721 of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 321, 342, 346, 348, 379e).

    2. Section 176.200 is amended in the table in paragraph (d)(3) by 
alphabetically adding a new entry under the headings ``List of 
substances'' and ``Limitations'' to read as follows:

Sec. 176.200  Defoaming agents used in coatings.

* * * * *
    (d) * * *
    (3) * * *

                                                                                                                
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                   List of substances                                          Limitations                      
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  *                    *                    *                    *                    *                    *    
                                                             *                                                  
-(Dinonylphenyl)--hydroxy-poly(oxy-   For use only in defoaming agents for the production of 
 1,2-ethanediyl), containing 7 to 24 moles of ethylene    styrene-butadiene coatings at a level not to exceed   
 oxide per mole of dinonylphenol (CAS Reg. No. 9014-93-   0.05 percent by weight of the finished coating.       
 1).                                                                                                            
  *                    *                    *                    *                    *                    *    
                                                             *                                                  
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[[Page 39773]]

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    Dated: June 10, 1997.
William K.Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-19428 Filed 7-23-97; 8:45 am]
BILLING CODE 4160-01-F