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Sodium thiosulfate; Exemption from the Requirement of a Tolerance
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[Federal Register: December 21, 2001 (Volume 66, Number 246)] [Rules and Regulations] [Page 65850-65856] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr21de01-13] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180 [OPP-301196; FRL-6811-6] RIN 2070-AB78 Sodium thiosulfate; Exemption from the Requirement of a Tolerance AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. ----------------------------------------------------------------------- SUMMARY: This regulation establishes an exemption from the requirement of a tolerance for residues of sodium thiosulfate when used as an inert ingredient (dechlorinator) in or on growing crops, or when applied to raw agricultural commodities after harvest. Eden Bioscience submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996 requesting an exemption from the requirement of a tolerance. This regulation eliminates the need to establish a maximum permissible level for residues of sodium thiosulfate. DATES: This regulation is effective December 21, 2001. Objections and requests for hearings, identified by docket control number OPP-301196, must be received by EPA on or before February 19, 2002. ADDRESSES: Written objections and hearing requests may be submitted by mail, in person, or by courier. Please follow the detailed instructions for each method as provided in Unit VIII. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, your objections and hearing requests must identify docket control number OPP-301196 in the subject line on the first page of your response. FOR FURTHER INFORMATION CONTACT: By mail: Kathryn Boyle, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-6304; and e-mail address: boyle.kathryn@epa.gov. SUPPLEMENTARY INFORMATION: I. General Information A. Does this Action Apply to Me? You may be affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to: ------------------------------------------------------------------------ Examples of Categories NAICS codes potentially affected entities ------------------------------------------------------------------------ Industry 111 Crop production 112 Animal production 311 Food manufacturing 32532 Pesticide manufacturing ------------------------------------------------------------------------ This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT. B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents? 1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select ``Laws and Regulations,'' ``Regulations and Proposed Rules,'' and then look up the entry for this document under the ``Federal Register--Environmental Documents.'' You can also go directly to the Federal Register listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR [[Page 65851]] part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/ Title_40/40cfr180_00.html, a beta site currently under development. 2. In person. The Agency has established an official record for this action under docket control number OPP-301196. The official record consists of the documents specifically referenced in this action, and other information related to this action, including any information claimed as Confidential Business Information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is (703) 305-5805. II. Background and Statutory Findings In the Federal Register of September 6, 2000 (65 FR 54015) (FRL- 6738-4), EPA issued a notice pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, as amended by the Food Quality Protection Act (FQPA) (Public Law 104-170) announcing the filing of a pesticide petition (PP 0E6177) by Eden Bioscience, 11816 Creek Parkway North, Bothell, Washington, 98011-8205. This notice included a summary prepared by the petitioner. There were no comments received in response to the notice of filing. The petition requested that 40 CFR 180.1001(c) be amended by establishing an exemption from the requirement of a tolerance for residues of sodium thiosulfate penthydrate (CAS Reg. No. 10102-17-7). The petition requested only the use of sodium thiosulfate pentahydrate; however, sodium thiosulfate is also available in an anhydrous form. The two chemical substances differ only in the attachment of the water molecules. The petition specified that sodium thiosulfate should be used at a concentration of 1 to 6% of the formulated product. The sodium thiosulfate will be used as a pretreatment for the water in tank mixes to remove chlorine or other reactant species, thus functioning as a dechlorinator or reducing agent. When mixed with chlorine-containing water, sodium thiosulfate reacts with the chlorine according to the equation Na2S2O3 + 4Cl2 + 5H2O2NaHSO4 + 8HCl. Sodium thiosulfate also reacts with hydrochloric acid (produced in the previous reaction) to form breakdown products such as sulfur, salt and water: Na2S2O3 + 2HCl 2NaCl + H2O + S + SO2. Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.'' This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .'' EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, EPA determines the toxicity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings. III. Inert Ingredient Definition Inert ingredients are all ingredients that are not active ingredients as defined in 40 CFR 153.125 and include, but are not limited to, the following types of ingredients (except when they have a pesticidal efficacy of their own): Solvents such as alcohols and hydrocarbons; surfactants such as polyoxyethylene polymers and fatty acids; carriers such as clay and diatomaceous earth; thickeners such as carrageenan and modified cellulose; wetting, spreading, and dispersing agents; propellants in aerosol dispensers; microencapsulating agents; and emulsifiers. The term ``inert'' is not intended to imply nontoxicity; the ingredient may or may not be chemically active. Generally, EPA has exempted inert ingredients from the requirement of a tolerance based on the low toxicity of the individual inert ingredients. IV. Toxicological Profile Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information in support of this action and considered its validity, completeness and reliability and the relationship of this information to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxic effects caused by sodium thiosulfate are discussed in this unit. The information submitted in support of this petition included portions of the Food and Drug Administration (FDA) generally recognized as safe (GRAS) determination (``Evaluation of the Health Aspects of Sodium Thiosulfate as a Food Ingredient''), articles from open literature, and an acute oral toxicity study. A. Medical Uses There are medical uses of sodium thiosulfate. It has been used as an antidote for acute cyanide poisoning (intravenous injection), and is an ingredient in various dermally-applied lotion formulations used to treat acne and ringworm. B. GRAS Determination Sodium thiosulfate pentahydrate has been classified as GRAS by the FDA when used as a formulation aid or reducing agent in alcoholic beverages (not to exceed 0.00005%) and table salt (not to exceed 0.1%). A GRAS determination means general recognition of safety by experts qualified by scientific training and experience to evaluate the safety of the substance for the specified use pattern. As noted by the limitations stated above, sodium thiosulfate has a very limited use pattern. EPA will use the information evaluated as part of the FDA GRAS determination to inform the Agency's decision. In its 1975 Evaluation, FDA reported the following information on the sodium thiosulfate absorption and metabolism: Sodium thiosulfate is a normal constituent of human body fluids and is excreted in the urine of man and higher animals. Quantitative studies have demonstrated the consistent presence of 2 to 17 milligrams (mg) of thiosulfate sulfur in 24-hour urine specimens of healthy young adults. Variations in excretion of thiosulfate are related to the extent of protein metabolism, activity of the intestinal flora, and the sulfur-amino [[Page 65852]] acid content of the diet. The sulfur-containing amino acids of dietary protein are the source of the endogenous thiosulfate pool. Orally administered thiosulfate that is absorbed from the gastrointestinal tract is excreted in the urine unchanged or after oxidation to sulfate. From 5 to 70% of an oral dose of sodium thiosulfate is considered to be absorbed from the gastrointestinal tract of man and the remainder to be excreted in the feces. According to the Evaluation, sodium thiosulfate was found to cause no mutagenic effects. The Evaluation also included a summary of the results of developmental studies on rats, mice, and hamsters. It was determined there was no effect on nidation, maternal or fetal survival, or fetal development. C. Open Literature Articles Three of the articles from open literature were reviewed to determine if the articles could supply information to the Agency on the genotoxicity of sodium thiosulfate. There is no indication of any mutagenic activity associated with exposure to sodium thiosulfate. D. Acute Oral Toxicity Study An acute oral toxicity study in the rat performed with sodium thiosulfate pentahydrate was submitted. The study was classified as acceptable, toxicity category IV. The LD50 is greater than 5,050 milligrams/kilograms (mg/kg) (males and females combined). E. Developmental Toxicity As part of the information submitted in support of the petition, the petitioner submitted the final reports for the rat, mouse, and hamster developmental studies that were discussed in the FDA Evaluation (dated 1972), as well as the final report for a rabbit developmental toxicity study (dated 1974). These studies were performed using the anhydrous form of sodium thiosulfate. Due to the passage of almost 30 years, as well as the changes in laboratory techniques that have occurred during this time, the data tables in the reports were reviewed to determine if any additional information were contained in the tables. 1.Mouse. Animals were tested at the following dose levels: Negative control, positive control, 5.5, 25.5, 118 or 550 mg/kg/day over a 10- day period from day 6 through day 15 of gestation. There was no indication of any effect on maternal or fetal survival, or in incidences of visceral or skeletal abnormalities. The male/female ratio of the fetuses were calculated to be, respectively, 1.08, 0.93, 0.74, 0.90, 0.88, or 0.68. The ratios at the lowest and highest dose levels are lower than the other ratios. 2. Rat. Animals were tested at the following dose levels: Negative control, positive control, 4.0, 19.0, 86.0, or 400 mg/kg/day over a 10- day period from day 6 through day 15 of gestation. There was no indication of any effect on maternal or fetal survival, or in incidences of visceral or skeletal abnormalities. The male/female ratio of the fetuses were calculated to be, respectively, 0.84, 0.78, 0.84, 0.98, 0.92, or 0.73. There is an indication of skewing (a lowering) in these ratios at the highest dose level and in the positive control. 3.Hamster. Animals were tested at the following dose levels: negative control, positive control, 4.0, 19.0, 86.0, or 400 mg/kg/day over a 5-day period from day 6 through day 10 of gestation. There was no indication of any effect on maternal or fetal survival, or in incidences of visceral or skeletal abnormalities. The male/female ratio of the fetuses were calculated to be, respectively, 0.52, 0.54, 0.59, 0.47, 0.40, or 0.53. These ratios (including those from the controls) are very unusual. 4. Rabbit. The results of the rabbit developmental study were not considered in the FDA Evaluation. Animals were tested over a 13-day period from day 6 through day 18 of gestation. There was no indication of any effect on maternal or fetal survival, or in incidences of visceral or skeletal abnormalities at the highest dose level of 580 mg/ kg/day. There was no indication of any effect on the male/female ratio of the fetuses since the ratio ranged from 1.13 to 1.26. F. Information from the Internet To ascertain whether additional information on sodium thiosulfate were available, the Agency also searched the Tox Net website at the National Library of Medicine (http://www.toxnet.nlm.nih.gov). This website contained only information on sodium thiosulfate anhydrous (CAS. Reg. No. 7772-98-7). The Tox Net website classified sodium thiosulfate as moderately toxic, and generally supported the information presented in the petition. The excerpts and summaries indicated that sodium thiosulfate is not mutagenic.No internet information indicated concerns for carcinogenicity or developmental/ reproductive toxicity. One study which investigated the ability of sodium thiosulfate to cross the placenta in sheep, concluded that maternally-administered sodium thiosulfate (50 mg/kg) does not increase fetal plasma thiosulfate concentrations. No information on sodium thiosulfate was available on the National Toxicology Program website, the Agency for Toxic Substances and Disease Registry website, or the Agency's Integrated Risk Information System website. The TSCATs database (http://esc.syrres.com/efdb/TSCATS.htm)