I 

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [Richard Gebkin, PM 10, (703) 305-6701] 

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert "NA-Remove" and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert 

company name]," with the information specific to your action. 

TEMPLATE: 

Gowan Company 

[Insert petition number] 

EPA has received a pesticide petition ([insert petition number]) from Gowan 

Company, LLC, P.O. Box 556 Yuma, AZ 85366 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. 

(Options (pick one) 

1. by establishing a tolerance for residues of 

Hexythiazox, (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-

oxothiazolidine-3-carboxamide) in or on the raw agricultural commodity 

bermudagrass, forage at 40 ppm and bermudagrass, hay at 70 ppm. 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 *•••• 

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1. Plant metabolism. The nature of the residues in plants is adequately •* * * / * ***** 

understood for purposes of this tolerance petition. Metabolism studies in fruit crops, ** , 

radish, tea and corn have been completed. The Agency has determined that the *.•*•* 

residues of concern are hex\'thiazox and its metabolites containing the • 

(4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moietj' calculated as the 

stoichiometric equivalent of hexjThiazox. * ,,, 
2. Analytical method. The basic analytical method was previously reviewed by 

the Agency in association with the establishment of the current tolerances with 

registrations of multiple commodities. The methods used in a new bermudagrass 

raw agricultural commodities study are described fully in the study report which is 

submitted concurrently with this petition. 

3. Magnitude of residues. A New Magnitude of the Residue data have been 

generated in bermudagrass in regions 9 and 10 to support regional registration. 

Four bermudagrass trials were conducted in EPA Regions 9 (one trial, AZ) and 10 

(three trials, CA) in 2013 and 2014. These field trials will support regional 

registration (Regions 9 and 10) for hexythiazox in bermudagrass. 

The results from these trials show that after one application of Onager® IE Miticide 

at 0.1875 lb ai/A (0.210 kg ai/ha) ± 5% residues of hexythiazox ranged from 6.58 to 

23.5 ppm (mean = 13.2 ppm ± 6.58) on eight bermudagrass forage RAC samples 

collected 0 DAA. Hexx thiazox residues ranged from 13.4 to 30.6 ppm (mean = 21.5 

ppm ± 7.22) on eight bermudagrass hay RAC samples collected 7 DAA. 

B. Toxicological Profile 

1. Acute toxicity. A battery of acute toxicitv" studies places technical grade 

hexythiazox in Toxicity' Category IV for acute oral toxicity (LDso > 5,000 mg/kg), 

Category III for acute dermal toxicity (LDso >5,000 mg/kg). Category HI for acute 

inhalation toxicity' (LCso >2.0 mg/L), Category' III for primary eye irritation 

(showed mild irritation (reddened conjunctiva) and Category IV for dermal 

irritation (non irritant). Hexythiazox is a non-sensitizer. 

2. Genotoxicity. A number of mutagenicity studies were conducted. These are 

a mammalian erythrocyte micronucleus test [MRID 45480101], a mammalian cell 

forward gene mutation assay [MRID 00155154], a rat primary hepatocy te 

unscheduled DNA synthesis assay [MRID 00156893], a clastogenic evaluation in an 

in vitro cytogenetic assay measuring chromosomal aberration in Chinese hamster 

ovary cells [MRID 00156894], and an Ames study with Salmonella [MRID 

44955710]. All these mutagenicity- tests were negative. 

3. Reproductive and developmental toxicity. In a developmental toxicity study 

with rats [MRID 00147578], the fetotoxicity NOEL yy as 240 mg/kg/day, and the 

compound yvas not embryotoxic at the highest dose tested, 2160 mg/kg/day. In a 

developmental toxicit)' study with rabbits [MRID 00146555], no developmental 

toxicity yvas observed at the highest dose tested, 1080 mg/kg/day. In a twogeneration reproduction study with rats [MRID 00147578 and 00151360], no •••*, 

reproductive effects yvere observed at 2400 ppm in the diet (>illO and >139 

mg/kg/day, males and females, respectively). It is concluded that the NOEL for 

developmental and reproductive effects is greater than 10 times the chronic NOEL. 

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4. Subchronic toxicity. In a 1-month feeding study in dogs, the NOAEL was 

1.75 mg/kg/day and the LOAEL yvas 12.5 mg/kg/day, based on increased liver and 

adrenal weights. 

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5. Chronic toxicity. In a 1-year feeding study in dogs, the NOAEL was 2.5 

mg/kg/day and the LOAEL was 12.5 mg/kg/day, based on increased alkaline 

phosphatase, increased adrenal and liver weights, and liver and adrenal lesions. In 

a carcinogenicity study in mice, the NOAEL was 36 mg/kg/day and the LOAEL was 

215 mg/kg/day. Effects were decreased bodyweight in males and increased 

hepatocellular carcinomas and combined adenoma/carcinomas. 

In a chronic feeding/carcinogenicitj' study in rats, the NOAEL (systemic) was 26 

mg/kg/day and the LOAEL (systemic) was 180 mg/kg/day based on decreased body 

weight gain and increased liver weights in both sexes. 

A 2009 report from the Cancer Assessment Review Committee (CARC) (September 

02,2009, PC Code 128849, TXR 0055255) noted that the NOAEL of 2.5 mg/kg/day, 

from the one year toxicity study in dogs, used in establishing the chronic reference 

dose (RfD) is approximately 65-fold lower than the lowest dose (163 mg/kg/day) that 

induced tumors. Thus, the chronic RfD of 0.025 mg/kg/day would be protective of 

all chronic effects including potential carcinogenicity of hexA'thiazox. The CARC 

concluded that the evidence as a whole was not strong enough to warrant the use of 

a linear low dose extrapolation model applied to the animal data (Ql*) for a 

quantitative estimation of human risk, as had been previously assessed in October 

16,1998, [63.FR55540]. 

6. Animal metabolism. The metabolism of hexv thiazox has been studied in 

goats, hens and rats. Metabolic pathways in the animal are similar to those in 

plants. 

7. Metabolite toxicology. There are no metabolites of toxicological concern 

based on a differential metabolism between plants and animals. 

8. Endocrine disruption. Information concerning possible endocrine effects of 

hexythiazox similar to effects produced by a naturally occurring estrogen, or other 

endocrine effects is available from the two-generation rat reproduction study, the 

rat and rabbit developmental studies and the rat and dog chronic studies. There is 

no evidence from these studies that hexj thiazox induces estrogenic or other 

endocrine effects. , , 

C. Aggregate Exposure *'*' •** * • 

• • • 1. Dietary exposure. Dietaiy Exposure from food. A dietary risk assessment -, . • • • • 

for all registered crops has been completed by the Agency (Federal Register, July . ••;**< 

17, 2013, pages 42693-42699). 

i. Food. Acute Exposure. No acute endpoint has been identified in the 

toxicological studies for hexythiazox; therefore, a quantitative acute dietarj' • 

exposure assessment is unnecessary. •* * 
Chronic Exposure. The proposed regional tolerances for hexj thiazox in 

bermudagrass will not add to dietarj' risk. A recent tier 1 chronic assessment shows 

employing tolerance residue values, the assumption of 100% crop treated and 

default processing factors shows that the maximally exposed subpopulation 

(children 1-2 years old) utilized 93.4% of the cPAD. 

ii. Drinking water. The Agency has previously used screening level surface 

water exposure models in dietary exposure analysis and risk assessment for 

hexythiazox in drinking water. Based on the Pesticide Root Zone Model /Exposure 

Analysis Modeling System (PRZM/EXAMS), the estimated drinking water 

concentration (EDWC) of hexj'thiazox for chronic assessment was estimated to be 

4.31 parts per billion (ppb). (Federal Register, July 17, 2013, pages 42693-42699) 

2. Xon-dietary exposure. EPA has previously determined that potential 

residential exposures to hexj thiazox are below levels of concern. 

D. Cumulative Effects 

EPA has not found that hexjThiazox shares a common mechanism of toxicity 

with any other substances. 

E. Safety Determination 

1. U.S. population. Acute risk. No adverse effect resulting from a single oral 

exposure to hexythiazox has been identified, thus hexj thiazox is not expected to pose 

an acute risk. 

Short-and intermediate term risk. EPA has previously concluded that there are no 

short term or intermediate term risks of concern from exposure to hexythiazox. 

Chronic risk. The proposed regional tolerances for hexythiazox in bermudagrass 

will not add to dietaiy risk. Chronic residential exposure to the residues of 

hexj'thiazox is not expected. 

2. Infants and children. EPA previously has determined that reliable data 

show the safety' of infants and children would be adequately protected if the FQPA 

SF were reduced to IX. Based on these risk assessments, it can be concluded 

that there is a reasonable certainty that no harm will result to the general 

population, or to infants and children from aggregate exposure to hexythiazox 

residues. •••*. 

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F. International Tolerances 

There are no international maximum residue levels established for 

hex>ihiazox on bermudagrass. 

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