[Federal Register Volume 62, Number 143 (Friday, July 25, 1997)]
[Rules and Regulations]
[Pages 39937-39940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-19568]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 96F-0291]


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 12-hydroxystearic 
acid-polyethylene glycol (minimum MW 200) block copolymer as a 
surfactant in the manufacture of paper and paperboard intended for use 
in contact with food. This action is in response to a petition filed by 
ICI Americas, Inc.

DATES: Effective July 25, 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: 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 August 26, 1996 (61 FR 43772), FDA announced that a food 
additive petition (FAP 6B4519) had been filed by ICI Americas, Inc., 
3411 Silverside Rd., Wilmington, DE 19850. The petition proposed to 
amend the food additive regulations in Sec. 176.170 Components of paper 
and paperboard in contact with aqueous and fatty foods (21 CFR 176.170) 
to provide for the safe use of 12-hydroxystearic acid-polyethylene 
glycol (minimum MW 200) block copolymer as a surfactant in the 
manufacture of paper and paperboard intended for use 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 unreacted 1,4-dioxane and 
ethylene oxide, carcinogenic impurities resulting from

[[Page 39938]]

the manufacture of the additive. Residual amounts of reactants and 
manufacturing aids, such as 1,4-dioxane and ethylene oxide, 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, 12-
hydroxystearic acid-polyethylene glycol (minimum MW 200) block 
copolymer as a surfactant in the manufacture of paper and paperboard 
will result in exposure to the additive of no greater than 15 parts per 
billion in the daily diet (3 kilogram (kg)) or an estimated daily 
intake of 45 microgram per person per day (ug/p/d) (Ref. 1).
    FDA does not ordinarily consider chronic toxicological testing 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 
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 1,4-dioxane and ethylene oxide, the 
carcinogenic chemicals that may be present as impurities in the 
additive. This risk evaluation of 1,4-dioxane and ethylene oxide 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. 1,4-Dioxane

    FDA has estimated the exposure to 1,4-dioxane from the petitioned 
use of the additive in the manufacture of paper and paperboard to be 
1.5 parts per quadrillion (pp quad) of the daily diet (3 kg) or 4.5 
picogram (pg)/person/day (Ref. 1). The agency used data from a 
carcinogenesis bioassay on 1,4-dioxane, conducted by the National 
Cancer Institute (Ref. 3), to estimate the upper-bound lifetime human 
risk from exposure to this chemical stemming from the petitioned use of 
the additive. The results of the bioassay on 1,4-dioxane demonstrated 
that the material was carcinogenic for female rats under the conditions 
of the study. The test material caused a significantly increased 
incidence of squamous cell carcinomas and hepatocellular tumors in 
female rats.
    Based on the agency's estimate that exposure to 1,4-dioxane will 
not exceed 4.5 pg/person/day, FDA estimates that the upper-bound limit 
of lifetime human risk from the use of the subject additives is 1.6 x 
10-13 (or 1.6 in 10 trillion) (Ref. 4). 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.

B. Ethylene oxide

    FDA has estimated the exposure to ethylene oxide from the 
petitioned use of the additive in the manufacture of paper and 
paperboard to be 1.5 pp quad of the daily diet (3 kg) or 4.5 pg/person/
day (Ref. 1). The agency used data from a carcinogenesis bioassay on 
ethylene oxide conducted by the Institute of Hygiene, University of 
Mainz, Germany (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 results of the bioassay on ethylene oxide 
demonstrated that ethylene oxide was carcinogenic for female rats under 
the conditions of the study. The test material caused significantly 
increased incidence of squamous cell carcinomas of the forestomach and 
carcinomas in situ of the glandular stomach.
    Based on the agency's estimate that the exposure to ethylene oxide 
will not exceed 4.5 pg/person/day, FDA estimates that the upper-bound 
limit of lifetime human risk from the petitioned use of the subject 
additives is 8.4 x 10-12 (or 8.4 in 1 trillion)) (Ref. 4). 
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.

C. Need for Specifications

    The agency has also considered whether specifications are necessary 
to control the amount of 1,4-dioxane and ethylene oxide 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 1,4-
dioxane and ethylene oxide may be expected to remain as impurities 
following production of the additives, the agency would not expect the 
impurities to become components of food at other than an extremely 
small level; and (2) the upper-bound limits of lifetime risk from 
exposure to 1,4-dioxane and ethylene oxide, even under worst-case 
assumptions, is very low, 1.6 in 10 trillion and 8.4 in 1 trillion, 
respectively.

III. 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. 176.170 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

[[Page 39939]]

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. 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.

V. Objections

    Any person who will be adversely affected by this regulation may at 
anytime on or before August 25, 1997 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.

VI. 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 Review Team, FDA, to the file 
concerning ``FAP 6B4519 (MATS #882, M2.0 & 2.1): ICI Americas Inc., 
dated July 23, 1996. Use of 12-hydroxystearic acid-propylene glycol 
(MW 200) Block Copolymer as an Adjuvant in the Manufacture of Paper 
and Paperboard,'' dated August 20, 1996.
    2. 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.
    3. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,'' 
National Cancer Institute, NCI-CG-TR-80, 1978.
    4. Memorandum from the Indirect Additives Branch, FDA, to the 
Executive Secretary, Quantitative Risk Assessment Committee, FDA, 
concerning ``Estimation of Upper-bound Lifetime Risk from Ethylene 
Oxide and 1,4-dioxane in 12-hydroxystearic acid-polyethylene glycol 
(MW 200) Block Copolymer as an Adjuvant in the Manufacture of Paper 
and Paperboard: Subject of Food Additive Petition No. 6B4519 (ICI 
Americas Inc.),'' dated March 3, 1996.
    5. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
propylene Oxide Upon Intrgastric Administration to Rats,'' British 
Journal of Cancer, 46: pp. 924-933, 1982.

List of Subjects in 21 CFR Part 175

     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 176.170 is amended in the table in paragraph (a)(5) by 
revising the entry for ``12-Hydroxystearic acid-polyethylene glycol 
block copolymers (CAS Reg. No. 70142-34-6)'' to read as follows:

Sec. 176.170  Components of paper and paperboard in contact with 
aqueous and fatty foods.

* * * * *
    (a) * * *
    (5) * * *

                                                                        
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          List of Substances                       Limitations          
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  *                    *                    *                    *      
                   *                    *                    *          
12-Hydroxystearic acid-polyethylene     For use only as a surfactant for
 glycol block copolymers (CAS Reg. No.   dispersions of polyacrylamide  
 70142-34-6) produced by the reaction    retention and drainage aids    
 of polyethylene glycol (minimum         employed prior to the sheet    
 molecular weight 200) with 12-          forming operation in the       
 hydroxystearic acid.                    manufacture of paper and       
                                         paperboard.                    
  *                    *                    *                    *      
                   *                    *                    *          
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    Dated: July 17, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-19568 Filed 7-24-97; 8:45 am]
BILLING CODE 4160-01-F