Document ID: EPA-HQ-OPP-2014-0325-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2014-08-04T04:00Z

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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 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 Oncologic™ 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.  

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 crop-specific 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 level of potential concern from the proposed
use as a conditioning agent, chelator, or sequestrant in pesticide
formulations.

F. International Tolerances

	NA-Remove

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