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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 received a pesticide petition (IN-10684) from Huntsman Corporation, 

8600 Gosling Road, The Woodlands, TX, 77381 requesting, 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

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), zinc (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. Analytical 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 dermal 
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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 tested 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 lymphoma cells. Sodium isethionate did not induce micronuclei in human 

lymphocytes 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. Necropsy of the pups did not reveal any 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 received 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 reticulocyte 

counts were reported in the 1000 mg/kg/day group. Gross pathology findings included 

increased 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 

discontinued. The NOAEL for 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 OncologicTM 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 bacterial and mammalian cell 

assays, 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 

pathways 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 in the 

available toxicity studies on isethionate and its salts. Toxicity related to endocrine 

disruption was not observed in the ammonium isethionate repeated dose reproduction / 

developmental toxicity study in rats. 
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C. Aggregate Exposure

1. Dietary exposure. The 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 cropspecific residues from preharvest 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 are 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 exposure. 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 identified as acceptable by industry experts. Use of these products is not 

expected to result in significant systemic exposure to isethionate salts. 

D. Cumulative Effects

To our knowledge there are no available data or other reliable information that 

suggests that any toxic effects produced by isethionate and its salts would be cumulative 

with those of any other chemical compounds. EPA has not made a common mechanism 

of toxicity finding as to isethionate and its salts and other compounds. Isethionate and its 

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 substances.

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 conditioning 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 any
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level of potential concern from the proposed use as a conditioning agent, chelator, or 

sequestrant in pesticide formulations.

F. International Tolerances

NA-Remove