[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] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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) * * * ------------------------------------------------------------------------ List of Substances Limitations ------------------------------------------------------------------------ * * * * * * * 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. * * * * * * * ------------------------------------------------------------------------ [[Page 39940]] * * * * * 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