EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division Contact: Kathryn Montague (703) 305-1243 

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:

[K-I CHEMICAL U.S.A., INC.]

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from K-I 

CHEMICAL U.S.A., INC. c/o Landis International, Inc., P. O. Box 5126 Valdosta, 

GA 31603-5126 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 by establishing 

tolerances for residues of the sum of pyroxasulfone [3-[[[5-(difluoromethoxy)-1-methyl3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]sulfonyl]-4,5-dihydro-5,5-

dimethylisoxazole] and its metabolite 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-

1H-pyrazol-4-carboxylic acid (M-3) calculated as the stoichiometric equivalent of 

pyroxasulfone, in or on the raw agricultural commodities corn, field, grain at 0.02 ppm 

(parts per million) and pyroxasulfone [3-[[[5-(difluoromethoxy)-1-methyl-3-

(trifluoromethyl)-1H-pyrazol-4-yl]methyl]sulfonyl]-4,5-dihydro-5,5-dimethylisoxazole] 

and its metabolites [5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-

yl]methanesulfonic acid (M-1), 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1Hpyrazol-4-carboxylic acid (M-3), and [5-(difluoromethoxy)-3-(trifluoromethyl)-1Hpyrazol-4-yl]methanesulfonic acid (M-25), calculated as the stoichiometric equivalent of 

pyroxasulfone, in or on the raw agricultural commodities corn, field, forage at 0.09 ppm 

(parts per million). 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.
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A. Residue Chemistry

1. Plant Metabolism. Plant metabolism studies were conducted and accepted by

the Agency for soybean and field corn. The plant and animal metabolism of 

pyroxasulfone is well understood. Primary metabolic processes are cleavage between the 

two ring structures, side chain oxidation to carboxylic acid and demethylation. 

Pyroxasulfone and its major metabolites M-1, M-3, and M-25 were metabolites in corn 

and soybean. The metabolism of pyroxasulfone in plants and animals is understood for 

the purposes of the proposed tolerances. Pyroxasulfone and its metabolites M-1, M-3, M25and M-28 are the residues of concern for tolerance setting purposes for soybean.

2. Analytical method. EPA has approved an analytical enforcement methodology

including liquid chromatography, mass spectrometry, and mass spectrometry 

(LC/MS/MS) to enforce the tolerance expression for pyroxasulfone. 

3. Magnitude of residues.

Corn Residue Data

Initially, a total of 37 corn residue raw agricultural commodity (RAC) field trials 

were conducted in regions 1, 2, 3, 5, 6, 10, 11 and 12 of the United States (MRID 

47701656). A total of 11 of these trials were sweet corn trials and the remaining were 

field corn trials. Three of these trials were residue decline trials to determine residue 

decline in the respective corn RAC matrices after application. Three comparison trials, on 

three different soil types; fine, medium and course, were conducted to compare five 

different application types in different plots at the same site including pre-plant to 

surface, pre-plant incorporated, post-planting but pre-emergence of weeds or crop, early 

postemergence and split application with pre-emergence and post-emergence. 

Application rates for these comparison trials were 166 g a.i./ha, 209 g a.i./ha and 300 g 

a.i.lha for the course, medium and fine soil type, respectively. For the remaining 34 

studies, application rates were 166 g a.i./ha on course soil types and 300 g a.i./ha on 

medium and fine soil types. Applications for these 34 trials were post-emergence 

applications (approximately V4 growth stage). One trial included a plot with a 5X 

application rate (post-emergence) in which the grain was collected for processing. 

Samples were collected from each plot at the appropriate time (normal maturity except 

samples from the residue decline trials which were collected earlier). Matrices were 

extracted with acetonitrile or aqueous methanol followed by various cleanup steps 

depending on the matrix and ana1yte. Analysis was performed using LC-MS/MS for 

pyroxasu1fone and its metabolites in all matrices. The LOQ was 0.005 ppm for all 

matrices except two metabolites one in meal and one in oil for the LOQs which were 0.01 

ppm. The residue in all field com grain samples was below LOQ. All field com processed 

commodity matrix samples showed residues less than the respective LOQ for that 

particular matrix.

A second study (MRID 48767101) was conducted to obtain RAC residue data for 

pyroxasulfone (KIH-485) and its metabolites M-1, M-3, and M-25 on corn following a 

single post-emergence application of pyroxasulfone 85 WG herbicide at the V3-V5 

growth stage with and without adjuvant and fertilizer to determine if adding fertilizer 
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and/or adjuvant to the spray solution affected the residues in the harvested crop. The 

matrices analyzed were forage, stover, and grain, and residues of KIH-485, M-1, M-3, 

and M-25 were analyzed. The study was conducted at three trial locations in the United 

States including: Georgia (GA), Missouri (MO), and Nebraska (NE), representing United 

States EPA Regions 2, 4 and 5, respectively. The protocol was designed according to a 

request from the EPA regarding the number of treated plots and treatments and the 

number of treated samples (4 treated samples collected per plot instead of 2 as required 

by the guideline). In each trial, there was one non-treated plot and three treated plots. 

Applications were made related to the soil type at a target rate of 0.148 lb ai/A (166 

grams ai/ha) for the coarse textured soil site (GA) and 0.268 lb ai/A (300 grams ai/ha) for 

the other two locations MO and NE (medium and fine textured soil sites, respectively). 

At the appropriate preharvest harvest intervals (PHIs), corn samples were collected for 

each matrix (forage, stover, and grain), frozen and shipped frozen to the analytical 

laboratory for analysis. A limit of quantitation (LOQ) of 0.005 ppm was determined for 

the parent molecule (KIH-485), M-1, M-3 and M-25. Concurrent recoveries were 

conducted with fortification levels of 0.005 ppm and 0.05 ppm. Most recoveries for all 

analyses of each analyte in each matrix were within the accepted range (70-120%). No 

residue of the parent pyroxasulfone molecule was seen in any corn matrix above the LOQ 

of 0.005 ppm. Residues of the metabolites of pyroxasulfone (M-1, M-3, and M-25) were 

found in selected samples. These residues were added to the OECD MRL calculator 

along with the original corn field trial residues without adjuvant to determine the 

appropriate tolerances. As indicted by EPA memo dated January 10, 2013 DP Barcode: 

D402247 (Pyroxasulfone. Summary of Residue Data for Pyroxasulfone Use on Corn with 

and without Adjuvant and Field Rotational Crop Residue Data) and EPA email dated 

March 20, 2013 the purpose of this tolerance petition is to increase the corn forage 

tolerance from 0.06 ppm to 0.09 ppm due the conservative tolerance determined by the 

OECD MRL calculator. 

Confined Rotational Crop Study

Pyrazole or isoxazoline ring labeled 14C KIH-485 was sprayed on confined plots 

of bare soil prior to planting soybean, radish and wheat at 30, 120 and 365 day intervals. 

There were two treated plots for each plantback interval, one of which was wheat only 

and the other was planted half with soybean and half with radish. All plots were treated 

at a target application rate of 300 g a.i./ha but the actual rate was 313 g a.i./ha. Samples 

were analyzed by combustion analysis and liquid scintillation counting. All treated crops 

contained radioactive residue >0.01 ppm and were subjected to further analysis. The 

highest total radioactive residue (TRR), 5.2 ppm was found at the 30 day rotational in 

wheat straw; the residue level declined to 0.02 ppm at 485 days. The primary metabolites 

were M-1 and M-3. 

Field Rotational Crop Study

A field rotational crop study was conducted in Georgia (GA) and Texas (TX) on a 

fine and coarse textured soil, respectively. The purpose of the study was to obtain raw 

agricultural commodity (RAC) residue data for pyroxasulfone and its metabolites M-1, 

M-3, M-25, M-28, and M-37 on rotational crops that are planted in plots that have been 

treated with Pyroxasulfone 85 WG at the proposed label rate and aged for various time 
4

intervals prior to planting the rotational plot. Each plot was treated at an appropriate time 

for growing the target crop and then allowed to age for the specified aging interval (120, 

270, 300 and 365 days, nominal intervals). There was no residue seen in any crop matrix 

at any sampling interval above the LOQ except for one replicate 120 day potato top 

sample which showed residue of M-1 at the LOQ (0.01 ppm). As a result, neither 

pyroxasulfone nor any of its metabolites are expected to accumulate in rotational crops 

when Pyroxasulfone 85 WG is applied to target crops at the labeled rates. 

 

Cow Feeding Study

Holstein dairy cows were treated orally with gelatin capsules fortified with 

pyroxasulfone. These were administered once daily for 28 consecutive days at dose 

levels of 0, 1.8, 5.4, and 18 ppm per cow/day on a dry weight basis amounting to 

concentrations of control, 1X, 3X and 10X dose groups, respectively. These dose levels 

were equivalent to 0, 35.8 mg/cow/day, 109.9 mg/cow/day and 367.4 mg/cow/day, 

respectively. Milk samples from the high dose animals (10X) were found to contain no 

residues of the parent compound or metabolites with the exception of 3 milk samples 

from day 7 which contained an average of 0.003 ppm parent pyroxasulfone. No other 

milk samples from the other dose levels were found to contain residues of pyroxasulfone 

or metabolites. No other matrix (muscle, liver, kidney or fat) was found to contain 

residues of pyroxasulfone or metabolites above LOQ. The LOQs were 0.001 ppm in 

milk and 0.01 ppm in all other matrices. Therefore, no tolerances for residues of 

pyroxasulfone and its metabolites are being proposed for meat, milk, eggs or other edible 

tissues of livestock or poultry.

B. Toxicological Profile

1. Acute Toxicity. Pyroxasulfone was found to be of low acute toxicity via oral, 

dermal and inhalation routes of administration. It was not irritating to skin or eyes and 

was not a sensitizing agent. The formulated product (85WG) was also of low acute 

toxicity and was found to be mildly irritating to skin, moderately irritating to eyes and 

was a dermal sensitizer. In an acute neurotoxicity study in rats, there were no test 

substance-related effects on body weights, food consumption, clinical observations, 

functional observational battery assessments, motor activity measurements, or gross and 

microscopic neuropathology. The NOEL was demonstrated to be >2000 mg/kg/day in 

adult male and female rats.

2. Genotoxicity. Pyroxasulfone and its metabolites and impurities do not induce 

gene mutations in bacterial cells. Pyroxasulfone does not induce gene mutations or 

chromosomal aberrations in in vitro mammalian cells or in vivo in the mouse 

micronucleus test. Pyroxasulfone is non-genotoxic.

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

rats, the NOEL for maternal and developmental toxicity was >1000 mg/kg/day, the 

highest dose tested.

In a developmental toxicity study in rabbits, there were slight test substance-
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related effects on fetal weight and number of implant resorptions at 1000 mg/kg/day, the 

highest dose tested. The NOEL for maternal toxicity was 1000 mg/kg/day. The NOEL 

for developmental toxicity was 500 mg/kg/day.

In a rat one-generation reproductive study no reproductive toxicity was observed 

up to and including the high dose of 5000 ppm. The NOEL for reproductive toxicity was

>5000 ppm, the highest dose tested. The NOEL for P1 adult rats was 25 ppm. The 

NOEL for F1 offspring was 250 ppm and the NOEL for F1 adults was 250 ppm.

In a rat two-generation reproduction study there were no test substance-related 

effects for reproductive toxicity at 2000 ppm, the highest concentration tested. The 

NOEL for reproductive toxicity was >2000 ppm, the highest concentration tested. Test 

substance-related effects were observed at 2000 ppm in both adults and offspring. 

Therefore, the NOAEL for systemic toxicity was demonstrated to be 100 ppm (6.94 –

11.76 mg/kg/day) in both parents and offspring.

In a developmental neurotoxicity study conducted on pyroxasulfone in mated 

female rats no reproductive effects were observed in the maternal animals at 2000 ppm, 

the highest concentration tested. No effects were observed on FOBs, auditory startle 

response habituation, pre-pulse inhibition, learning and memory of offspring. A slight 

(5%) decrease in absolute brain weight at 900 mg/kg/day was present on PD 66, although 

no effect was present when evaluated on a % body weight basis. Based on the effects 

observed in this study, the maternal and offspring systemic NOAEL is 900 mg/kg/day. 

The NOEL for functional development was judged to be 900 mg/kg/day. A NOEL for 

histomorphological development of the brain of the offspring was judged to be 300 

mg/kg/day.

Two studies were performed to assess the availability of the test substance to the 

pup. These studies indicated that pyroxasulfone was available in the milk to nursing 

pups.

4. Subchronic toxicity. Pyroxasulfone was evaluated in a 28-day inhalation 

toxicity study in rats. There were no test substance-related effects. The NOEL was >200 

mg/m3, the highest dose tested.

In a 28-day dermal toxicity study there was a test substance-related increase in the 

incidence of minimal to mild cardiac myofiber degeneration with inflammation observed 

in males and females dosed with 1000 mg/kg/day and cutaneous myofiber degeneration 

with inflammation observed in the treated skin of males dosed with 1000 mg/kg/day. 

The NOEL was 100 mg/kg/day.

Immunotoxicity was evaluated in rats and mice following dietary exposure for 28 

days. There were no test substance related effects for any of the immunotoxicity

parameters examined. In the rat, systemic toxicity was limited to reductions in body

weight and food consumption. The NOEL for immunotoxicity was 7500 ppm (529 and 

570 mg/kg in males and females) and the NOEL for systemic effects was 250 ppm (18 
6

and 19 mg/kg in males and females). In the mouse, the NOEL for immunotoxicity was 

4000 ppm (633 mg/kg/day males: 791 mg/kg/day females) and the NOEL for systemic 

effects was 400 ppm (61 mg/kg males: 77 mg/kg females).

Pyroxasulfone was evaluated in 13-week oral toxicity studies in rats, mice and 

dogs. In the 13 week mouse study, no test substance-related effects on in-life and clinical 

pathology parameters were observed at any level tested. Test substance-related effects at 

2500 ppm were limited to an increased incidence of minimal to mild chronic progressive 

nephropathy in female mice and increased liver weight in males and females fed 2500 

ppm. The NOEL was 250 ppm for female mice (51.2 mg/kg/day). The NOEL for male 

mice was 2500 ppm (394.0 mg/kg/day).

In the 13 week rat study, a NOEL of 250 ppm for male and female rats 

corresponded to mean daily intake values of 16.4 and 20.6 mg/kg/day in males and 

females, respectively. Test substance related effects were increased cardiac myofiber 

degeneration with inflammation and diffuse mucosal hyperplasia of the urinary bladder. 

Increased liver weights and centrilobular hypertrophy were also observed in 2500 ppm 

males and females. In a second study evaluating recovery, full or partial recovery was 

evident in all the above effects apart from kidney weights in females with all microscopic 

findings in the liver, heart, muscle and pancreas of 5000 ppm animals comparable to 

control rats indicating a complete reversal of the treatment-related findings noted at the 

terminal sacrifice.

In an oral 90 day toxicity study in beagle dogs administered pyroxasulfone in a 

capsule, the NOEL was 2.0 mg/kg. The only effects noted were degeneration of muscle 

fiber of the musculature portion of the diaphragm, hyperplasia of the satellite cell of the 

muscle and nerve fiber degeneration of the sciatic nerve in one 10mg/kg/day group male 

only. In a second study dosed with 0 or 15 mg/kg of pyroxasulfone, male dogs showed a 

decrease in body weight and histopathology similar to the full study.

Pyroxasulfone was evaluated in a subchronic 90 day neurotoxicity dietary study

in rats. There were no effects on body weights, food consumption, clinical observations, 

FOB assessments, motor activity measurements, or gross and microscopic 

neuropathology. The NOEL was >2500 ppm, the highest dose tested, for male and female 

rats corresponding to mean daily intake values of 161.48 and 199.59 mg/kg/day in males 

and females, respectively.

5. Chronic toxicity. Chronic toxicity studies were conducted in the rat and dog. In 

the rat one year chronic toxicity study test substance-related effects occurred at 1000 ppm 

and above that included reduced body weight parameters and microscopic findings in the 

liver (centrilobular hepatocellular hypertrophy in males), heart (increased 

cardiomyopathy in females) and urinary bladder (mucosal hyperplasia in males and 

females) and urinary bladder hyperplasia considered to be secondary to inflammation or 

irritation. At 2000 ppm, these effects were accompanied by increased clinical 

observations of red discharge from the penis and associated red-stained cageboards as 

well as increased liver and kidney weights. A slight increase in liver and kidney weights 
7

was observed in the 2000 ppm male and female dietary exposure groups. The NOEL is 

50 ppm (2.22 and 3.12 mg/kg/day for males and females, respectively).

In a one-year dog study beagle dogs/sex/dose were administered capsules 

containing 0.0, 0.2, 2.0 and 10.0 mg/kg/day. Adverse test article-related findings were 

limited to the 10.0 mg/kg/day group, the highest dose tested and not all animals at the 10 

mg/kg/day dosage had clear test-article related abnormal observations. Adverse changes 

in the clinical pathology parameters were increases in creatine kinase, aspartate 

aminotransferase and change in the pathology limited to the sciatic nerve and spinal cord. 

The NOAEL is 2.0 mg/kg/day.

The carcinogenic potential of pyroxasulfone was evaluated in rats and mice. The 

Agency has classified pyroxasulfone as “Not likely to be carcinogenic to humans” at 

doses that do not cause crystals with subsequent calculi formation resulting in cellular 

damage of the urinary tract.

6. Animal metabolism. In the rat, pyroxasulfone is rapidly and completely 

eliminated. Between 80 to 90% of pyroxasulfone was eliminated in the urine during the 

first 24 hours and elimination was essentially complete after 48 to 72 hours. Absorption 

was calculated (bile and urine) at 76%. Maximum plasma concentrations were achieved 

at 2 hours in the low and 11 hours in the high dose animals. At 96 hours only 7% of the 

low dose and <0.5% of the high dose was present in the carcass demonstrating the near 

complete elimination of pyroxasulfone. Of the radioactivity present in the animals, the 

highest levels were seen in the liver and kidney. The major metabolites were a 

carboxylated (pyrazole ring methyl group) and cleavage products between the isoxazoline 

and pyrazole ring structure with subsequent carboxylation. The absorption, distribution, 

metabolism and elimination of pyroxasulfone is unaffected by sex or treatment regimen. 

In a preliminary study in the dog, pyroxasulfone is rapidly eliminated with 76.9% 

of radioactivity excreted within 24 hours. Excretion is approximately equal in urine and 

feces. The terminal half life was 89.58 hr and 40.80 hr in blood and plasma, respectively. 

The feces were found to contain only unchanged pyroxasulfone while no parent molecule 

was found in the urine. At 120 hr after dosing, the levels of radioactivity in the tissues 

were highest in the liver and blood. 

In a preliminary mouse metabolism study, 73% of the applied dose of 

pyroxasulfone was excreted in urine within 24 hours of dosing. Pyroxasulfone was 

rapidly absorbed and distributed through the tissues of the mouse but by 24 hours after 

dosing, radioactivity concentrations in the majority of tissues were indistinguishable from 

background levels.

Metabolism studies in livestock and poultry (Nature of Residue Studies with Goat 

and Hen) with repeated dose established that pyroxasulfone was rapidly metabolized and 

excreted and that there was minimal transmittal of residues of pyroxasulfone and its 

metabolites to meat or milk. For goats fed 10 ppm of radiolabeled pyroxasulfone, the 

highest residues (TRR) were seen in liver and kidney. In the hen, fed 10 ppm, the highest 

residue was seen in liver and muscle. 
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7. Metabolite toxicology. Three plant metabolites and three impurities were 

evaluated in acute oral toxicity studies. All six test substances evaluated showed LD50’s 

>2000 mg/kg similar to the parent, pyroxasulfone. Two metabolites were further 

assessed in a 14 day toxicity study in rats. The NOEL for each of the metabolites was > 

1000 mg/kg. The same three metabolites and impurities were evaluated in a bacterial 

gene mutation test with and without activation. All test substances were non-genotoxic. 

8. Endocrine disruption. Pyroxasulfone does not belong to a class of chemicals 

known or suspected of having adverse effects on the endocrine system. There is no 

evidence that pyroxasulfone has any effect on endocrine function in developmental, 

reproduction or developmental neurotoxicity studies. Furthermore, histological 

investigation of endocrine organs in chronic dog, rat and mouse studies did not indicate 

that the endocrine system is targeted by pyroxasulfone.

C. Aggregate Exposure

1. Dietary exposure. It can be concluded with reasonable certainty that residues of 

pyroxasulfone in food will not result in unacceptable levels of human health risk. Using 

proposed tolerances for corn, soybean and wheat, both the acute and chronic dietary

exposure MOEs for the overall US population and 25 population subgroups are above the 

EPA level of concern.

i. Food. Acute and chronic dietary exposure assessments were conducted using a 

Tier I approach. This Tier I assessment incorporated tolerance level residues and 100% 

crop-treated in the DEEMTM (Dietary Exposure Evaluation Model; Exponent, Inc., 2003) 

software system. The acute toxicological endpoint selected for assessment of risk 

following acute dietary exposure was 300 mg/kg/day based on the Developmental 

Neurotoxicity Study with a NOEL 300 mg/kg/day for motor activity and brain 

morphology. The acute reference dose (aRfd) was determined to be 3 mg/kg/day

assuming the aRdf is 1 percent of the NOEL. The chronic toxicological endpoint selected 

for assessment of risk following chronic dietary exposure was 2 mg/kg/day based on the 

one-year chronic feeding dog study with a NOEL of 2 mg/kg/day. The chronic reference 

dose (cRfd) was determined to be 0.02 mg/kg/day assuming the cRfd is 1 percent of the 

NOEL. Using proposed tolerances for corn, soybean, wheat, and cotton the acute and 

chronic dietary exposure Margin of Exposure (MOEs) for the overall US population and 

25 population subgroups are above the EPA level of concern. It can be concluded with 

reasonable certainty that residues of pyroxasulfone in food will not result in unacceptable 

levels of human health risk.

ii. Drinking water. Based on the Pesticide Root Zone Model/Exposure Analysis 

Modeling System (PRZM/EXAMS) and Pesticide Root Zone Model Ground Water 

(PRZM GW), the estimated drinking water concentrations (EDWCs) of pyroxasulfone 

for acute exposure are estimated to be 17 ppb for surface water and 210 ppb for ground 

water. EDWCs of pyroxasulfone for chronic exposures for non-cancer assessments are 

estimated to be 3.2 ppb for surface water and 174 ppb for ground water. It can be 
9

concluded with reasonable certainty that residues of pyroxasulfone in drinking water will 

not result in unacceptable levels of human health risk. 

2. Non-dietary exposure. Pyroxasulfone is not intended for any specific use 

patterns that would result in residential exposures.

D. Cumulative Effects

Pyroxasulfone represents a new class of pyrazole herbicides. No other products 

are known to have the same mode of action as pyroxasulfone. Therefore, a cumulative 

assessment is not appropriate at this time.

E. Safety Determination

1. U.S. population. The toxicity database for pyroxasulfone is complete. Based on 

the NOEL of 2 mg/kg/day from a 1-year toxicity study in the dog, proposed uses 

represent 1 percent of the cRfD of 0.02 mg/kg/day. Based on the NOEL of 300 

mg/kg/day from a developmental neurotoxicity study, the proposed uses represent 1 

percent of the RfD of 3 mg/kg/day. There is reasonable certainty that no harm to the U.S. 

population will result from the proposed uses of pyroxasulfone.

2. Infants and children. The toxicity database for pyroxasulfone is complete. The 

database includes acute, subchronic, chronic, mutagenicity, genotoxicity, developmental, 

reproduction, neurotoxicity and immunotoxicity studies on pyroxasulfone and acute 

mutagenicity and genotoxicity studies on several metabolites. The weight of evidence 

indicates that infants and children are not expected to be more sensitive to pyroxasulfone 

than are adults. Consequently, EPA reduced the FQPA Safety Factor from 10x to 1x.

F. International Tolerances

Tolerances are approved on wheat, barley and triticale in Australia. Tolerances 

are simultaneously being sought in Canada at the same levels and for the same crops as 

for the U.S.