Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657 

PC Code: 090099 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 30-January-2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

Subject: Pyroxasulfone. Acute and Chronic Aggregate Dietary Exposure and Risk 

Assessments for the Section 3 Registration Request for Use ofPyroxasulfone on 

Soybean. 

PC Code: 090099 DP Barcode: D406657 

Decision No.: 462689 Registration No.: 63588-9 I, 63588-92 and 63588-93 

Petition No.: 2F8005 Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single Chemical, Dietary Case No.: NA 

TXR No.: NA CAS No.: 447399-55-5 

MRIDNo.: NA 40CFR: 180.659 - ./d--

Reviewer: Thurston G. Morton, Chemist ~ f"'Cf_A../ ~ Risk Assessment Branch IV!He£t'h Effects Division (RABIV/HED; 7509P) 

Through: Donna Davis, Senior Chemist ~~ ./ 

ldeliz Negron-Encarnacion , Chemist 7{/tt, L__.-::-

Dietary Exposure Science Advisory Council ,:@)ESAC) 

And 

Susan V. Hummel, Senior Chemist 

RABIVIHED (7509P) 

To: Thurston G. Morton, Risk Assessor 

RABIV IHED (7509P) 

And 

Erik Kraft 

Herbicide Branch/RD (7505P) 

Page I of II 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: 0406657 

PC Code: 090099 

Executive Summary 

Pyroxasulfone is proposed for use on soybean. Partially refined acute and chronic aggregate 

(food and water) assessments were conducted using maximum residues for com and tolerance 

level residues for soybean along with 100 % crop treated (CT). 

The resulting aggregate (food and water) acute exposure estimates were less than HED's level of 

concern ( <1 00% aP AD) for general U.S. population (1.2% aP AD) and all population sub-groups; 

the most highly exposed population subgroup was All Infants <1 year old with 3.6% aPAD at the 

95th percentile. 

The resulting aggregate (food and water) chronic exposure estimates were less than HED's level of 

concern ( <1 00% cPAD) for general U.S. population (19% cP AD) and all population sub-groups; the 

most highly exposed population subgroup was All Infants <1 year old with 48% cP AD. 

I. Introduction 

Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute 

and chronic assessments, the risk is expressed as a percentage of a maximum acceptable dose 

(i.e., the dose which HED has concluded will result in no unreasonable adverse health effects). 

This dose is referred to as the population adjusted dose (PAD). The PAD is equivalent to point 

of departure (POD, NOAEL, LOAEL, e.g.) divided by the required uncertainty or safety factors. 

For acute and non-cancer chronic exposures, HED is concerned when estimated dietary risk 

exceeds 100% of the PAD. HED is generally concerned when estimated cancer risk exceeds one 

in one million. References which discuss the acute and chronic risk assessments in more detail 

are available on the EPA/pesticides web site: "Available Information on Assessing Exposure 

from Pesticides, A User's Guide," 21-JUN-2000, web link: http://www.epa.gov/fedrgstr/EPAPEST/2000/July/Day-12/606l.pdf; or see SOP 99.6 (20-AUG-1 999). 

Pyroxasulfone had a previous dietary risk assessment conducted (T. Morton, 0365234, 

12/ 15/ 11). 

II. Residue Information 

The registrant (K-1 Chemical, U.S.A. Inc.) has submitted a petition to register pyroxasulfone for use 

on soybean. DEEM® residue inputs for soybean commodities used tolerance level residue values for 

soybean and maximum field trial residue levels for com (T. Morton, D365229, 12/15/201 1). The 

existing tolerances are listed in 40 CFR § 180.659. Tolerances for residues of pyroxasulfone raw 

agricultural commodities (RACs) will be established as follows based on field trial data: 

Soybean, seed .................................................................................. 0.06 ppm 

Page 2 of II 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 3 of 11

Residues of concern are summarized in the table below (G. Kramer, D379930, 7/30/2010):

Table 1. Compounds to be Included in the Risk Assessment and Tolerance Expression.

Matrix Residues included in Risk Assessment

Residues included in Tolerance 

Expression for Compliance 

Monitoring

Plants Cereal Grains Pyroxasulfone, M1, M3, M25 Pyroxasulfone, M1, M3, M25***

Soybeans Pyroxasulfone, M1, M3, M25, M28** Pyroxasulfone, M3, M25, M28*

Drinking Water Pyroxasulfone, M1, M3 Not Applicable

Pyroxasulfone = 3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]sulfonyl]-4,5-

dihydro-5,5-dimethylisoxazole.

M1 = [5-(difluoromethoxy)-l-methyl-3-(trifluoromethyl)-lH-pyrazol-4-yl)]methanesulfonic acid.

M3 = 5-(difluoromethoxy)-l-methyl-3-(trifluoromethyl)-lH-pyrazole-4-carboxylic acid.

M25 = [5-(difluoromethoxy)-3-(trifluoromethyl)-1H-pyrazol-4-yl)]methanesulfonic acid.

M28 = 3-[1-carboxy-2-(5,5-dimethyl-4,5-dihydroisoxazol-3-ylthio)ethylamino]-3-oxopropanoic acid.

Metabolite C = 3-[1-carboxy-2-(5,5-dimethyl-4,5-dihydroisoxazol-3-ylthio)ethenylamino]-3-oxopropanoic acid.

* reanalysis of the seed samples showed residues of M28 and therefore M28 needs to be included in both the

tolerance expression and risk assessment as a residue of concern in soybean seed. M-1 is included for soybean 

forage and hay.

** residues of concern for soybean seed is pyroxasulfone and metabolite M-3, M-25, & M-28.

***residues of concern for corn, field, grain and corn, sweet, kernel plus cob with husks removed is 

 pyroxasulfone and metabolite M-3. 

III. Drinking Water Data

The drinking water estimates used in the dietary risk assessment were provided by the 

Environmental Fate and Effects Division (EFED; Memo, J. Hetrick, 1-June-2011; D390221). 

EFED conducted a Tier II PRZM GW drinking water assessment from groundwater sources for 

the proposed new active ingredient. Residues of concern for drinking water for risk assessment 

purposes were parent, M1, and M3. The estimated drinking water residues for peak

concentration (used in the acute assessment) and average (used in the chronic assessment) were

0.210 and 0.174 mg/L (ppm), respectively. 

IV. DEEM-FCID Program and Consumption Information

Pyroxasulfone acute and chronic dietary exposure assessments were conducted using the Dietary 

Exposure Evaluation Model software with the Food Commodity Intake Database DEEMFCIDTM, Version 3.16, which incorporates consumption data from USDA’s National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). This dietary 

survey was conducted from 2003 to 2008. The data are based on the reported consumption of 

more than 20,000 individuals over two non-consecutive survey days. Foods “as consumed” (e.g., 

apple pie) are linked to EPA-defined food commodities (e.g. apples, peeled fruit - cooked; fresh 

or N/S; baked; or wheat flour - cooked; fresh or N/S, baked) using publicly available recipe 

translation files developed jointly by USDA/ARS and EPA. For chronic exposure assessment, 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 4 of 11

consumption data are averaged for the entire U.S. population and within population subgroups, 

but for acute exposure assessment are retained as individual consumption events. Based on 

analysis of the 2003-2008 WWEIA consumption data, which took into account dietary patterns 

and survey respondents, HED concluded that it is most appropriate to report risk for the 

following population subgroups: the general U.S. population, all infants (<1 year old), children 1-

2, children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50-99 years 

old.

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total average 

estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent of the 

cPAD. This procedure is performed for each population subgroup.

For acute exposure assessments, individual one-day food consumption data are used on an 

individual-by-individual basis. The reported consumption amounts of each food item can be 

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a 

deterministic exposure assessment, or “matched” in multiple random pairings with residue values 

and then summed in a probabilistic assessment. The resulting distribution of exposures is 

expressed as a percentage of the aPAD on both a user (i.e., only those who reported eating 

relevant commodities/food forms) and a per-capita (i.e., those who reported eating the relevant 

commodities as well as those who did not) basis. In accordance with HED policy, per capita 

exposure and risk are reported for all tiers of analysis. However, for tiers 1 and 2, any significant 

differences in user vs. per capita exposure and risk are specifically identified and noted in the risk 

assessment.

V. Toxicological Information

The toxicological doses and endpoints for pyroxasulfone for use in the dietary assessment are 

summarized in Table 2.
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 5 of 11

Table 2. Toxicological Doses and Endpoints for Pyroxasulfone for Use in Dietary Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD & PAD Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

NOAEL= 100 

mg/kg

UFA= 10 x

UFH=10 x

FQPA SF=1x

Acute RfD = 

1.0 mg/kg

aPAD = 1.0 

mg/kg

Developmental neurotoxicity study (DNT) in 

rats, MRID 47701724.

The LOAEL of 300 mg/kg/day is based on 

decreased brain weight in both sexes, reduced 

thickness of the hippocampus, corpus callosum 

and cerebellum in PND 21 female offspring.

Chronic Dietary 

(All Populations)

NOAEL= 2 

mg/kg/day

UFA= 10 x

UFH=10 x

FQPA SF=1x

Chronic RfD 

= 0.02

mg/kg/day

cPAD = 0.02 

mg/kg/day

One- year chronic dog study, MRID 47701707

The LOAEL of 10 mg/kg/day is based on 

impaired hind limb function, ataxia, hind limb 

twitching and tremors; clinical pathology: 

increased creatine kinase, aspartate 

aminotransferase; axonal/myelin degeneration of 

the sciatic nerve and spinal cord sections.

Cancer (all routes) “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. Risk is quantified using a non-linear (i.e., 

RfD) approach. 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 6 of 11

VI. Results/Discussion

As stated above, for acute and chronic assessments, HED is concerned when dietary risk exceeds 

100% of the PAD. The following summarizes the DEEM-FCID (ver. 3.16) chronic exposure 

analyses.

Acute and chronic aggregate (food + water) analyses were performed using DEEM-FCID

estimating the dietary exposure of the U.S. population and various population subgroups. The 

results are summarized in Table 2. 

The resulting acute food and water exposure estimates were less than HED’s level of concern (-

<100% aPAD) for the general U.S. population and all population sub-groups. The resulting 

chronic food and water exposure estimates were less than HED’s level of concern (<100% 

cPAD) for the general U.S. population and all population sub-groups; All Infants <1 yr old had 

the highest dietary exposure at 48 % cPAD. 

Table 2. Results of Acute and Chronic Dietary Exposure Analysis for Pyroxasulfone (Food and Water)

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

General U.S. Population 0.011572 1.2 0.003728 19

All Infants (< 1 year old) 0.036099 3.6 0.009569 48

Children 1-2 years old 0.017929 1.8 0.005463 27

Children 3-5 years old 0.014714 1.5 0.004527 23

Children 6-12 years old 0.011088 1.1 0.003333 17

Youth 13-19 years old 0.009640 1.0 0.002747 14

Adults 20-49 years old 0.011374 1.1 0.003706 19

Adults 50-99 years old 0.010165 1.0 0.003644 18

Females 13-49 years old 0.011527 1.2 0.003690 18
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 7 of 11

VII. Characterization of Inputs/Outputs

HED has conducted a highly conservative, health protective assessment for the new proposed use 

of pyroxasulfone on soybean. Maximum residues for corn commodities and tolerance level 

residues for soybean commodities along with 100 % CT were used in the acute and chronic 

dietary exposure assessments. In addition, DEEM default processing factor of 1.5x was used for 

corn syrup. Residues do not warrant the need for further refinement at this time. 

VIII. Conclusions

Partially refined acute and chronic aggregate (food + water) dietary risk assessments were

conducted for pyroxasulfone using the DEEM-FCID (ver. 3.16) model using maximum

residues, DEEM default processing factor, and 100 % CT. The resulting acute aggregate 

exposure estimate was less than HED’s level of concern. For the general U.S. population and all 

population subgroups in the acute analysis all dietary exposure estimates were ≤4% aPAD). The 

resulting chronic aggregate exposure estimate was less than HED’s level of concern. For the 

general U.S. population, the cPAD was 19% while the most highly-exposed population 

subgroups in the chronic analysis was All Infants <1 year old (48% cPAD). 

IX. Attachments

List of Attachments:

Attachment 1: Residue Information.

Attachment 2: Acute Results.

Attachment 3: Chronic Results.

cc with all attachments: T. Morton (RABIV)

RDI: Donna Davis and Ideliz Negrón-Encarnación - DESAC (23-October-2012); S. Hummel (30-January-2013)

Petition Number(s): 2F8005

DP#: 406657

PC Code: 090099

T. Morton:S10838:PY1:(703)305-6691
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 8 of 11

Attachment 1: Residue Information.

Acute Analysis

Filename: C:\Documents and Settings\tmorton\My Documents\MyFiles\DEEM Files\090099 

Pyroxasulfone\Soybean\090099ACUTEFOODANDWATER.R08

Chemical: Pyroxasulfone

RfD(Chronic): .02 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): 1 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last modified: 11-08-2012/10:10:34 Program ver. 3.16, 03-08-d

-----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

0600347000 6 Soybean, seed 0.060000 1.000 1.000 

0600349000 6 Soybean, soy milk 0.060000 1.000 1.000 

0600349001 6 Soybean, soy milk-babyfood or in 0.060000 1.000 1.000 

0600350000 6 Soybean, oil 0.060000 1.000 1.000 

0600350001 6 Soybean, oil-babyfood 0.060000 1.000 1.000 

0601349500 6AB Soybean, vegetable 0.060000 1.000 1.000 

0603348000 6C Soybean, flour 0.060000 1.000 1.000 

0603348001 6C Soybean, flour-babyfood 0.060000 1.000 1.000 

1500120000 15 Corn, field, flour 0.025000 1.000 1.000 

1500120001 15 Corn, field, flour-babyfood 0.025000 1.000 1.000 

1500121000 15 Corn, field, meal 0.025000 1.000 1.000 

1500121001 15 Corn, field, meal-babyfood 0.025000 1.000 1.000 

1500122000 15 Corn, field, bran 0.025000 1.000 1.000 

1500123000 15 Corn, field, starch 0.025000 1.000 1.000 

1500123001 15 Corn, field, starch-babyfood 0.025000 1.000 1.000 

1500124000 15 Corn, field, syrup 0.025000 1.500 1.000 

1500124001 15 Corn, field, syrup-babyfood 0.025000 1.500 1.000 

1500125000 15 Corn, field, oil 0.025000 1.000 1.000 

1500125001 15 Corn, field, oil-babyfood 0.025000 1.000 1.000 

1500126000 15 Corn, pop 0.025000 1.000 1.000 

1500127000 15 Corn, sweet 0.028000 1.000 1.000 

1500127001 15 Corn, sweet-babyfood 0.028000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.210000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.210000 1.000 1.000 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 9 of 11

Chronic Analysis

Filename: C:\Documents and Settings\tmorton\My Documents\MyFiles\DEEM Files\090099 

Pyroxasulfone\Soybean\090099CHRONICFOODANDWATER.R08

Chemical: Pyroxasulfone

RfD(Chronic): .02 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

RfD(Acute): 1 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last modified: 11-08-2012/10:11:13 Program ver. 3.16, 03-08-d

-----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

0600347000 6 Soybean, seed 0.060000 1.000 1.000 

0600349000 6 Soybean, soy milk 0.060000 1.000 1.000 

0600349001 6 Soybean, soy milk-babyfood or in 0.060000 1.000 1.000 

0600350000 6 Soybean, oil 0.060000 1.000 1.000 

0600350001 6 Soybean, oil-babyfood 0.060000 1.000 1.000 

0601349500 6AB Soybean, vegetable 0.060000 1.000 1.000 

0603348000 6C Soybean, flour 0.060000 1.000 1.000 

0603348001 6C Soybean, flour-babyfood 0.060000 1.000 1.000 

1500120000 15 Corn, field, flour 0.025000 1.000 1.000 

1500120001 15 Corn, field, flour-babyfood 0.025000 1.000 1.000 

1500121000 15 Corn, field, meal 0.025000 1.000 1.000 

1500121001 15 Corn, field, meal-babyfood 0.025000 1.000 1.000 

1500122000 15 Corn, field, bran 0.025000 1.000 1.000 

1500123000 15 Corn, field, starch 0.025000 1.000 1.000 

1500123001 15 Corn, field, starch-babyfood 0.025000 1.000 1.000 

1500124000 15 Corn, field, syrup 0.025000 1.500 1.000 

1500124001 15 Corn, field, syrup-babyfood 0.025000 1.500 1.000 

1500125000 15 Corn, field, oil 0.025000 1.000 1.000 

1500125001 15 Corn, field, oil-babyfood 0.025000 1.000 1.000 

1500126000 15 Corn, pop 0.025000 1.000 1.000 

1500127000 15 Corn, sweet 0.028000 1.000 1.000 

1500127001 15 Corn, sweet-babyfood 0.028000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.174000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.174000 1.000 1.000 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 10 of 11

Attachment 2:Acute Results

U.S. EPA Ver. 3.16, 03-08-d

DEEM-FCID ACUTE Analysis for PYROXASULFONE NHANES 2003-2008 2-Day

Residue file: 090099ACUTEFOODANDWATER.R08 Adjustment factor #2 used.

Analysis Date: 01-30-2013/10:04:44 Residue file dated: 01-30-2013/10:01:43

RAC/FF intake summed over 24 hours

Run Comment: ""

===============================================================================

Summary calculations--per capita:

 95th Percentile 99th Percentile 99.9th Percentile

Exposure % aRfD Exposure % aRfD Exposure % aRfD 

 ---------- -------- ---------- -------- ---------- --------

Total US Population:

 0.011572 1.16 0.019009 1.90 0.036310 3.63 

All Infants:

 0.036099 3.61 0.048713 4.87 0.071395 7.14 

Children 1-2:

 0.017929 1.79 0.027136 2.71 0.065558 6.56 

Children 3-5:

 0.014714 1.47 0.022349 2.23 0.035613 3.56 

Children 6-12:

 0.011088 1.11 0.018126 1.81 0.027935 2.79 

Youth 13-19:

 0.009640 0.96 0.015809 1.58 0.023824 2.38 

Adults 20-49:

 0.011374 1.14 0.016808 1.68 0.024520 2.45 

Adults 50-99:

 0.010165 1.02 0.015218 1.52 0.023945 2.39 

Female 13-49:

 0.011527 1.15 0.016825 1.68 0.023688 2.37 
Pyroxasulfone Dietary Exposure and Risk Assessment DP Number: D406657

PC Code: 090099

Page 11 of 11

Attachment 3:Chronic Results

U.S. EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for PYROXASULFONE NHANES 2003-2008 2-day

Residue file name: C:\Documents and Settings\tmorton\My Documents\MyFiles\DEEM Files\090099 

Pyroxasulfone\Soybean\090099CHRONICFOODANDWATER.R08

 Adjustment factor #2 used.

Analysis Date 01-30-2013/10:03:15 Residue file dated: 01-30-2013/10:02:26

Reference dose (RfD, Chronic) = .02 mg/kg bw/day

===============================================================================

 Total exposure by population subgroup

-------------------------------------------------------------------------------

 Total Exposure

 -----------------------------------

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

-------------------------------------- ------------- ----------------

Total US Population 0.003728 18.6%

Hispanic 0.003575 17.9%

Non-Hisp-White 0.003828 19.1%

Non-Hisp-Black 0.003095 15.5%

Non-Hisp-Other 0.004289 21.4%

Nursing Infants 0.003360 16.8%

Non-Nursing Infants 0.012342 61.7%

Female 13+ PREG 0.003506 17.5%

Children 1-6 0.004867 24.3%

Children 7-12 0.003169 15.8%

Male 13-19 0.002604 13.0%

Female 13-19/NP 0.002888 14.4%

Male 20+ 0.003462 17.3%

Female 20+/NP 0.003885 19.4%

Seniors 55+ 0.003571 17.9%

All Infants 0.009569 47.8%

Female 13-50 0.003694 18.5%

Children 1-2 0.005463 27.3%

Children 3-5 0.004627 23.1%

Children 6-12 0.003333 16.7%

Youth 13-19 0.002747 13.7%

Adults 20-49 0.003706 18.5%

Adults 50-99 0.003644 18.2%

Female 13-49 0.003690 18.4%

-------------------------------------------------------------------------------