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**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER**  **EPA Registration**  **Division contact: PV Shah, (703) 308**  **- 1846**  **TEMPLATE:** Huntsman Corporation IN
- 10684 EPA has rec eived a pesticide petition ( IN
- 10684 ) from Huntsman Corporation , 8600 Gosling Road, The Woodlands, TX, 77381 request ing, 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 establis h an exemption from the requirement of a tolerance for **Ethanesulfonic acid, 2 -**  **hydroxy -**  **(CAS #107 -**  **36 -**  **8), and the corresponding ammonium (CAS #57267**  **- 78**  **- 4), sodium (CAS # 1562**  **- 00**  **- 1), potassium (CAS # 1561**  **- 99**  **- 5),**  **calcium (10550**  **- 47**  **- 7)**  **, magnesium (17345**  **- 56**  **- 1)**  **, zi nc (CAS # 129756**  **- 32**  **- 7), salts**  in or on all raw agricultural commodities under 40 CFR 180.910 and 180.930 . 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 1. Plant metabolism. NA
- Remove 2. Analy tical method. NA
- Remove 3. Magnitude of residues
. Residues are expected to be low based on the ready biodegradability

of ethanesulfonic acid, 2
- hydroxy
- monoammonium salt and the estimated ready biodegradability of the other isethionate salts
. Residues are also expected to be low based on the low proposed application concentration of approximately 2%. B. Toxicological Profile 1. Acute toxicity. Isethionic acid and the corresponding salts are low in acute oral and dermal toxicity . Sodium isethionate has reported oral and dermal LD50 values> 5,000 mg/kg. Ammonium isethionate has acute oral and dermal LD50 values >1,000 mg/kg, the highest doses tested. The salts of isethionic acid did not cause dermal2

irritation and minimal to no ocular irritation. Ammonium isethionate and sodium isethionate have both been shown to be non
- sensitizing in dermal sensitization studies. 2. Genotoxicty. Ammonium isethionate was negative in the bacterial reverse mutation assay

with and without S9 activation. Strains t ested were Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and E. coli strain WP2 uvrA. Sodium isethionate was negative in an in vitro mammalian cell gene mutation test with mouse ly mphoma cells. Sodium isethionate did not induce micronuclei in human ly mphocy tes in the in vitro mammalian cell micronucleus test. 3. Reproductive and developmental toxicity. The developmental and reproductive effects of exposure to ammonium isethionate were evaluated in a screening level combination repeated dose study . There were no significant effects on reproduction, including no effect on fertility , or pre - implantation loss compared to controls. There were no clinical signs of toxicity in the offspring from birth to postnatal day 4, and no effects on average pup weight. Necrops y of the pups did not reveal an y findings. The no - observed
- adverse
- effect
- level (NOAEL) was the high dose tested for the study , 500 mg/kg/day
. 4. Subchronic toxicity. A 90
- day oral dose toxicity

study was conducted on rats that rec eived sodium isethionate at doses of 50, 200 or 1000 mg/kg body weight/day

via gavage. A decrease in mean hemoglobin concentration and an increase in reticulocy te counts were reported in the 1000 mg/kg/day group. Gross pathology

findings included increas ed spleen weights and macroscopic changes in the liver in rats at 1000 mg/kg/day
. Histopathology

findings in the 1000 mg/kg/day group included microscopic changes in the liver, bile duct, and spleen. Effects showed complete reversal after exposure was di scontinued. The NOAELfor sodium isethionate was identified in this study as 200 mg/kg body weight/day. 5. Chronic toxicity. No chronic exposure studies are available for isethionic acid and its corresponding salts. Structure
- activity modeling using O ncologicTM indicates that there is a low concern for potential carcinogenicity from chronic exposure to isethionic acid. Isethionic acid does not contain structural alerts of potential concern for carcinogenicity
. Based on the lack of genotoxicity in bact erial and mammalian cell assay s, there is a low concern for isethionic acid and corresponding salts as potential carcinogens. 6. Animal metabolism. There are no data available that describe the metabolic pathway s of isethionic acid in mammals. There are reports in the literature that a portion of ingested taurine may

be metabolized to isethionic acid and eliminated in the urine. 7. Metabolite toxicology
. NA
- Remove 8. Endocrine disruption
. There is no evidence of endocrine disruptor effects i n the available toxicity

studi es on isethionate and its salts
. T oxicity related to endocrine disruption was not observed in the ammonium isethionate repeated dose reproduction / developmental toxicity study in rats.3

C. Aggregate Exposure 1. Dietary exposure. T he estimated dietary exposure to isethionate and its salts was determined using methods to estimate chronic dietary exposure for a generic inert ingredient in the DEEM model . This assessment considers drinking water and crop
specific residues from pre harvest applications of agricultural insecticides, herbicides and fungicides, assuming the highest established tolerance level residue for each commodity
. The assessment assumes that the inert ingredient is used on all crops, and that 100% of all crops ar e treated with the inert. The inert ingredient is assumed to be present in all commodities treated with 57 of the most significant active ingredients at the maximum tolerance level as identified by the U.S. EPA for the default assessment
. The estimated chronic exposure for the total US population is 0.189 mg/kg/day , or 9.5% of the chronic population adjusted dose ( cPAD ) for sodium isethionate . Children age 1 to 2 years old have the highest estimated exposure of 0.706 mg/kg/day at 35.3% of the cPAD. i. Food. The estimated dietary exposures for all sub populations are below any level of potential concern
. ii. Drinking water. Drinking water is assumed to contain 100 ppb of isethionate salt for the dietary

exposure assessment . 2. Non
- dietary expos ure . Dermal exposure is expected to occur from the use of personal care products including soaps and other similar products that contain sodium isethionate. The concentration of isethionate salts in these products is generally well below the level identif

ied as acceptable b y industry experts. Use of these products is not exp ected to result in significant sy stemic exposure to isethionate salts
. D. Cumulative Effects To our knowledge there are no available data or other reliable information that sugges ts that an y toxic effects produced b y isethionate and its salts would be cumulative with those of an y other chemical compounds. EPA has not made a common mechanism of toxicity

finding as to isethio nate and its salts and other compounds. Isethionate and i ts salts do not appear to produce toxic metabolites in common with other substances. For the purpose of the tolerance exemption actions proposed, it is assumed that isethionate and its salts do not share a common mechanism of toxicity with other substance s. E. Safety Determination 1. U.S. population. The estimated dietary and nondietary

exposure of the general population to isethionic acid and its corresponding salts is expected to be below any level of potential concern from the proposed use as a condi tioning agent, chelator, or sequestrant in pesticide formulations. 2. Infants and children
. The estimated dietary and nondietary

exposure of infants and children to isethionic acid and its corresponding salts is expected to be below any4

level of potent ial concern from the proposed use as a conditioning agent, chelator, or sequestrant in pesticide formulations. F. International Tolerances NA
- Remove