Document ID: EPA-HQ-OPP-2013-0175-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-06-05T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: W. Cutchin, 703-305-7990

Winfield Solutions, LLC

2E8093

	EPA has received a pesticide petition (2E8093) from Winfield Solutions, LLC, PO Box 64589, St. Paul, MN 55164, proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. to establish an exemption from the requirement of a tolerance for sodium metabisulfite (CAS No. 7681-57-4) under 40 CFR 180.920, when used as an inert ingredient (preservative), at not more than 0.5% by weight, in pesticide formulations applied to growing crops only. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry  As a result of the low initial concentration of sodium metabisulfate in pesticide formulations and its proposed use on growing crops, food residues are not expected to be significant. This information is not required for the establishment of a tolerance exemption.
	1. Plant metabolism. NA-Remove

	2. Analytical method. NA-Remove

	3. Magnitude of residues. NA-Remove

B. Toxicological Profile

	1. Acute toxicity.  Sodium metabisulfite has an acute oral LD50 of 1131 mg/kg in female rats, an acute dermal LD50 greater than 2000 mg/kg, is not a dermal sensitizer, is not irritating to the skin but is an eye irritant (U.S. Environmental Protection Agency's Reregistration Eligibility Decision (US EPA RED)  -  Inorganic Sulfites  -  May 2007).

	2. Genotoxicty. Sodium metabisulfite was negative in an Ames/microsome assay (SRI International 1978b as cited by CIR 2003). Negative results were also reported for a host-mediated assay using mice to test mutagenicity against bacteria and yeast, in a cytogenetic assay using rats (Litton Bionetics 1972 as cited in CIR 2003), and a cytogenetic assay using sulfite oxidase-deficient hamsters and mice (Renner and Wever 1983 as cited in CIR 2003). Sodium metabisulfite was negative in one dominant lethal assay using rats while another study indicated further testing was needed (CIR 2003). However, genetic toxicity studies summarized by the OECD 2001 indicate sodium metabisulfite is equivocal in in vitro testing, but is not genotoxic in the in vivo testing (US EPA RED  -  Inorganic Sulfites  -  May 2007).

	3. Reproductive and developmental toxicity. No evidence of reproductive toxicity was observed in rats exposed orally to 942 mg/kg bw/day of sodium metabisulfite (2% in the diet) in a diet supplemented with thiamine (Organization for Economic Co-operation and Development (OECD) 2001). Developmental studies reported by the CIR 2003 indicate sodium metabisulfite produced no adverse findings, either maternal or fetal, in mice up to 160 mg/kg in a water solution, in rats up to 110 mg/kg in the diet, in hamsters up to 120 mg/kg in the diet, or in rabbits up to 123 mg/kg in the diet. These results are supported by developmental information reported by World Health Organization (WHO; 1999) in which no effects were observed on implantation, or on maternal or fetal survival in sodium metabisulfite doses of up to 150, 110 and 120 mg/kg bw in mice, rats, and hamsters, respectively (WHO Series 18; US EPA RED  -  Inorganic Sulfites  -  May 2007).

	4. Subchronic toxicity. The predominant effect in a subchronic feeding study in rats conducted over a period of 30 to 104 weeks was the induction of stomach lesions due to local irritation.  The lowest dose to illicit that effect was 454 mg/kg of body weight per day.  The NOAEL for systemic effects was established as the highest dose tested, 942 mg/kg of body weight per day [OECD SIDS (Screening Information Data Set). 2001. Disodium disulphite (CAS No. 7681-57-4)]. 

	5. Chronic toxicity. Sodium metabisulfite is currently not classifiable (Group 3) as to its carcinogenicity to humans (IARC 1992). As for laboratory animals, conclusions of the OECD SIDS report indicated 2% sodium metabisulfite via feed (20,000 ppm or 1,000 mg/kg/day) for 104 weeks was not carcinogenic in Wistar rats (US EPA RED  -  Inorganic Sulfites  -  May 2007).

	6. Animal metabolism. Sodium metabisulfite is rapidly eliminated as sulphate in humans.  When sulphite is present in the tissues in sufficiently high concentrations, it may be metabolized to inorganic thiosulphate that is then excreted in urine [OECD SIDS. 2001. Disodium disulphite (CAS No. 7681-57-4)]. 

	7. Metabolite toxicology. When mixed with water, sodium metabisulfite releases sulfur dioxide. Sulfur dioxide is also EPA registered as a fungicide/ preservative for use on grapes and is generally recognized as safe by the U.S. Food and Drug Administration (FDA) when used in accordance with good manufacturing practice with the same exceptions as for sodium metabisulfite (see Aggregate Exposure  -  Food, below). Sulfur dioxide and sodium metabisulfite were the inorganic sulfites specifically assessed in the US EPA RED for Inorganic Sulfites, May, 2007. Both were determined to be eligible for reregistration.
Sulfur dioxide's toxicology was thoroughly examined during the reregistration process and is summarized within the RED.

	8. Endocrine disruption. See reproductive and developmental toxicity. 

C. Aggregate Exposure

	1. Dietary exposure. Sodium metabisulfite will be used as a preservative in pesticide formulations that will be applied to growing food and/or feed crops. It will be present in the formulations at a maximum level of 0.5% by weight. 

	i. Food. Sodium metabisulfite (21CFR 182.3766) is listed as generally recognized as safe (GRAS) by the FDA, with limitations, as a food preservative. Sulfites are found in many foods, primarily as a result of the GRAS preservative use. It is estimated that sulfite concentrations of >100 ppm may be found in dried fruits (excluding dark raisins and prunes), lemon and lime juices, wine, molasses, and sauerkraut juice. Dried potatoes, grape juice, wine vinegar, gravies, fruit topping, and maraschino cherries may contain between 50 and 100 ppm sulfur dioxide.
Foods containing between 10 ppm and 50 ppm include pectin, fresh shrimp, corn syrup, sauerkraut, pickled foods, corn starch, hominy, frozen potatoes, maple syrup, imported jams and jellies, and fresh mushrooms. Sodium metabisulfite is also used as a fungicidal control agent on grapes (US EPA RED  -  Inorganic Sulfites  -  May 2007).

	ii. Drinking water. It is unlikely that the proposed use of sodium metabisulfite will contaminate drinking water sources. 

	2. Non-dietary exposure. In addition to food related uses, sodium metabisulfite is used up to a concentration of 1% as an antioxidant in hair care products, as a reducing agent in cosmetic formulations, as a preservative in pharmaceuticals, as a waste water dechlorinating agent and as a lab reagent. 

D. Cumulative Effects

	There is not, at this time, available data to determine whether inorganic sulfites have a common mechanism of toxicity with other substances. A common mechanism of toxicity finding as to inorganic sulfites and any other substances, and inorganic sulfites do not appear to produce a toxic metabolite produced by other substances. An assumption has been made that inorganic sulfites do not have a common mechanism of toxicity with other substances (US EPA RED  -  Inorganic Sulfites  -  May 2007).

E. Safety Determination

	1. U.S. population. Taking into consideration available information on sodium metabisulfite, the proposed use pattern and anticipated limited exposure potential, FDA's classification of sodium metabisulfite as GRAS, the historical presence of sodium metabisulfite in cosmetics and hair care products, and the use of sodium metabisulfite on postharvest grapes, the use of sodium metabisulfite as an inert ingredient (preservative) in pesticide formulations applied to growing crops is unlikely to pose a significant risk to the general population or any population subgroup. 

	2. Infants and children. The RED for Inorganic Sulfites concluded that there was sufficient toxicological information for sodium metabisulfite to address Food Quality Protection Act (FQPA) considerations. The available information indicated that there is no evidence of increased quantitative or qualitative susceptibility of the offspring after in utero or post-natal exposure. Based on this information, there was no concern for increased sensitivity to infants and children to sodium metabisulfite when used on postharvest grapes.  It is likewise not expected that there would be an increased sensitivity to infants and children to sodium metabisulfite when also used as an inert ingredient in pesticide formulations applied to food or feed crops. 

F. International Tolerances

   o  	The Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2000, 2010a) has approved the use of sodium metabisulfate as a member of the sulfite group as a food additive (antioxidant, bleaching agent, flour treatment agent, and preservative) in a broad range of beverage, confectionary, and general food uses at levels ranging from 500 to 4000 mg/kg. There will be no harmonization issues with the requested use of sodium metabisulfate when used as an inert ingredient (preservative), at not more than 0.5% by weight, in pesticide formulations applied to growing crops only.