NEW CHEMICAL REGISTRATION 

(Section 3) 

 ECOLOGICAL RISK ASSESSMENT 

Pyroxasulfone: Herbicide 

USEPA PC # 090099 

Chemical Name(s): 3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol4-yl]methyl]sulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (CAS) 

 5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-

ylmethyl 4,5-dihydro-5,5-dimethyl-1,2-oxazol-3-yl sulfone 

 Or 

 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-

ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-oxazole 

 (IUPAC) 

Chemical Abstracts Service (CAS) Number: 447399-55-5 

Chemical Family: Oxazole herbicide, pyrazole herbicide 

Pesticidal Mode of Action: Sulfonylioxazoline (acetolactase synthase, ALS inhibitor); 

Inhibits biosynthesis of very-long-chain fatty acids 

(VLCFAs)1

; K3 group of herbicides

Proposed End-use Product: Pyroxasulfone 85 WG (85% a.i.; EPA Reg.No.63588-xx)a

; 

V-10233 Herbicide (42.5% pyroxasulfone; 33.5% flumioxazin)b water dispersible 

granule; Pyroxasulfone Technical (99.2% a.i.; EPA Reg No. 63588-xx) for formulation 

only into registered end-use herbicide products; 

 

Target Pest(s): Weeds

 

1

 Shimizu., T., Y. Tanetani, K.Kaku, K. Kawai, and T. Fujioka. 2009. Action mechanism of a novel 

herbicide, pyroxasulfone. Pesticide Biochemistry and Physiology, Vol. 95, Issue 1, p. 47-55. (also 

submitted as MRID 47701754) 
2

Proposed Target Crop(s): a

Field corn, popcorn, sweet corn, soybeans, winter wheat; 

b

field corn, soybean, fallow land, non-crop areas around farms, orchards and vineyards 

and to maintain bare ground on non-crop areas 

Date of Risk Assessment Completion: 6.6.2011 

Risk Assessors: Tanja Crk, MA, Biologist 

 James A. Hetrick, PhD, Senior Scientist 

Environmental Risk Branch III 

 Environmental Fate and Effects Division 

Secondary Reviewers: Melissa Panger, PhD, Senior Scientist 

 Katrina White, Acting RAPL 

Environmental Risk Branch III 

 Environmental Fate and Effects Division 

Through: Dana Spatz, Branch Chief 

Environmental Risk Branch III 

 Environmental Fate and Effects Division 
3

Table of Contents 

I. EXECUTIVE SUMMARY ...................................................................................... 6 

A. Nature of the Chemical Stressor ............................................................................. 6 

B. Potential Risks to Non-target Organisms ................................................................ 6 

C. Environmental Fate Summary ................................................................................ 8 

D. Ecological Effects Summary ................................................................................... 9 

E. Uncertainties and Data Gaps ................................................................................. 14 

1. Environmental Fate and Exposure .................................................................... 14 

2. Ecological Effects Data ..................................................................................... 14 

F. Endangered Species Considerations .................................................................... 15 

II. PROBLEM FORMULATION .......................................................................... 16 

A. Nature of Regulatory Action ................................................................................. 16 

B. Stressor Source and Distribution .......................................................................... 16 

1. Nature of the Chemical Stressor ................................................................... 17 

a. Mode of Action (MoA) of Pyroxasulfone ................................................... 19 

b. Environmental Fate Summary ...................................................................... 19 

2. Overview of Pesticide Use and Usage ............................................................. 20 

C. Receptors............................................................................................................... 21 

1. Aquatic and Terrestrial Effects ......................................................................... 21 

2. Ecosystems Potentially at Risk ......................................................................... 23 

D. Assessment Endpoints .......................................................................................... 23 

E. Conceptual Model ................................................................................................. 23 

1. Risk Hypothesis ................................................................................................ 23 

2. Conceptual Diagrams ........................................................................................ 24 

F. Analysis Plan ....................................................................................................... 29 

1. Conclusions from Previous Risk Assessments ................................................. 29 

2. Preliminary Identification of Data Gaps ........................................................... 30 

3. Measures of Exposure and Effects .................................................................... 31 

a. Aquatic Exposure Models ............................................................................. 31 

b. Terrestrial Exposure Models ......................................................................... 32 

III. ANALYSIS .......................................................................................................... 36 

A. Use Characterization ............................................................................................. 36 

B. Exposure Characterization .................................................................................... 36 

1. Environmental Fate and Transport.................................................................... 36 

2. Measures of Aquatic Exposure ......................................................................... 41 

a. Aquatic Exposure Modeling ......................................................................... 41 

b. Aquatic Exposure Monitoring and Field Data .............................................. 46 

c. Aquatic Bioaccumulation Assessment .......................................................... 46 

3. Measures of Terrestrial Exposure ..................................................................... 47 

a. Terrestrial Exposure Modeling ..................................................................... 47 

C. Ecological Effects Characterization ...................................................................... 51 

1. Aquatic Effects Characterization ...................................................................... 51 

a. Aquatic Animals ........................................................................................... 51 
4

(1) Acute Effects ........................................................................................ 51 

(2) Chronic Effects ..................................................................................... 56 

b. Aquatic Plants ............................................................................................... 59 

2. Terrestrial Effects Characterization .................................................................. 68 

a. Terrestrial Animals ....................................................................................... 68 

(1) Acute Effects ......................................................................................... 68 

(2) Chronic Effects ..................................................................................... 82 

b. Terrestrial Plants ........................................................................................... 89 

IV. RISK CHARACTERIZATION ......................................................................... 92 

A. Risk Estimation - Integration of Exposure and Effects Data ............................... 92 

1. Risk to Aquatic Animals and Plants ................................................................. 92 

a. Aquatic Animals ........................................................................................... 92 

(1) Risk Following Acute Exposure ........................................................... 92 

(2) Risk Following Chronic Exposure ........................................................ 93 

b. Aquatic Plants ............................................................................................... 94 

2. Risk to Terrestrial Animals and Plants ............................................................. 95 

a. Terrestrial Animals ....................................................................................... 95 

(1) Risk Following Acute Exposure ........................................................... 96 

(2) Risk Following Chronic Exposure ........................................................ 98 

b. Terrestrial Plants ......................................................................................... 100 

B. Risk Description.................................................................................................. 102 

1. Risk to Aquatic Animals and Plants ............................................................... 103 

a. Aquatic Animals ......................................................................................... 103 

(1) Risk Following Acute Exposure ......................................................... 103 

(2) Risk Following Chronic Exposure ...................................................... 105 

b. Aquatic Plants ............................................................................................. 107 

2. Risk to Terrestrial Animals and Plants ........................................................... 109 

a. Terrestrial Animals ..................................................................................... 109 

(1) Risk Following Acute Exposure ......................................................... 109 

(2) Risk Following Chronic Exposure ...................................................... 111 

b. Terrestrial Plants ......................................................................................... 113 

3. Review of Incident Data ................................................................................. 114 

4. Endocrine Effects ............................................................................................ 114 

5. Federally Threatened and Endangered (Listed) Species.. ............................... 115 

a. Action Area ................................................................................................. 116 

b. Taxonomic Groups Potentially at Risk ....................................................... 116 

(1) Discussion of Risk Quotients .............................................................. 117 

(2) Probit Dose Response Relationship .................................................... 118 

(3) Data Related to Under-represented Taxa ............................................ 118 

c. Indirect Effects Analysis ............................................................................. 118 

d. Critical Habitat ............................................................................................ 119 

e. Co-occurrence Analysis .............................................................................. 120 

C. Description of Assumptions, Limitations, Uncertainties, Strengths and Data Gaps

 ...............................................................................................122 
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1. Assumptions, Limitations, and Uncertainties Related to Exposure For All 

Taxa.................. ........................................................................122 

 a. Maximum UseScenario............................................................122 

2. Assumptions, Limitations and Uncertainties Related to Exposure for Terrestrial 

Species .................................................................................................................... 122 

a. Location of Wildlife Species ...................................................................... 122 

b. Routes of Exposure ..................................................................................... 122 

c. Dietary Intake and Other Limitations of Oral Studies in Terrestrial Species

 123 

d. Incidental Releases Associated With Use ................................................... 125 

e. Residue Levels Selection ............................................................................ 125 

f. TerrPlant Model .......................................................................................... 125 

3. Assumptions, Limitations and Uncertainties Related to Effects Assessment . 126 

a. Sublethal Effects ......................................................................................... 126 

b. Age Class and Sensitivity of Effects Thresholds ........................................ 126 

c. Use of Most Sensitive Species Tested ........................................................ 126 

5. Assumptions, Limitations, Uncertainties, Strengths and Data Gaps Related to 

the Acute and Chronic LOC’s ................................................................................. 126 

V. LITERATURE CITED ........................................................................................ 127 

VI. LIST OF APPENDICES ................................................................134 

VII. LIST OF FIGURES......................................................................135 

VIII. LIST OF TABLES........................................................................135 
6

I. Executive Summary 

A. Nature of the Chemical Stressor 

Pyroxasulfone is a new pesticide active ingredient being proposed as an herbicide to 

control weeds in various use sites (field corn, popcorn, sweet corn, soybeans, winter 

wheat; fallow land, non-crop areas around farms, orchards and vineyards and to maintain 

bare ground on non-crop areas). It is in the pyrazole class; also considered an oxazole, 

K-3 herbicide, and a sulfonylioxazoline (acetolactase synthase, ALS inhibitor). What is 

known is that the chemical inhibits biosynthesis of very-long-chain fatty acids (VLCFAs) 

- that are contained in the plasma membrane of plant cells - by preventing fatty acid 

precursors (medium- and long-chain fatty acids, which are formed in the chloroplast) 

from elongating into chains (in the endoplasmic reticulum). Ultimately, this effect leads 

to inhibition of plant shoot growth. Weedy species such as barnyard millet and Italian 

ryegrass, but also rice were determined to be sensitive to pyroxasulfone; wheat and corn 

to a lesser degree (Shimizu et al. 2009 MRID 47701754). It is unclear at this time to what 

degree the mechanism of VLCFA formation in animal cells might be affected as a result 

of exposure to pyroxasulfone. 

 

The maximum single application rate of pyroxasulfone is 0.2136 lbs ai/A with a seasonal 

maximum rate of 0.267 lbs ai/A. Pyroxasulfone can be applied using broadcast or 

banded ground spray as well as aerial spray. Application timing is pre- and early post 

emergent. Other recommended applications include fall treatment (before ground freeze) 

and through dry fertilizer treatments. Depending on the crop, the recommended crop 

rotation intervals range 4 to 12 months. Several end-use products have been proposed 

including: Pyroxasulfone 85 WG (85% a.i.; EPA Reg.No.63588-xx); V-10233 Herbicide 

(42.5% pyroxasulfone; 33.5% flumioxazin) water dispersible granule; Pyroxasulfone 

Technical (99.2% a.i.; EPA Reg No. 63588-xx) for formulation only into registered enduse herbicide products. 

B. Potential Risks to Non-target Organisms 

The results of this screening-level assessment indicate a potential for direct adverse 

effects to non-target aquatic (non-vascular and vascular RQs of 1.03-22.07) and 

terrestrial plants (monocots in semi-aquatic areas RQs 1.35-1.75 exceed listed species 

LOC), birds (chronic dietary-based RQ 1.07) and mammals (chronic dose-based RQs 

1.17-3.86) following chronic exposure. Due to the potential for direct adverse effects to 

aquatic/terrestrial plants, birds, and mammals associated with the application of 

pyroxasulfone on corn, soybean, winter wheat, and non-crop sites, indirect effects may 
7

consequently affect other aquatic and terrestrial species. Data were not submitted for the 

marine/estuarine fish and invertebrates via chronic exposure. Without data, risk cannot be 

ruled out for these taxa (either non-listed or federally listed species) with certainty. 

However, this assessment assumes that estuarine/marine organisms are of comparable 

sensitivity to pyroxasulfone as freshwater organisms are, which implies that risk to 

estuarine/marine organisms from chronic exposure to pyroxasulfone is not expected. 

Metabolite/degradate data were submitted only for non-vascular and vascular aquatic 

plants and mammals (acute oral studies). With the exception of two terrestrial plant 

studies and two non-guideline terrestrial invertebrate studies, no data using formulations 

of pyroxasulfone were submitted leading to uncertainty in the assessment of risk for end 

use products. This does not affect the conclusions made on the technical grade active 

ingredient and metabolites (where available). 

Table 1. Summary of Environmental Risk Conclusions for Aquatic Animals and Plants from Proposed 

Pyroxasulfone Uses 

Taxonomic 

Group 

Assessment 

Endpoint

Summarized Risk Characterization and Important 

Uncertainties

Freshwater Fish 

and Aquatic Phase 

Amphibians 

Mortality Acute risk is not expected. 

Growth (wet wt, 

length) 

Chronic risk is not expected. 

Freshwater 

Invertebrates 

Immobility Acute risk is not expected. 

Reproduction, 

growth, survival 

Chronic risk is not expected. 

Marine/ 

Estuarine Fish 

Mortality Acute risk is not expected. 

Reproduction, 

growth etc. 

No studies submitted. Chronic risk not expected. 

Marine/ 

Estuarine 

Invertebrates 

Mortality Acute risk is not expected. 

Reproduction, 

growth etc. 

No studies submitted. Chronic risk not expected. 

Aquatic Plants 

Growth (frond 

count1 , cell 

density2

)

Risk is expected (from the technical grade active ingredient, but not 

the metabolites). 

* Consult ‘Risk Description’ section for further details. Also, risk in this table implies risk to technical grade 

active ingredient unless otherwise specified that metabolites and/or formulations were assessed as well. 1

 Vascular plants 

2

 Non-vascular plants 
8

Table 2. Summary of Environmental Risk Conclusions for Terrestrial Animals and Plants from Proposed 

Pyroxasulfone Uses 

Taxonomic 

Group Risk Endpoint

Summarized Risk Characterization and Important 

Uncertainties

Birds, Reptiles and 

Terrestrial Phase 

Amphibians 

Mortality Acute risk is not expected. 

Reproduction 

(hatchability) 

Chronic risk is expected.

Mammals 

Mortality Acute risk is not expected (from technical grade active ingredient, 

metabolites/degradates, or formulated products WG85 and V10233). 

Growth (body wt 

gain) 

Chronic risk is expected. 

Non-target 

Invertebrates 

Mortality 

Acute risk to honeybees is not expected (from technical grade active 

ingredient). Acute and chronic1 risk to earthworms (from technical 

grade active ingredient) and acute risk to terrestrial invertebrates 

(non-gln) is not expected (from formulated product WG85). 

Terrestrial Plants Growth (length or 

height, weight) 

Risk to terrestrial plants is expected (based on EUP). 

* Consult ‘Risk Description’ section for further details. Also, risk in this table implies risk to technical grade 

active ingredient unless otherwise specified that metabolites and/or formulations were assessed as well. 1

 In addition to mortality, other endpoints considered in the earthworm reproduction and growth study include 

body wt loss and juvenile counts

C. Environmental Fate Summary 

Pyroxasulfone is mobile (Koc= 57-119 L/kg) and persistent (t1/2= 142 to 533 days) in 

terrestrial and aquatic environments. The major routes of dissipation are expected to be 

associated with microbial-mediated degradation, leaching, and runoff. Pyroxasulfone is 

stable to hydrolysis and photodegradation in water and soil. Volatility is not expected to 

be a major dissipation pathway because of the low vapor pressure (1.8E-8 torr) and 

Henry’s Constant (2.65E-9 atm-m3/mole). Also, the bioaccumulation potential of 

pyroxasulfone is expected to be low due to a low octanol: water coefficient (log 

Kow=2.39). Field dissipation studies indicate rapid dissipation (t1/2= 4 to 35 days) of 

pyroxasulfone. Degradation of pyroxasulfone was identified as a potential route of 

dissipation in field studies. Leaching also was identified as a route of dissipation of the 

metabolite 5-difluoromethoxy-1H-pyrazol-4-yl) methanesulfonic acid (M1). This 

degradation product was very persistent (extrapolate t1/2~ 8 to 65 years) in laboratory 

metabolism studies. 

Another major degradation product (present at ≥10% applied radioactivity) was identified 

as 5-difluoro methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M3). 

Minor degradation products (<10% of applied radioactivity) of pyroxasulfone are: 

 3-(5-Difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-

dihydro-5,5-dimethylisoxazole (M5), 

 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl 

methanesulfonyl)-4,5-dihydro-5,5-dimethylisoxazol-4-ol (M6), 

 (5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl) methanol (M8), 
9

 5-difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M9), 

 5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carbaldehyde 

(M10), and 

 [3-5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-

(ylmethanesulfonyl)-4,5-dihydro-5-methylisoxazol-5-yl] methanol (M11). 

 

The Residue of Concern Knowledgebase Subcommittee (ROCKS) in the Office of 

Pesticide Programs (OPP) identified pyroxasulfone, M1, and M3 as residues of concern 

in the human health risk assessment. 

Additionally, there was a high percentage of applied radioactivity (8-25% of applied 

radioactivity) in “unextracted” soil/sediment residues. Because the extraction of 

pyroxasulfone residues was conducted using only acetonitrile/water without the use of 

sequentially harsher extractants, there is uncertainty regarding the identity and 

availability of the unextracted soil residues. 

D. Ecological Effects Summary 

Aquatic Animals 

Acute

Freshwater and marine/estuarine fish were tested on the technical grade active ingredient 

and did not show (sub)lethal effects at limit concentrations (2.2 mg a.i./L for rainbow 

trout, MRID 47701626; 2.8 mg a.i./L for bluegill sunfish, MRID 47701627) or up to the 

highest concentration tested (3.3 mg a.i./L for sheepshead minnow, MRID 47701628); 

LC50 values indicate that pyroxasulfone is at most moderately toxic to freshwater and 

estuarine/marine fish. 

Similarly, the freshwater and estuarine/marine invertebrates were tested on the technical 

grade active ingredient and did not show (sub)lethal effects at the limit concentration (4.4 

mg a.i./L for water flea, MRID 47701623) or up to the highest concentration tested (3.6 

mg a.i./L for eastern oyster, MRID 47701624; 1.4 mg a.i./L for saltwater mysid, MRID 

47701625); EC50 values indicate that pyroxasulfone is at most moderately toxic to 

freshwater and marine/estuarine invertebrates. 

Chronic

Unlike the acute toxicity study which lead to a non-definitive endpoint, the chronic 

toxicity study using the technical grade active ingredient on freshwater fish determined a 

definitive endpoint (28-day NOAEC of 2.0 mg a.i./L for fathead minnow, MRID 

47701630) on the basis of wet weight and length (growth endpoints) reductions at the 

highest concentration tested (3.9 mg a.i./L). 

A chronic freshwater invertebrate study using the technical grade active ingredient 

determined a non-definitive endpoint (NOAEC ≥1.9 mg a.i./L for water flea, MRID 
10

47701629) given that differences between treatment groups and controls were not 

statistically significant and sublethal effects (discoloration, injury, and lethargy) were 

infrequent, comparable to controls, and not considered treatment related. 

Chronic toxicity studies on the marine/estuarine fish and invertebrates were not submitted 

by the registrant. 

Aquatic Plants 

The vascular aquatic plant data on the technical yielded a definitive endpoint (7-day EC50

of 6.0 g a.i./L, NOAEC of 0.18 g a.i./L for duckweed, MRID 47701640) on the basis 

of frond count; however, two studies on the metabolites (M-1, M-3) indicated that none 

of the endpoints of interest (frond count, biomass, growth rate) were affected leading to a 

non-definitive endpoint for both studies (7-day EC50 > 123 mg a.i./L, NOAEC ≥123 mg 

a.i./L, MRIDs 47701641, 47701642). Chlorosis and necrosis were consistently observed 

in all three studies. 

On the other hand, three non-vascular aquatic plant studies on the freshwater green algae 

yielded definitive endpoints for the technical (96-hr EC50 of 0.00038 mg a.i./L, NOAEC 

of 0.0001 mg a.i./L, MRID 47701643), metabolite M-1 (96-hr EC50 of 56 mg a.i./L, 

NOAEC of 31 mg a.i./L, MRID 47701647), and metabolite M-3 (96-hr EC50 of 38 mg 

a.i./L, NOAEC of 15 mg a.i./L, MRID 47701648). In all three studies, all three endpoints 

of interest (cell density, biomass, and growth rate) were affected, with cell density 

generally being the most sensitive of the three endpoints; however, no sublethal effects 

were observed. Similarly, the marine diatom indicated sensitivity to the technical grade 

active ingredient yielding a definitive endpoint for the most sensitive endpoint, cell 

density (96-hr EC50 of 0.66 mg a.i./L, NOAEC of 0.14 mg a.i./L, MRID 47701646), 

though all three endpoints of interest were affected and cell aggregation (apparently a 

symptom at relatively high cell densities) was observed in all treatment levels. The 

freshwater blue-green algae on the technical yielded a non-definitive EC50 for all three 

endpoints, but on the basis of the NOAEC (0.16 mg a.i./L, MRID 47701644), cell density 

and growth rate were deemed most sensitive and biomass less so (NOAEC 1.6 mg a.i./L). 

Cell aggregation and long chains were observed in all treatment levels and controls. 

Finally, the freshwater diatom indicated no sensitivity to the technical whereby the cell 

density, biomass, and growth rate endpoints were all non-definitive (96-hr EC50 >3.2 mg 

a.i./L, NOAEC ≥ 3.2 mg a.i./L, MRID 47701645) and cell aggregation was observed in 

all treatment levels and controls. 

Terrestrial Animals 

Acute

Upland, waterfowl, and passerine birds were tested on the technical grade active 

ingredient. The acute oral studies did not show (sub)lethal effects at limit concentrations 

(2250 mg a.i./kg-bw for zebra finch, MRID 47701632) or up to the highest concentration 

tested (2250 mg a.i./kg-bw for northern bobwhite quail, MRID 47701631); LD50 values 

indicate that pyroxasulfone is practically non-toxic to birds on an acute oral basis. An 

acute dietary study determined a non-definitive endpoint (8-day LC50> 5620 mg a.i./kgdiet and NOAEC≥5620 mg a.i./kg-diet for northern bobwhite quail, MRID 47701633) 
11

given that the study indicated no mortalities, overt signs of toxicity, or treatment-related 

effects on body weight or food consumption at the dosage levels tested; in addition, 

sublethal effects (leg lesions, limping, wing droop) were not considered treatment related. 

A second acute dietary study determined a non-definitive endpoint (8-day LC50> 5620 

mg a.i./kg-diet for mallard duck, MRID 47701634) given that the study indicated no 

mortalities, overt signs of toxicity, or treatment-related effects on food consumption at 

the dosage levels tested. However, relative to the control, the highest two treatment 

groups 3160 and 5620 mg a.i./kg-diet had a reduced increase in body weight that was 

significantly different from the control. The reductions in body weight increase led to a 

determination of an 8-day NOAEC of 1780 mg a.i./kg-diet (EPA calculation) and a 5-day 

NOAEC of 1000 mg a.i./kg-diet (APVMA calculation). The LC50 values from the acute 

dietary studies indicate that pyroxasulfone is practically non-toxic to birds on an acute 

oral basis 

Eight acute oral studies were conducted on female rats to satisfy OCSPP guidance 

870.1100 (OECD 425) – one technical and seven degradate/metabolite (M-1, M-3, M-25, 

I-3, I-4, I-5, M-28). All of the studies were deemed acceptable and indicated that the test 

compound was practically non-toxic with toxicity category III. However, all of the 

studies were conducted at a limit dose of 2000 mg a.i./kg-bw and without control groups. 

Two formulation studies were conducted on female rats to satisfy OCSPP guidance 

870.1100 (OECD 425) – one on WG85 (85%a.i.) and one on V-10233 (42.2% 

pyroxasulfone; 33.6 flumioxazin). Both studies were limit tests and deemed acceptable; 

however, no control groups were used in the study design. The single active ingredient 

product tested (MRID 47701916) is at most slightly toxic (category III), while the coformulated product (MRID 47702105) is practically non-toxic (category IV) at the 

respective limit doses. No deaths or sublethal effects were observed in either study. 

Terrestrial Invertebrates 

A 48-hour acute contact study using the technical grade active ingredient on the honey 

bee indicated no effect to mortality and sporadic sublethal effects such as lethargy, loss of 

equilibrium, and immobility. The compound is considered practically non-toxic to honey 

bees on the basis of a non-definitive endpoint (LD50 > 100 g a.i./bee, MRID 47701637). 

A couple non-guideline studies on formulation WG85 (84.7% purity) indicated effects to 

fecundity that did not reach a 50% reduction at any level of exposure (parasitization of 

aphids in parasitoid wasps, 48-hour ER50 and LR50 >0.892 lbs a.i./A, MRID 47889323) 

as well as mortality and fecundity that did reach a 50% reduction but was not deemed 

dose dependent (overall eggs produced per female predatory mite per day, 7-day ER50

and LR50 >0.892 lbs a.i./A, MRID 47701753). 

Another couple of non-guideline studies using the technical grade active ingredient on the 

earthworm indicated no effects at the concentrations tested which resulted in nondefinitive endpoints for the 14-day study (LC50 > 997 mg a.i./kg dry soil, MRID 

47701748) and 28-day reproduction and growth study (NOAEC ≥ 1000 mg a.i./kg dry 

soil, MRID 47933801). 
12

Chronic

Out of the two 1-generation reproduction studies for birds, mallard duck was more 

sensitive (NOAEC of 60 mg a.i./kg diet on the basis of biologically significant effect on 

hatchability, MRID 47701636) than the northern bobwhite quail (NOAEC ≥ 1000 mg 

a.i./kg diet on the basis of no apparent treatment related effects on adult or offspring body 

weight, reproductive performance, and eggshell thickness, MRID 47701635). 

Out of four chronic mammalian studies available all on the technical grade active 

ingredient, the 2-generation reproduction study on the rat yielded the most sensitive 

endpoint (NOAEL of 7.2 mg/kg-bw/day for males on the basis of decreased body weight, 

body weight gain, and food consumption in the parent generation, MRID 47701706). 

Terrestrial Plants 

According to a registrant submitted open literature study (Shimizu et al. 2009, MRID 

47701754), which identifies the mode of action of pyroxasulfone, also indicates that the 

chemical leads to an inhibition of shoot growth to monocots grown for 6-7 days from 

seed at concentrations on the order of 10-7 – 10-5M (80 to near 100% inhibition in rice, 

Italian ryegrass, and barnyard millet) and 10-6 – 10-5 M (approximately 25 to 75% 

inhibition for wheat) and to a much lesser extent at these concentrations for corn (less 

than 20% inhibition). The concentrations in solution 10-7, 10-6, and 10-5M on a mass: 

volume basis equate to 0.04, 0.4, and 4 mg/L [ppm] (given that M = moles/L; 

concentration in M * 367 g/mol *103 mg/g) and 40, 400, and 4000 g/L [ppb]. However, 

these concentrations exceed the aquatic EECs (maximum concentration calculated in 

PRZM/EXAMS is 8.4 g/L, see Table 14) by at least an order of magnitude. The 

concentrations in solution 10-7, 10-6, and 10-5M on a mass: mass basis equate to 0.00734, 

0.0734, and 0.734 mg a.i./kg soil [ppm] (given that M = moles/L; concentration in M * 

0.001 L/mL* 1mL/g H2O * 367 g/mol *103 mg/g *20 g H2O/100 g dry soil *100 * 

1000g/1kg) and 0.015, 0.15, and 1.5 lbs a.i./A (mg a.i./kg soil * 2 million lbs soil in an 

acre 6 inches deep). The higher of these concentrations (0.15 and 1.5 lbs a.i./A) exceed 

the highest terrestrial plant EECs (0.02 and 0.03 lbs a.i./A, see Table 17) for semi aquatic 

areas given ground spray application at rates of 0.206 and 0.267 lbs a.i./A (respectively), 

but the lowest concentration (0.015 lbs a.i./A) is slightly below these terrestrial plant 

EECs, for which the listed LOC is exceeded for monocots in semi-aquatic areas. 

Similarly, the aerial application of 0.120 lbs a.i./A leads to a terrestrial plant EEC of 

0.018 lbs a.i./A, a value comparable to the lowest concentration in the mode of action 

study (0.015 lbs a.i./A), for which the listed plant LOC is exceeded for monocots in semiaquatic areas. These calculations imply that at the higher ground spray applications and 

the aerial application for one of the formulations, an effect on shoot growth is possible on 

target weeds Italian ryegrass, barnyard millet, but also on rice and potentially other nontarget monocots. Furthermore, the seedling emergence study (MRID 47701638) indicated 

that wheat dry weight (MSD 41.21%) had the following percent reductions 22, 22, 12, 

2.5, and 28% relative to the control which were not detected as statistically significant at 

0.0168, 0.0334, 0.0669, 0.1338, and 0.2676 lbs a.i./A concentrations, respectively. This 

indicates that the study may not capture what it was intended to capture as there was high 

variability in the raw data. However, for wheat, this still implies that sublethal effects 
13

may be observed below maximum application levels (in the study as well the given 

labels) and below the lowest tested concentration. 

Despite some limitations (on account of variability in the raw data) in detecting plant 

sensitivity to pyroxasulfone, the seedling emergence study led to identification of the 

most sensitive monocot (onion, EC25 of 0.0669 lbs a.i./A and NOAEC of 0.0168 lbs 

a.i./A) and dicot species (kidney bean, EC25 of 0.2615 lbs a.i./A [just below the highest 

concentration tested – i.e., 0.2676 lbs a.i./A] and NOAEC of 0.1338 lbs a.i./A) based on 

observed changes in length. 

The vegetative vigor study (MRID 47701639), indicated that monocots, overall, did not 

exhibit signs of treatment-related toxicity, whereas dicots did. However, there is some 

uncertainty in these results considering that potential weeds or pest species are monocots 

(e.g., barnyard millet, Italian ryegrass). As a result determining the most sensitive 

monocot (i.e., onion) was based on the lowest EC25 of the monocots for which the 

endpoint was available. However, the ECx’s for onion (as well as most monocot data) did 

not indicate convergence whereby an algorithm was not plotted against the data 

indicating clear inhibition with increasing concentration. As a result, for onion the EC25 > 

0.2676 lbs a.i./A (the highest concentration tested) and the NOAEC is equal to the 

highest concentration tested. On the other hand, the most sensitive dicot was the pumpkin 

(EC25 of 0.0748 lbs a.i./A and NOAEC of 0.0168 lbs a.i.A).

In addition, given that pyroxasulfone may leach into groundwater, predicted 

concentrations of pyroxasulfone (equivalent to the equilibrium concentration taken over a 

30 year period) were used to estimate the potential phytotoxic effects from irrigation 

water to plants and sensitive crops on the treated field. If listed monocot and dicot 

species and/or sensitive crops are exposed on the treated field to the estimated amounts of 

pyroxasulfone in irrigation water, then effects will be expected. 

Risk Conclusions 

Based on the available ecotoxicity data and predicted environmental exposures, risks to 

aquatic (non-vascular and vascular, listed and non-listed) and terrestrial (listed) plants as 

well as listed and non-listed birds (as well as reptiles and amphibians) and mammals 

following chronic exposure are expected. In addition, risk to listed terrestrial plants and 

potentially sensitive crops located on the irrigated/treated field are expected as a result of 

use of pyroxasulfone contaminated irrigation water at the estimated levels. The 

pyroxasulfone degradates, M-1 and M-3, are not considered degradates of concern for 

duckweed (vascular aquatic plant) or freshwater green algae (non-vascular aquatic plant). 

The pyroxasulfone degradates, M-1, M-3, M-25, I-3, I-4, I-5, M-28, are not considered 

degradates of concern for mammals (on an acute basis). The formulations WG85 (84.7% 

a.i.) and V-10233 (42.2% pyroxasulfone; 33.6% flumioxazin) are not considered to pose 

a risk to mammals (on an acute basis). The formulation WG85 (84.7% a.i.) is considered 

to not pose a risk to (non-guideline) terrestrial invertebrates (parasitoid wasp, predatory 

mite). 
14

E. Uncertainties and Data Gaps 

1. Environmental Fate and Exposure 

The submitted fate database is incomplete for pyroxasulfone on account of the need for 

ground water monitoring data. In addition, an uncertainty in the environmental fate data 

is the identification and availability of unextracted residues in soil and aquatic 

metabolism studies. These residues account for a high percentage of applied 

radioactivity (8-25% of applied radioactivity). Although there is an uncertainty regarding 

the identification and quantification of unextracted soil/sediment residues, this 

uncertainty does not substantially affect the estimated exposure levels due to the 

persistence of pyroxasulfone. For a list of submitted environmental fate studies for 

pyroxasulfone see SectionV. 

Data needs: 

Because pyroxasulfone is mobile and persistent in soil it has the potential to leach into 

groundwater. This behavior was predicted using Tier II PRZM GW model. This 

modeling showed that pyroxasulfone has the potential to accumulate in groundwater. 

 Prospective ground water monitoring study. 

 

2. Ecological Effects Data 

The submitted ecotoxicity database is incomplete. For a list of submitted ecological 

effects studies for pyroxasulfone see Section V. The following studies are considered 

data gaps: 

Chronic Marine/Estuarine Fish Study

No chronic studies on marine/estuarine fish were submitted by the registrant. Therefore, 

a quantitative estimation of risk could not be conducted. According to CFR 40 Part 158, 

this data is conditionally required and although pyroxasulfone is stable to hydrolysis (at 

pHs 4, 7, and 9) and aqueous photolysis (half life = 119 days), comparison to freshwater 

fish data suggests that chronic risk to marine/estuarine fish is not expected as a result of 

pyroxasulfone (TGAI) use on corn, soybean wheat, and non-crop sites. Therefore, a 

chronic marine/estuarine fish study is not required. 

Chronic: Fish early-life stage (saltwater: Cyprinodon variegatus) (850.1400; 72-

4), TGAI 

Chronic Marine/Estuarine Invertebrate Study

No chronic studies on marine/estuarine invertebrates were submitted by the registrant. 

Therefore, a quantitative estimation of risk cannot be conducted. According to CFR 40 

Part 158, this data is conditionally required and although pyroxasulfone is stable to 

hydrolysis (at pHs 4, 7, and 9) and aqueous photolysis (half life = 119 days), 

comparison to freshwater invertebrate data suggests that chronic risk to marine/estuarine 

invertebrates is not expected as a result of pyroxasulfone (TGAI) use on corn, soybean, 
15

wheat, and non-crop sites. Therefore, a chronic marine/estuarine invertebrate study is not 

required. 

Chronic: Marine/estuarine invertebrate (Americamysis bahia) (850.1350; 72-4), 

TGAI 

Fish Bioaccumulation Study

A bioaccumulation in fish study was not submitted to support the proposed registration. 

According to CFR 40 Part 158, this data is conditionally required and although 

pyroxasulfone is mobile and persistent, the low octanal:water partitioning coefficient (log 

Kow= 2.39) is expected to limit bioconcentration and bioaccumulation of pyroxasulfone. 

Based on the log Kow of 2.39, the expected BCF assuming no metabolism and 5% lipids 

would be approximately 12 L/kg wet weight (i.e., 102.39 * 0.05). This low BCF combined 

with the low acute toxicity to birds and mammals indicates that risks to piscivorous 

wildlife would not be expected. Therefore, a fish bioaccumulation study is not required. 

 Fish Bioaccumulation study (850.1730; 72-6, 165-4), TGAI 

F. Endangered Species Considerations 

Table 3 summarizes the listed species at risk associated with either direct or indirect 

effects following application of pyroxasulfone for the proposed uses. 

Concerns For Federally Listed as Endangered and/or Threatened Species 

Table 3. Listed Species Risks Associated With Direct or Indirect Effects from Pyroxasulfone use 

Listed Taxon Direct Effects Indirect Effects

Terrestrial and semi-aquatic plants - monocots Yes Yes4

 

Terrestrial and semi-aquatic plants – dicots No Yes4

Terrestrial invertebrates No Yes4

Birds Yes (chronic) Yes4

Terrestrial-phase amphibians1 Yes (chronic) Yes4

Reptiles1 Yes (chronic) Yes4

Mammals Yes (chronic) Yes4

 Aquatic non-vascular plants Yes Yes4

Aquatic vascular plants Yes Yes4

Freshwater (FW) fish No Yes4

Aquatic-phase amphibians2 No Yes4

Freshwater (FW) invertebrates No Yes4

Marine/estuarine (M/E) fish No3 Yes4

Marine/estuarine (M/E) invertebrates (mollusk) No3 Yes4

1

 Results from birds used as surrogate for assessing risk to terrestrial-phase amphibians and reptiles 

2

 Results from freshwater fish used as surrogate for assessing risk to aquatic-phase amphibians 3

 Assumption of no expected risk or direct effect is made on the basis of freshwater fish and invertebrate data. 

4 From effects to mammals, birds, plants 
16

II. Problem Formulation 

The purpose of this problem formulation is to provide the foundation for the ecological 

risk assessment being conducted for the herbicide pyroxasulfone. As such, it articulates 

the purpose and objectives of the risk assessment, evaluates the nature of the problem, 

and provides a plan for analyzing the data and characterizing the risk (EPA, 1998). 

A. Nature of Regulatory Action 

Pyroxasulfone is a new pesticide active ingredient being proposed as an herbicide to 

control weeds in various use sites (field corn, popcorn, sweet corn, soybeans, winter 

wheat; fallow land, non-crop areas around farms, orchards and vineyards and to maintain 

bare ground on non-crop areas). As a new active ingredient submitted for registration, 

there are no previously prepared ecological risk assessments by the Agency for 

pyroxasulfone uses. However, the chemical is undergoing a global review in which 

Australian Pesticides and Veterinary Medicines Authority, APVMA (Australia) and Pest 

Management Regulatory Agency, PMRA (Canada) have contributed to secondary review 

of fate and ecotoxicity studies. 

B. Stressor Source and Distribution 

The proposed crop use sites are corn (sweet, field, popcorn), soybean, and winter wheat. 

Additionally, non-crop use sites include fallow land and non-crop areas around farms, 

orchards, and vineyards. Fallow land and crop use treatment requires consideration of 

rotation intervals because of the persistence of pyroxasulfone. Recommended rotation 

intervals into treated fields are 4 months for winter wheat, 8 months for spring wheat, 9 

months for corn, sunflower, dry common beans, canola, 11 months for alfalfa, barley, 

canola, and 12 months for all other crops. The extent of potential crop use areas for 

pyroxasulfone are shown in Figure 1. The extent of non-crop uses cannot be spatially 

identified due to the generalized nature of the use pattern as well as the lack of adequate 

GIS overlays for non-crop use areas. 

 A) Corn 
17

 B) Soybean 

 C) Winter Wheat 

Figure 1: Potential Crop Use Areas for Pyroxasulfone 

(From USDA 2008 and 2009 County Crop Programs available at: 

http://www.rma.usda.gov/data/cropprograms.html). 

1. Nature of the Chemical Stressor 

Figure 2 provides the chemical structure of pyroxasulfone. Table 4 identifies the 

physical and chemical properties of pyroxasulfone from experimental data. 

 
18

Figure 2. Chemical Structure of Pyroxasulfone

Table 4: Environmental Fate Properties of Pyroxasulfone 

PARAMETER VALUE 

Chemical and Physical Properties 

Chemical name(s) 

3[(5-difluoromethoxy-1-methyl-3-

trifluoromethylpyrazol-4-yl) methylsulfonyl]-

4,5-dihydro-5,5-dimethylisoxazole 

CAS Number 44739-55-5

Molecular Weight (grams/mole) 367 g/mole

Aqueous solubility (at 25C) 3.49 mg/L

Vapor Pressure 1.8 x 10-8 torr

Henry’s Law Constant 2.65 x 10-9 atm m3/mol

Octanol Partitioning Coefficient (log Kow ) 

@25oC 2.39 

Environmental Fate Properties 

Hydrolysis half life (pH 4, pH 7, pH 9) Stable

Aqueous photolysis half life 119 days

Soil photolysis half life Stable (>30 days)

Aerobic soil metabolism half-lives 142-533 days

Anaerobic soil metabolism half-lives 145 -156 days

Aerobic aquatic metabolism half-lives 

( )

108 -109 days* 

Anaerobic aquatic metabolism half-lives 69-70 days* 

Soil-water distribution coefficient (Koc) 57-119 

* Calculated from combined residues of the test compound measured in both the aqueous and the soil/sediment 

phases of a given test system. 
19

Proposed End-use Products: Pyroxasulfone 85 WG (85% a.i.; EPA Reg.No.63588-xx); 

V-10233 Herbicide (42.5% pyroxasulfone; 33.5% flumioxazin) water dispersible granule; 

Pyroxasulfone Technical (99.2% a.i.; EPA Reg No. 63588-xx) for formulation only into 

registered end-use herbicide products. 

 

a. Mode of Action (MoA) of Pyroxasuflone 

Pyroxasulfone is a new herbicide in the pyrazole class; also considered an oxazole, K-3 

herbicide, and a sulfonylioxazoline (acetolactase synthase, ALS inhibitor). What is 

known is that the chemical inhibits biosynthesis of very-long-chain fatty acids (VLCFAs) 

- that are contained in the plasma membrane of plant cells - by preventing fatty acid 

precursors (medium- and long-chain fatty acids, which are formed in the chloroplast) 

from elongating into chains (in the endoplasmic reticulum). Ultimately, this effect leads 

to inhibition of plant shoot growth. Weedy species such as barnyard millet and Italian 

ryegrass, but also rice were determined to be sensitive to pyroxasulfone; wheat and corn 

to a lesser degree (Shimizu et al. 2009 MRID 47701754). It is unclear at this time to what 

degree the mechanism of VLCFA formation in animal cells might be affected as a result 

of exposure to pyroxasulfone. 

b. Environmental Fate Summary 

Pyroxasulfone is mobile (Koc= 57-119 L/kg) and persistent (t1/2= 142 to 533 days) in 

terrestrial and aquatic environments (Table 3). The major routes of dissipation are 

expected to be associated with microbial-mediated degradation, leaching, and runoff. 

Pyroxasulfone is stable to hydrolysis and photodegradation in water and soil. Volatility is 

not expected to be a major dissipation pathway because of the low vapor pressure (1.8E-8

torr) and Henry’s Constant (2.65E-9 atm-m3/mole). Also, the bioaccumulation potential 

of pyroxasulfone is expected to be low due to a low octanol: water coefficient (log 

Kow=2.39). Field dissipation studies indicate rapid dissipation (t1/2= 4 to 35 days) of 

pyroxasulfone. The presence of degradates (see Appendix E for structures) in the 

terrestrial field dissipation studies indicated that degradation was a potential route of 

pyroxasulfone dissipation in field studies. Leaching also was identified as a route of 

dissipation for the metabolite 5-difluoromethoxy-1H-pyrazol-4-yl) methanesulfonic acid 

(M1). This degradation product was very persistent (extrapolate t1/2~ 8 to 65 years) in 

laboratory metabolism studies. 

Another major degradation product (present at ≥10% applied radioactivity) was identified 

as 5-difluoro methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M3). 

Minor degradation products (<10% of applied radioactivity) of pyroxasulfone are: 

 3-(5-Difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-

dihydro-5,5-dimethylisoxazole (M5), 

 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl 

methanesulfonyl)-4,5-dihydro-5,5-dimethylisoxazol-4-ol (M6), 

 (5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl) methanol (M8), 
20

 5-difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M9), 

 5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carbaldehyde 

(M10), and 

 [3-5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-

(ylmethanesulfonyl)-4,5-dihydro-5-methylisoxazol-5-yl] methanol (M11). 

Additionally, there was a high percentage of applied radioactivity (8-25% of applied 

radioactivity) in unextracted soil/sediment residues. Because the extraction of 

pyroxasulfone residues was conducted using only acetonitrile/water without the use of 

sequentially harsher extractants, there is uncertainty regarding the identity and 

availability of the unextracted soil residues. 

2. Overview of Pesticide Use and Usage 

As a new pesticide active ingredient, the actual usage of pyroxasulfone is not known. 

The registrant is proposing four product labels for pyroxasulfone including KIH-485 

W85, Pyroxasulfone 85W, V10233 Herbicide Water Dispersible Granule (Commerical), 

and V10233 Herbicide (Table 5). Two products, V10233 Herbicide Water Dispersible 

Granule and V10233 Herbicide, are a mixture of pyroxasulfone (42.5%) and flumioxazin 

(33.5%). Additionally, according to the proposed labels, pyroxasulfone can be tank 

mixed with 2,4-D, bromacil, chlorsulfuron, dicamba, diuron, chlorpyralid, glyphosate, 

hexinone, imazapic, imazapyr, metsulfuron methyl, norfurazon, oryzalin, pendimethalin, 

picloram, pramitol, simazine, sulfometuron methyl, tebuthiuron, and triclopyr. 

Table 5. Proposed Label Pyroxasulfone Use Information 

Product Crops Application Timing Application 

Method 

Single Maximum 

Application Rate 

(lbs ai/A) 

Maximum 

Seasonal 

Application 

Rate 

(lbs ai/A) 

KIH-485 W85 Corn Soybean Pre-plant, Pre/postemergent, Fall 

application, Dry 

Fertilizer 

Broadcast or Soil 

IncorporatedGround Spray 

(no aerial spray 

applications) 

0.0801 to 0.2136 0.267 

Pyroxasulfone 

85W 

Corn, 

soybean, 

winter wheat 

Pre-plant, Pre/postemergent, Fall 

application, Dry 

Fertilizer 

Broadcast or Soil 

IncorporatedGround Spray 

(no aerial spray 

applications) 

0.0801 to 0.2136 0.267 

V-10233 

Herbicide 

Water 

Dispersible 

Granules 

Commercial 

Soybean 

Fallow land 

Non-Crop 

Fall Burndown 

Spring Burndown 

Pre-emergent 

Broadcast or Soil 

IncorporatedGround Spray 

(no aerial spray 

applications) 

0.062-0.093 (soy) 

0.124-0.206 (non crop) 

0.096 (soy) 

0.206 non crop 

V-10233 

Herbicide 

Corn 

Soybean 

Fallow Land 

Non-Crop 

 Broadcast , Band 

or Soil 

IncorporatedGround /Aerial 

Spray 

0.080-0.120 0.120 
21

 

Two of the pyroxasulfone labels have standard runoff and ground water label advisory 

statements for uses on corn, soybean, fallow land, and non-crop areas. Additionally, 

required spray drift buffer distances are stated on theV10233 Herbicide Water 

Dispersible Granule (Commercial) and V10233 Herbicide labels (Table 6). As KIH-485 

W85 and Pyroxasulfone 85W do not have required spray drift buffers, pyroxasulfone 

could be used on corn, soybean, and winter wheat without a spray drift buffer. 

Table 6. Proposed Spray Drift Buffers 

Product Label Required Spray Drift Buffers 

V-10233 Herbicide 

Water Dispersible Granules 

Commercial 

Aquatic Spray Drift Buffers (ground spray): 

Soybean 6.5-9.8 ft 

Noncrop 9.8-16.4 ft 

Terrestrial Spray Drift Buffers (ground spray): 

Soybean -32 ft 

Non-crop-82 ft 

V-10233 Herbicide Spray Drift Buffers (aerial spray): 

40 ft –non-target plants 

100 ft- emerged cotton plants 

40 ft – surface water (streams, wetlands, marshes, lakes, reservoirs) 

The maximum single application rate of pyroxasulfone is 0.2136 lbs ai/A for corn, 

soybean and winter wheat with a seasonal maximum rate of 0.267 lbs ai/A (Table 7). 

Pyroxasulfone can be applied using broadcast or banded ground spray as well as aerial 

spray. Application timing is pre- and early post emergent. Other recommended 

applications include fall treatment (before ground freeze) and through dry fertilizer 

treatments. 

Table 7. Pyroxasulfone use and application information based on the proposed label

Use 

Max. Single 

App. Rate 

(lbs a.i./A) 

# of 

App. / 

Season 

Seasonal Max. 

Rate (lbs a.i./A) 

Minimum App. 

Interval (days) 

Corn, soybean, winter wheat 0.2136 1 – 2 0.267 Not specified 

Corn, soybean, fallow land, noncrop 0.12 1 0.12 Not applicable 

Fallow land, non-crop 0.206 1 0.206 Not applicable 

Soybean 0.093 1 - 2 0.096 Not specified 

C. Receptors 

1. Aquatic and Terrestrial Effects 

The receptor is the biological entity that is exposed to the stressor (EPA, 1998). Based on 

the proposed uses for pyroxasulfone, it is expected that the aquatic and terrestrial 

receptors will include freshwater fish and invertebrates, marine/estuarine fish and 

invertebrates, aquatic plants, terrestrial plants, birds, mammals, and terrestrial 

invertebrates. 
22

Consistent with the process described in the Overview Document (EPA, 2004), this risk 

assessment uses a surrogate species approach in its evaluation of pyroxasulfone. 

Toxicological data generated from surrogate test species, which are intended to be 

representative of broad taxonomic groups, are used to extrapolate to potential effects on a 

variety of species (receptors) included under these taxonomic groupings. 

Acute and chronic toxicity data from studies submitted by pesticide registrants are used 

to evaluate the potential direct effects of pyroxasulfone to the aquatic and terrestrial 

receptors identified in this section. This includes toxicity data on the technical grade 

active ingredient, any major transformation products, and when available, formulated 

products (e.g. “Six-Pack” studies, terrestrial plant studies). 

Table 8 provides a summary of the taxonomic groups and the surrogate species tested to 

help understand potential acute ecological effects of pesticides to these non-target 

taxonomic groups. In addition, the table provides a preliminary overview of the potential 

acute toxicity of pyroxasulfone by providing the acute toxicity classifications. 

Table 8. Test Species Evaluated for Assessing Potential Ecological Effects of Pyroxasulfone and the 

Associated Acute Toxicity Classification 

Taxonomic Group Surrogate Species Acute Toxicity Classification 

Birds1

Mallard Duck (Anas platyrhynchos) 

Bobwhite Quail (Colinus virginianus) 

Zebra finch (Poephila guttata) 

Practically nontoxic 

Practically nontoxic 

Practically nontoxic 

Mammals Laboratory rat (Rattus norvegicus Practically non-toxic 

Insects Honey bee (Apis mellifera L.) Practically non-toxic 

Freshwater fish2 Bluegill sunfish (Lepomis macrochirus) 

Rainbow trout (Oncorhynchus mykiss) 

At most, moderately toxic 

At most, moderately toxic 

Freshwater invertebrates Water flea (Daphnia magna) At most, moderately toxic 

Marine/estuarine fish Sheepshead minnow (Cyprinodon variegatus) At most, moderately toxic 

Marine/estuarine 

invertebrates 

Mysid shrimp (Americamysis bahia)

Eastern oyster (Crassostrea virginica)

At most, moderately toxic 

At most, moderately toxic 

Terrestrial plants3 Monocots – most sensitive species 

Dicots – most sensitive species No Classification 

Aquatic plants and algae 

Duckweed (Lemna gibba) 

Cyanobacteria/blue-green algae (Anabaena flos-aquae) 

Marine diatom (Skeletonema costatum) 

Freshwater diatom (Navicula pelliculosa) 

Algae (Pseudokirchneriella subcapitata; previously 

known as Selenastrum capricornutum) 

No classification 

1

 Birds represent surrogates for terrestrial-phase amphibians and reptiles. 2 Freshwater fish may be surrogates for aquatic-phase amphibians. 3

 Normally four species of two families of monocots, of which one is corn; six species of at least four dicot families, of which one is 

soybeans. 
23

2. Ecosystems Potentially at Risk 

The ecosystems at risk are often extensive in scope, and as a result it may not be possible 

to identify specific ecosystems during the development of a baseline risk assessment. 

However, in general terms, terrestrial ecosystems potentially at risk could include the 

treated field and areas immediately adjacent to the treated field that may receive drift or 

runoff. Areas adjacent to the treated field could include cultivated fields, fencerows and 

hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats, and other 

uncultivated areas. 

Aquatic ecosystems potentially at risk might include but are not necessarily limited to 

water bodies adjacent to or downstream from, the treated field and might include 

impounded bodies such as ponds, lakes and reservoirs, or flowing waterways such as 

streams or rivers. For uses in coastal areas, aquatic habitat also includes marine 

ecosystems, including estuaries. 

D. Assessment Endpoints 

Assessment endpoints represent the actual environmental value that is to be protected, 

defined by an ecological entity (species, community, or other entity) and its attribute or 

characteristics (EPA, 1998). Generally, the ecological entities may include the following: 

freshwater as well as marine/estuarine fish and invertebrates, aquatic and terrestrial 

plants, birds, reptiles, amphibians, mammals, and non-target insects. The attributes for 

each of these entities may include growth, reproduction, and survival. 

E. Conceptual Model 

A conceptual model provides a written description and visual representation of the 

predicted relationships between pyroxasulfone residues, potential routes of exposure, and 

the predicted effects for the assessment endpoint. A conceptual model consists of two 

major components: risk hypothesis and a conceptual diagram (EPA, 1998). 

1. Risk Hypothesis 

For a pesticide to pose an ecological risk, it must reach ecological non-target organisms 

(receptors) at biologically significant concentrations. An exposure pathway is the means 

by which a pesticide moves in the environment from the application site to non-target 

organisms. The evaluation of the ecological exposure pathways in this assessment 

includes an examination of the source and potential transport pathways for pyroxasulfone 

and the determination of exposure routes of non-target species. Based on the application 

methods, mode of action, fate and transport, and the sensitivity of non-target aquatic and 

terrestrial species, pyroxasulfone has the potential to reduce survival, reproduction, 

and/or growth in non-target aquatic plants (non-vascular and vascular), terrestrial plants, 

birds, reptiles, amphibians, and mammals when used in accordance with the proposed 

labels. These non-target organisms include listed and non-listed species. 
24

2. Conceptual Diagrams 

The conceptual model diagram is a generic graphic depiction of the risk hypothesis 

identified in the previous section. It is assumed that pyroxasulfone is capable of affecting 

exposed terrestrial and aquatic organisms if environmental concentrations are sufficiently 

elevated as a result of proposed label uses. Through a preliminary process of examining 

fate and effects data, the risk hypotheses and conceptual model have been refined to 

reflect possible exposure pathways and the organisms that are most relevant and 

applicable to this assessment (see figures below). If exposed at sufficient levels, 

mortality may occur, as well as sublethal effects. Direct effects on a taxonomic group 

may result in indirect effects (i.e., loss of habitat, food resources) to other taxonomic 

groups. This assessment will examine the potential for these effects to occur within the 

surrogate taxa with the intent to extrapolate to actual effects within the environment. 

In order for an exposure pathway to be complete, it must have a source, a release 

mechanism, an environmental transport medium for pyroxasulfone and/or its 

transformation products, a point of exposure for ecological receptors, and a feasible route 

of exposure. The assessment of these pathways thus includes an examination of the 

sources and potential migration pathways for constituents, and the determination of 

potential exposure routes. 

Long-range transport 

Exposure to pyroxasulfone is expected to be dominated by runoff, leaching, and spray 

drift. Long-range transport of pyroxasulfone in the gas phase is not considered as a 

dominant route of exposure. Atmospheric transport is represented by dotted lines given 

the low likelihood of volatilization of pyroxasulfone (i.e. vapor pressure = 1.8 x 10-8 torr, 

MRID 47701752; and, Henry’s law constant at 25oC of 2.65 x 10-9 atm m3/mol). 

Bioaccumulation potential 

This screening-level assessment for ground and aerial spray applications of pyroxsulfone 

considered dietary exposure (Figures 3 and 4). Log Kow (2.39) is below the range (4-8) 

prescribed for addressing consumption of aquatic food items by piscivorous mammals 

and birds via KABAM v. 1.0.; this exposure route was thus eliminated from the 

conceptual model. Other routes of exposure that were not considered quantitatively in the 

assessment are incidental soil ingestion exposure and dermal exposure. 

Partitioning to sediment 

The partitioning properties of pyroxasulfone (Koc 57-119) indicate that exposure to 

benthic (sediment-dwelling) invertebrates is not an exposure route of concern relative to 

exposure through the water column. 
25

Dermal exposure 

The dermal route of exposure for terrestrial wildlife can be divided into a few sub-routes. 

These include organisms exposed: 

 In the treated field at the time of application or in the areas adjacent to the treated 

field and within the aerial drift plume that may come in direct contact with 

applied material. 

 While conducting daily activities within treated or drift-impacted areas whereby 

exposure may occur via contact with dislodgeable residues of the pesticide on 

treated vegetation. 

 To the pesticide deposited on soil particles either through contact with 

contaminated soil through portions of the body contacting the ground, dust 

bathing, or through incidental contact with fugitive dust emissions from treated or 

drift-impacted areas. 

 Via dermal contact with the pesticide that is dissolved in puddle water on the 

treated field or in areas impacted by drift and run-off. 

 To volatile compounds in the vapor phase integument via direct absorption. 

At the present time, the Agency does not have a method to quantify these levels of 

exposure, and data are limited to quantify the contribution of such exposures to the toxic 

burden an organism experiences. The Agency is actively working on a screening method 

to quantify exposure from direct impingement of applied foliar sprays and from 

incidental contact with dislodgeable foliar pesticide residues from treated or driftimpacted vegetation. 

Inhalation exposure 

The Screening Tool for Inhalation Risk (STIR v.1.0, November 19, 2010) was used to 

calculate an upper bound estimate of exposure using pyroxasulfone’s vapor pressure (1.8 

x 10-8 torr) and molecular weight (367 g/mol) for vapor phase exposure as well as the 

maximum application rate and method of application for spray drift. STIR incorporates 

results from several toxicity studies including acute oral and inhalation rat toxicity 

endpoints obtained from the “six-pack” of core studies, which are a series of six guideline 

studies that are submitted to the Registration Division of the Office of Pesticide Programs 

for technical and formulated products of a pesticide (acute oral LD50 >2000 mg a.i./kgbw, MRID 47701677; and, acute inhalation LC50 > 6.56 mg a.i./L, a test duration of 4.5 

hours MRID 47701685) as well as the most sensitive acute oral avian toxicity endpoint 

(acute oral LD50>2250 mg a.i./kg-bw for the northern bobwhite quail, MRID 47701631). 

Based on the results of the STIR model, inhalation exposure alone not determined to be a 

potential pathway of concern for both avian and mammalian species on an acute basis. 

Inhalation exposure via spray drift and vapor-phase of the pesticide alone does not appear 

to be of concern. The maximum seasonal and single rates were used in the tool for 

ground spray (0.267 and 0.2136 lbs a.i./A, respectively) and aerial spray (0.120 lbs a.i./A) 

applications; all yielded the same result (see Appendix A for a sample result). The 

analysis of the inhalation route in STIR does not consider that aggregation with other 
26

exposure pathways such as dietary, dermal, or drinking water may contribute to a total 

exposure that has a potential for effects to non-target animals. However, the Agency 

does consider the relative importance of other routes of exposure in situations where data 

indicate that pesticide exposures through other routes may be potentially significant 

contributors to wildlife risk (USEPA, 2004). The risk characterization section, discusses 

the impact of consideration of other routes of exposure, particularly ingestion, that have 

been identified as potentially important and the degree of certainty associated with 

screening-level risk assessment conclusions. Detailed information about STIR v.1.0, as 

well as the tool, can be found on the EPA’s website at: 

http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial. 

Drinking water exposure 

Drinking water for the purposes of terrestrial organism risk assessment is defined as that 

portion of an organism’s daily water intake that is not met by dietary or metabolic 

sources and must be consumed in liquid form. Typical drinking water sources for wildlife 

in pesticide use areas may include on-field puddles, irrigation equipment (e.g., drip 

irrigation in grape cultivation), dew deposited on treated plants, and off-field surface 

water exposures. 

The Screening Imbibition Program (SIP v.1.0, Released June 15, 2010) was used to 

calculate an upper bound estimate of exposure using pyroxasulfone’s solubility (3.49 

mg/L at 25oC), the most sensitive acute (LD50>2250 mg a.i./kg-bw for the northern 

bobwhite quail, MRID 47701631) and chronic (NOAEC of 60 mg a.i./kg-diet for the 

mallard duck, MRID 47701636) avian toxicity endpoints and the most sensitive acute 

(LD50 > 2000 mg a.i./kg-bw for the rat, MRID 47701677) and chronic (NOAEL of 7.2 

mg/kg-bw/day for the rat, MRID 47701706) mammalian toxicity endpoints. Drinking 

water exposure alone was not determined to be a potential pathway of concern for either 

avian or mammalian species on either an acute or chronic basis (see Appendix B). 

Although drinking water exposure alone does not appear to be of concern, this does not 

take into account that when aggregated with other exposure pathways (dietary food 

sources, dermal, inhalation) drinking water may contribute to a total exposure that has a 

potential for effects on non-target animals and should be explored further. Because there 

is a high degree of conservatism in the SIP 1.0 exposure estimate, there is limited 

expectation that use scenarios not triggering a SIP 1.0 concern would contribute 

significantly to aggregate risks from water plus diet when a refined water exposure model 

is incorporated in the actual quantitative risk assessment. Detailed information about SIP 

v.1.0, as well as the tool, can be found on the EPA’s website at 

http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial. 
27

Figure 3. Conceptual model depicting stressors, exposure pathways, and potential 

effects to aquatic organisms from pyroxasulfone use on corn, soybeans, wheat, fallow 

land, and non-crop areas. Dotted lines indicate exposure pathways that have a low 

likelihood of contributing to ecological risk. 

 

Stressor 

Source 

Receptors 

Attribute 

Change 

Pyroxasulfone applied as broadcast or banded ground spray and aerial 

Spray drift 

Aquatic animals 

Invertebrates 

Vertebrates 

 

Individual organisms 

Reduced survival 

Reduced growth 

Reduced reproduction 

Food chain

Reduction in algae and 

 vascular plants 

Reduction in prey 

Modification of PCEs 

 related to prey availability 

Habitat integrity 

Reduction in primary productivity

Reduced cover 

Community change 

Modification of PCEs related to 

 habitat 

Surface water/ 

Sediment 

Runoff 

Aquatic Animals

Invertebrates 

Vertebrates 

Exposure 

Media 

Uptake/gills 

or integument 

Ingestion Ingestion

Atmospheric 

transport 

Wet/dry deposition 

Soil Leaching to 

Groundwater 

Uptake/gills 

or integument

Aquatic Plants

Non-vascular 

Vascular

Uptake/cell, 

roots, leaves Riparian plants

terrestrial 

exposure 

pathways see 

Figure 4 
28

Figure 4. Conceptual model depicting stressors, generic exposure pathways, and 

potential effects to terrestrial organisms from pyroxasulfone use on corn, soybeans, 

wheat, fallow land, and non-crop areas. Dotted lines indicate exposure pathways that 

have a low likelihood of contributing to ecological risk. 

* See Figure 5 for drinking water and inhalation exposure pathways for terrestrial vertebrates and ingestion of residues in dew by 

terrestrial invertebrates 

Stressor 

Source 

Attribute 

Change 

Pyroxasulfone applied as broadcast or banded ground spray and aerial spray 

Direct 

application Spray drift

Terrestrial 

vertebrates* 

Terrestrial 

Inverts* 

Individual 

organisms 

Reduced survival 

Reduced growth 

Food chain

Reduction in prey and 

food 

Modification of PCEs 

Habitat integrity 

Reduction in primary productivity

Reduced cover 

Community change 

Modification of PCEs related 

 to habitat 

Terrestrial plants

grasses/forbs, fruit, seeds

(trees, shrubs) 

Runoff 

Terrestrial 

vertebrates* 

Exposure Media 

& Receptors Soil

Ingestion 

Ingestion

Dermal uptake/Ingestion 

Atmospheric 

transport

Root uptake/contact 

Wet/dry deposition 

Ingestion

Leaching to 

Groundwater

Irrigation 

water 
29

Figure 5. Conceptual model depicting stressors, drinking water and inhalation exposure 

pathways, and potential effects to terrestrial animals from use of pyroxasulfone on corn, 

soybeans, wheat, fallow land, and non-crop areas. Dotted lines indicate exposure 

pathways that have a low likelihood of contributing to ecological risk. 

F. Analysis Plan 

The structure of this risk assessment is based on guidance contained in U.S. EPA’s 

Guidance for Ecological Risk Assessment (U.S. EPA, 1998) and is consistent with 

procedures and methodology outlined in the Overview Document (U.S. EPA, 2004). 

1. Conclusions from Previous Risk Assessments 

There are no previous Agency ecological risk assessments because this is the first 

registration petition for pyroxasulfone for use on field corn, popcorn, sweet corn, 

soybeans, winter wheat, fallow land, non-crop areas around farms, orchards and 

vineyards and to maintain bare ground on non-crop areas in the United States. 

Stressor 

Source 

Attribute 

Change 

Pyroxasulfone applied as broadcast or banded ground spray and aerial spray 

Direct 

application Spray drift

Terrestrial 

vertebrates 

Terrestrial 

invertebrates

Individual 

organisms 

Reduced survival 

Reduced growth 

Food chain

Reduction in prey and 

food 

Modification of PCEs 

Habitat integrity 

Reduction in primary productivity

Reduced cover 

Community change 

Modification of PCEs related 

 to habitat 

Runoff

Exposure Media Dew (formed on 

terrestrial plants)

Atmospheric 

transport

Receptors 

Puddles (formed 

on treated fields)

Inhalation Ingestion 

Air
30

2. Preliminary Identification of Data Gaps 

Review of the submitted studies indicated the following points: 

Environmental Fate 

The submitted fate database is incomplete for pyroxasulfone on account of the need for 

ground water monitoring data. In addition, an uncertainty in the environmental fate data 

is the identification and availability of unextracted residues in soil and aquatic 

metabolism studies. These residues account for a high percentage of applied 

radioactivity (8-25% of applied radioactivity). Although there is an uncertainty regarding 

the identification and quantification of unextracted soil/sediment residues, this 

uncertainty does not substantially affect the estimated exposure levels due to the 

persistence of pyroxasulfone. For a list of submitted environmental fate studies for 

pyroxasulfone, see Section V. 

Data needs: 

Because pyroxasulfone is mobile and persistent in soil it has the potential to leach into 

groundwater. This behavior was predicted using Tier II PRZM GW model. This 

modeling showed that pyroxasulfone has the potential to accumulate in groundwater. 

 Prospective ground water monitoring study. 

Ecotoxicity 

The submitted ecotoxicity database is incomplete. For a list of submitted ecological 

effects studies for pyroxasulfone see Section V. The following studies are considered 

data gaps: 

Chronic Marine/Estuarine Fish Study

No chronic studies on marine/estuarine fish were submitted by the registrant. Therefore, 

a quantitative estimation of risk could not be conducted. According to CFR 40 Part 158, 

this data is conditionally required and although pyroxasulfone is stable to hydrolysis (at 

pHs 4, 7, and 9) and aqueous photolysis (half life = 119 days), comparison to freshwater 

fish data suggests that chronic risk to marine/estuarine fish is not expected as a result of 

pyroxasulfone (TGAI) use on corn, soybean wheat, and non-crop sites. Therefore, a 

chronic marine/estuarine fish study is not required. 

Chronic: Fish early-life stage (saltwater: Cyprinodon variegatus) (850.1400; 72-

4), TGAI 

Chronic Marine/Estuarine Invertebrate Study

No chronic studies on marine/estuarine invertebrates were submitted by the registrant. 

Therefore, a quantitative estimation of risk cannot be conducted. According to CFR 40 

Part 158, this data is conditionally required and although pyroxasulfone is stable to 

hydrolysis (at pHs 4, 7, and 9) and aqueous photolysis (half life = 119 days), 

comparison to freshwater invertebrate data suggests that chronic risk to marine/estuarine 

invertebrates is not expected as a result of pyroxasulfone (TGAI) use on corn, soybean, 
31

wheat, and non-crop sites. Therefore, a chronic marine/estuarine invertebrate study is not 

required. 

Chronic: Marine/estuarine invertebrate (Americamysis bahia) (850.1350; 72-4), 

TGAI 

Fish Bioaccumulation Study

A bioaccumulation in fish study was not submitted to support the proposed registration. 

According to CFR 40 Part 158, this data is conditionally required and although 

pyroxasulfone is mobile and persistent, the low octanal:water partitioning coefficient (log 

Kow= 2.39) is expected to limit bioconcentration and bioaccumulation of pyroxasulfone. 

Based on the log Kow of 2.39, the expected BCF assuming no metabolism and 5% lipids 

would be approximately 12 L/kg wet weight (i.e., 102.39 * 0.05). This low BCF combined 

with the low acute toxicity to birds and mammals indicates that risks to piscivorous 

wildlife would not be expected. Therefore, a fish bioaccumulation study is not required. 

 Fish Bioaccumulation study (850.1730; 72-6, 165-4), TGAI 

3. Measures of Exposure and Effects

EFED uses a tiered system of pesticide exposure modeling to assess ecological risk 

following a registered application of that pesticide. This tiered system is designed to 

minimize the amount of analysis which is required to register any given chemical. Each 

of the tiers is designed to screen out pesticides by requiring higher, more complex levels 

of investigation only for those that have not passed the next lower tier. Each tier screens 

out a percentage of pesticides from having to undergo a more rigorous review prior to 

registration or re-evaluation. 

a. Aquatic Exposure Models

Tier II PRZM and EXAMS2

 simulation models were used to estimate the exposure 

concentrations of pyroxasulfone in surface water for the proposed use on corn, soybean, 

wheat, and noncrop areas. The results are presented in Appendix C. The data used as 

input parameters come solely from the environmental fate studies and proposed product 

labels submitted by the petitioner to support the United States registration of 

pyroxasulfone. 

 

2

 PRZM 3.1.2.2 (5/16/05) and EXAMS 2.98.04(4/25/04) were used rather than GENEEC2 (4/25/04) in 

anticipation of toxicity concerns for aquatic organisms. 
32

b. Terrestrial Exposure Models

T-REX Model 

The focus of terrestrial wildlife exposure estimates is for birds (also acting as surrogate 

for reptiles and terrestrial-phase amphibians) and mammals with an exposure route 

emphasis on uptake through the diet. The residues in or on potential dietary sources for 

mammals and birds (e.g., vegetation, insects, and seeds) were estimated using the Tier I 

model T-REX (Version 1.4.1, 2008). In this Tier I assessment, it was assumed that 

organisms are exposed to one active ingredient in a given exposure scenario. In all 

screening-level assessments, the organisms are assumed to consume 100% of their diet as 

one food type and one food source. The T-REX output is presented in the Risk 

Characterization section of this document as well as an example in Appendix D. 

The approach used to estimate exposure of terrestrial animals to pyroxasulfone was based 

on potential foliar applications of pyroxasulfone. Upper-bound exposure levels were 

calculated for spray applications of proxasulfone using maximum proposed application 

rates for one application for the proposed uses. The exposure estimates are based on a 

database of pesticide residues on wildlife food sources associated with specified 

application rates (Kenaga, 1972; Fletcher et al., 1994). Essentially, for a single 

application, there is a linear relationship between the amount of pesticide applied and the 

amount of pesticide residue present on a given food item. Food item residue levels are 

then linearly adjusted based on application rate. The upper-bound estimates are used to 

estimate risks since these values represent the high-end exposure that may be encountered 

for terrestrial species that consume food items that have received label-specified pesticide 

application. Although these represent higher-end estimates, they do not represent the 

highest possible exposure estimates. With regard to bare ground applications, T-REX 

EECs account for residue values on potential dietary items (terrestrial invertebrates 

and/or plants) found immediately adjacent to or on the treated field. These assumptions 

are relevant for labels that include non-crop uses for this particular chemical, including 

V-10233 Herbicide and the water dispersible granule version. However, these labels are 

multi-active ingredient products (i.e., containing 42.2% pyroxasulfone and 33.6 

flumioxazin), the mixture of which is not accounted for by TREX. Instead, the model 

calculates EECs on a single active ingredient (i.e., pyroxasulfone only) basis.

T-REX is a simulation model that, in addition to incorporating the relationship between 

application rate and food item residue concentrations, accounts for pesticide degradation 

in the estimation of terrestrial EECs. T-REX calculates pesticide residues on each type of 

food item on a daily interval for one year. A first-order decay function is used to calculate 

the residue concentration at each day based on the concentrations present from both 

initial and all subsequent applications. The decay rate is dependent on the foliar 

dissipation half-life. The food item concentration on any given day is the sum of all 

residues up to that day, taking into account the first-order degradation. The initial 
33

application occurs on day 0 (t=0) and the model runs for 365 days. Over the 365-day run, 

the highest residue concentration is the measure of exposure (EEC) used to calculate risk 

quotients (RQs). 

The foliar dissipation half-life and residue decline studies can be important in estimating 

exposure because they essentially determine how long the pesticide remains in or on food 

items after application. In many cases, neither empirically determined foliar dissipation 

nor residue decline half-life (with a day 0 residue) values are available, in which case the 

default value of 35 days is used (Willis and McDowell, 1987). That was the case for this 

assessment. The maximum seasonal application rate was used to calculate RQs given that 

the maximum single application rates were either equal or approximately equal to the 

seasonal rate. In addition, given that application intervals were not reported on the labels 

and pyroxasulfone’s persistence in water (half-lives ranging from 69 to 119 days) and 

soil (half-lives ranging from 142 to 533 days), the maximum seasonal rate was assumed 

appropriate for RQ calculations. Furthermore, the seasonal application rate was assumed 

to be equivalent to annual application rate. 

In cases where RQs exceeded LOCs at the maximum seasonal rate, two applications (that 

totaled the maximum seasonal rate) were modeled and used for risk characterization. TREX does not currently allow for variable application rates/applications or different 

application intervals between applications. Therefore, to account for the variable 

application rates described on the proposed labels for corn, soybean, and winter wheat, 

the EECs for the different potential food items were estimated by summing the 3-day 

EEC for the initial application (0.2136 lbs a.i./A) with the peak EEC value (day 0) for the 

subsequent application (0.0534 lbs a.i./A). The summed EECs were calculated in this 

manner for each food type and the values were used as a basis for generating equivalent 

dietary-based EECs in T-REX to calculate RQ values (Table 32). 

TERRPLANT Model 

The TerrPlant (Ver.1.2.2) model is used to predict EECs from terrestrial uses for 

terrestrial plants located in dry and semi-aquatic areas adjacent to the treated field or 

treated water body. A semi-aquatic area is defined as a low-lying area of terrestrial 

habitat that is wet but may dry up at times throughout the year. TerrPlant incorporates 

two similar conceptual models for depicting dry and semi-aquatic areas of terrestrial 

habitats. For both models, a non-target area is adjacent to the target area. Pesticide 

exposures to plants in the non-target area are estimated to receive runoff and spray drift 

from the target area. 

For a dry area adjacent to the treatment area, runoff exposure is estimated as sheet runoff. 

Sheet runoff is the amount of pesticide in water that runs off of the soil surface of a target 

area of land which is equal in size to the non-target area (1:1 ratio of areas). In the sheet 

runoff scenario, the treated area generating runoff is assumed to drain into an area with 

equal size containing seedlings, resulting in 1, 2, or 5% of the application rate being 

deposited. For semi-aquatic areas, runoff exposure is estimated as channel runoff. 
34

Channel runoff is the amount of pesticide that runs off of a target area 10 times the size of 

the non-target area (10:1 ratio of areas). In the channel runoff scenario, a ten-to-one ratio 

of watershed area to receiving area results in 10, 20, or 50% of the application rate being 

deposited on soil with emerging or emerged seedlings. The magnitude of runoff is 

assumed to be dependent on the water solubility of the pesticide active ingredient. For 

pesticides with a solubility of <10, 10 to 100, or >100 ppm, runoff fractions of 0.01, 0.02 

or 0.05 respectively are selected by the model user. 

 

Exposures through runoff and spray drift are then compared to measures of survival and 

growth (e.g. effects to seedling emergence and vegetative vigor) to develop RQ values. 

The model compares the combined deposition estimates from runoff and spray drift to 

adverse effect levels measured in seedling emergence studies. In addition, RQs are 

derived for plants with consideration for spray drift exposures. For monocots and for 

dicots, TerrPlant compares estimated spray drift deposition, without a runoff exposure 

component, to the more sensitive measure of effect, either seedling emergence or 

vegetative vigor (USEPA 2005). 

Not unlike the modeling in T-REX, the maximum seasonal application rate was used to 

calculate RQs given that the maximum single application rates were either equal or 

approximately equal to the seasonal rate. In addition, given that application intervals were 

not reported on the labels and pyroxasulfone’s persistence in water (half-lives ranging 

from 69 to 119 days) and soil (half-lives ranging from 142 to 533 days), the maximum 

seasonal rate was assumed appropriate for RQ calculations. Nevertheless, in cases where 

RQs exceeded LOCs, lower application rates were used for risk characterization. 

Furthermore, the seasonal application rate was assumed to be equivalent to annual 

application rate. 

Irrigation Model 

Because pyroxasulfone is a mobile and persistent herbicide, there is potential for 

terrestrial plant effects from exposure through irrigation water. Although this is not a 

standard modeling approach in OPP, it is being implemented for incorporation into 

ecological risk assessments for pesticides with phytotoxic effects. 

To estimate exposure to plants when groundwater contaminated by pyroxsulfone is 

applied to crops, the following method was used. It is assumed a one-acre field is 

irrigated with one inch of water containing pyroxsulfone. Pyroxsulfone concentrations 

were estimated using beta version of the PRZM GW Tier II model. This model is 

currently undergoing an implementation process in OPP. The model provides ground 

concentration as predicted through the Pesticide Root Zone Model (PRZM). 

Table 9 summarizes the measures of ecological effects and exposure used to assess 

ecological risk following exposure to pyroxasulfone with the proposed uses. 
35

Table 9. Measures of Ecological Effects and Exposure for Pyroxasulfone 

Assessment Endpoint Surrogate Species and 

Measures of Ecological Effect1,2 

Measures of Exposure 

Birds3 Survival Bobwhite Quail acute oral LD50, 

subacute dietary LC50 

Mallard Duck subacute dietary 

LC50 

Zebra Finch acute oral LD50

Upper bound residues on food 

items (foliar) 

Reproduction and growth Bobwhite Quail reproduction 

NOAEC/LOAEC 

Mallard Duck reproduction 

NOAEC/LOAEC 

Mammals Survival Laboratory rat acute oral LD50 

Reproduction and growth Laboratory rat reproduction and 

development NOAEL/LOAEL 

Rabbit development 

NOAEL/LOAEL 

Freshwater fish4 Survival Rainbow trout 96-hr LC50 

Bluegill sunfish 96-hr LC50

Peak EEC5

Reproduction and growth Fathead minnow 

NOAEC/LOAEC 

60-day average EEC5

Freshwater invertebrates Survival Water flea 48-hr EC50 Peak EEC5

Reproduction and growth Water flea NOAEC/LOAEC 21-day average EEC5

Marine/estuarine fish Survival Sheepshead minnow 96-hr LC50 Peak EEC5

Reproduction and growth No study available 60-day average EEC5

Marine/estuarine 

invertebrates 

Survival Eastern oyster 96-hr EC50

Saltwater mysid 96-hr LC50

Peak EEC5

Reproduction and growth Saltwater mysid NOAEC/LOAEC 21-day average EEC5

Terrestrial plants6 Survival and growth Monocot Seedling emergence 

EC25, NOAEC or EC05 

Monocot Vegetative Vigor 

EC25, NOAEC or EC05 

Dicot Seedling emergence 

EC25, NOAEC or EC05 

Dicot Vegetative Vigor 

EC25, NOAEC or EC05

Estimates of runoff and spray 

drift to non-target areas 

Terrestrial invertebrates Survival Honey bee acute contact 48-hr 

LD50, Parasitoid wasp & 

predatory mite ER50/LR50, 

Earthworm 14-day LC50, 28-day 

NOAEC 

Maximum application rate 

Aquatic plants and algae Survival and growth Duckweed 7-day EC50, NOAEC 

Freshwater green algae 96-hr 

EC50, NOAEC 

Freshwater blue-green algae 96-hr 

EC50, NOAEC 

Freshwater diatom 96-hr EC50, 

NOAEC 

Marine diatom 96-hr EC50, 

NOAEC 

Peak EEC5

1

LD50 = Lethal dose to 50% of the test population; NOAEC = No observed adverse effect concentration; LOAEC = Lowest observed adverse

effect concentration; LC50 = Lethal concentration to 50% of the test population; EC50/EC25 = Effect concentration to 50%/25% of the test 

population. 

2

 Species listed in this table represent the most commonly encountered species from registrant-submitted studies, risk assessment guidance 

indicates the most sensitive species tested within each taxonomic group are to be used for baseline risk assessments. 3

 Birds represent surrogates for amphibians (terrestrial phase) and reptiles. 4

 Freshwater fish may be surrogates for amphibians (aquatic phase). 5

 One in 10-year return frequency. 

6

 Four species of two families of monocots - one is corn, six species of at least four dicot families, of which one is soybeans. 
36

III. Analysis 

A. Use Characterization 

Pyroxasulfone is a new herbicide in the pyrazole class; also considered an oxazole, K-3 

herbicide, and a sulfonylioxazoline (acetolactase synthase, ALS inhibitor). What is 

known is that the chemical inhibits biosynthesis of very-long-chain fatty acids (VLCFAs) 

- that are contained in the plasma membrane of plant cells - by preventing fatty acid 

precursors (medium- and long-chain fatty acids, which are formed in the chloroplast) 

from elongating into chains (in the endoplasmic reticulum). Ultimately, this effect leads 

to inhibition of plant shoot growth. Weedy species such as barnyard millet and Italian 

ryegrass, but also rice were determined to be sensitive to pyroxasulfone; wheat and corn 

to a lesser degree (Shimizu et al. 2009 MRID 47701754). It is unclear at this time to what 

degree the mechanism of VLCFA formation in animal cells might be affected as a result 

of exposure to pyroxasulfone. 

 

The maximum single application rate of pyroxasulfone is 0.2136 lbs ai/A with a seasonal 

maximum rate of 0.267 lbs ai/A. Pyroxasulfone can be applied using broadcast or 

banded ground spray as well as aerial spray. Application timing is pre- and early post 

emergent. Other recommended applications include fall treatment (before ground freeze) 

and through dry fertilizer treatments. Depending on the crop, the recommended crop 

rotation intervals range 4 to 12 months. At this time pyroxasulfone use is proposed only 

on certain major crops (corn, soybeans, and wheat); there is an expansive exposure 

potential to pyroxasulfone and its degradation products with these crop uses. 

B. Exposure Characterization 

1. Environmental Fate and Transport 

Summary 

Pyroxasulfone is mobile (Koc= 57-119 L/kg) and persistent (t1/2= 142 to 533 days) in 

terrestrial and aquatic environments (Table 3). The major routes of dissipation are 

expected to be associated with microbial-mediated degradation, leaching, and runoff. 

Pyroxasulfone is stable to hydrolysis and photodegradation in water and soil. Volatility is 

not expected to be a major dissipation pathway because of the low vapor pressure (1.8E-8

torr) and Henry’s Constant (2.65E-9 atm-m3/mole). Also, the bioaccumulation potential 

of pyroxasulfone is expected to be low due to a low octanol: water coefficient (log 

Kow=2.39). Field dissipation studies indicate rapid dissipation (t1/2= 4 to 35 days) of 

pyroxasulfone. The presence of degradates (see Appendix E for structures) in the 

terrestrial field dissipation studies indicated that degradation was a potential route of 

pyroxasulfone dissipation in field studies. Leaching also was identified as a route of 

dissipation for the metabolite 5-difluoromethoxy-1H-pyrazol-4-yl) methanesulfonic acid 

(M1). This degradation product was very persistent (extrapolate t1/2~ 8 to 65 years) in 

laboratory metabolism studies. 
37

Another major degradation product (present at ≥10% applied radioactivity) was identified 

as 5-difluoro methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M3). 

Minor degradation products (<10% of applied radioactivity) of pyroxasulfone are: 

 3-(5-Difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-

dihydro-5,5-dimethylisoxazole (M5), 

 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl 

methanesulfonyl)-4,5-dihydro-5,5-dimethylisoxazol-4-ol (M6), 

 (5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl) methanol (M8), 

 5-difluoromethoxy-3-trifluoromethyl-1H-pyrazol-4-carboxylic acid (M9), 

 5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-carbaldehyde 

(M10), and 

 [3-5-Difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-

(ylmethanesulfonyl)-4,5-dihydro-5-methylisoxazol-5-yl] methanol (M11). 

Additionally, there was a high percentage of applied radioactivity (8-25% of applied 

radioactivity) in unextracted soil/sediment residues. Because the extraction of 

pyroxasulfone residues was conducted using only acetonitrile/water without the use of 

sequentially harsher extractants, there is uncertainty regarding the identity and 

availability of the unextracted soil residues. 

In Tier II PRZM/EXAMS modeling the post-plant application of pyroxasulfone in the 

MS corn scenario produced the highest estimated exposure concentrations (EECs). The 

maximum 1 in 10 year for pyroxasulfone was 8.341 μg/L for daily peak EEC, 8.137 μg/L 

for 21-day average EEC, and 7.779 μg/L for 60-day average EEC. Degradation products 

were not considered in the exposure modeling because of the persistence of 

pyroxasulfone. In addition, surface water modeling for total residues (parent+M1+M3) 

showed a small difference in exposure concentrations when compared with modeling for 

the parent. 

Persistence 

Pyroxasulfone was stable to abiotic hydrolysis in pH 5, 7, and 9 buffer solutions (MRID 

47701733). It was also essentially stable to photodegradation in water and soil (MRID 

47701734 and 47701735). The photodegradation half-life in water was 119 days. 

Pyroxasulfone was persistent in aerobic soil with half-lives ranging from 142 to 533 days 

across ten soils (MRID 47701737 and 47701736). The mean aerobic soil metabolism 

half-life was 343.8 days (N=10) with a standard deviation of 119.9 days. In two 

anaerobic soils, pyroxasulfone half-lives range from 145 to 156 days (MRID 47701739). 

Pyroxasulfone was moderately persistent in aerobic and anaerobic aquatic environments 

(MRID 47701741and 47701740). The mean total sediment and aquatic half-life was 

108.5days (SD= 0.7 days; N=2) and 70.25 days (SD=0.8 days; N=2) in aerobic aquatic 

environments and anaerobic aquatic environments, respectively. 
38

Degradation Products 

Metabolite identification was conducted on acetonitrile/water (2:1 v:v) extractable 

residues from water, soil, and sediment. Major metabolites (≥10% of applied 

radioactivity) of pyroxasulfone in laboratory metabolism studies were 5-

difluoromethoxy-1H-pyrazol-4-yl) methanesulfonic acid (M1) and 5-difluoro methoxy-1-

methyl-3-trifluoromethyl-1H-pyrazol-4- carboxylic acid (M3). 

Minor metabolites (<10% of applied radioactivity) were 3-(5-Difluoromethoxy-3-

trifluoromehyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-dihydro-5,5-dimethylisoxazole 

(M5), 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl 

methanesulfonyl)-4,5-dihydro-5,5-dimethylisoxazol-4-ol (M6), (5-difluoromethoxy-1-

methyl-3-trifluoromethyl-1H-pyrazol-4-yl) methanol (M8), 5-difluoromethoxy-3-

trifluoromethyl-1H-pyrazol-4-carboxylic acid (M9), 5-Difluoromethoxy-1-methyl-3-

trifluoromethyl-1H-pyrazol-4-carbaldehyde (M10), and [3-5-Difluoromethoxy-1-methyl3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-4,5-dihydro-5-methylisoxazol-5-yl] 

methanol (M11). Unidentified residues in metabolism studies accounted for 1.2 to 3.3% 

of applied radioactivity. Bound soil/sediment residues (post acetonitrile/water extraction) 

account for 8 to 25% of the applied radioactivity. 

Table 10 shows the maximum concentration of each degradation product in each 

laboratory environmental fate study. 

Table 10. Degradation Product Identification in Laboratory Studies 

Degradation Product Study Max% Applied Radioactivity (day) MRID 

 KIH-485 M1 

Aerobic Soil Metabolism 

49 (365d) 47701736 

42.3 (181d) 

47701737 

1.2 (180d) 

27.5 (365d) 

1.6 (365 d) 

27.6 (365d) 

1.0 (120d) 

35.9 (365d) 

1.0 (181d) 

Aerobic Aquatic Metabolism 16.1 (180 d) 47701740 

0.6 (180 d) 

Anaerobic Aquatic Metabolism 20.6 (365 d) 47701741 

 KIH-485 M3 

Aerobic Soil Metabolism 

7.1 (90d) 47701736 

3.4 (90 d) 

47701737 

2.3 (120 d) 

6.8 (181 d) 

10.3 (365d) 

7.1 (90d) 

Aerobic Aquatic Metabolism 12.8 (180 d) 47701740 
39

Anaerobic Aquatic Metabolism 6.5 (181 d) 47701741 

 KIH-485 M5 Soil Photolysis 0.3 (30d) 47701735 

KIH-485 M6 

Aerobic Soil Metabolism 

2.3(90d) 47701736 

2.2(90d) 

47701737 1.4 (365 d) 

0.6 (182 d) 

1.0 (181d) 

Anaerobic Soil Metabolism 1.5 (61 d) 47701739 

Soil Photolysis 0.5 (21 d) 47701735 

Aerobic Aquatic Metabolism 0.9 (61d) 47701740 

KIH-485 M8 

Anaerobic Soil Metabolism 3.7 (303 d) 47701739 

Aerobic Aquatic Metabolism 3.8 (29 d) 47701740 

Anaerobic Aquatic Metabolism 6.4 (120d) 47701741 

KIH-485 M9 

Aerobic Soil Metabolism 1.8(90d) 47701736 

Anaerobic Soil Metabolism 1.4 (30 d) 47701739 

Aerobic Aquatic Metabolism 6.2 (120 d) 47701740 

Anaerobic Aquatic Metabolism 2.1 (120 d) 47701741 

KIH-485 M10 

Anaerobic Soil Metabolism 6.2 (180 d) 47701739 

Aerobic Aquatic Metabolism 0.6 (61 d) 47701740 

Anaerobic Aquatic Metabolism 7.8 (365d) 47701741 

KIH-485 M11 Aerobic Aquatic Metabolism 

0.5 (61 d) 

47701740 

1.2 (180 d) 

KIH-485 M13 

Aerobic Aquatic Metabolism 1.9 (180 d) 47701740 

2.9 (180 d) 

Anaerobic Aquatic Metabolism 2 (181 d) 47701741 
40

Mobility 

Pyroxasulfone and its degradation products M1, M3, and M6 were highly mobile to 

mobile in four soil and aquatic environments (MRID 47701742, 47701743, 47701744). 

The Freundlich adsorption coefficient for pyroxasulfone was 1.93 L/kg (1/n=1; Koc=104) 

in sandy clay loam, 1.93 L/kg (1/n=0.9880; Koc=99) in clay loam, 1.59 L/kg (1/n=0.9898; 

Koc=119), and 2.00 L/kg (1/n=1; Koc=57) in loam. The Freundlich desorption coefficient 

was 4.10 L/kg (1/n=0.9590; Koc=216) in sandy clay loam, 7.44 L/kg (1/n=0.9289; 

Koc=169) in clay loam, 3.16 L/kg (1/n=0.9208; Koc=226), and 4.16 L/kg (1/n=0.9650; 

Koc=119) in loam. Pyroxasulfone was leached through packed soil columns; 42.5 to 

90.3% of applied radioactivity was detected in the soil column leachate. The 

radioactivity in leachate samples were identified as pyroxasulfone (72.6 to 84% of 

applied dose), M1 (7.5 to 18.6% of applied dose), M3 (2.6 to 4.2% of applied dose), and 

M6 (1.1 to 6.7% of applied dose). The column Kd for pyroxasulfone was 1.19 mL/g in IL 

silt loam soil, 1.10 mL/g in GA sandy loam soil, 0.635 mL/g in CA silt loam soil and 

1.98 mL/g in NY clay loam. The soil column Kd for M1 is 0.754 mL/g in IL silt loam 

soil, 0.620 mL/g in GA sandy loam soil, 0.568 mL/g in CA silt loam soil and 0.816 mL/g 

in NY clay loam. 

Field Dissipation Studies 

Pyroxasulfone (formulated as KIH-485 WG85) was broadcast spray applied at 67.2 g 

ai/A (0.15 lbs ai/A) in CA, 84.6 (0.19 lbs ai/A) in IL and GA, and 121.4 g ai/A (0.27 lbs 

ai/A) in NY (MRID 47701745). The dissipation DT50 for pyroxasulfone in surface soil 

(0-15 cm) was 35 days in CA, 16.7 days in IL, 24 days in GA, and 4 days in NY. 

Pyroxasulfone was predominately detected in the surface soil (0-15 cm). There were 

sporadic detections of pyroxasulfone with soil depth at the CA and GA site. 

Pyroxasulfone residue leaching was determined in 6 inch soil samples to a soil depth of 

36 inches. The maximum depth of pyroxasulfone leaching was 12 to 18 inches (0.011 

mg/kg) at the CA site and 12 to 18 inches (0.007 mg/kg) at the GA site. The degradation 

product M3 was detected at concentration of 0.006 mg/kg in the 12 month after treatment 

(MAT) surface soil (0-6 inches) at the CA site, 0.003 mg/kg in the 1 month after 

treatment (MAT) surface soil (0-6 inches) at the NY site, and 0.003 mg/kg in the 14 days 

after treatment (DAT) surface soil (0-6 inches) at the IL site. The degradation product 

M1 was detected at concentration of 0.006 mg/kg in the 10 month after treatment (MAT) 

surface soil (0-6 inches) at the CA site, 0.013 mg/kg in the 1 MAT surface soil (0-6 

inches) at the NY site, 0.011 mg/kg in the 14 DAT surface soil (0-6 inches) at the GA 

site. There were detections of M1with depth at the IL (6-12 inches at 0.004 mg/kg) and 

GA (18-24 inches at 0.005 mg/kg). 

Pyroxasulfone (formulated as KIH-485 WG85P) was broadcast spray applied at 121.4 g 

ai/A (0.27 lbs ai/A) at CA and AR field sites (MRID 47701747). The sites were flooded 

immediately after pyroxasulfone application and then drained after 130 to152 days after 

application. Samples were taken to represent sediment, flood water, and soil after 

flooding. The dissipation DT50 for pyroxasulfone in surface sediment (0-6 inches) was 
41

77 days in CA and 64.8 days in AR. The dissipation DT50 for pyroxasulfone in water 

was 16 days at both sites. Pyroxasulfone was the only residue in flood water. M1 and 

M3 were not detected in the flood water. Pyroxasulfone, M1, and M3 were not detected 

in post flood soils (0-18 inches). 

Bioaccumulation in Fish 

A bioaccumulation in fish study was not submitted to support the proposed registration. 

Although the pyroxasulfone is mobile and persistent, the low octanal:water partitioning 

coefficient (log Kow= 2.39) is expected to limit bioconcentration and bioaccumulation of 

pyroxasulfone. Based on the log Kow of 2.39, the expected BCF assuming no metabolism 

and 5% lipids would be approximately 12 L/kg wet weight (i.e., 102.39 * 0.05). This low 

BCF combined with the low acute toxicity to birds and mammals indicates that risks to 

piscivorous wildlife would not be expected. 

2. Measures of Aquatic Exposure 

a. Aquatic Exposure Modeling 

The estimated environmental concentrations (EECs) reported in the assessment were 

calculated using the Tier II model for surface water (PRZM/EXAMS). Sample inputs and 

outputs of the model are presented in Appendix C. 

PRZM (v3.12.2, May 2005) and EXAMS (v2.98.4.6, April 2005) are screening 

simulation models coupled with the input shell pe5.pl (Aug 2007) to generate daily 

exposures and 1-in-10 year EECs of pyroxasulfone that may occur in surface water 

bodies adjacent to application sites receiving pyroxasulfone through runoff and spray 

drift for specific scenarios. PRZM simulates pesticide application, movement and 

transformation on an agricultural field and the resultant pesticide loadings to a receiving 

water body via runoff, erosion and spray drift. EXAMS simulates the fate of the 

pesticide and resulting concentrations in the water body. The standard scenario used for 

ecological pesticide assessments assumes application to a 10-hectare agricultural field 

that drains into an adjacent 1-hectare water body, 2-meters deep (20,000 m3

 volume) with 

no outlet. PRZM/EXAMS was used to estimate screening-level exposure of aquatic 

organisms to pyroxasulfone residues. The measure of exposure for aquatic species is the 

1-in-10 year return peak or rolling mean concentrations. The 1-in-10 year daily peak 

concentration is used for estimating acute exposures of direct effects to aquatic organisms 

as well as indirect effects. The 1-in-10-year 60-day mean concentration is used for 

assessing chronic exposure to fish. The 1-in-10 year 21-day mean concentration is used 

for assessing chronic exposures to aquatic invertebrates. Degradation products were not 

considered in the exposure modeling because of the persistence of pyroxasulfone. In 

addition, surface water modeling for total residues (parent+M1+M3) showed a small 

difference in exposure concentrations when compared with modeling for the parent. 
42

Input Parameters

The appropriate input parameters were selected from the physical/chemical properties 

and environmental fate data submitted by the petitioner to support registration of 

pyroxasulfone (Table 11). Input parameters were selected in accordance with US EPAOPP EFED water model parameter selection guidelines, Guidance for Selecting Input 

Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version 2.1, 

November 10, 2009. Expanded information about the models, selection of input 

parameters and scenarios can be obtained from 

http://www.epa.gov/oppefed1/models/water/index.htm. 

Table 11. PRZM/EXAMS Modeling Inputs for Pyroxasulfone 

Paremeter Pyroxasulfone Comment Reference 

Aerobic Soil Metabolism Half-life (days) 396.22 

90th

 percentile of 

confidence bound of 

the mean 

N=10 

Mean=343.8 days 

SD=119.8 days 

47701736 

47701737 

Organic Carbon Partition Coefficient 

(Koc) (mL/ goc) 94.75 Average 

(104, 99, 119, 57) 47701742 

Aerobic Aquatic 

Half-Life (days) 146.74 

90th

 percentile of 

confidence bound of 

the mean 

N=2 

Mean=108.5 days 

SD=0.7 days 

47701740 

Anaerobic Aquatic 

half-life (days) 71.94 

90th

 percentile of 

confidence bound of 

the mean 

N=2 

Mean=70.25 days 

SD=0.8 days 

47701741 

Aqueous Photolysis 

half-life (days) 119 Half-life value 47701734 

Hydrolysis 

half-life (days) Stable 47701733 

Molecular Weight (g/mole) 367 Physical Property 

Henry’s Law constant 

(atm-m3

/mol) 2.65E-9 Calculated 47701752 

Water Solubility @ 25°C 

(mg/L) 3.49 47701752 

Vapor Pressure (torr) 1.8E-8 47701752 
43

Spray drift fractions were estimated to account for the required drift buffers on the V10233 Herbicide Water Dispersible Granules Commercial and V-10233 Herbicide labels. 

The AgDrift model (version 2.01) was used to estimate the impact of spray drift buffers 

on drift fractions. It is important to recognize that the default aerial spray drift fraction 

(0.05) is greater than the adjusted spray fraction for the label recommended drift buffers. 

The edge-of-pond AgDrift model drift fraction is 0.1266. In contrast, the ground spray 

buffers for a low boom spray are consistent with the default drift fraction (0.01). 

Regardless of input parameters used, utilizing the buffers would reduce EECs. 

 

Table 12. Spray Drift Fraction Used in Aquatic Exposure Modeling 

Buffer 

Size (ft) 

Spray Default 

Spray Drift 

Fractions 

without a Buffer 

AgDrift 

Spray Drift 

Fractions without a 

Buffer 

Adjusted Spray 

Drift Fraction for 

Buffer 

9.8 Aerial 0.05 0.1266 0.109 

40 Aerial 0.05 0.1266 0.081 

9.8 Ground 0.01 0.0616 0.0091 

32 Ground 0.01 0.0616 0.0137 

PRZM/EXAMS scenario selection was focused on standard corn and wheat scenarios 

(Table 13). Because corn and soybeans is a common crop rotation, standard corn 

scenarios were selected to serve as surrogate scenarios for pyroxasulfone application on 

corn and soybeans. Agronomic practices including application rate, application timing, 

number of applications, application interval, and application method were modeled to 

represent proposed label practices. Fallowland use of pyroxasulfone was not explicitly 

modeled because the standard PRZM/EXAMS scenarios are associated with crops. Some 

proposed pyroxasulfone labels allow application to non-crop areas such as bare ground 

areas around orchards, vineyards, and farms. The surrogate scenarios used to model 

applications to non-crop areas were TN nursery, PA apple, and NY grapes. It is 

anticipated the EECs for fallowland will be represented in the range of modeled crop and 

non-crop uses. The corn scenarios apply to both corn and soybean uses. Because the 

pyroxasulfone products are applied by aerial or ground spray applications, the foliar 

chemical application method (CAM=2) was used in the exposure modeling. 
44

Table 13: PRZM/EXAMS Simulated Application Rates, Method, and Timing According to 

Proposed Label 

Standard 

Scenario 

Label 

Application 

Time 

Scenario 

Emerge 

Date 

(monthday) 

PRZM 

Application 

Time 

(monthday) 

Number 

of Apps 

Application 

Interval 

Spray 

Method 

Application 

Rate 

(lbs/A) 

OH Corn Preemerg 5-1 4-25 1 NA Air 0.120 

Pre-plant 4-1 1/2 180 Ground 0.2136/0.1335 

Pre-plant 

(soil incorp) 4-16 1/2 180 Ground 0.2136/0.1335 

Post-emerg 5-15 1/2 180 Ground 0.2136/0.1335 

Fall 10-15 1 NA Ground/Air 0.2136/0.120 

IL Corn Preemerg 5-1 4-25 1 NA Air 0.120 

Pre-plant 4-1 1/2 180 Ground 0.2136/0.1335 

Pre-plant 

(soil incorp) 4-16 1/2 180 Ground 0.2136/0.1335 

Post 5-15 1/2 180 Ground 0.2136/0.1335 

Fall 10-15 1 NA Ground/Air 0.2136/0.120 

IA Corn Preemerg 5-25 5-20 1 NA Air 0.120 

Pre-plant 4-25 1/2 180 Ground 0.2136/0.1335 

Pre-plant 

(soil incorp) 5-5 1/2 180 Ground 0.2136/0.1335 

Post 6-1 1/2 180 Ground 0.2136/0.1335 

Fall 10-15 1 NA Ground/Air 0.2136/0.120 

MS Corn Preemerg 4-10 4-5 1 NA Air 0.120 

Pre-plant 3-10 1/2 180 Ground 0.2136/0.1335 

Pre-plant 

(soil incorp) 3-25 1/2 180 Ground 0.2136/0.1335 

Post 4-25 1/2 180 Ground 0.2136/0.1335 

Fall 11-15 1 NA Ground/Air 0.2136/0.120 

NDWheat Pre-plant 

(Fall) 9-1 1 NA Ground 0.1068 

Fall 9-1 1 NA Ground 0.267 

Non-Crop 

Use 

 NS NS NS Ground 0.2625 

Abbreviations: NA=not applicable, NS = not specified, post=post plant, preemerg=preemergent 

1-180 days represent the label specified retreatment interval 

Pre-plant = 30 day prior to emergence date 

Pre-plant soil incorporated = 15 day prior emergence 

Post-plant = 14 days post-emergence to V4 growth stage (corn) or an application date no later than June 1. 

Rates represent a single application (spring)@ 0.2136 lbs ai/A and spring/fall application @ 0.1335 lbs ai/A. Labels 

state total application per crop cannot exceed 0.267 lbs ai/A. 

Tier II- PRZM/EXAMS

Tier II estimated environmental concentrations for pyroxasulfone residues in surface water are 

shown in Table 14. 
45

Table 14: Estimated Environmental Concentrations of Pyroxasulfone in Surface Water 

Standard 

Scenario 

Label 

Application 

Time

Number of 

Apps 

Method 

of App 

Spray 

Drift 

Buffer 

(feet) 

App Rate 

(lbs/A) 

Estimated Concentration 

(ug/L) 

1 in 10 yr 

Peak 

1 in 10 yr 

21-day 

Average 

1 in 10 yr 

60-day 

Average 

IA Corn Preemerg 1 Air None 0.120 2.088 1.997 1.814 

 1 Air 9.8 0.120 2.722 2.602 2.362 

 1 Air 40 0.120 2.421 2.315 2.102 

 Pre-plant 1 Ground None 0.2136 2.072 2.021 1.901 

 2 Ground None 0.1335 2.498 2.441 2.292 

 Pre-plant (soil 

incorp) 1 Ground None 0.2136 1.583 1.523 1.411 

 2 Ground None 0.1335 1.635 1.582 1.470 

 Post Plant 1 Ground None 0.2136 1.508 1.443 1.325 

 2 None 0.1335 3.031 2.973 2.300 

 Fall 1 Ground None 0.2136 3.441 3.375 3.251 

 1 Air None 0.120 2.538 2.484 2.392 

 1 Air 9.8 0.120 3.240 3.165 3.042 

 1 Air 40 0.120 2.097 2.841 2.732 

IL Corn Preemerg 1 Air None 0.120 3.615 3.480 3.260 

 1 Air 9.8 0.120 4.202 4.048 3.788 

 1 Air 40 0.120 3.923 3.778 3.537 

 Pre-plant 1 Ground None 0.2136 7.271 7.090 6.938 

 2 Ground None 0.1335 7.832 7.635 7.400 

 Pre-plant (soil 

incorp) 1 Ground None 0.2136 3.304 3.218 3.039 

 2 Ground None 0.1335 3.198 3.102 2.969 

 Post Plant 1 Ground None 0.2136 7.271 7.090 6.938 

 2 None 0.1335 7.382 7.635 7.400 

 Fall 1 Ground None 0.2136 5.821 5.730 5.556 

 1 Air None 0.120 2.281 2.223 2.150 

 1 Air 9.8 0.120 2.912 2.845 2.734 

 1 Air 40 0.120 2.613 2.554 2.456 

OH Corn Preemerg 1 Air None 0.120 3.006 2.887 2.705 

 1 Air 9.8 0.120 3.636 3.492 3.261 

 1 Air 40 0.120 3.215 3.124 2.915 

 Pre-plant 1 Ground None 0.2136 5.980 5.788 5.567 

 2 Ground None 0.1335 6.172 5.973 5.648 

 Pre-plant (soil 

incorp) 1 Ground None 0.2136 1.927 1.857 1.724 

 2 Ground None 0.1335 2.034 1.970 1.842 

 Post Plant 1 Ground None 0.2136 5.980 5.788 5.567 

 2 None 0.1335 6.172 5.973 5.648 

 Fall 1 Ground None 0.2136 3.990 3.891 3.833 

 1 Air None 0.120 2.859 2.787 2.735 

 1 Air 9.8 0.120 3.542 3.450 3.373 

 1 Air 40 0.120 3.218 3.135 3.070 

MS Corn Preemerg 1 Air None 0.120 3.514 3.364 3.138 

 1 Air 9.8 0.120 4.028 3.868 3.593 

 1 Air 40 0.120 3.784 2.629 3.377 

 Pre-plant 1 Ground None 0.2136 8.388 8.137 7.641 

 2 Ground None 0.1335 8.341 8.115 7.779 

 Pre-plant (soil 

incorp) 1 Ground None 0.2136 3.489 3.346 3.091 

 2 Ground None 0.1335 3.618 3.484 3.268 

 Post Plant 1 Ground None 0.2136 8.388 8.137 7.641 

 2 None 0.1335 8.341 8.115 7.779 

 Fall 1 Ground None 0.2136 7.308 7.198 5.833 

 1 Air None 0.120 6.737 6.579 5.800 

 1 Air 9.8 0.120 7.307 7.131 6.291 

 1 Air 40 0.120 7.037 6.868 6.057 

NDWheat Pre-plant (Fall) 1 Ground None 0.1068 2.765 2.701 2.623 

 Fall 1 Ground None 0.267 6.912 6.752 6.557 

Non-Crop Use 

TN Nursery 1 Ground None 0.2625 4.002 3.883 3.645 

PA apple 1 Ground None 0.2625 2.254 2.171 2.020 

NY grapes 1 Ground None 0.2625 4.044 3.952 3.755 
46

Uncertainty 

There is a high percentage of applied radioactivity (8-25% of applied radioactivity) 

identified as unextracted soil/sediment residues. Because the extraction of pyroxasulfone 

residues was conducted using only acetonitrile/water without the use of sequentially 

harsher soil extractants, there is uncertainty regarding the identity and availability of the 

unextracted soil residues. The uncertainty with identification of unextracted residues is 

not expected to alter the exposure assessment because of the high persistence of 

pyroxasulfone, 

Additionally, the major degradation product M1 is very persistent and mobile in 

laboratory and field studies. It is a potential groundwater contaminant because of the fate 

properties. 

The aquatic exposure modeling was not conducted on fallow land use of pyroxasulfone. 

This modeling approach was taken because the PRZM/EXAMS standard scenarios 

represent scenarios with crops. It is anticipated the EECs for fallow land uses will be 

adequately represented by the exposure scenario for crops and non-crops uses. 

b. Aquatic Exposure Monitoring and Field Data 

Because pyroxasulfone is a new pesticide, there are no monitoring data in surface water 

and ground water. 

c. Aquatic Bioaccumulation Assessment 

Available data on the octanol-water partition coefficient (Kow) for pyroxasulfone 

indicates that this pesticide has a low bioaccumulation potential in aquatic food webs. 

Because the log Kow is < 4.0, KABAM v.1.0 was not used to estimate concentrations of 

pyroxasulfone in tissues of aquatic organisms resulting from bioaccumulation. 
47

3. Measures of Terrestrial Exposure 

a. Terrestrial Exposure Modeling 

T-REX 

Exposure of free-ranging terrestrial animals is a function of the timing and extent of 

pesticide application with respect to the location and behavior of those species. OPP’s 

terrestrial exposure model generates exposure estimates assuming that the animal is 

present on the use site at the time that pesticide levels are highest. The upper-bound 

pesticide residue concentration on food items is calculated from both initial applications 

and any additional applications, taking into account pesticide degradation between 

applications. Although this approach is conservative, it is reasonable, particularly when 

considering acute risks. For acute risks, the assumption is that the duration of exposure is 

a single day and, again, occurs when residue levels are highest. In evaluating chronic 

risks, longer-term exposure estimates are also based on the assumption that the animal is 

present on the use site when residue levels are highest and furthermore that it repeatedly 

forages on the use site. 

The current screening-level approach does not directly relate timing of exposure to 

critical or sensitive population, community, or ecosystem processes. Given that the 

application timing and location is crop-dependent, it is difficult to address the temporal 

and spatial co-occurrence of pyroxasulfone use and sensitive ecological processes. 

However, pesticides are frequently used from spring through fall; crop cultivation 

frequently starts in the spring, hence uses of pyroxasulfone are likely to occur in spring 

and perhaps summer depending on the region. Spring and early summer are typically 

seasons of active migrating, feeding, and reproduction for many wildlife species. The 

increased energy demands associated with these activities (as opposed to hibernation, for 

example) can increase the potential for exposure to pesticide-contaminated food items 

since agricultural areas can represent a concentrated source of relatively easily obtained, 

high-energy food items. In this assessment, the spatial extent of exposure for terrestrial 

animal species is limited to the use area only and the area immediately surrounding the 

use area. 

Currently, the Agency does not require toxicity studies on reptiles and amphibians in 

support of pesticide registrations. To accommodate this data gap, birds are used as 

surrogates for terrestrial-phase amphibians and reptiles. It is assumed that, given the 

usually lower metabolic demands of reptiles and amphibians compared to birds, exposure 

to birds would be greater due to higher relative food consumption. The lack of toxicity 

data on reptiles and amphibians represents a source of uncertainty in this assessment. 

Tables 15 and 16 list selected predicted EECs for birds, reptiles, terrestrial amphibians, 

and mammals obtained from T-REX simulations for the proposed uses of pyroxasulfone 

at the maximum seasonal label rates. 
48

Table 15. Terrestrial Food-Item Residue Estimates for Birds with Pyroxasulfone Proposed Uses 

with a Foliar Dissipation Half-life default value of 35 Days. 

Crop Food Item 

Maximum 

Dose-Based 

EECs (mg/kgbw)1

Maximum 

Dose-Based 

EECs (mg/kgbw)2

Maximum 

Dose-Based 

EECs (mg/kgbw)3

Dietary-Based EECs 

(mg/kg-diet) 

Corn, 

soybean, 

winter wheat 

(0.267 lbs 

a.i./A)a 

Short grass 72.98 41.62 18.63 64.08 

Tall grass 33.45 19.07 8.54 29.37 

Broadleaf plants/ small insects 41.05 23.41 10.48 36.05 

Fruits, pods, seeds, lg. insects 4.56 2.60 1.16 4.01 

Granivores 1.01 0.58 0.26 -- 

Non-crop 

sites 

(0.206 lbs 

a.i./A)b 

Short grass 56.31 32.11 14.38 49.44 

Tall grass 25.81 14.72 6.59 22.66 

Broadleaf plants/ small insects 31.67 18.06 8.09 27.81 

Fruits, pods, seeds, lg. insects 3.52 2.01 0.90 3.09 

Granivores 0.78 0.45 0.20 -- 

Corn, 

soybean, 

fallow land, 

non-crop 

sites (0.120 

lbs a.i./A)c 

Short grass 32.80 18.70 8.37 28.80 

Tall grass 15.03 8.57 3.84 13.20 

Broadleaf plants/ small insects 18.45 10.52 4.71 16.20 

Fruits, pods, seeds, lg. insects 2.05 1.17 0.52 1.80 

Granivores 0.46 0.26 0.12 -- 

Soybean 

(0.096 lbs 

a.i./A)d 

Short grass 26.24 14.96 6.70 23.04 

Tall grass 12.03 6.86 3.07 10.56 

Broadleaf plants/ small insects 14.76 8.42 3.77 12.96 

Fruits, pods, seeds, lg. insects 1.64 0.94 0.42 1.44 

Granivores 0.36 0.21 0.09 -- 1

Based on 20 gram birds 

2Based on 100 gram birds 

3

 Based on 1000 gram birds 

a

 Single application at the maximum seasonal rate of 0.267 lbs a.i./A for corn, soybean, and winter wheat (KIH-485 W85 and Pyroxasulfone 85W labels) b

 Single application at the maximum seasonal rate of 0.206 lbs a.i./A for non-crop sites (V-10233 Herbicide Water Dispersible Granules commercial label) c

 Single application at the maximum seasonal rate of 0.120 lbs a.i./A for corn, soybean, fallow land, and non-crop sites (V-10233 Herbicide label) d

 Single application at the maximum seasonal rate of 0.096 lbs a.i./A for soybean (V-10233 Herbicide Water Dispersible Granules commercial label) 
49

Table 16. Terrestrial Food-Item Residue Estimates for Mammals with Pyroxasulfone Proposed 

Uses with a Foliar Dissipation Half-life default value of 35 Days. 

Crop Food Item 

Maximum 

Dose-Based 

EECs (mg/kgbw)1

Maximum 

Dose-Based 

EECs (mg/kgbw)2

Maximum 

Dose-Based 

EECs (mg/kgbw)3

Dietary-Based EECs 

(mg/kg-diet) 

Corn, 

soybean, 

winter wheat 

(0.267 lbs 

a.i./A)a 

Short grass 61.10 42.23 9.79 64.08 

Tall grass 28.00 19.35 4.49 29.37 

Broadleaf plants/ small insects 34.37 23.75 5.51 36.05 

Fruits, pods, seeds, lg. insects 3.82 2.64 0.61 4.01 

Granivores 0.85 0.59 0.14 -- 

Non-crop 

sites 

(0.206 lbs 

a.i./A)b 

Short grass 47.14 32.58 7.55 49.44 

Tall grass 21.60 14.93 3.46 22.66 

Broadleaf plants/ small insects 26.51 18.33 4.25 27.81 

Fruits, pods, seeds, lg. insects 2.95 2.04 0.47 3.09 

Granivores 0.65 0.45 0.10 -- 

Corn, 

soybean, 

fallow land, 

non-crop 

sites (0.120 

lbs a.i./A)c 

Short grass 27.46 18.98 4.40 28.80 

Tall grass 12.59 8.70 2.02 13.20 

Broadleaf plants/ small insects 15.45 10.67 2.48 16.20 

Fruits, pods, seeds, lg. insects 1.72 1.19 0.28 1.80 

Granivores 0.38 0.26 0.06 -- 

Soybean 

(0.096 lbs 

a.i./A)d 

Short grass 21.97 15.18 3.52 23.04 

Tall grass 10.07 6.96 1.61 10.56 

Broadleaf plants/ small insects 12.36 8.54 1.98 12.96 

Fruits, pods, seeds, lg. insects 1.37 0.95 0.22 1.44 

Granivores 0.31 0.21 0.05 -- 1

Based on 15 gram mammal 

2Based on 35 gram mammal 

3

 Based on 1000 gram mammal 

a

 Single application at the maximum seasonal rate of 0.267 lbs a.i./A for corn, soybean, and winter wheat (KIH-485 W85 and Pyroxasulfone 85W labels) b

 Single application at the maximum seasonal rate of 0.206 lbs a.i./A for non-crop sites (V-10233 Herbicide Water Dispersible Granules commercial label) c

 Single application at the maximum seasonal rate of 0.120 lbs a.i./A for corn, soybean, fallow land, and non-crop sites (V-10233 Herbicide label) d

 Single application at the maximum seasonal rate of 0.096 lbs a.i./A for soybean (V-10233 Herbicide Water Dispersible Granules commercial label) 

TERRPLANT 

Effects on non-target terrestrial plants are most likely to occur as a result of spray drift 

and/or runoff from ground applications. These are important factors in characterizing the 

risk of pyroxasulfone to non-target plants, which is assumed to reach off-site soil. The 

TerrPlant (Ver.1.2.2) model predicts EECs for terrestrial plants located in dry and semiaquatic areas adjacent to the treated field. The EECs are based on the application rate 

and solubility of the pesticide in water and drift characteristics. The amount of 

pyroxasulfone that runs off is a proportion of the application rate and is assumed to be 

1%, based on pyroxasulfone’s solubility of <10 ppm (i.e. 3.49 mg/L) in water. Drift from 

ground applications are assumed to be 1% the application rate; drift from aerial 

applications are assumed to be 5% the application rate. An incorporation depth was not 

referenced in the label, which meant setting the default value to 1 inch for ground 

applications. For a standard scenario on an agricultural field, the runoff scenario for 

terrestrial plants inhabiting dry areas adjacent to a field is characterized as “sheet runoff” 
50

(one treated acre to an adjacent acre; a 1:1 ratio) and inhabiting semi-aquatic areas 

adjacent to a field is characterized as “channelized runoff” (10 treated acre to an adjacent 

low-lying acre; a 10:1 ratio). The TerrPlant model EECs are presented in Table 17. 

Table 17. Estimated Environmental Concentrations of Pyroxasulfone for Terrestrial Plants 

Application 

Method

Application 

Rate (lbs a.i./A)* 

Dry areas (lb/A) 1 Semi-Aquatic Areas (lb/A)2 Spray Drift (lb/A)3

Ground 0.267 0.00534 0.02937 0.00267 

Ground 0.206 0.00412 0.02266 0.00206 

Ground 0.12 0.0024 0.0132 0.0012 

Ground 0.096 0.00192 0.01056 0.00096 

Aerial 0.12 0.0072 0.018 0.006 

1

 EEC = Sheet Runoff + Drift (1% for ground or 5% for aerial) 

2 EEC = Channelized Runoff + Drift = 1% for ground or 5% for aerial 

3

 EEC for ground (appl rate x 1% drift) and aerial (appl rate x 5% drift) *

Maximum seasonal application rates 

Ground Water Modeling 

To estimate exposure to plants when groundwater contaminated by pyroxasulfone is 

applied to crops, the following method was used. Predicted groundwater concentrations 

of pyroxasulfone (equivalent to the equilibrium concentration taken over a 30 year 

period) were used to estimate the potential phytotoxic effects from irrigation water to 

plants and sensitive crops on the treated field. It is assumed that a one-acre field is 

irrigated with one inch of water containing pyroxasulfone at the equilibrium 

concentration. Pyroxasulfone concentrations were estimated using a beta version of the 

PRZM GW Tier II model. This model is currently undergoing an implementation process 

in OPP. Model input parameters are shown in Table 18. The model provides ground 

concentrations as predicted through Pesticide Root Zone Model (PRZM) (Table 19). 

Table 18. PRZM GW Tier II Model Input Parameters

Input Parameter Value Source

Application Rate 0.267 lbs ai/A Label

Hydrolysis Halflife Stable 47701733 

Soil Half-life 369 days 47701736 

47701737

Koc 94.75 47701742
51

Table 19. GW Tier II Model and SCIGROW Estimated Pyroxasulfone in Groundwater and 

Estimated Concentrations in Soil from Irrigation Water 

Scenario Peak (ppb) Post Breakthrough Average (ppb) EECs (lbs a.i./A)1

GA 33.3 28.7 0.007 

FL Potato 46.7 38.2 0.009 

FL Citrus 76.5 54.7 0.012 

DE 94.1 83 0.019 

NC 50.7 43.4 0.010 

WI 181 149 0.034 

SCIGROW 1.93 0 1

 EEC calculation: Assuming a one-acre field is irrigated with one inch of water containing pyroxasulfone. 

One acre has 6,272,640 cubic inches of water on the field. The1 acre field with 1 inch of water has 3,630 cubic ft of 

water (6,272,640 x 0.00058 cubic ft/cubic inch). The field has 27,156 gallons of water (3,630 cubic ft x 7.481 

gallons/cubic ft). Therefore, 1 inch of water on the 1 acre field weighs 226,625 lbs (27,156 gallons x 8.3453 

lbs/gallon of water). 

 226,625 lb of water/acre * [post breakthrough ave in ppb] = EEC in lbs a.i./A 

 1,000,000,000 

C. Ecological Effects Characterization 

1. Aquatic Effects Characterization 

a. Aquatic Animals 

(1) Acute Effects 

Freshwater Fish and Aquatic-Phase Amphibians -Technical

The freshwater fish studies on rainbow trout (Oncorhynchus mykiss, MRID 47701626) 

and bluegill sunfish (Lepomis macrochirus, MRID 47701627) are classified as acceptable 

limit tests. As the endpoints are non-definitive, they are not useful for RQ calculations, 

but can contribute to risk description. 

Freshwater Fish and Aquatic-Phase Amphibians – Metabolites / Degradates

There are no acute data on metabolites/degradates for freshwater fish and aquatic- phase 

amphibians. 

Freshwater Fish and Aquatic-Phase Amphibians -Formulations

There are no acute data on formulations for freshwater fish and aquatic-phase 

amphibians. Based on the proposed use pattern, aquatic EECs and lack of toxicity to 

freshwater fish at the limit of solubility, toxicity data on formulations (Technical End Use 

Products) would not be required. 
52

Table 20. Freshwater Fish Acute Toxicity Data 

Common Name %AI Study parameters LC50/NOAEC/LOAEC MRID Classification/ 

Category

Technical KIH-485 

Rainbow trout 

Oncorhynchus 

mykiss 

(cold water species) 

99.1 96 hour static 

renewal study 

(limit test) 

3 reps / 10 fish per 

rep. 

Mean-measured: 

negative control 

(<LOQ = 0.28 mg 

a.i./L), 2.2 mg 

a.i./L 

96-hr LC50 > 2.22 mg a.i./L

NOAEC ≥ 2.2 mg a.i./L 

Endpoint(s) affected: None. 

Sublethal effects: None. 

47701626 Acceptable 

At most 

moderately toxic1 

Bluegill sunfish 

Lepomis 

macrochirus 

(warm water 

species) 

99.1 96 hour static 

renewal study 

(limit test) 

3 reps / 10 fish per 

rep. 

Mean-measured: 

negative control 

(<LOQ = 0.28 mg 

a.i./L), 2.8 mg 

a.i./L 

96-hr LC50 > 2.8 mg a.i./L 

NOAEC ≥ 2.8 mg a.i./L 

Endpoint(s) affected: None. 

Sublethal effects: None. 

47701627 Acceptable 

At most 

moderately toxic1

1

Based on LC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic 

2 Bold values used in risk description

Freshwater Invertebrates -Technical

The freshwater invertebrate study using the technical grade active ingredient on water 

flea (Daphnia magna, MRID 47701623) is classified as an acceptable limit test. As the 

endpoints are non-definitive, they are not useful for RQ calculations, but can contribute 

to risk description. 

Freshwater Invertebrates –Metabolites / Degradates 

There are no acute data on metabolites/degradates for freshwater invertebrates. 

Freshwater Invertebrates –Formulations 

There are no acute data on formulations for freshwater invertebrates. Based on the 

proposed use pattern, aquatic EECs and lack of toxicity to freshwater invertebrates at the 

limit of solubility, toxicity data on formulations (Technical End Use Products) would not 

be required. 
53

Table 21. Freshwater Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters EC50/NOAEC/LOAEC MRID Classification

/ 

Category

Technical KIH-485

Water flea 

Daphnia 

magna

Not 

provided 

(possibly 

≥ 98.1% 

w/w) 

48 hour static study 

(limit test) 

4 reps per test group, 2 

reps per control group; 10 

invertebrates per rep 

Mean-measured: 

Negative control (<LOQ 

= 0.000022 mg a.i./L), 

4.43

 mg a.i./L 

48-hr EC50 > 4.42

 mg a.i./L 

48-hr NOAEC ≥ 4.4 mg a.i./L 

Endpoint(s) affected: None. 

Endpoint(s) considered: 

immobility, adverse reactions 

Sublethal effects: None. 

47701623 Acceptable 

At most, 

Moderately 

toxic1

1

Based on EC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic 

2 Bold values used in risk description 3

 On account of this test compound being poorly soluble, the test was conducted at the solubility limit for the compound using 

the column elution method to achieve saturation. 

Marine/Estuarine Fish – Technical 

A definitive marine/estuarine fish study using the technical grade active ingredient on 

sheepshead minnow Cyprinodon variegatus (MRID 47701628) is classified as 

acceptable. The NOAEC ≥ 3.3 mg a.i./L and the EC50 > 3.3 mg a.i./L because no 

treatment related effects were observed at the highest test concentration. As the endpoints 

are non-definitive, they are not useful for RQ calculations, but can contribute to risk 

description.

Marine/Estuarine Fish – Metabolites/Degradates 

There are no acute data on metabolites/degradates for marine/estuarine fish. 

Marine/Estuarine Fish – Formulations 

There are no acute data on formulations for marine/estuarine fish. Based on the proposed 

use pattern, aquatic EECs and lack of toxicity to marine/estuarine fish at the limit of 

solubility, toxicity data on formulations (Technical End Use Products) would not be 

required. 
54

Table 22. Marine/ Estuarine Fish Acute Toxicity Data 

Common Name %AI Study parameters LC50/NOAEC/LOAEC MRID Classification/ 

Category

Technical KIH-485 

Sheepshead 

Minnow 

Cyprinodon 

variegatus

99.1 96-hour flow-through 

study 

2 reps; 10 fish per 

rep.; 20 fish per test 

concentration 

Mean-measured: 

Negative control 

(<LOQ = 0.1 mg 

a.i./L), DMF, 0.29, 

0.59, 1.2, 2.0, and 3.3 

mg a.i./L 

96-hr LC50 > 3.32 mg a.i./L 

96-hr NOAEC ≥ 3.3 mg a.i./L 

Endpoint(s) affected: None. 

Endpoint(s) considered: 

mortality. 

Sublethal effects: None. 

47701628 Acceptable/ 

At most, 

moderately toxic1

1

Based on LC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic 

2 Bold values used in risk description

Marine/Estuarine Invertebrates – Technical 

A definitive marine/estuarine invertebrate study using the technical grade active 

ingredient on eastern oyster Crassostrea virginica (MRID 47701624) is classified as 

acceptable. The NOAEC ≥ 3.6 mg a.i./L and the EC50 > 3.6 mg a.i./L because no 

treatment related effects were observed at the highest test concentration. As the endpoints 

are non-definitive, they are not useful for RQ calculations, but can contribute to risk 

description. However, only one replicate was used per treatment and in each control. 

Guidance recommends a minimum of two replicates of 10 oysters in each replicate for a 

total of 20 oysters per treatment and in each control. An EC50 and NOAEC are not 

calculable since linear regression indicates no dose-response and estimation of any 

parameter using this method would likely be an under-estimation (i.e., less protective or 

conservative estimate) of true sensitivity. 

The marine/estuarine invertebrate study using the technical grade active ingredient on 

saltwater mysid Americamysis bahia (MRID 47701625) is classified as supplemental 

because results of a range-finding test which would determine the most sensitive age for 

testing was not reported. Nevertheless, juveniles (28-45 hours old) were used for testing. 

Current guidance suggests using juveniles <24 hours old or young adults 5-6 days old, 

depending on range-finding test results. Juveniles used in this test yielded a NOAEC ≥

1.4 mg a.i./L and an LC50 >1.4 mg a.i./L. As the endpoints are non-definitive, they are 

not useful for RQ calculations, but can contribute to risk description. 
55

Marine/Estuarine Invertebrates – Metabolites/Degradates 

There are no acute data on metabolites/degradates for marine/estuarine invertebrates. 

Marine/Estuarine Invertebrates – Formulations 

There are no acute data on formulations for marine/estuarine invertebrates. Based on the 

proposed use pattern, aquatic EECs and lack of toxicity to marine/estuarine invertebrates 

at the limit of solubility, acute toxicity data on formulations (Technical End Use 

Products) would not be required. 

Table 23. Marine/ Estuarine Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters EC50/LC50/NOAEC/LOAEC MRID Classification/ 

Category

Technical KIH-485

Eastern oyster 

Crassostrea 

virginica 

99.1 96 hour flow-through 

study 

20 bivalves per level 

(1 replicate)* 

Mean-measured: 

negative control 

(<LOQ = 0.1 mg 

a.i./L), DMF, 0.30, 

0.60, 1.2, 2.1, and 

3.63

 mg ai/L 

*

 Guidance recommends a 

minimum of two replicates 

of 10 oysters in each 

replicate for a total of 20 

oysters per treatment and 

in each control. An EC50

and NOAEC are 

effectively not calculable 

since linear regression 

indicates no dose-response 

and estimation of any 

parameter using this 

method would likely be an 

under-estimation (i.e., less 

protective or conservative 

estimate) of true 

sensitivity.

96-hr EC50 > 3.6 mg a.i./L 

NOAEC ≥ 3.6 mg a.i./L 

Endpoint(s) affected: None. 

Endpoints considered: mortality, 

shell deposition (at 96 hours) 

Sublethal effects: None. 

47701624 Acceptable / 

At most, 

moderately 

toxic1 
56

Table 23. Marine/ Estuarine Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters EC50/LC50/NOAEC/LOAEC MRID Classification/ 

Category

Saltwater 

mysid 

Americamysis 

bahia 

99.1 96 hour flow-through 

study 

2 reps.;10 mysids per 

rep.; 20 mysids per 

treatment 

Mean-measured: 

negative control 

(<LOQ = 0.05 mg 

a.i./L), DMF, 0.083, 

0.17, 0.34, 0.68, and 

1.4 mg ai/L 

96-hr LC50 > 1.42

 mg a.i./L

NOAEC ≥ 1.4 mg a.i./L 

Endpoint(s) affected: None. 

Endpoint(s) considered: mortality 

Mortality

One mortality was observed in the 

0.083 mg a.i./L mean-measured 

treatment group, but was not 

dose-responsive and so was not 

considered to be treatment 

related. 

Sublethal effects: None. 

47701625 Supplemental / 

At most, 

moderately 

toxic1

1

Based on EC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic 

2 Bold values used in risk description 3

 Apparent solubility limit in saltwater was not reported. Stated to be the highest concentration tested. On account of this test 

compound being poorly soluble, precipitate was observed in the 2.5 and 5.0 mg a.i./L treatment group test chambers. As a 

result, analytical methodology included centrifugation of samples per Guideline 850.1000. 

(2) Chronic Effects 

Freshwater Fish and Aquatic-Phase Amphibians – Technical 

The early life-cycle freshwater fish study on fathead minnow (Pimephales promelas, 

MRID 47701630) is classified as acceptable. The growth endpoints (wet weight and 

length) of surviving fish (which were used in the study since <24 hours old) at the end of 

the exposure period (28-days) indicated statistically significant reductions (Dunnett’s test, 

p = 0.05) in the highest test concentration leading to a NOAEC of 2.0 mg a.i./L and 

LOAEC of 3.9 mg a.i./L. The growth endpoint for dry weight of surviving fish did not 

show statistically significant reductions at any level. 

Hatching occurred at all levels on Days 4 and 5. Hatching success was 98% in the 

negative and solvent control groups and was at 99-100% for all treatment levels, with no 

statistically significant differences observed. Post-hatch survival (28-days post-hatch) in 

both the negative and solvent controls was 90% at test termination. Larval survival in the 

mean-measured test concentrations 0.30, 0.58, 1.2, 2.0, and 3.9 mg a.i./L was 93, 76, 89, 

91, and 89%, respectively. The 14% reduction observed in the 0.58 mg a.i./L mean 

measured test concentration (from the negative control with 90% survival) was 

statistically significantly different (Dunnett’s test, p = 0.05; MSD3

 value of 9.1%) relative 

 

3

 MSD = minimum significant difference 
57

to the negative control, but was not considered treatment related as higher concentrations 

did not exhibit similar or increasing effects to the test compound. 

Most organisms appeared normal in the control and treatment groups. Weakness, small 

size, and a curled/crooked spine were also observed; the frequency of occurrence of 

abnormalities in the treatment groups did not appear to differ greatly from the controls. 

Freshwater Fish and Aquatic-Phase Amphibians –Metabolites / Degradates 

There are no chronic data on metabolites/degradates for freshwater fish and aquaticphase amphibians. 

Freshwater Fish and Aquatic-Phase Amphibians –Formulations 

There are no chronic data on formulations for freshwater fish and aquatic- phase 

amphibians, as these data are not required. 

Table 24. Freshwater Fish Chronic Toxicity Data 

Common Name %AI Study parameters NOAEC/LOAEC MRID Classification

/Category

Technical KIH-485 

Fathead minnow 

Pimephales 

promelas 

99.1 28-day flow-through 

early life-stage test 

80 embryos per level, 

split into 20 embryos 

per cup, 1 cup per 

aquarium, 4 rep. 

aquaria per treatment 

Mean-measured: 

Negative control 

(<LOQ = 0.10 mg 

a.i./L), DMF control, 

0.30, 0.58, 1.2, 2.0, and 

3.92

 mg a.i./L

28-day NOAEC: 2.01

 mg a.i./L

28-day LOAEC: 3.9 mg a.i./L 

Most sensitive endpoint: wet 

weight, length 

Additional endpoints affected: 

A significant reduction in percent 

survival relative to the controls 

was observed in the 0.58 mg a.i./L 

mean measured concentration, but 

was not considered treatment 

related as higher concentrations 

did not exhibit similar or 

increasing effects to the test 

compound. 

Sublethal effects: 

Most organisms appeared normal 

in the control and treatment 

groups. Weakness, small size, and 

a curled/crooked spine were also 

observed; the frequency of 

occurrence of abnormalities in the 

treatment groups did not appear to 

differ greatly from the controls. 

47701630 Acceptable 

1

Bold used in risk quotient calculations 

2

 Reported solubility limit in freshwater: < 5.0 mg a.i./L (likely approximates the highest mean-measured concentration tested 

~3.9 mg a.i./L) 
58

Freshwater Invertebrates – Technical 

A chronic freshwater invertebrate study (MRID 47701629) with pyroxasulfone technical 

(99.1%) is classified as acceptable. Statistically analyzed endpoints (Dunnett’s test, 

p>0.05) including first-generation Daphnid survival, reproduction (number of live young 

produced per reproductive day), and growth (length and dry weight at day 21), indicated 

no statistically significant difference from pooled control, negative control, and solvent 

control. As the endpoints are non-definitive, they are not useful for RQ calculations, but 

can contribute to risk description. 

Freshwater Invertebrates –Metabolites / Degradates 

There are no chronic data on metabolites/degradates for freshwater invertebrates. 

Freshwater Invertebrates –Formulations 

There are no chronic data on formulations for freshwater invertebrates, as these data are 

not required. 

Table 25. Freshwater Invertebrate Chronic Toxicity Data 

Common Name %AI Study parameters NOAEC/LOAEC MRID Classification

/Category

Technical KIH-485 

Water flea 

Daphnia magna 

99.1 21-day flow-through 

test 

2 reps. per treatment 

and control group; 10 

Daphnids per rep; 20 

Daphnids per treatment 

Mean-measured: 

Negative control 

(<LOQ = 0.03 mg 

a.i./L), DMF control, 

0.05, 0.13, 0.30, 0.77, 

and 1.9 mg a.i./L 

NOAEC ≥ 1.91

 mg a.i./L

LOAEC > 1.9 mg a.i./L 

Endpoint(s) affected: None. 

Endpoint(s) considered: 1st

generation survival, reproduction 

(number of live young produced 

per reproductive day), and growth 

Sublethal effects: Discoloration 

(pale), injury, and lethargy were 

infrequent, comparable to controls, 

and not considered treatment 

related. 

47701629 Acceptable 

1 Bold value used in risk description. 

Marine/Estuarine Fish 

No chronic marine/estuarine fish studies were submitted for review. 

Marine/Estuarine Invertebrates

No chronic marine/estuarine invertebrate studies were submitted for review. 
59

b. Aquatic Plants 

Vascular Aquatic Plants - Technical 

The vascular aquatic plant study (MRID 47701640) on duckweed (Lemna gibba) is 

classified as supplemental because of a major guideline deviation. A small amount of test 

material (0.0405 g a.i./L) was detected in the solvent control at test initiation, which is 

slightly above the limit of quantitation (0.0255 g a.i./L); none was detected at test 

termination. Contamination of controls with the test substance is reason to question the 

validity of the study (per OPPTS 850.4400). However, there were no statistically 

significant differences between the negative and solvent control groups when compared 

using a two-tailed Student’s t-test (p=0.05). In addition, EFED guidance indicates that 

statistically significant differences be determined between only the negative control and 

the treatment groups, which implies that endpoint calculations would not be affected as a 

result. Indeed, endpoint calculations indicate that statistically significant effects (relative 

to the negative control) were observed at concentrations just beyond the lowest level 

tested (i.e., 7-day NOAEC = 0.18 g a.i./L based on frond count). In addition, the 7-day 

EC50 is 6.0 g a.i./L based on frond count. 

Vascular Aquatic Plants – Metabolites/ Degradates 

The two metabolite vascular aquatic plant studies (MRID 47701641 on M-1; and, MRID 

47701642 on M-3) on duckweed (Lemna gibba) are classified as acceptable. Statistically 

significant growth inhibition was not detected at any test level relative to the negative 

control for either study leading to a 7-day NOAEC of ≥123 mg a.i./L and 7-day EC50 of 

>123 mg a.i./L. As the endpoints are non-definitive, they are not useful for RQ 

calculations, but can contribute to risk description. 

Vascular Aquatic Plants – Formulations 

There are no data on formulations for vascular aquatic plants, as these data are not 

required. 

Non-vascular Aquatic Plants - Technical 

The non-vascular aquatic plant study on freshwater green algae Pseudokirchneriella 

subcapitata (MRID 47701643) is classified as supplemental (but upgradable) on account 

of high variability in analytic recovery of test samples, which were attributed to 

chromatographic interference. As a result, nominal concentrations were used to determine 

the endpoints (96-hour EC50 0.00038 mg a.i./L based on cell density; 96-hour NOAEC 

0.00005 mg a.i./L based on biomass). If raw laboratory results for the quantities and 

volumes used to make up the solutions are provided (i.e., information beyond the study 

Appendix I ‘Verification of Test Concentrations’ where it is indicated that the presence 

of algae significantly affected the test chemical recovery), then the study can be 

upgraded. The raw data would serve as a record to confirm the expected nominal 

concentrations in addition to analytical results at levels above where interference affects 

analytical detection. In addition, random assignment of treatments and test vessels were 

not reported in the test protocol; this information would also be required for the study to 

be upgradable. 
60

The non-vascular aquatic plant study on freshwater blue-green algae/cyanobacteria 

Anabaena flos-aquae (MRID 47701644) is classified as acceptable. All three endpoints 

(cell density, biomass, and growth rate) yielded a 96-hour EC50 >3.5 mg a.i./L (as this 

endpoint is non-definitive, it is not useful for RQ calculations, but can contribute to risk 

description); cell density and growth rate yielded NOAECs of 0.16 mg a.i./L and biomass 

yielded a NOAEC of 1.6 mg a.i./L. 

Similarly, the non-vascular aquatic plant study on freshwater diatom Navicula pelliculosa

(MRID 47701645) is classified as acceptable. All three endpoints (cell density, biomass, 

and growth rate) yielded a 96-hour EC50 > 3.2 mg a.i./L and NOAEC ≥ 3.2 mg a.i./L. As 

the endpoints are non-definitive, they are not useful for RQ calculations, but can 

contribute to risk description. 

The non-vascular aquatic plant study on marine diatom Skeletonema costatum (MRID 

47701646) is classified as supplemental. The reason being that after 96 hours, the 

increase in cell density was approximately 14 times, resulting in a cell density of ~ 1.1 × 

106 cells/mL in the controls. This is slightly less than the OPPTS 850.5400 guideline 

requirement that cell density should reach 1.5 × 106

 cells/mL at 96 hours to demonstrate 

logarithmic growth. Although the guideline requirement was not met, the final cell 

density was only marginally below that required and inhibition of algal growth was 

demonstrated during the exposure to pyroxasulfone. However, due to the growth in the 

controls not being fully exponential some uncertainty exists to the accuracy of the results 

obtained. All three endpoints (cell density, biomass, growth rate) yielded a NOAEC of 

0.14 mg a.i./L; the most sensitive endpoint on the basis of EC50 (= 0.66 mg a.i./L) is cell 

density. 

Non-vascular Aquatic Plants – Metabolites / Degradates 

The non-vascular aquatic plant study on freshwater green algae Pseudokirchneriella 

subcapitata (MRID 47701647) with metabolite M-1 (97.54% a.i.) is classified as 

supplemental on account of pH values that deviated from guideline recommendations and 

neutral levels. More specifically, the pH values were above and below the guideline 

recommended value (7.5 ± 0.1) for P. subcapitata. The values were higher at test 

termination (8.0-8.1) than they were at test initiation (6.1-7.8) for the control and all 

concentrations except the highest concentration, which had the lowest pH values (3.8, 

3.9) for the two observation times. All three endpoints (cell density, biomass, growth 

rate) yielded a NOAEC of 31 mg a.i./L; the most sensitive endpoint on the basis of EC50

(= 56 mg a.i./L) is cell density. 

Similarly, the non-vascular aquatic plant study on freshwater green algae 

Pseudokirchneriella subcapitata (MRID 47701648) with metabolite M-3 (99.6 % a.i.) is 

classified as supplemental on account of pH values that deviated from guideline 

recommendations and neutral levels. More specifically, the pH values were above and 

below the guideline recommended value (7.5 ± 0.1) for P. subcapitata. The values were 

higher at test termination (8.5-8.9) than they were at test initiation (6.9-7.4) for the 

control and all concentrations except the two highest concentrations, which had the 

lowest pH values (4.9, 6.5 for 61 mg a.i/L; 3.6, 4.2 for 123 mg a.i./L) for the two 
61

observation times (initiation, termination, respectively). All three endpoints (cell density, 

biomass, growth rate) yielded a NOAEC of 15 mg a.i./L; the most sensitive endpoint on 

the basis of EC50 (= 38 mg a.i./L) is cell density. 

Non-vascular Aquatic Plants – Formulations 

There are no data on formulations for non-vascular aquatic plants, as these data are not 

required. 

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Technical KIH-485 

Vascular Aquatic Plants 

Duckweed 

Lemna gibba G3 

98.1 Tier II study 

7 day static study 

3 reps. / 4 plants (12 

fronds) per rep. 

Mean measured: 

Negative control 

(<LOQ = 0.0255 g 

a.i./L), DMF control, 

0.075, 0.18, 0.43, 1.0, 

2.3, 5.2, 12, 27 g a.i./L 

Frond count 

7-day EC50 : 6.01

 (4.9-7.3) g 

a.i./L 

7-day NOAEC: 0.183 g a.i./L 

Biomass 

7-day EC50 : 9.0 (6.5-13) g 

a.i./L 

7-day NOAEC: 0.43 g a.i./L 

Growth rate (based on frond 

number) 

7-day EC50 : 16 (15-17) g 

a.i./L 

7-day NOAEC: 1.0 g a.i./L 

Most sensitive endpoint: frond 

count based on EC50 and 

NOAEC 

Endpoint(s) affected: 

frond count, biomass, growth 

rate (based on frond number) 

Sublethal effects: 

Root destruction and curled 

fronds were noted in the 2.3 

g a.i./L treatment level, 

while root destruction, curled 

fronds, and small fronds were 

noted in the 5.2, 12, and 27 g 

a.i./L treatment levels. A 

marked increase in chlorotic 

and necrotic fronds were 

noted in the 5.2, 12, and 27 g 

a.i./L test levels. Appearance 

of chlorotic and necrotic 

plants increased over the 

duration of the study.

47701640 Supplemental 

Metabolites/ Degradates 
62

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Vascular Aquatic Plants 

Duckweed 

Lemna gibba G3 

97.54% 

M-1 

Tier II study 

7 day static renewal 

study 

3 reps. / 4 plants (12 

fronds) per rep. 

Mean measured: 

Negative control 

(<LOQ = 4.0 mg a.i./L), 

7.7, 16, 31, 61, and 123 

mg a.i./L 

Frond count, biomass, growth 

rate (based on frond number 

and biomass): 

7-day EC50 > 1232

 mg a.i./L 

7-day NOAEC ≥ 123 mg a.i./L 

Endpoint(s) affected: None. 

(Sub)lethal effects: 

Duckweed plants in each 

control replicate exhibited 

normal growth throughout the 

test. After 7 days of exposure, 

the percent of chlorotic fronds 

observed on the plants in the 

negative control and the 31 

and 61 mg a.i./L treatment 

groups was 0.51, 0.43, and 

0.22% of the total number of 

fronds, respectively. The 

percent of necrotic fronds in 

the 7.7, 31, 61, and 123 mg 

a.i./L was 0.58, 0.47, 0.22, and 

0.20% of the total fronds, 

respectively. Mortality in the 

7.7, 61, and 123 mg a.i./L was 

0.22, 0.23, and 0.38% of the 

total fronds, respectively. The 

percentage of dead, chlorotic, 

and necrotic fronds increased 

over the duration of the study. 

47701641 Acceptable 
63

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Duckweed 

Lemna gibba G3 

99.6% 

M-3 

Tier II study 

7 day static renewal 

study 

3 reps. / 4 plants (12 

fronds) per rep. 

Mean measured: 

Negative control 

(<LOQ = 4.0 mg a.i./L), 

7.6, 16, 31, 60, and 123 

mg a.i./L 

Frond count, biomass, growth 

rate (based on frond number 

and biomass): 

7-day EC50 > 1232

 mg a.i./L 

7-day NOAEC ≥ 123 mg a.i./L 

Endpoint(s) affected: None. 

(Sub)lethal effects: 

Duckweed plants in each 

control replicate exhibited 

normal growth throughout the 

test. After 7 days of exposure, 

the percent of chlorotic fronds 

observed on the plants in the 

negative control and the 7.6, 

16, 31, and 123 mg a.i./L 

treatment groups was 0.16, 

0.18, 0.19, 0.34, and 0.39% of 

the total number of fronds, 

respectively. The percent of 

necrotic fronds in the negative 

control and the 7.6, 16, 31, 60 

mg a.i./L treatment groups 

was 0.16, 0.54, 0.58, 0.17, and 

0.77% of the total fronds, 

respectively. Dead fronds were 

observed only in the 123 mg 

a.i./L treatment group (on day 

7 only) with the percent 

mortality of 0.19% of the total 

fronds. Chlorosis and necrosis 

was observed by day 5; the 

percentage observed with 

these characteristics increased 

by day 7. 

47701642 Acceptable 

Technical KIH-485 

Non-Vascular Aquatic Plants 
64

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Freshwater Green 

Algae 

Pseudokirchneriella 

subcapitata 

99.1 Tier II study 

96-hour static study 

3 reps. 

Nominal 

concentrations*: 

negative control (<LOQ 

= 0.000022 mg a.i./L), 

0.00005, 0.0001, 

0.0002, 0.0004, and 

0.0008 mg a.i./L 

*Mean measured 

concentrations were 

highly variable; 

justified by study 

authors as resulting 

from chromatographic 

interference 

Cell density: 

96-hr EC50: 0.000381

(0.00035-0.00041) mg a.i./L 

96-hr NOAEC: 0.00013

 mg 

a.i./L 

Biomass: 

96-hr EC50 > 0.0008 mg a.i./L 

96-hr NOAEC: 0.00005 mg 

a.i./L 

Growth rate 

96-hr EC50: 0.00077 (0.00073-

0.00082) mg a.i./L 

96-hr NOAEC: 0.0002 mg 

a.i./L 

Most sensitive endpoint: 

Cell density (EC50), biomass 

(NOAEC) 

Endpoint(s) affected: cell 

density, biomass, growth rate 

Sublethal effects: 

There were no abnormalities 

detected in any of the control 

or test cultures. 

47701643 Supplemental 

(but 

upgradable) 
65

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Freshwater Bluegreen algae 

Anabaena flos-aquae

98.1 Tier II study 

96-hour static study 

3 reps. 

Mean-measured: 

Negative control 

(<LOQ = 0.102 mg 

a.i./L), DMF, 0.16, 

0.35, 0.80, 1.6, and 3.5 

mg a.i./L 

Cell density: 

96-hr EC50 >3.5 mg a.i./L 

96-hr NOAEC: 0.16 mg a.i./L 

Growth rate 

96-hr EC50 > 3.5 mg a.i./L 

96-hr NOAEC: 0.16 mg a.i./L 

Biomass: 

96-hr EC50 > 3.5 mg a.i./L 

96-hr NOAEC: 1.6 mg a.i./L 

Most sensitive endpoint: 

Cell density and growth rate 

(on the basis of the NOAEC) 

Endpoint(s) affected: cell 

density, growth rate, biomass 

Sublethal effects: 

Cell aggregation and long 

chains were observed in all 

treatment levels and controls. 

47701644 Acceptable 

Freshwater Diatom 

Navicula pelliculosa

98.1 Tier II study 

96-hour static study 

4 reps. 

Mean measured: 

Negative control 

(<LOQ = 0.204 mg 

a.i./L), DMF, 0.23, 

0.47, 0.97, 1.8, and 3.2 

mg a.i./L 

Cell density, biomass, growth 

rate: 

96-hour EC50 > 3.2 mg a.i./L 

96-hour NOAEC ≥ 3.2 mg 

a.i./L 

Endpoint(s) affected: None. 

Sublethal effects: 

Cell aggregation was 

observed in all treatment 

levels and controls. 

47701645 Acceptable 
66

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Marine Diatom 

Skeletonema 

costatum 

98.1 Tier II study 

96-hour static study 

3 reps. 

Mean measured: 

negative control (<LOQ 

= 0.0102 mg a.i./L), 

DMF, 0.013, 0.029, 

0.063, 0.14, 0.30, 0.68, 

1.4, and 2.9 mg/L 

Cell density: 

96-hr EC50: 0.66 (0.4-1.1) mg 

a.i./L 

96-hr NOAEC: 0.14 mg a.i./L 

Biomass: 

96-hr EC50 > 2.9 mg a.i./L 

96-hr NOAEC: 0.14 mg a.i./L 

Growth rate 

96-hr EC50 > 2.9 mg a.i./L 

96-hr NOAEC: 0.14 mg a.i./L 

Most sensitive endpoint: 

Cell density (based on EC50) 

Endpoint(s) affected: cell 

density, biomass, growth rate 

Sublethal effects:

There was evidence of cell 

aggregation in all treatment 

levels without significant 

growth inhibition including 

the controls. Because 

aggregation is typically 

observed with higher cell 

density, this observation was 

not considered to be a 

treatment related effect. 

47701646 Supplemental 

Metabolites / Degradates 

Non-Vascular Aquatic Plants 
67

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC50/NOAEC MRID 

No. 

Study 

Classification

Freshwater Green 

Algae 

Pseudokirchneriella 

subcapitata 

97.54 

M-1 

Tier II study 

96 hour static study 

3 reps 

Mean-measured: 

Negative control 

(<LOQ = 4.0 mg a.i./L), 

7.9, 16, 31, 61, and 122 

mg a.i./L 

Cell density 

EC50: 561

 (47-67) mg a.i./L 

NOAEC: 313

 mg a.i./L 

Growth rate 

EC50: 78 (68-89) mg a.i./L 

NOAEC: 31 mg a.i./L 

Biomass 

EC50 > 120 mg a.i./L 

NOAEC: 31 mg a.i./L 

Most sensitive endpoint: 

cell density 

Endpoint(s) affected: cell 

density, growth rate, biomass 

Sublethal effects: 

None. 

47701647 Supplemental 

Freshwater Green 

Algae 

Pseudokirchneriella 

subcapitata

99.6 

M-3 

Tier II study 

96-hour static study 

3 reps. 

Mean-measured: 

Negative control 

(<LOQ = 4.0 mg a.i./L), 

7.0, 15, 32, 61, and 123 

mg a.i./L 

Cell density 

EC50: 381 (2.2-670) mg a.i./L 

NOAEC: 153

 mg a.i./L 

Growth rate 

EC50: 40 (3.6x 10-21 – 4.4x1023) 

mg a.i./L 

NOAEC: 15 mg a.i./L 

Biomass 

EC50 > 120 mg a.i./L 

NOAEC: 15 mg a.i./L 

Most sensitive endpoint: 

cell density 

Endpoint(s) affected: cell 

density, growth rate, biomass 

Sublethal effects: 

None. 

47701648 Supplemental 

1

Bold value used in risk quotient calculation for non-listed plant species whereby RQ = EEC/EC50 2

Bold value used in risk description for non-listed (EC50 value) and listed (NOAEC value) plant species 3

Bold value used in risk quotient calculation for listed plant species whereby RQ = EEC/NOAEC 
68

Non-vascular Aquatic Plants (Non-guideline study) – Technical 

The non-vascular aquatic plant study on freshwater green algae Pseudokirchneriella 

subcapitata (MRID 47701751) on technical grade pyroxasulfone (99.1% a.i.) is classified 

as supplemental given it is a non-guideline study. In addition, a negative (untreated) 

control was not included in the study; only a solvent control was used for comparison 

with a single test treatment concentration. It is also unclear from the study protocol why a 

test concentration (nominal) of 2 g a.i./L was used in the study. The study was intended 

to assess the recovery potential of the green algae after a 72-hour exposure period. 

According to the study authors and primary reviewer (APVMA) re-calculations of 

growth rate the effect of pyroxasulfone on green algae (P. subcapitata) was algistatic 

rather than algicidal at the tested concentration (2.13 g a.i./L). 

Table 27. Aquatic Plant Toxicity Data: Non-guideline studies

Species %A.I. Study Parameters Endpoint MRID 

No. 

Study 

Classification

Technical KIH-485 

Non-vascular Aquatic Plants 

Freshwater green 

algae 

Pseudokirchneriella 

subcapitata 

99.1 Algicidal vs. algistatic 

effects static study 

72-hour exposure 

phase; 144-hour 

recovery phase 

3 reps. 

Mean measured: 

DMF, 2.13 g a.i./L 

% Inhibition of growth rate: 

51.4% during exposure phase

47701751 Supplemental 

2. Terrestrial Effects Characterization 

a. Terrestrial Animals 

(1) Acute Effects 

Birds – Technical 

The acute avian oral studies (MRID 47701631, 47701632) on 23-week old Northern 

bobwhite quail (Colinus virginianus) and zebra finch (Poephila guttata) of unspecified 

age, respectively, assessed over 14 days are classified as acceptable. KIH-485 Technical 

was administered to the birds via gavage (single dose of test substance in corn oil orally 

intubated into the crop or proventriculus of the bird) at nominal levels of 0 (negative 

control), 292, 486, 810, 1350, and 2250 mg a.i./kg-bw for the bobwhite study and only 0 

(negative control) and 2250 mg a.i./kg-bw for the zebra finch (a limit test). The 14-day 
69

acute oral LD50 from both studies was >2250 mg ai/kg bw; similarly, the 14-day NOAEL 

≥2250 mg ai/kg bw. As the endpoints are non-definitive, they are not useful for RQ 

calculations, but can contribute to risk description. The quail study indicated no 

mortalities, overt signs of toxicity, or treatment-related effects on body weight or food 

consumption at the dosage levels tested. The finch study indicated no mortalities or overt 

signs of toxicity in the single treatment group tested, there were no apparent treatmentrelated effects upon body weight, and the estimated food consumption over the duration 

of the study was not reported. KIH-485 Technical (pyroxasulfone) would be classified as 

practically non-toxic to young adult Northern bobwhite quail (C. virginianus) as well as 

to zebra finch (P. guttata) of unspecified age in accordance with the classification system 

of the U.S. EPA. 

The acute avian dietary studies (MRID 47701633, 47701634) on 10-day old Northern 

bobwhite quail (Colinus virginianus) and 9-day old mallard duck (Anas platyrhynchos), 

respectively, assessed over 8 days are classified as acceptable. KIH-485 Technical was 

administered to the birds in the diet at nominal concentrations of 0 (negative control), 

562, 1000, 1780, 3160, and 5620 mg a.i./kg-diet. The 8-day acute dietary LC50 is >5620 

mg a.i./kg diet and the 8-day NOAEC is ≥ 5620 mg a.i./kg-diet for the quail study. As the 

endpoints are non-definitive, they are not useful for RQ calculations, but can contribute 

to risk description. The quail study indicated no mortalities, overt signs of toxicity, or 

treatment-related effects on body weight or food consumption at the dosage levels tested. 

The 8-day acute dietary LC50 is also >5620 mg a.i./kg diet for the duck study. However, 

relative to the control, the highest two treatment groups 3160 and 5620 mg a.i./kg-diet 

had a reduced increase in body weight that was significantly different from the control 

(based on Bonferroni T-test results using TOXSTAT v3.0). The reductions in body 

weight increase led to a determination of an 8-day NOAEC of 1780 mg a.i./kg-diet for 

the duck study. This NOAEC is based on the total change in body weight from day 0 to 

day 8. The APVMA primary reviewer calculated the 5-day NOAEC instead and 

determined it to be 1000 mg a.i./kg-diet. The use of one or the other will depend on 

physico-chemical properties and use of pyroxasulfone. For example, if pyroxasulfone is 

short lived and used infrequently then the 0-8 day value would be more applicable; 

however, if the chemical is more stable and/or used frequently then an interest in 

transient weight loss during exposure would vindicate the use of the 0-5 day value as 

exposure in the field would be expected to be higher longer. Given the stability of 

pyroxasulfone the latter statement and the 1000 mg a.i./kg-diet value would apply. The 

duck study indicated no mortalities, overt signs of toxicity, or treatment-related effects on 

food consumption at the dosage levels tested. 

Bird – Metabolites/Degradates 

There are no acute data on metabolites/degradates for birds. 

Bird – Formulations 

There are no acute data on formulations for birds, as these data are not required. 
70

Table 28. Avian Acute Toxicity Data 

Common Name %AI Study parameters LD50/LC50 NOAEL/ 

LOAEL

MRID Classification

/Category

Technical KIH-485

Northern 

Bobwhite Quail 

Colinus 

virginianus

99.1 Acute oral study 

1 replicate of 5♂ and 5♀ birds 

per treatment group and 

control (10 birds/treatment 

and control; 2 pens per 

treatment and control group 

with 5 birds of one sex per 

pen) 

14 day observation period 

Nominal: negative control, 

292, 486, 810, 1350, and 2250 

mg a.i./kg-bw

14-day LD50 > 22503

 mg 

a.i./kg bw 

14-day NOAEL ≥ 2250 mg 

a.i./kg bw 

Endpoint(s) affected: None. 

Sublethal effects: None. 

47701631 Acceptable/ 

Practically 

non-toxic1 

Zebra finch 

Poephila guttata

98.82 Acute oral study (limit test) 

1 replicate of 5♂ and 5♀ birds 

per treatment group and 

control (10 birds/treatment 

and control); birds were 

housed in pairs 

14 day observation period 

Nominal: negative control, 

2250 mg a.i./kg-bw 

14-day LD50 > 2250 mg 

a.i./kg bw 

14-day NOAEL ≥ 2250 mg 

a.i./kg bw 

Endpoint(s) affected: None. 

Sublethal effects: None. 

47701632 Acceptable/ 

Practically 

non-toxic1
71

Table 28. Avian Acute Toxicity Data 

Common Name %AI Study parameters LD50/LC50 NOAEL/ 

LOAEL

MRID Classification

/Category

Northern 

Bobwhite Quail 

Colinus 

virginianus

99.1 Acute dietary study 

3 in control (30 birds total; 6 

pens with 5 birds/pen); 1 in 

treatment (10 birds/treatment; 

2 pens with 5 birds of 

undetermined sex/pen) 

5-day exposure period, 3 

additional days observation 

with untreated basal diet 

Nominal: negative control, 

562, 1000, 1780, 3160, and 

5620 mg a.i./kg-diet 

8-day LC50 >56203

 mg a.i./kg 

diet 

8-day NOAEC ≥ 5620 mg 

a.i./kg diet 

Endpoint(s) affected: None. 

Sublethal effects: A couple of 

control birds were observed 

with leg lesions and were 

limping. Similarly, one bird 

in each of the 1780 mg a.i./L 

and 5620 mg a.i./L treatment 

groups was observed limping. 

The bird in the 5620 mg a.i./L 

treatment group also 

exhibited wing droop. Likely 

due to pen-mate aggression 

and not treatment related. 

47701633 Acceptable/ 

Practically 

non-toxic2 

Mallard Duck 

Anas 

platyrhynchos

99.1 Acute dietary study 

3 in control (30 birds total; 6 

pens with 5 birds/pen); 1 in 

treatment (10 birds/treatment; 

2 pens with 5 birds of 

undetermined sex/pen) 

5-day exposure period, 3 

additional days observation 

with untreated basal diet 

Nominal: negative control, 

562, 1000, 1780, 3160, and 

5620 mg a.i./kg-diet 

8-day LC50 > 5620 mg a.i./kg 

diet

8-day NOAEC: 1780 mg 

a.i./kg diet* 

Endpoint(s) affected: body 

weight increase 

Sublethal effects: change in 

body weight. 

*NOAEC is based on the total 

change in body weight from day 0 to 

day 8. The APVMA primary reviewer 

calculated the 5-day NOAEC as 1000 

mg a.i./kg-diet. The use of one or the 

other will depend on physicochemical properties and use of 

pyroxasulfone: if short lived and 

used infrequently then the 0-8 day 

value would be more applicable; 

however, if the chemical is more 

stable and/or used frequently then an 

interest in transient weight loss 

during exposure would vindicate the 

use of the 0-5 day value as exposure 

in the field would be expected to be 

higher longer. 

47701634 Acceptable/ 

Practically 

non-toxic2 
72

Table 28. Avian Acute Toxicity Data 

Common Name %AI Study parameters LD50/LC50 NOAEL/ 

LOAEL

MRID Classification

/Category

1

 Based on LD50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately toxic; 501-2000 slightly toxic; >2000 

practically nontoxic 

2 Based on LC50 (mg/kg) <50 very highly toxic; 50-500 highly toxic; 501-1000 moderately toxic; 1001-5000 slightly toxic; 

>5000 practically nontoxic 

3

Bold value used in risk description 

Mammals - Technical and degradate/metabolite 

Eight acute oral studies were conducted on female rats to satisfy OCSPP guidance 

870.1100 (OECD 425) – one technical and seven degradate/metabolite (M-1, M-3, M-25, 

I-3, I-4, I-5, M-28). All of the studies were deemed acceptable and indicated that the test 

compound was practically non-toxic with toxicity category III. However, all of the 

studies were conducted at a limit dose of 2000 mg a.i./kg-bw and without control groups. 

Mammals – Formulations 

Two formulation studies were conducted on female rats to satisfy OCSPP guidance 

870.1100 (OECD 425) – one on WG85 (85%a.i.) and one on V-10233 (42.2% 

pyroxasulfone; 33.6 flumioxazin). Both studies were limit tests and deemed acceptable; 

however, no control groups were used in the study design. The single active ingredient 

product tested (MRID 47701916) is at most slightly toxic (category III), while the coformulated product (MRID 47702105) is practically non-toxic (category IV) at the 

respective limit doses. No deaths or sublethal effects were observed in either study. 

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Technical KIH-485 

Rat, 

IGSBR 

strain 

(♀ only) 

99.1 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in 0.5% aqueous 

sodium 

carboxymethylcellulose with 

Tween 80 (60:1) 

administered by gavage 

2 groups of 3 rats (9wks old; 

172-195g) 

15-day observation period 

Acute oral LD50 ♀>20002

 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: None. No 

deaths or clinical signs. All 

rats gained weight during the 

first and second weeks of obs. 

period except for one animal 

which showed a slight loss in 

body weight during the 

second week.

47701677 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 
73

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Metabolites/Degradates 

Rat, 

IGSBR 

strain 

(♀ only) 

99.95% M-1 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in distilled water 

administered by gavage 

2 groups of 3 rats (8-12 wks 

old; 186-206g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: No 

deaths. Systemic toxicity 

signs included hunched 

posture, lethargy, piloerection, decreased respiratory 

rate, tiptoe gait. One animal 

appeared normal throughout 

test; remaining animals 

appeared normal 2-6 days 

after dosing.

47701678 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 

Rat, 

IGSBR 

strain 

(♀ only) 

100% M-3 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in arachis oil BP (b/c 

test matl. did not dissolve in 

distilled water) 

administered by gavage 

2 groups of 3 rats (8-12 wks 

old; 194-219g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: No 

deaths. Hunched posture obs 

in all animals. Animals 

appeared normal 1-3 days 

after dosing.

47701679 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 
74

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Rat, SPF 

strain 

(♀ only) 

98.72% M-25 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in purified water 

administered by gavage 

2 groups of 3 rats (11 wks old; 

180.8-196.5g) 

15-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: No 

deaths. 3/6 rats did not show 

any clinical signs throughout 

test. Two hours post-dosing, 

a slightly ruffled fur was 

observed in 3 females which 

persisted up to the 5-hour 

observation. Slight sedation 

was observed in two rats 2-5 

hrs after treatment. Hunched 

posture and slightly poor 

coordination obs in 3 rats 

during the same observation 

period. Additionally, one rat 

was observed with shut eyes 

2-5 hours post-dose. The 3 

rats were free of clinical signs 

from test day 2-15. 

47701680 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 

Rat, 

IGSBR 

strain 

(♀ only) 

96.59% I-3 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in dimethyl sulphoxide 

(b/c test matl. did not dissolve 

in distilled water or arachis oil 

BP) 

administered by gavage 

5 rats treated at given dose 

level (8-12 wks old; 211-256 

g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: No 

deaths. Increased salivation 

obs in one rat. 

47701681 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 
75

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Rat, 

IGSBR 

strain 

(♀ only) 

96.86% I-4 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in dimethyl sulphoxide 

(b/c test matl. did not dissolve 

in distilled water or arachis oil 

BP) 

administered by gavage 

5 rats treated at given dose 

level (8-12 wks old; 207-268 

g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: No 

deaths. Hunched posture and 

ataxia were noted during the 

day of dosing in 2 rats. 

47701682 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 

Rat, 

IGSBR 

strain 

(♀ only) 

99.95% I-5 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in dimethyl sulphoxide 

(b/c test matl. did not dissolve 

in distilled water or arachis oil 

BP) 

administered by gavage 

5 rats treated at given dose 

level (8-12 wks old; 208-258 

g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: None. 

47701683 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 
76

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Rat, 

IGSBR 

strain 

(♀ only) 

99.65% M-28 Acute oral study 

Dose level: 2000 mg a.i./kg 

bw (limit test) – i.e., a.i. 

mixed in purified water 

administered by gavage 

2 groups of 3 rats (8-12 wks 

old; 192-233 g) 

14-day observation period 

Acute oral LD50 ♀>2000 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects: 2 deaths. 

Piloerection, salivation, 

underactivity, reduced body 

tone, hunched posture, and 

body weight loss prior to 

death. Darkened tissues of 

lungs, kidneys, liver obs after 

death. Piloerection, 

underactivity, unsteady gait, 

and reduced body temp obs in 

remaining rats but resolved by 

day 4. 

47701755 Acceptable/ 

Practically 

non-toxic1 

Toxicity 

category III 

Formulations 

Rat, SPF 

strain 

(♀ only) 

85% 

WG85 

Acute oral study 

Dose level 1,700 mg a.i./kgbw (limit test: 2000 mg 

form/kg-bw) – i.e. mixed in 

purified water 

administered by gavage 

2 groups of 3 rats (11 wks old; 

177.2-193.6 g) 

15-day observation period 

Acute oral LD50 ♀> 1,700 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects:None. 

47701916 Acceptable/ 

At most, 

slightly toxic1

Toxicity 

category III 
77

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Rat, 

SpragueDawley 

(♀ only) 

42.2% 

pyroxasulfone; 

33.6 

flumioxazin 

V-10233 

(VC1763) 

Acute oral study 

Dose level 2,110 mg a.i./kgbw (limit test: 5000 mg 

form/kg-bw) – i.e. mixed in 

50% w/w distilled water 

administered by gavage 

1 group of 3 rats (11 wks old; 

190-215g) 

14-day observation period 

Acute oral LD50 ♀>2,110 mg 

a.i./kg bw 

NOAEL: No NOAEL 

LOAEL: No LOAEL 

Endpoint(s) affected: None. 

(Sub)lethal effects:None. 

47702105 Acceptable / 

Practically 

non-toxic1

Toxicity 

category IV 

Inhalation studies (870.1300) for STIR – Technical and formulations 

Rat, 

IGSBR 

strain 

99.1 (TGAI) Acute inhalation toxicity 

(limit test) 

Atmospheric concentration of 

6.56 mg/L (MMAD = 4.18 

m; GSD = 1.91) 

Exposed by inhalation (nose 

only) route; 5♂ & 5♀ (8 wks 

old; ♂: 243-278 g; ♀: 182-

210 g) 

4-hour (4 hours and 29 

minutes) exposure period; 

observed for 15 days 

LC50 ♂ > 6.56 mg a.i./L 

LC50 ♀ > 6.56 mg a.i./L 

LC50 Combined > 6.563

 mg 

a.i./L 

Endpoint(s) affected: None. 

(Sub)lethal effects: During 

exposure effects to breathing 

pattern and tail pinch reflex 

were observed. After exposure 

effects included hunched 

posture, piloerection, stained 

fur, and nasal discharge. 

47701685 Acceptable / 

Toxicity 

Category IV 
78

Table 29. Mammalian Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification/

Category

Rat, 

albino 

SPF strain 

85 (WG 85) Acute inhalation toxicity 

(limit test) 

Analytically determined mean 

concentration of 5.8 mg 

form/L (MMAD = 3.45-3.62 

m; GSD = 2.73-3.62); 4.93 

mg a.i./L 

Exposed by inhalation (nose 

only flow past) route; 5♂ & 

5♀ (8 wks old; ♂: 256.2-

276.2 g; ♀: 171.4-181.8 g) 

4-hour exposure period; 

observed for 15 days 

LC50 ♂ > 4.93 mg a.i./L 

LC50 ♀ > 4.93 mg a.i./L 

LC50 Combined > 4.93 mg 

a.i./L 

Endpoint(s) affected: None. 

(Sub)lethal effects: None. 

47701918 Acceptable / 

Toxicity 

Category IV 

Rat, 

albino 

SpragueDawley 

42.2% 

pyroxasulfone; 

33.6 

flumioxazin 

V-10233 

(VC1763) 

Acute inhalation toxicity 

(limit test) 

Gravimetric concentration of 

2.04 mg form/L (MMAD = 

3.6 m; GSD = 1.99); 0.86 

mg a.i./L 

Exposed by inhalation (nose 

only flow past) route; 5♂ & 

5♀ (10-11 wks old; ♂: 333-

367 g; ♀: 215-247 g) 

4-hour exposure period; 

observed for 14 days 

LC50 ♂ > 0.86 mg a.i./L 

LC50 ♀ > 0.86 mg a.i./L 

LC50 Combined > 0.86 mg 

a.i./L 

Endpoint(s) affected: None. 

(Sub)lethal effects: None. 

47702107 Acceptable / 

Toxicity 

Category IV 

1

 Based on LD50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately toxic; 501-2000 slightly toxic; >2000 

practically nontoxic 

2

Bold value used in risk description 3

Bold value used in STIR; though the formulation studies indicate lower concentrations on a %a.i. basis, the TGAI study had 

an indication of sublethal effects (though apparently transient). 

Terrestrial Invertebrates – Technical 

The terrestrial invertebrate study on honey bees (Apis mellifera, MRID 47701637) is 

classified as acceptable. The acute contact test cumulative mortality over the 48 hour 

testing period for the negative control, solvent control (acetone), and nominal test 

concentrations 1.94, 4.27, 9.4, 20.7, 45.5, and 100 g a.i./bee was 11.7, 3.3, 21.7, 10, 6.7, 

15, 15, and 10% , respectively. As a result, the 48-hour LD50 > 100 g a.i./bee (the 

highest concentration tested). For the positive control (dimethoate) nominal test 
79

concentrations 0.05, 0.1, and 0.3g a.i./bee, cumulative mortality was 8.3, 11.7, and 

100%. Sub-lethal effects were sporadic and apparently not treatment-related, but include 

lethargy, loss of equilibrium, and immobility. More specifically, there were sporadic 

occurrences of lethargy (two cases during the first half hour in the 9.4 and 100 g a.i./L 

concentration; one case at 1.5 hours in the 100 g a.i./L concentration), loss of 

equilibrium (one case after 24 hours in the 20.7 g a.i./L concentration), and immobility 

(three cases after 48 hours: one in the 1.94 g a.i./L concentration and two in the 4.27 g 

a.i./L concentration). 

Non-guideline studies – Technical and Formulations 

A terrestrial invertebrate study on parasitoid wasp (Aphidius rhopalosiphi, MRID 

47889323) using the pyroxasulfone proposed formulation WG85 (84.7% purity) is 

classified as supplemental by the Agency on account of being a non-guideline study. The 

review and toxicity calculations were performed by APVMA; the study received a ‘fully 

reliable’ rating. There were no mortalities or toxic effects in the control or any of the 

treatment groups. William’s test was used to calculate effects on fecundity which showed 

a significant decrease in the reproduction parameter (i.e., mean number of parasitized 

aphids per female) at the two highest test concentrations. However, the primary reviewer 

noted that the application of KIH-485 (pyroxasulfone) WG85 to the parasitoid wasp 

resulted in up to 45% reduction in fecundity. As 50% reduction in fecundity was not 

reached at any level of exposure to pyroxasulfone, an ER50 was not calculated from the 

data available and was thus considered as greater than the highest concentration tested 

(i.e., >1000 g a.i./ha). 

A terrestrial invertebrate study on predatory mite (Typhlodromus pyri, MRID 47701753) 

using the pyroxasulfone proposed formulation WG85 (84.7% purity) is classified by the 

Agency as supplemental on account of being a non-guideline study. The review and 

toxicity calculations were performed by APVMA; the study was considered valid and 

received a ‘fully reliable’ rating. Fisher’s exact test was used to assess mortality and 

Williams test to assess fecundity (i.e., eggs produced per female per day). Mite mortality 

in the water control reached 3% within 7 days of exposure. Corrected mortality for KIH485 (pyroxasulfone) WG85 applied at rates of 62.5, 125, 250, 500 and 1000 g a.i./ha was 

6, 6, 8, 3 and 8% respectively within 7 days. Positive control (dimethoate) mortality was 

94% by seven days. The 7-day LR50 was > 1000 g a.i./ha. There were statistically 

significant reductions in fecundity in all the KIH-485 (pyroxasulfone) WG85 treated 

groups compared to the control group. The application of KIH-485 (pyroxasulfone) 

WG85 resulted in up to 50% reduction in total beneficial effect (i.e., E = 100% - (100% - 

Ma) × Er), where Ma is corrected mortality and Er is the proportional difference in 

reproduction) of predatory mites. However, the response was not dose dependent. 

Therefore, based on nominal concentration, the 7-day LR50 of KIH-485 (pyroxasulfone) 

WG85 to Typhlodromus pyri was >1000 g a.i./ha. 

A terrestrial invertebrate study on earthworm (Eisenia fetida, MRID 47701748) using the 

pyroxasulfone technical (98.82% purity) is classified by the Agency as supplemental on 

account of being a non-guideline study. The review and toxicity calculations were 

performed by APVMA; the study received a ‘fully reliable’ rating. There were no 
80

mortalities in the control group or any of the treatment groups during the 14-day test. 

The average total weight change in the control was -0.11 ± 0.013 g (SD) and -0.14 ± 

0.017 g in the highest treatment group. The weight loss did not appear to be dose 

responsive. Treatment-related effects were not observed in the test. All earthworms in the 

control group and treatment groups were normal in appearance and behavior throughout 

the test period. Earthworms in both the control and treatment groups exhibited no 

aversion to the soil during observations of burrowing behavior on Days 0 and 7. The LC50

and NOAEC were determined by visual examination of the mortality and clinical 

observation data. 

A terrestrial invertebrate study on earthworm (E. fetida, MRID 47933801) testing growth 

and reproduction and using the pyroxasulfone technical (99.21% purity) is classified by 

the Agency as supplemental on account of being a non-guideline study. The review and 

toxicity calculations were performed by APVMA; the study received a ‘fully reliable’ 

rating. There were no adult mortalities in any of the treatments or controls. Adult 

bodyweight increases were similar in treated groups to the control. Production of 

juveniles was similar in each group. Under the conditions of this study it can be 

concluded that reproductive performance in E. fetida was unaffected by pyroxasulfone at 

soil concentrations of up to 1000 ppm (presumably mg a.i./kg dry soil). 

Table 30. Terrestrial Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification

/Category

Technical KIH-485

Honey bees 

Apis 

Mellifera

99.1 48-hour acute contact 

3 reps.; 20 bees per rep.; 

60 bees per treatment 

Nominal: 

negative control, solvent 

control (acetone), 1.94, 

4.27, 9.4, 20.7, 45.5, and 

100 g a.i./bee; for 

positive control 

(dimethoate): 0.05, 0.1, 

and 0.3g a.i./bee 

48 hour LD50 > 1002 g ai/bee

NOAEC: 100 μg a.i./bee 

LOAEC > 100 μg a.i./bee 

Endpoint(s) affected: None. 

Endpoint(s) considered: 

mortality. 

Sublethal effects: 

Sporadic and apparently not 

treatment-related, but include 

lethargy, loss of equilibrium, 

and immobility. 

47701637 Acceptable/ 

Practically 

non-toxic1 

Non-guideline studies – Technical and Formulation 
81

Table 30. Terrestrial Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification

/Category

Parasitoid 

wasp 

Aphidius 

rhopalosiphi 

Formulation 

WG85 

(84.7%) 

48 hour exposure period; 

parasitized aphids 

counted on day 11 

4 reps (of 5♀: 5♂) / 40 

bees per treatment 

Nominal: 0 (water 

control), 12.35, 37.04, 

111.11, 333.33, and 

1000 g a.i./ha; 

0, 0.011, 0.033, 0.099, 

0.297, and 0.892 lbs 

a.i./A 

48-hour ER50 / LR504

 > 1000 g 

a.i./ha 

(equivalent to >0.892 lbs a.i.A) 

Endpoint(s) affected: fecundity 

(parasitization of aphids) 

Endpoint(s) considered: 

mortality, fecundity 

Sublethal effects: No toxic 

effects recorded in control or 

treatment groups. 

47889323 Supplemental3 

Predatory mite 

Typhlodromus 

pyri 

Formulation 

WG85 

(84.7%) 

7-day exposure period; 

endpoints also assessed 

on day 9, 11, and 14 

5 reps (of 20mites) / 100 

mites per treatment 

Nominal: 0 (water 

control), 62.5, 125, 250, 

500, and 1000 g a.i./ha; 

0, 0.056, 0.112, 0.223, 

0.446, and 0.892 lbs 

a.i./A 

7-day ER50 / LR504

 > 1000 g 

a.i./ha 

(equivalent to >0.892 lbs a.i.A) 

Endpoint(s) affected: mortality, 

fecundity (overall eggs per 

female per day) 

Endpoint(s) considered: 

mortality, fecundity 

Sublethal effects: No toxic 

effects recorded in control or 

treatment groups. 

47701753 Supplemental3

Earthworm 

Eisenia fetida 

98.82 14-day exposure period 

(in artificial soil) 

4 reps (of 10 

earthworms) / 40 

earthworms per 

treatment 

Nominal: 0, 62.3, 125, 

249, 499, and 997 mg 

a.i./kg dry soil 

14-day LC50 > 997 mg a.i./kg 

dry soil 

14-day NOAEC: 997 mg a.i./kg 

dry soil 

Endpoint(s) affected: None. 

Endpoint(s) considered: 

mortality, bodywt loss 

Sublethal effects: None. 

47701748 Supplemental3
82

Table 30. Terrestrial Invertebrate Acute Toxicity Data 

Common 

Name

%AI Study parameters LD50 /NOAEL MRID Classification

/Category

Earthworm 

Eisenia fetida

99.21 4 week exposure period 

of adults; 2nd 4-wk obs 

pd for juvenile worms; 

reproduction and growth 

study 

4 reps (of 10 

earthworms) / 40 

earthworms per 

treatment 

Nominal: 0, 1.6, 8.0, 40, 

200 and 1000 ppm 

28-day NOAEC ≥ 1000 ppm5

 

Endpoint(s) affected: None. 

Endpoint(s) considered: 

mortality, bodywt loss, juvenile 

counts 

Sublethal effects: None. 

47933801 Supplemental3

1

 Based on acute contact LD50 (g a.i./bee) <2 highly toxic; 2-10.99 moderately toxic; ≥11 practically non-toxic 2

Bold value used in risk description 3

 Supplemental on account of being a non-guideline study. 

4

 ER50: effect level corresponds to fecundity calculation; LR50: lethal level corresponds to mortality calculation 5

 Presumed to refer to following units: mg a.i./kg dry soil 

(2) Chronic Effects 

Birds - Technical 

The one-generation reproductive toxicity study (MRID 47701635) using 16 pairs per 

level of 34-week old Northern bobwhite quail (Colinus virginianus) over 20 weeks was 

classified as acceptable. KIH-485 technical was administered to the birds in the diet at 

nominal concentrations of 0 (control), 100, 300, 1000 mg a.i./kg-diet. Mean-measured 

concentrations were <25 (control), 97.1, 295.5, 1004.5 mg a.i./kg-diet, respectively. 

There were no apparent treatment-related effects upon adult body weight, reproductive 

performance, eggshell thickness, or offspring body weight at any of the concentrations 

tested. The lack of dose response in this case indicates that the NOAEC ≥ 1,000 mg 

a.i./kg diet and LOAEC will be > 1,000 mg a.i./kg diet. As the endpoints are nondefinitive, they are not useful for RQ calculations, but can contribute to risk description. 

The one-generation reproductive toxicity study (MRID 47701636) used 16 pairs per level 

of ca. 24-week old mallard duck (Anas platyrhynchos) over 20 weeks was classified as 

acceptable. KIH-485 technical was administered to the birds in the diet at nominal 

concentrations of 0 (control), 60, 240, and 600 mg a.i./kg-diet. Mean-measured 

concentrations were <25 (control), 60.9, 243, and 621.5 mg a.i./kg-diet, respectively. At 

the 600 mg a.i./kg-diet nominal test concentration, there was a slight, treatment related 

decrease in adult body weight during the period from week 4 to week 8. There were no 

apparent treatment related effects on egg shell thickness at any concentration tested. At 
83

the 600 mg a.i./kg-diet nominal test concentration, there were treatment-related decreases 

in body weight of both hatchling and 14-day old survivors that were statistically 

significant. For the nominal concentrations 0, 60, 240, and 600 mg a.i./kg-diet, the total 

number of eggs set is 620, 534, 553, and 381, respectively. When hatchability, with 

respect to the number of hatchlings hatched out of the number of eggs set, above 70% per 

pair was considered, it was found that in the control group, hatchability was above 70% 

in 9 of 15 pairs (i.e., those alive and with hatchlings; a total of 16 pairs were used in the 

study), while in the 240 and 600 mg a.i./kg-diet treatment group only 2 of 13 pairs were 

above 70%; the 60 mg a.i./kg-diet was comparable to the control with 7 of 12 pairs above 

70%. Furthermore, according to OCSPP guidance 850.2300, normal values for 

hatchability for mallards are between 50 and 90%; when hatchability above 50% per pair 

was considered, it was found that in the control group, hatchability was at or above 50% 

in 11 of the 15 pairs (i.e., those alive and with hatchlings), while in the 240 and 600 mg 

a.i./kg-diet treatment groups only 2 and 5, respectively, out of 13 pairs were above 50%; 

the 60 mg a.i./kg-diet was again comparable to the control with 10 of 12 pairs above 

50%. The means (standard deviation) for hatchability across the control and three test 

concentrations are 59% (25), 74% (19), 39% (21), and 28% (27), which includes pairs for 

which eggs were set but not hatched – this makes for 16 pairs in the control, 12, 14, and 

14 in the respective concentrations. As a result, there appears to be a dose-dependent 

effect on hatchability. Therefore, on a biological significance basis, the NOAEC was 

determined to be 60 mg a.i./kg-diet and the LOAEC 240 mg a.i./kg-diet. 

Bird – Metabolites/Degradates 

There are no chronic data on metabolites/degradates for birds. 

Bird – Formulations 

There are no chronic data on formulations for birds, as these data are not required. 
84

Table 31. Avian Chronic Toxicity Data 

Common Name %AI Study Parameters NOAEC/LOAEC MRID Classification

Technical KIH-485 

Northern 

Bobwhite Quail 

Colinus 

virginianus

99.1 1-generation reproduction study 

Dietary study 

20 weeks 

2 birds per pen (1 ♂: 1♀); 16 

pens per neg. control and 

treatment 

Nominal: 

Negative control, 100, 300, 1000 

mg a.i./kg-diet 

Mean measured: 

Negative control (<25), 97.1, 

295.5, 1004.5 mg a.i./kg-diet 

(based on week 1 results) 

NOAEC ≥ 1000 mg 

a.i./kg diet

LOAEC > 1000 mg 

a.i./kg diet 

Endpoint(s) affected: 

none. 

Mortality: 

Three incidental 

mortalities occurred 

during the test, two in the 

100 mg a.i./kg-diet and 

one in the 300 mg a.i./kgdiet treatment group, but 

were not considered 

treatment related. 

Sublethal effects: 

Clinical observations 

indicated incidental 

injuries not atypical for 

penwear such as feather 

loss, lesions (feet, legs, 

head, back or wings), 

lameness, loss of 

coordination, and ruffled 

appearance. Necropsy 

findings were apparently 

not attributed to 

treatment. 

47701635 Acceptable 
85

Table 31. Avian Chronic Toxicity Data 

Common Name %AI Study Parameters NOAEC/LOAEC MRID Classification

Mallard Duck 

Anas 

platyrhynchos 

99.1 1-generation reproduction study 

Dietary study 

20 weeks 

2 birds per pen (1 ♂: 1♀); 16 

pens per neg. control and 

treatment 

Nominal: Negative control, 60, 

240, and 600 mg a.i./kg-diet 

Mean measured: Negative 

control (<25), 60.9, 243, and 

621.5 mg a.i./kg-diet 

NOAEC: 601

 mg a.i./kg 

diet

LOAEC: 240 mg a.i./kg 

diet 

Endpoint(s) affected: 

reproductive performance 

(hatchability) 

Mortality: 

Single incidental 

mortalities occurred 

during the test in both the 

60 and 600 mg a.i./kgdiet treatment groups, but 

were not considered 

treatment related. 

Sublethal effects:

Clinical observations 

indicated incidental 

injuries not atypical for 

penwear such as feather 

loss, swollen sinus, 

swelling around the eye, 

foot lesions, lameness, 

and reduced reaction to 

external stimuli. 

Necropsy findings were 

apparently not attributed 

to treatment. 

47701636 Acceptable 

1

Bold value used in risk quotient calculation 

Mammals - Technical 

A non-guideline 1-generation rat reproduction study (MRID 47701705) was classified as 

acceptable. The LOAEL for parental (P) toxicity is 5000 mg a.i./kg-diet (equivalent to 

339/383 mg/kg-bw/day in males/females, respectively) based on microscopic effects in 

the heart, liver, muscle, and sciatic nerve of males and females, decreased body weight 

gains in the P males and females and decreased food efficiency in the P dams. The 

NOAEL for parental toxicity is 250 mg a.i./kg-diet (equivalent to 16/20 mg/kg-bw/day in 

males/females, respectively). The LOAEL for offspring toxicity is 5000 mg a.i./kg-diet 

(equivalent to 339/383 mg/kg-bw/day in males/females, respectively) based on decreased 
86

body weight gains in the P males and females and decreased food efficiency in the P 

dams. The NOAEL for offspring toxicity is 250 mg a.i./kg-diet (equivalent to 16.0/19.6 

mg/kg-bw/day in males/females, respectively). The LOAEL for reproductive toxicity was 

not observed. The NOAEL for reproductive toxicity is 5000 mg a.i./kg-diet (equivalent to 

339/383 mg/kg-bw/day in males/females, respectively), the highest concentration tested. 

A rat 2-generation reproduction study (MRID 47701706) was classified as acceptable. 

The LOAEL for parental toxicity is 2000 mg a.i./kg-diet (equivalent to 144/165 mg/kgbw/day in males/females, respectively) based on decreased body weights, body weight 

gains, and food consumption. The NOAEL is 100 mg a.i./kg-diet (equivalent to 7.2/8.4 

mg/kg-bw/day in males/females, respectively). The LOAEL for offspring toxicity is 2000 

mg a.i./kg-diet (equivalent to 144/165 mg/kg-bw/day in males/females, respectively) 

based on decreased pup body weights and body weight gains. The NOAEL is 100 mg 

a.i./kg-diet (equivalent to 7.2/8.4 mg/kg-bw/day in males/females, respectively). The 

LOAEL for reproductive toxicity was not observed. The NOAEL for reproductive 

toxicity is 2000 mg a.i./kg-diet (equivalent to 144/165 mg/kg-bw/day in males/females, 

respectively), the highest dose tested. 

A rat developmental toxicity study (MRID 47701702) was classified as acceptable. The 

maternal and developmental LOAELs were not observed. The maternal and 

developmental NOAELs are 1000 mg/kg/day (limit dose). 

A rabbit developmental toxicity study (MRID 47701704) was classified as acceptable. 

The LOAEL for maternal toxicity was not observed. The NOAEL for maternal toxicity is 

1000 mg/kg/day (limit dose). The LOAEL for developmental toxicity is 1000 mg/kg/day 

(limit dose) based on reduced fetal weight and increased fetal resorptions. The NOAEL 

for developmental toxicity is 500 mg/kg/day.
87

Table 32. Mammalian Chronic Toxicity Data 

Common Name %AI Study Parameters NOAEC/ 

LOAEC

MRID Classification/

Category

Technical KIH-485 

Rat, IGS BR 

strain 

97.2 1-generation reproduction study 

12 CD Sprague-Dawley 

rats/sex/concentration, by 

feeding (diet); fed for ≥28 days 

prior to mating (P generation) 

3 treatment groups; 1 untreated 

diet control group 

Nominal: 0, 25, 250, 5000 ppm 

Parental toxicity 

NOAEL2

 (M/F): 

16/20 mg/kg bw/day

LOAEL3 (M/F): 

339/383 (HDT) mg/kg 

bw/day 

Offspring Toxicity 

NOAEL (M/F): 

16/19.6 mg/kg bw/day

LOAEL (M/F): 

339/383 (HDT) mg/kg 

bw/day4

 

Reproductive Toxicity 

NOAEL (M/F): 

339/383 mg/kg 

bw/day 

LOAEL (M/F): not 

attained

47701705 Acceptable / 

Non-Guideline 

*

 Provides data for 

use in dose 

selection for 

definitive 2-

generation 

reproductive 

toxicity study in 

rats 

Rat, IGS BR 

strain 

99.1 2-generation reproduction study 

30 CD Sprague-Dawley 

rats/sex/concentration, by 

feeding (diet); fed test diets for 

10 wks prior to mating (P and 

F1 generations) 

3 treatment groups; 1 untreated 

diet control group 

Nominal: 0, 5, 1001

, 2000 ppm 

♂:0, 0.4, 7.2, 144 mg/kg-bw/day 

♀: 0, 0.4, 8.4, 165 mg/kgbw/day 

Parental toxicity 

NOAEL (M/F): 

7.21

/8.4 mg/kg bw/day

LOAEL5 (M/F): 

144/165 mg/kg 

bw/day 

Offspring Toxicity 

NOAEL (M/F): 

7.2/8.4 mg/kg bw/day

LOAEL6

 (M/F): 

144/165 mg/kg 

bw/day 

Reproductive Toxicity 

NOAEL (M/F): 

144/165 mg/kg 

bw/day 

LOAEL (M/F): not 

attained

47701706 Acceptable / 

Guideline 
88

Table 32. Mammalian Chronic Toxicity Data 

Common Name %AI Study Parameters NOAEC/ 

LOAEC

MRID Classification/

Category

Rat (time-mated 

♀ only) 

99.1 Developmental toxicity study 

22 CD Sprague-Dawley rats per 

dose, by gavage. 

3 treatment groups; 1 untreated 

control group 

0, 100, 500, 1000 mg a.i./kg 

bw/day 

Maternal 

NOAEL: 1000 

mg/kg/day 

LOAEL: not attained 

Developmental 

NOAEL: 1000 

mg/kg/day 

LOAEL: not attained 

47701702 Acceptable/ 

Guideline 

Rabbit (timemated ♀ only) 99.1 Developmental toxicity study 

22 Hra: (NZW) SP rabbits per 

group, by gavage. 

3 treatment groups; 1 untreated 

control group 

0, 250, 500, 1000 mg a.i./kgbw/day 

Maternal7

NOAEL: 1000 mg 

a.i./kg-bw/day 

LOAEL: not attained 

Developmental

NOAEL: 500 mg 

a.i./kg-bw/day 

LOAEL8

: 1000 mg 

a.i./kg-bw/day 

47701704 Acceptable/ 

Guideline 

1 Bold value is the value that will be used to calculate risk quotients 2

 Decreased body wt gains at the 250 ppm (i.e., 16/20 mg/kg bw/day) dose were transient and mostly not statistically significant; but body wts were not 

affected. Therefore, effects at 250 ppm are equivocal. 

3

 Based on microscopic effects in the heart, liver, muscle, and sciatic nerve in males and females, body wt gain in P males and females, and decreased food 

efficiency in P dams. 

4

Based on decreased pup wt and delayed sexual maturation in both sexes 5

Based on decreased body wt, body wt gain, and food consumption 6

Based on decreased pup body wts and body wt gains. 

7

Seven females died or were euthanized prior to scheduled necropsy, 3 due to premature abortion and 4 because of intubation injury. One abortion occurred 

at 250 mg a.i./kg-bw/day and two occurred at 1000 mg a.i./kg-bw/day. However, there were no test-substance related deaths or sublethal effects in dams at 

any level tested. 

8

Based on reduced fetal weight and increased fetal resorptions (total and early) at 1000 mg a.i./kg-bw/day
b. Terrestrial Plants 

The seedling emergence study (MRID 47701638) is classified as supplemental because it 

is scientifically sound but does not satisfy the data requirement for a Tier II seedling 

emergence toxicity study. The study was intended to identify a ≥25% effect on 

emergence, survival, height, and dry weight for 10 species of plants. A most sensitive 

monocot and dicot were identified. However, some of the data indicate ≥25% effect at 

higher concentrations that are not statistically significant. For example, sunflower (dicot) 

had a 23 and 52% increase in dry weight at the two highest concentrations (0.1338 and 

0.2676 lbs a.i./A) that were not detected as statistically significant. Furthermore, wheat 

(monocot) dry weight (MSD 41.21%) had the following percent reductions 22, 22, 12, 

2.5, and 28% relative to the control which were not detected as statistically significant at 

0.0168, 0.0334, 0.0669, 0.1338, and 0.2676 lbs a.i./A concentrations, respectively. This 

indicates that the study may not capture what it was intended to capture as there was high 

variability in the raw data. For wheat, this implies that sublethal effects may be observed 

below maximum application levels and below the lowest tested concentration. The most 

sensitive monocot was the onion (Allium cepa) with an EC25 of 0.0669 lbs a.i./A and 

NOAEC of 0.0168 lbs a.i./A based on the observed changes in length. However, the 

significant effect on survival (3, 33, 12, 6, 27 and 42% relative to the control at 0.00418, 

0.00837, 0.0168, 0.0334, 0.0669 and 0.1338 lbs a.i./A, respectively; MSD of 28%) may 

have confounded the results for the length parameter. The most sensitive dicot was the 

kidney bean (Phaseolus vulgaris) with an EC25 of 0.2615 lbs a.i./A (just below the 

highest concentration tested – i.e., 0.2676 lbs a.i./A) and NOAEC of 0.1338 lbs a.i./A 

based on observed changes in length. 

The vegetative vigor study (MRID 47701639), however, is classified as acceptable 

because it is scientifically sound and satisfies the data requirement for a Tier II vegetative 

vigor toxicity study. Monocots, overall, did not exhibit signs of treatment-related toxicity, 

whereas dicots did. However, there is some uncertainty in these results considering that 

potential weeds or pest species are monocots (e.g., barnyard millet, Italian ryegrass). As a 

result determining the most sensitive monocot (i.e., onion A. cepa) was based on the 

lowest EC25 of the monocots for which the endpoint was available. However, the ECx’s 

for onion (as well as most monocot data) did not indicate convergence whereby an 

algorithm was not plotted against the data indicating clear inhibition with increasing 

concentration. As a result, for onion the EC25 > 0.2676 lbs a.i./A (the highest 

concentration tested) and the NOAEC is equal to the highest concentration tested. On the 

other hand, the most sensitive dicot was the pumpkin (Cucurbita mixta) with an EC25 of 

0.0748 lbs a.i./A and NOAEC of 0.0168 lbs a.i.A.
90

Table 33. Terrestrial Plant Toxicity Data 

Study Type %AI Study Parameters EC05/EC25/NOAEC MRID Classification

KIH-485 TEP 

Seedling 

Emergence – 

Tier II 

85 21 days 

4 reps per test group; 10 seeds 

per rep. 

Concentrations tested: 

negative control, 9.38, 18.8, 

37.5, 75, 150, 300 g a.i./ha (for 

R. sativa) 

negative control, 4.69, 9.38, 

18.8, 37.5, 75, 150 g a.i./ha (for 

A. cepa) 

negative control, 18.8, 37.5, 75, 

150, 300 g a.i./ha (for all 

others)

[Concentrations in lbs a.i./A 

(from lowest to highest tested): 

0.0048, 0.00837, 0.0168, 

0.0334, 0.0669, 0.1338, 0.2676 

lbs a.i./A] 

Most sensitive dicot

Kidney bean (Phaseolus 

vulgaris; Fabaceae) – 

length 

EC05: 0.1044 (0.024-0.45) 

lbs a.i./A 

EC25: 0.2615 (0.17-0.41) 

lbs a.i./A 

EC50: 0.4950 (0.17-1.46) 

lbs a.i./A 

NOAEC: 0.1338 lbs 

a.i./A 

Most sensitive monocot

Onion (Allium cepa; 

Liliaceae) – length 

EC05: 0.0048 (0.0003-

0.08) lbs a.i./A 

EC25: 0.0669 (0.02-0.19) 

lbs a.i./A 

EC50: 0.4164 (0.12-1.46) 

lbs a.i./A 

NOAEC: 0.0168 lbs 

a.i./A 

Endpoints affected: 

length (or height), dry 

weight 

Sublethal effects:

Incidental observations of 

chlorosis, necrosis, stem 

curl, leaf curl. Typically, 

the effects were observed 

at or above the LOAEC 

for height or weight. 

 

47701638 Supplemental 
91

Table 33. Terrestrial Plant Toxicity Data 

Study Type %AI Study Parameters EC05/EC25/NOAEC MRID Classification

Vegetative 

Vigor – Tier II 

85 21 days 

6 reps per test group; 5 plants 

per rep. 

Concentrations tested: negative 

control, 18.8, 37.5, 75, 150, 300 

g a.i./ha 

[Concentrations in lbs a.i./Acre: 

0.0168, 0.0334, 0.0669, 0.1338, 

0.2676 lbs a.i./A] 

Most sensitive dicot

Pumpkin (Cucurbita 

mixta: Cucurbitaceae)– 

weight 

EC05: 0.0071 (0.001-0.05) 

lbs a.i./A 

EC25: 0.0748 (0.03-0.17) 

lbs a.i./A 

EC50: 0.3834 (0.20-0.72) 

lbs a.i./A 

NOAEC: 0.0168 lbs 

a.i./A 

Most sensitive monocot

Onion1 (Allium cepa; 

Liliaceae) – length 

EC05: 0.2626 (0.25-0.27) 

lbs a.i./A 

EC25 >0.2676 lbs a.i./A 

EC50 >0.2676 lbs a.i./A 

NOAEC: 0.2676 lbs 

a.i./A 

Endpoints affected: 

length (or height), dry 

weight 

Sublethal effects: 

Signs of toxicity 

primarily observed on 

plants included necrosis, 

leaf curl, mortality, stem 

curl, and chlorosis. 

Generally, monocots did 

not exhibit treatmentrelated signs of toxicity, 

whereas dicots did. 

 

47701639 Supplemental 

1

 The ECx’s for onion did not indicate convergence whereby an algorithm was not plotted against the data indicating clear 

inhibition with increasing concentration. As most monocot data had similar results, the onion was chosen on the basis of 

the lowest EC25 of the monocots for which the endpoint was available. 

2 Bold values used to calculate risk quotients and/or in risk description 
IV. Risk Characterization 

A. Risk Estimation –Integration of Exposure and Effects Data 

A quantitative estimation of risk integrates EECs and toxicity estimates and 

evaluates the likelihood of adverse ecological effects to non-target species. In a 

deterministic approach, an exposure estimate is divided by a single point estimate of 

toxicity to calculate a risk quotient (RQ). The RQ is then compared to Agency Levels of 

Concern (LOCs, Appendix F), which serve as criteria for categorizing potential risk to 

non-target organisms and the need to consider regulatory action. 

1. Risk to Aquatic Animals and Plants 

A majority of the aquatic studies yielded non-definitive endpoints with little to no 

sublethal effects. For those studies that yielded non-definitive endpoints but presented 

sublethal effects, endpoints were used in risk description, however, RQs were not 

calculated; this includes chronic data for freshwater invertebrates and vascular plant data 

on the degradates (M-1, M-3). Risk quotient calculations were made using definitive 

endpoints for the vascular (parent only) and non-vascular (parent and degradates: M-1, 

M-3) aquatic plants, chronic data on the freshwater fish. Chronic data for the 

marine/estuarine fish and invertebrates were not provided by the registrant; although 

acute data on these taxa indicate no effect at the highest tested concentrations, risk to 

these taxa on a chronic basis cannot be precluded. However, equivalent toxicity to 

freshwater fish and invertebrates is assumed for the estuarine/marine fish and 

invertebrates, thereby negating the risk conclusion. It is important to note that discussion 

of corn scenarios in the aquatic assessment below applies to soybeans as well and that 

non-crop sites include the several scenarios. Therefore, corn/soybean scenarios include 

IA corn, IL corn, OH corn, and MS corn for pre-emergent, pre-plant, pre-plant (soil 

incorporated), post-plant, and fall applications; winter wheat scenario includes ND wheat 

for fall pre-plant applications, and non-crop scenarios include TN nursery, PA apple, and 

NY grapes. 

a. Aquatic Animals 

1. Risk following acute exposure

Freshwater Fish and Aquatic-Phase Amphibians

The acute aquatic RQs for freshwater fish and aquatic-phase amphibians were not 

calculated on the basis of a non-definitive endpoint observed in both freshwater fish 

studies with no sublethal effects. However, taking the lowest limit dose (rainbow trout, 

MRID 47701626) value and comparing it to the EECs for the corn scenarios (IA, IL, OH, 

MS), wheat and non-crop uses indicates that the lowest LOC (0.05, for listed species) is 

not exceeded. 
93

Freshwater Invertebrates

The acute aquatic RQs for freshwater invertebrates were not calculated on the basis of a 

non-definitive endpoint with no sublethal effects observed in the provided study. 

However, taking the limit dose (Daphnia, MRID 47701623) value and comparing it to 

the EECs for the corn scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates that 

the lowest LOC (0.05, for listed species) is not exceeded. 

Marine/Estuarine Fish

The acute aquatic RQs for marine/estuarine fish were not calculated on the basis of a 

non-definitive endpoint with no sublethal effects observed in the provided study. 

However, taking the highest concentration tested (sheepshead minnow, MRID 47701628) 

and comparing it to the EECs for the corn/soybean scenarios (IA, IL, OH, MS), wheat 

and non-crop uses indicates that the lowest LOC (0.05, for listed species) is not exceeded. 

Marine/Estuarine Invertebrates

The acute aquatic RQs for marine/estuarine invertebrates were not calculated on the basis 

of a non-definitive endpoint with no sublethal effects observed in the provided study. 

However, taking the highest concentration tested (saltwater mysid, MRID 47701625) and 

comparing it to the EECs for the corn/soybean scenarios (IA, IL, OH, MS), wheat and 

non-crop uses indicates that the lowest LOC (0.05, for listed species) is not exceeded. 

2. Risk following chronic exposure

Freshwater Fish and Aquatic-Phase Amphibians

The chronic aquatic RQs (all <0.01) for freshwater fish and aquatic-phase amphibians did 

not exceed the chronic LOC for any of the uses analyzed (the corn, soybean, winter 

wheat and non-crop uses). 

Freshwater Invertebrates

The chronic aquatic RQs for freshwater invertebrates were not calculated on the basis of 

a non-definitive endpoint observed in the provided study. However, sublethal effects 

were observed. Taking the highest concentration tested (NOAEC ≥ 1.9 mg a.i./L 

Daphnia, MRID 47701629) and comparing it to the EECs for the corn/soybean scenarios 

(IA, IL, OH, MS), wheat and non-crop uses indicates that the lowest LOC (0.05, for 

listed species) is not exceeded. 

Marine/Estuarine Fish

No chronic studies on marine/estuarine fish were submitted by the registrant. Therefore, 

a quantitative estimation of risk cannot be conducted. Chronic risk to marine/estuarine 
94

fish cannot be precluded on this basis alone. However, both freshwater and 

marine/estuarine acute data indicate that pyroxasulfone is at most, moderately toxic to the 

tested organisms (i.e., no effects were observed at comparable concentrations) suggesting 

that a comparison between freshwater and marine/estuarine fish may be appropriate in the 

particular case of pyroxasulfone. Furthermore, comparison of EEC values with acute 

endpoints for freshwater and marine/estuarine fish, respectively, as well as chronic RQs 

(<0.01) for freshwater fish and aquatic-phase amphibians suggest that chronic risk to 

marine/estuarine fish is not expected. 

Marine/Estuarine Invertebrates

No chronic studies on marine/estuarine invertebrates were submitted by the registrant. 

Therefore, a quantitative estimation of risk cannot be conducted. Chronic risk to 

marine/estuarine invertebrates cannot be precluded on this basis alone. However, both 

freshwater and marine/estuarine acute data indicate that pyroxasulfone is at most, 

moderately toxic to the tested organisms (i.e., no effects were observed at the highest 

concentrations tested) suggesting that a comparison between freshwater and 

marine/estuarine invertebrates may be appropriate in the particular case of pyroxasulfone. 

Furthermore, comparison of EEC values with acute endpoints for freshwater and 

marine/estuarine invertebrates, respectively, as well as chronic RQs (<0.01) for 

freshwater invertebrates suggest that chronic risk to marine/estuarine invertebrates is not 

expected. 

b. Aquatic Plants 

Vascular plants

The RQ calculations (1.03-1.4) based on a duckweed study (EC50: 0.006 mg a.i./L based 

on frond count, MRID 47701640) using technical grade active ingredient indicate aquatic 

non-listed plant LOC exceedances for a majority of the corn/soybean scenarios (IL/OH: 

pre and post plant, MS: pre and post plant, fall application), ND wheat (fall) but not the 

IA corn scenario, ND wheat (pre-plant) scenario, and non-crop uses. Similarly, the RQ 

calculations (8.38-46.6) based on the same study (NOAEC 0.00018 mg a.i./L based on 

frond count) indicate aquatic listed plant LOC exceedances for all of the corn/soybean 

scenarios (IA/IL/OH/MS), all wheat scenarios (ND pre-plant and ND fall), as well as all 

non-crop scenarios (TN nursery, PA apple, and NY grapes). 

The vascular plant RQs for metabolites (M-1, M-3) were not calculated on the basis of a 

non-definitive endpoint observed in the provided studies (frond count, biomass, and 

growth rate, MRIDs 47701641, 47701642). However, sublethal effects were observed. 

Taking the highest concentration tested (123 mg a.i./L) and comparing it to the EECs for 

the corn/soybean scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates that the 

non-listed and listed plant LOC is not exceeded. 
95

Non-vascular plants

The RQ calculations (3.97- 22.07) based on a freshwater green algae study (EC50: 

0.00038 mg a.i./L based on cell density, MRID 47701643) using technical grade active 

ingredient indicate aquatic non-listed plant LOC exceedances for all corn/soybean 

scenarios (IA/IL/OH/MS: pre-emergence, pre-plant, pre-plant soil incorporated, postplant, and fall applications), ND wheat scenarios, and non-crop uses. Similarly, the RQ 

calculations (15.08 – 83.88) based on the same study (NOAEC 0.0001 mg a.i./L based on 

cell density) indicates aquatic listed plant LOC exceedances for all corn/soybean 

scenarios (IA/IL/OH/MS: pre-emergence, pre-plant, pre-plant soil incorporated, postplant, and fall applications), ND wheat scenarios, and non-crop uses. 

The RQ calculations (all <0.01) based on a freshwater green algae study (EC50: 56 mg 

a.i./L and NOAEC: 31 mg a.i./L based on cell density, MRID 47701647) using 

metabolite (M-1) indicate no aquatic listed or non-listed plant LOC exceedances for any 

scenario assessed. Similarly, there are no listed or non-listed plant LOC exceedances for 

the other metabolite (M-3) tested on the freshwater green algae (EC50: 38 mg a.i./L and 

NOAEC: 15 mg a.i./L based on cell density, MRID 47701648). 

2. Risk to Terrestrial Animals and Plants 

a. Terrestrial Animals 

To assess risks of pyroxasulfone to non-target birds and mammals, EECs and acute and 

chronic RQs for residues on various forage categories (short grass, tall grass, broadleaf 

plants/small insects, fruits/pods/large insects, and seeds) were obtained from the Tier I 

model, T-REX v. 1.4.1 for broadcast, ground, and/or aerial spray as well as band or soil 

incorporated applications to the proposed crops. The model assumes initial 

concentrations on plant surfaces based on Kenaga-predicted maximum residues as 

modified by Fletcher et al. (1994), and assumes first-order dissipation. In this case, one 

application of 0.267 a.i./A was used to address corn, soybean, winter wheat (per the KIH485 W85 and Pyroxasulfone 85W labels), 0.096 lbs a.i./A for soy and 0.206 lbs a.i./A for 

non-crop uses (per the V-10233 Herbicide Water Dispersible Granules Commercial label) 

and 0.120 lbs a.i./A for corn, soybean, and non-crop uses (per the V-10233 Herbicide 

label). In all cases, the default foliar dissipation half-life of 35 days was used. 

For birds, acute RQs are derived using dose-based and dietary-based acute toxicity 

values. For mammals, acute RQs are derived using a dose-based acute toxicity value, 

and chronic RQs are derived using a dose-based chronic toxicity value and a dietarybased chronic toxicity value using the standard FDA laboratory rat conversion value 

provided in the T-REX model. Dietary-based RQs are calculated using EECs expressed 

in terms of residue concentration for the various forage categories and toxicity values 

(LC50 or NOAEC) expressed in units of dietary concentration. Dose-based RQs are 

calculated using a body weight-adjusted LD50 and consumption-weighted equivalent dose 
96

sorted by food source and body size. For both birds and mammals, three weight 

categories (or sizes) are considered. 

1. Risk following acute exposure

Birds

The acute oral and dietary endpoints are both greater than the highest concentrations 

tested (LD50 >2250 mg a.i./kg bw and LC50 >5620 mg a.i./kg diet, respectively). There 

were no mortalities or treatment related clinical signs of toxicity in the two acute oral 

studies (bobwhite quail, MRID 47701631; zebra finch, MRID 47701632) and one of the 

two dietary studies (bobwhite quail, MRID 47701633). However, the dietary study on 

mallard duck (MRID 47701634) indicated sublethal effects statistically significant from 

the controls that led to a definitive NOAEC calculation. Nevertheless, the acute RQ 

values are not reported on account of the non-definitive LD50/LC50 values. However, 

taking the highest concentrations tested and comparing them to the T-REX generated 

EECs indicates that the lowest LOC (0.1, for listed species) is not exceeded for any of the 

application rates examined relating to corn, soybean, wheat, and non-crop uses. 

Potential risk to piscivorous birds 

The potential risk to piscivorous birds considers exposure via consumption of fish 

contaminated with pyroxasulfone residues. However, given that the log Kow for 

pyroxasulfone is below the 4-8 range required to trigger use of the KABAM v.1.0, acute 

RQ values are not reported for this exposure route. Furthermore, substantial 

bioaccumulation in aquatic food webs is not expected given the low log Kow of 

pyroxasulfone (2.39). 

Mammals 

The acute endpoint for mammals is greater than the limit dose (LD50 >2000 mg a.i./kg 

bw, rat, MRID 47701677) for the parent compound. There were no mortalities or 

treatment related clinical signs of toxicity in the acute oral rat study using the parent 

compound. Therefore, acute RQ values are not reported. However, taking the tested limit 

dose and comparing it to the T-REX generated EECs indicates that the lowest LOC (0.1, 

for listed species) is not exceeded for any of the application rates examined relating to 

corn, soybean, wheat, and non-crop uses. The seven degradate/metabolite acute oral rat 

studies had determined the same endpoint value, however, a majority of these studies also 

indicated sublethal effects in the test animals. Furthermore, two additional studies on two 

pyroxasulfone formulations determined comparable endpoint values. However, all studies 

were performed on a small subset of organisms (either one or two groups of three to five 

female rats), at a limit dose, and without control groups. 
97

Potential risk to piscivorous mammals 

The potential risk to piscivorous mammals considers exposure via consumption of fish 

contaminated with pyroxasulfone residues. However, given that the log Kow for 

pyroxasulfone is below the 4-8 range required to trigger use of the KABAM v.1.0, acute 

RQ values are not reported for this exposure route. Furthermore, substantial 

bioaccumulation in aquatic food webs is not expected given the low log Kow of 

pyroxasulfone (2.39). 

Terrestrial invertebrates

Honeybee 

Pyroxasulfone is classified as ‘practically non-toxic’ to honey bees on an acute contact 

basis (LD50 >100 g a.i./bee, MRID 47701637) for the technical grade active ingredient. 

In addition, the interim listed species LOC for terrestrial invertebrates is 0.05. To lead to 

LOC exceedances (given the toxicity value is 781.25 g a.i./g of bee, whereby the LD50 is 

100 g a.i./bee and one bee weighs approximately 0.128g), the EEC would have to equal 

or exceed 39 g a.i./g of bee (or ppm). However, the dietary-based EECs for small (36.05 

ppm) and large (4.01 ppm) insects is below this value given the highest seasonal

maximum application rate of 0.267 lbs a.i./A. Meaning, that the interim LOC is not 

exceeded at the highest application rates indicated on the labels. 

Parasitoid wasp, predatory mite, and earthworm (Non-guideline studies) 

The two formulation (WG 85, 84.7% a.i.) studies (wasp, 48-hours long, MRID 

47889323; mite, 7-days long, MRID 47701753) indicate that this particular 

pyroxasulfone formulation is considered to lead to effects (fecundity in both studies and 

mortality in the mite study) but not in 50% of the population or greater up to the highest 

concentration tested. Both studies indicate that the ER50 and LR50 values are greater than 

the highest concentration tested (i.e., >1000 g a.i./ha). 

Given a non-guideline acute earthworm study (14-days long, MRID 47701748) using the 

technical active ingredient, pyroxasulfone is considered to be non-lethal to earthworms 

up to a concentration of 997 mg a.i./kg dry soil. Similarly, a non-guideline study (28-

days long, MRID Pending) testing earthworm growth and reproduction indicates that 

mortality and reproductive performance are not affected at soil concentrations up to 1000 

ppm (i.e., presumed units of mg a.i./kg dry soil). However, given the persistence of 

pyroxasulfone in soil (i.e., anaerobic soil metabolism half life is up to 156 days; aerobic 

soil metabolism half-life is up to 533 days), which is greater than the durations of the 

submitted studies, the chronic effect to earthworms and other soil dwelling organisms is 

uncertain at this time. 
98

2. Risk following chronic exposure

Birds

Utilizing the chronic endpoint (60 mg a.i./kg diet) from a 1-generation reproduction study 

(MRID 47701636) conducted with the mallard duck and the T-REX model v.1.4.1, the 

chronic avian dietary-based RQ exceeds the chronic LOC for birds only for the short 

grass food item and only for the highest maximum seasonal application rate (0.267 lbs 

a.i./A, see Table 34). Assuming that a concentration of 0.0534 lbs a.i./A is applied three 

days after the maximum single application rate (0.2136 lbs a.i./A) also leads to a chronic 

LOC exceedance (i.e., RQ is 1.02) for birds for the short grass food item (Table 34). 

Table 34. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients 

NOAEC 

(ppm) 

EECs and RQs1,2,3 

Short Grass Tall Grass Broadleaf Plants/

Small Insects 

Fruits/Pods/ 

Seeds/ 

Large Insects 

EEC RQ EEC RQ EEC RQ EEC RQ 

60a 64.08 1.074 29.37 0.49 36.05 0.60 4.01 0.07 

60b 49.44 0.82 22.66 0.38 27.81 0.46 3.09 0.05 

60c 28.80 0.48 13.20 0.22 16.20 0.27 1.80 0.03 

60d 23.04 0.38 10.56 0.18 12.96 0.22 1.44 0.02 

60e 61.20 1.024 28.05 0.47 34.43 0.57 3.83 0.06 1

 Risk Quotients are calculated using the following formula: EEC / NOAEC 

2

 Chronic risk LOC = 1 

3

 Based on avian chronic NOAEC = 60 mg a.i./kg diet 

4 Bolded values exceed LOC a

 Single application at the maximum seasonal rate of 0.267 lbs a.i./A for corn, soybean, and winter wheat 

(KIH-485 W85 and Pyroxasulfone 85W labels) 

b

 Single application at the maximum seasonal rate of 0.206 lbs a.i./A for non-crop sites (V-10233 

Herbicide Water Dispersible Granules commercial label) c

 Single application at the maximum seasonal rate of 0.120 lbs a.i./A for corn, soybean, fallow land, and 

non-crop sites (V-10233 Herbicide label) 

d

 Single application at the maximum seasonal rate of 0.096 lbs a.i./A for soybean (V-10233 Herbicide 

Water Dispersible Granules commercial label) 

e

 Two applications of variable value applied at a 3-day interval. The application of 0.2136 lbs a.i./A (the 

maximum single application rate) and 0.0534 lbs a.i./A sum to the maximum seasonal application rate of 

0.267 lbs a.i./A. 

Potential risk to piscivorous birds 

The potential risk to piscivorous birds considers exposure via consumption of fish 

contaminated with pyroxasulfone residues. However, given that the log Kow for 

pyroxasulfone is below the 4-8 range required to trigger use of the KABAM v.1.0, 
99

chronic RQ values are not reported for this exposure route. Furthermore, substantial 

bioaccumulation in aquatic food webs is not expected given the low log Kow of 

pyroxasulfone (2.39). 

Mammals

Utilizing the chronic endpoint (7.2 mg a.i./kg-bw parental toxicity for male rats; 

equivalent to 100 mg a.i./kg-diet) from a 2-generation reproduction study (MRID 

47701706) conducted with the rat and the T-REX model v.1.4.1, the chronic mammalian 

dietary-based RQs do not exceed the chronic LOC for mammals. However, the chronic 

mammalian dose-based RQs do exceed the chronic LOC for mammals for the short grass 

food item (in all size classes: 15, 35, and 1000g) as well as the tall grass and broadleaf 

plants/small insects categories (in the smaller two size classes: 15 and 35 g) for a couple 

of maximum seasonal application rates (0.267 lbs a.i./A, 0.206 lbs a.i./A see Table 35). 

LOC exceedances for the short grass food item (in the smaller two size classes: 15 and 

35g) occurs for the remaining maximum seasonal application rates (0.120 lbs a.i./A and 

0.096 lbs a.i./A, Table 35). 

Table 35. Upper Bound Kenaga, Chronic Mammalian Dose-Based Risk Quotients 

Size Class 

(grams) 

Adjusted 

NOAEL 

EECs and RQs1,2, 3 

Short Grass Tall Grass 

Broadleaf 

Plants/ 

Small Insects 

Fruits/Pods/

Seeds/ 

Large 

Insects 

Granivore 

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ 

15a 15.82 61.10 3.864 28.00 1.77 34.37 2.17 3.82 0.24 0.85 0.05 

35a 12.80 42.23 3.30 19.35 1.51 23.75 1.86 2.64 0.21 0.59 0.05 

1000a 5.54 9.79 1.77 4.49 0.81 5.51 0.99 0.61 0.11 0.14 0.02 

15b 15.82 47.14 2.98 21.60 1.37 26.51 1.68 2.95 0.19 0.65 0.04 

35b 12.80 32.58 2.54 14.93 1.17 18.33 1.43 2.04 0.16 0.45 0.04 

1000b 5.54 7.55 1.36 3.46 0.63 4.25 0.77 0.47 0.09 0.10 0.02 

15c 15.82 27.46 1.74 12.59 0.80 15.45 0.98 1.72 0.11 0.38 0.02 

35c 12.80 18.98 1.48 8.70 0.68 10.67 0.83 1.19 0.09 0.26 0.02 

1000c 5.54 4.40 0.79 2.02 0.36 2.48 0.45 0.28 0.05 0.06 0.01 

15d 15.82 21.97 1.39 10.07 0.64 12.36 0.78 1.37 0.09 0.31 0.02 

35d 12.80 15.18 1.19 6.96 0.54 8.54 0.67 0.95 0.07 0.21 0.02 

1000d 5.54 3.52 0.64 1.61 0.29 1.98 0.36 0.22 0.04 0.05 0.01 1

 Risk Quotients are calculated using the following formula: EEC / NOAEC 

2

 Chronic risk LOC = 1 

3

 Based on mammalian chronic dose-based NOAEL: 7.2 mg a.i./kg bw/day 

4 Bolded values exceed LOC a

 Single application at the maximum seasonal rate of 0.267 lbs a.i./A for corn, soybean, and winter wheat (KIH-485 

W85 and Pyroxasulfone 85W labels) 

b

 Single application at the maximum seasonal rate of 0.206 lbs a.i./A for non-crop sites (V-10233 Herbicide Water 

Dispersible Granules commercial label) 

c

 Single application at the maximum seasonal rate of 0.120 lbs a.i./A for corn, soybean, fallow land, and non-crop 

sites (V-10233 Herbicide label) 

d

 Single application at the maximum seasonal rate of 0.096 lbs a.i./A for soybean (V-10233 Herbicide Water 

Dispersible Granules commercial label) 
100

Potential risk to piscivorous mammals 

The potential risk to piscivorous mammals considers exposure via consumption of fish 

contaminated with pyroxasulfone residues. However, given that the log Kow for 

pyroxasulfone is below the 4-8 range required to trigger use of the KABAM v.1.0, 

chronic RQ values are not reported for this exposure route. Furthermore, substantial 

bioaccumulation in aquatic food webs is not expected given the low log Kow of 

pyroxasulfone (2.39). 

b. Terrestrial Plants 

Utilizing the toxicity endpoints (MRID 47701638 - seedling emergence: monocot EC25 = 

0.0669 lbs a.i./A, NOAEC = 0.0168 lbs a.i./A and dicot EC25 = 0.2615 lbs a.i./A, 

NOAEC = 0.1338 lbs a.i./A; MRID 47701639 - vegetative vigor: monocot EC25 > 0.2676 

lbs a.i./A, NOAEC = 0.2676 lbs a.i./A and dicot EC25 = 0.0748 lbs a.i./A, NOAEC = 

0.0168 lbs a.i./A), assuming liquid ground spray (1% drift fraction) and aerial spray (5% 

drift fraction) application method, a default incorporation depth of 1 inch, and a solubility 

limit in water of 3.49 mg/L (at 25oC), the RQ calculations indicate that monocots in semiaquatic areas exposed to runoff and spray drift from either ground or aerial spray 

applications are most sensitive given that the listed species LOC (of 1) is exceeded for 

several maximum seasonal application rates (0.267 lbs a.i./A, 0.206 lbs a.i./A for ground 

spray applications and 0.120 lbs a.i./A for aerial spray applications, see Table 36). 

Changing the application rate from 0.267 to 0.2136 lbs a.i./A (the maximum single 

application rate) alters the RQ from 1.75 to 1.40 but does not change the risk conclusion 

for ground spray applications with KIH-485/Pyroxasulfone W85 formulations. The 

maximum seasonal and maximum single application rate for the V-10233 Herbicide 

Water Dispersible Granules commercial label is the same (i.e., 0.206 lbs a.i./A); 

therefore, the RQ calculations and risk conclusions for ground spray applications with 

this formulation do not change. Similarly, the maximum seasonal and maximum single 

application rate for the V-10233 Herbicide label, which is the only label with proposed 

aerial spray applications, is the same (i.e., 0.120 lbs a.i./A); therefore, the RQ calculations 

and risk conclusions specifically regarding aerial spray applications with this formulation 

do not change. 
101

Table 36. RQ values for plants in dry and semi-aquatic areas exposed to Pyroxasulfone through runoff and/or 

spray drift1,2 

Plant Type Listed Status Dry Semi-Aquatic Spray Drift 

Ground spray (1% drift fraction) 

Monocota non-listed <0.1 0.44 <0.1 

Monocota listed 0.32 1.753 0.16 

Dicota non-listed <0.1 0.11 <0.1 

Dicota listed <0.1 0.22 0.16 

Monocotb non-listed <0.1 0.34 <0.1 

Monocotb listed 0.25 1.353 0.12 

Dicotb non-listed <0.1 <0.1 <0.1 

Dicotb listed <0.1 0.17 0.12 

Monocotc non-listed <0.1 0.20 <0.1 

Monocotc listed 0.14 0.79 <0.1 

Dicotc non-listed <0.1 <0.1 <0.1 

Dicotc listed <0.1 <0.1 <0.1 

Monocotd non-listed <0.1 0.16 <0.1 

Monocotd listed 0.11 0.63 <0.1 

Dicotd non-listed <0.1 <0.1 <0.1 

Dicotd listed <0.1 <0.1 <0.1 

Aerial Spray (5% drift fraction) 

Monocotc non-listed 0.11 0.27 <0.1 

Monocotc listed 0.43 1.073 0.36 

Dicotc non-listed <0.1 <0.1 <0.1 

Dicotc listed <0.1 0.13 0.36 1

 Risk Quotients are calculated using the following formula: EEC / NOAEC or EC05 (listed); EEC / EC25 (non-listed) 2

 Chronic risk LOC = 1. If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group. 3 Bolded values exceed LOC a

 Single application at the maximum seasonal rate of 0.267 lbs a.i./A for corn, soybean, and winter wheat (KIH-485 

W85 and Pyroxasulfone 85W labels) 

b

 Single application at the maximum seasonal rate of 0.206 lbs a.i./A for non-crop sites (V-10233 Herbicide Water 

Dispersible Granules commercial label) 

c

 Single application at the maximum seasonal rate of 0.120 lbs a.i./A for corn, soybean, fallow land, and non-crop 

sites (V-10233 Herbicide label) 

d

 Single application at the maximum seasonal rate of 0.096 lbs a.i./A for soybean (V-10233 Herbicide Water 

Dispersible Granules commercial label) 

Contamination via irrigation water

Predicted groundwater concentrations of pyroxasulfone (equivalent to the equilibrium 

concentration taken over a 30 year period) were used to estimate the potential phytotoxic 

effects from irrigation water to plants and sensitive crops on the treated field. It is 

assumed that a one-acre field is irrigated with one inch of water containing pyroxasulfone 

at the equilibrium concentration. Table 37 illustrates the RQ calculations obtained given 

the estimated concentrations. There are no non-listed plant LOC exceedances (on the 

basis of EEC/ EC25); however, given the estimates for the DE and WI scenarios, listed 

plant LOCs are exceeded (on the basis of EEC/NOAEC) with RQs of 1.12 and 2.01 for 

both monocot and dicot species, which implies that effects may be expected for listed 

species that may be on the irrigated field. 
102

Table 37. Estimated Concentrations in Soil from Irrigation Water and RQs for Terrestrial 

Plants 

Scenario Post Breakthrough 

Average (ppb) 

EECs 

(lbs 

a.i./A)1 

Monocot 

non-listed 

RQ2 

Dicot 

non-listed 

RQ2 

Monocot & 

Dicot listed 

RQ4 

GA Peanuts 28.7 0.007 0.10 0.09 0.39 

FL Potato 38.2 0.009 0.13 0.12 0.52 

FL Citrus 54.7 0.012 0.19 0.17 0.74 

DE Sweet Corn 83 0.019 0.28 0.25 1.125

NC Cotton 43.4 0.010 0.15 0.13 0.59 

WI Corn 149 0.034 0.50 0.45 2.015

SCIGROW 1.93 0 0.01 0.01 0.03 1

 EEC calculation: Assuming a one-acre field is irrigated with one inch of water containing pyroxasulfone. 

One acre has 6,272,640 cubic inches of water on the field. The1 acre field with 1 inch of water has 3,630 cubic ft of 

water (6,272,640 x 0.00058 cubic ft/cubic inch). The field has 27,156 gallons of water (3,630 cubic ft x 7.481 

gallons/cubic ft). Therefore, 1 inch of water on the 1 acre field weighs 226,625 lbs (27,156 gallons x 8.3453 lbs/gallon 

of water). 

 226,625 lb of water/acre * [post breakthrough ave in ppb] = EEC in lbs a.i./A 

 1,000,000,000 

2

 Based on seedling emergence study (MRID 47701638) most sensitive monocot, onion EC25 = 0.0669 lbs a.i./A 3

 Based on vegetative vigor study (MRID 47701639) most sensitive dicot, pumpkin EC25 = 0.0748 lbs a.i./A 4

 Based on the studies and species from footnotes 2 and 3 above; NOAEC = 0.0168 lbs a.i./A for both species 

5 Bold values indicate listed plant LOC exceedance given EEC/ NOAEC > 1

B. Risk Description 

Based on the available ecotoxicity data and predicted environmental exposures, risks to 

aquatic (non-vascular and vascular, listed and non-listed) and terrestrial (listed) plants as 

well as non-listed and listed birds and mammals following chronic exposure are 

expected. The pyroxasulfone degradates, M-1 and M-3, are not considered degradates of 

concern for duckweed (vascular aquatic plant) or freshwater green algae (non-vascular 

aquatic plant). The pyroxasulfone degradates, M-1, M-3, M-25, I-3, I-4, I-5, M-28, are 

not considered degradates of concern for mammals (on an acute basis). The formulations 

WG85 (84.7% a.i.) and V-10233 (42.2% pyroxasulfone; 33.6% flumioxazin) are not 

considered to pose a risk to mammals (on an acute basis). The formulation WG85 (84.7% 

a.i.) is considered to not pose a risk to (non-guideline) terrestrial invertebrates (parasitoid 

wasp, predatory mite). 
103

1. Risk to Aquatic Animals and Plants 

a. Aquatic Animals 

1. Risk following acute exposure

Freshwater Fish and Aquatic-Phase Amphibians

Technical 

The acute aquatic RQs for freshwater fish and aquatic-phase amphibians were not 

calculated on the basis of a non-definitive endpoint observed in both freshwater fish 

studies with no sublethal effects. However, taking the lowest limit dose (2.2 mg a.i./L for 

rainbow trout, MRID 47701626) value and comparing it to the EECs for the corn 

scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates that the lowest LOC 

(0.05, for listed species) is not exceeded. The pyroxasulfone limit of water solubility is 

reported as 3.49 mg/L at 25oC. Given these studies and assuming that pyroxasulfone 

concentrations in the environment reach the solubility limit, the effect of the technical 

grade active ingredient on freshwater fish is likely to be low. However, according to the 

model estimated EECs (0.002 - 0.008 mg/L, which includes pyroxasulfone only 

residues), levels of pyroxasulfone at the solubility limit are not expected to occur in 

surface water given the proposed corn, soybean, wheat, and non-crop uses. Therefore, 

acute risk to freshwater fish and aquatic-phase amphibians is not expected as a result of 

pyroxasulfone use on corn, wheat, and non-crop sites given the results from the studies 

using technical grade active ingredient. 

Metabolites/Degradates 

No acute data on metabolites/degradates for freshwater fish and aquatic-phase 

amphibians was provided. Risk cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for freshwater fish and aquatic-phase 

amphibians was provided. Risk cannot be precluded on the basis of no data available. 

Freshwater Invertebrates

Technical 

The acute aquatic RQs for freshwater invertebrates were not calculated on the basis of a 

non-definitive endpoint with no sublethal effects observed in the provided study. 

However, taking the limit dose (4.4 mg a.i./L, Daphnia, MRID 47701623) value and 

comparing it to the EECs for the corn scenarios (IA, IL, OH, MS), wheat and non-crop 

uses indicates that the lowest LOC (0.05, for listed species) is not exceeded. The 

pyroxasulfone limit of water solubility is reported as 3.49 mg/L at 25o

C. However, for the 

particular study and on account of poor solubility, column elution methodology was 

utilized to achieve saturation at the limit dose, a higher value. The difference in reported 

solubility limits may be a factor of water quality parameters such as pH and dissolved 

salts. Given this study and assuming that pyroxasulfone concentrations in the 
104

environment reach the solubility limit, the effect of the technical grade active ingredient 

on freshwater invertebrates is likely to be low. According to the model estimated EECs 

(0.002 - 0.008 mg/L, which includes pyroxasulfone only residues), levels of 

pyroxasulfone at the solubility limit are not expected to occur in surface water given the 

proposed corn, wheat, and non-crop uses. Therefore, acute risk to freshwater 

invertebrates is not expected as a result of pyroxasulfone use on corn, soybean, wheat, 

and non-crop sites given the results from the Daphnid study using technical grade active 

ingredient. 

Metabolites/Degradates 

No acute data on metabolites/degradates for freshwater invertebrates was provided. Risk 

cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for freshwater invertebrates was 

provided. Risk cannot be precluded on the basis of no data available. 

Marine/Estuarine Fish

The acute aquatic RQs for marine/estuarine fish were not calculated on the basis of a 

non-definitive endpoint with no sublethal effects observed in the provided study. 

However, taking the highest concentration tested (3.3 mg a.i./L sheepshead minnow, 

MRID 47701628) and comparing it to the EECs for the corn scenarios (IA, IL, OH, MS), 

wheat and non-crop uses indicates that the lowest LOC (0.05, for listed species) is not 

exceeded. The pyroxasulfone limit of water solubility is reported as 3.49 mg/L at 25o

C. 

Given this study and assuming that pyroxasulfone concentrations in the environment 

reach the solubility limit, the effect of the technical grade active ingredient on 

marine/estuarine fish is likely to be low. According to the model estimated EECs (0.002 - 

0.008 mg/L, which includes pyroxasulfone only residues), levels of pyroxasulfone at the 

solubility limit or at the highest concentration tested are not expected to occur in surface 

water given the proposed corn, wheat, and non-crop uses. Therefore, acute risk to 

marine/estuarine fish is not expected as a result of pyroxasulfone use on corn, soybean, 

wheat, and non-crop sites given the results from the sheepshead minnow study using 

technical grade active ingredient. 

Metabolites/Degradates 

No acute data on metabolites/degradates for marine/estuarine fish was provided. Risk 

cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for marine/estuarine fish was provided. 

Risk cannot be precluded on the basis of no data available. 
105

Marine/Estuarine Invertebrates

The acute aquatic RQs for marine/estuarine invertebrates were not calculated on the basis 

of a non-definitive endpoints with no sublethal effects observed in the provided studies 

(although one mortality was observed at the lowest test concentration but was not 

considered treatment related in the saltwater mysid study). However, taking the highest 

concentration tested (1.4 mg a.i./L, saltwater mysid, MRID 47701625) and comparing it 

to the EECs for the corn scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates 

that the lowest LOC (0.05, for listed species) is not exceeded. The pyroxasulfone limit of 

water solubility is reported as 3.49 mg/L at 25oC. Given this study and assuming that 

pyroxasulfone concentrations in the environment reach the solubility limit, the effect of 

the technical grade active ingredient on marine/estuarine invertebrates is likely to be low. 

According to the model estimated EECs (0.002 - 0.008 mg/L, which includes 

pyroxasulfone only residues), levels of pyroxasulfone at the solubility limit or at the 

highest concentration tested are not expected to occur in surface water given the proposed 

corn, wheat, and non-crop uses. Therefore, acute risk to marine/estuarine invertebrates is 

not expected as a result of pyroxasulfone use on corn, soybean, wheat, and non-crop sites 

given the results from the saltwater mysid study using technical grade active ingredient. 

Metabolites/Degradates 

No acute data on metabolites/degradates for marine/estuarine invertebrates was provided. 

Risk cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for marine/estuarine invertebrates was 

provided. Risk cannot be precluded on the basis of no data available. 

2. Risk following chronic exposure

Freshwater Fish and Aquatic-Phase Amphibians

The chronic aquatic RQs for freshwater fish and aquatic-phase amphibians did not exceed 

the chronic LOC for any of the uses analyzed (the corn, wheat and non-crop uses). The 

RQ was based on the 28-day NOAEC of 2.0 mg a.i./L from the chronic fathead minnow 

study (MRID 47701630). In this study, there was a significant reduction in percent 

survival relative to the controls in the second lowest mean-measured concentration tested 

(0.58 mg a.i./L) but was not considered treatment related. Sublethal effects were observed 

in the study such as weakness, small size, and a curled/crooked spine, but the frequency 

of these effects did not appear to differ from the controls. The pyroxasulfone limit of 

water solubility is reported as 3.49 mg/L at 25o

C. Given this study (the 28-day LOAEC is 

3.9 mg a.i./L) and assuming that pyroxasulfone concentrations in the environment reach 

the solubility limit and persist for at least 109 days (per aerobic aquatic metabolism halflife study; note that the duration of the chronic fish study is 28-days), the effect of the 

technical grade active ingredient on freshwater fish and aquatic-phase amphibians is still 

likely to be low. According to the model estimated EECs (0.002 - 0.008 mg/L, which 
106

includes pyroxasulfone only residues), levels of pyroxasulfone at the solubility limit or at 

the highest concentration tested are not expected to occur in surface water given the 

proposed corn, soybean, wheat, and non-crop uses. Therefore, chronic risk to freshwater 

fish and aquatic-phase amphibians is not expected as a result of pyroxasulfone use on 

corn, wheat, and non-crop sites given the results from the fathead minnow study using 

technical grade active ingredient. 

Metabolites/Degradates 

No chronic data on metabolites/degradates for freshwater fish and aquatic-phase 

amphibians was provided. Risk cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for freshwater fish and aquatic-phase 

amphibians was provided. Risk cannot be precluded on the basis of no data available. 

Freshwater Invertebrates

The chronic aquatic RQs for freshwater invertebrates were not calculated on the basis of 

a non-definitive endpoint observed in the provided study. However, sublethal effects 

were observed such as pale discoloration, injury, and lethargy, which were infrequent, 

comparable to controls, and not considered treatment related. Taking the highest 

concentration tested (1.9 mg a.i./L, Daphnia, MRID 47701629) and comparing it to the 

EECs for the corn scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates that the 

lowest LOC (0.05, for listed species) is not exceeded. The pyroxasulfone limit of water 

solubility is reported as 3.49 mg/L at 25o

C. Given this study (the 21-day LOAEC is >1.9 

mg a.i./L) and assuming that pyroxasulfone concentrations in the environment reach the 

solubility limit and persist for at least 109 days (per aerobic aquatic metabolism half-life 

study; note that the duration of the chronic fish study is 28-days), the effect of the 

technical grade active ingredient on freshwater invertebrates is unknown since the study 

did not test up to the solubility limit. However, the effect is likely to be low given that 

model estimated EECs (0.002 - 0.008 mg/L, which includes pyroxasulfone only 

residues), suggest that levels of pyroxasulfone at the solubility limit or at the highest 

concentration tested are not expected to occur in surface water given the proposed corn, 

wheat, and non-crop uses. Therefore, chronic risk to freshwater invertebrates is not

expected as a result of pyroxasulfone use on corn, soybean, wheat, and non-crop sites 

given the results from the Daphnia study using technical grade active ingredient. 

Metabolites/Degradates 

No chronic data on metabolites/degradates for freshwater invertebrates was provided. 

Risk cannot be precluded on the basis of no data available. 

Formulations 

No acute data on formulations of pyroxasulfone for freshwater invertebrates was 

provided. Risk cannot be precluded on the basis of no data available. 
107

Marine/Estuarine Fish

No chronic studies on marine/estuarine fish were submitted by the registrant. Therefore, 

a quantitative estimation of risk cannot be conducted. Chronic risk to marine/estuarine 

fish cannot be precluded on the basis of no data available for the technical grade active 

ingredient, metabolite/degradate, or formulation. However, both freshwater and 

marine/estuarine acute data indicate that pyroxasulfone is at most, moderately toxic to the 

tested organisms (i.e., no effects were observed at comparable concentrations) suggesting 

that a comparison between freshwater and marine/estuarine fish may be appropriate in the 

particular case of pyroxasulfone. Therefore, given the results of the freshwater fish 

analysis (fathead minnow study using technical grade active ingredient), and assuming 

that marine/estuarine organisms are of approximately equal sensitivity to pyroxasulfone 

as freshwater organisms are, chronic risk to marine/estuarine fish is not expected as a 

result of pyroxasulfone (TGAI) use on corn, soybean, wheat, and non-crop sites. 

Marine/Estuarine Invertebrates

No chronic studies on marine/estuarine invertebrates were submitted by the registrant. 

Therefore, a quantitative estimation of risk cannot be conducted. Chronic risk to 

marine/estuarine invertebrates cannot be precluded on the basis of no data available for 

the technical grade active ingredient, metabolite/degradate, or formulation. However, 

both freshwater and marine/estuarine acute data indicate that pyroxasulfone is at most, 

moderately toxic to the tested organisms (i.e., no effects were observed at the highest 

concentrations tested) suggesting that a comparison between freshwater and 

marine/estuarine invertebrates may be appropriate in the particular case of pyroxasulfone. 

Therefore, given the results of the freshwater invertebrate analysis (Daphnia study using 

technical grade active ingredient), and assuming that marine/estuarine organisms are of 

approximately equal sensitivity to pyroxasulfone as freshwater organisms are, chronic 

risk to marine/estuarine invertebrates is not expected as a result of pyroxasulfone (TGAI) 

use on corn, soybean, wheat, and non-crop sites. 

b. Aquatic Plants 

Vascular plants

Technical 

The RQ calculations (1.03-1.4) based on a duckweed study (EC50: 0.006 mg a.i./L based 

on frond count, MRID 47701640) using technical grade active ingredient indicate aquatic 

non-listed plant LOC exceedances for a majority of the corn/soybean scenarios (IL/OH: 

pre and post plant, MS: pre and post plant, fall application), ND wheat (fall) but not the 

IA corn scenario, ND wheat (pre-plant) scenario, and non-crop uses. Similarly, the RQ 

calculations (8.38-46.6) based on the same study (NOAEC 0.00018 mg a.i./L based on 

frond count) indicate aquatic listed plant LOC exceedances for all of the corn/soybean 

scenarios (IA/IL/OH/MS), all wheat scenarios (ND pre-plant and ND fall), as well as all 
108

non-crop scenarios (TN nursery, PA apple, and NY grapes). Biomass and growth rate 

were also affected in the study and sublethal effects were noted including root 

destruction, curled fronds, small fronds, chlorotic and necrotic plants. Given the 

sensitivity of aquatic vascular plants to pyroxasulfone and expected surface water 

concentrations, risk to aquatic listed and non-listed vascular plants is expected as a result 

of pyroxasulfone use on corn, soybeans, wheat, and non-crop uses (listed species). 

Metabolites/Degradates 

The vascular plant RQs for metabolites (M-1, M-3) were not calculated on the basis of a 

non-definitive endpoint observed in the provided studies (frond count, biomass, and 

growth rate, MRIDs 47701641, 47701642). However, sublethal effects (chlorosis and 

necrosis) were observed in both studies. Taking the highest concentration tested (123 mg 

a.i./L) and comparing it to the EECs for the corn/soybean scenarios (IA, IL, OH, MS), 

wheat and non-crop uses indicates that the plant LOC is not exceeded. There is some 

uncertainty in these estimates as the EECs are based on pyroxasulfone residues only and 

the solubility limit of these metabolites was not provided by the registrant. However, 

surface water modeling for total residues (parent+M1+M3) showed small difference in 

exposure concentrations when compared with modeling for the parent and EPISuite 

calculations indicate that the solubility limit of these degradates is large (M-1: 15,990 – 

984,030 mg/L; M-3: 206.9-458 mg/L) relative to the parent (approximately 3.49 mg/L). 

Overall, risk to aquatic listed and non-listed vascular plants is not expected as a result of 

exposure to metabolites of pyroxasulfone post-use on corn, soybean, wheat, and non-crop 

sites. 

Formulations

No aquatic vascular plant data on formulations of pyroxasulfone was provided. Risk 

cannot be precluded on the basis of no data available. 

Non-vascular plants

Technical 

The RQ calculations (3.97- 22.07) based on a freshwater green algae study (EC50: 

0.00038 mg a.i./L for cell density, MRID 47701643) using technical grade active 

ingredient indicate non-listed aquatic plant LOC exceedances for all corn/soybean 

scenarios (IA/IL/OH/MS: pre-emergence, pre-plant, pre-plant soil incorporated, postplant, and fall applications), ND wheat scenarios, and non-crop uses. Similarly, the RQ 

calculations (15.08 – 83.88) based on the same study (NOAEC 0.0001 mg a.i./L based on 

cell density) indicates aquatic listed plant LOC exceedances for all corn/soybean 

scenarios (IA/IL/OH/MS: pre-emergence, pre-plant, pre-plant soil incorporated, postplant, and fall applications), ND wheat scenarios, and non-crop uses. Given the 

sensitivity of aquatic non-vascular plants to pyroxasulfone and expected surface water 

concentrations, risk to listed and non-listed aquatic non-vascular plants is expected as a 

result of pyroxasulfone use on corn, soybean, wheat, and non-crop sites. 
109

Metabolites/degradates 

The RQ calculations (all <0.01) based on a freshwater green algae study (EC50: 56 mg 

a.i./L and NOAEC: 31 mg a.i./L based on cell density, MRID 47701647) using 

metabolite (M-1) indicate no aquatic listed or non-listed plant LOC exceedances for any 

scenario assessed. Similarly, there are no listed or non-listed plant LOC exceedances for 

the other metabolite (M-3) tested on the freshwater green algae (EC50: 38 mg a.i./L and 

NOAEC: 15 mg a.i./L based on cell density, MRID 47701648). There is some 

uncertainty in these estimates as the EECs are based on pyroxasulfone residues only and 

the solubility limit of these metabolites was not provided by the registrant. However, 

surface water modeling for total residues (parent+M1+M3) showed small difference in 

exposure concentrations when compared with modeling for the parent and EPISuite 

calculations indicate that the solubility limit of these degradates is large (M-1: 15,990 – 

984,030 mg/L; M-3: 206.9-458 mg/L) relative to the parent (approximately 3.49 mg/L). 

Overall, risk to aquatic non-vascular plants is not expected as a result of exposure to 

metabolites of pyroxasulfone post-use on corn, soybean, wheat, and non-crop sites. 

Formulations

No aquatic non-vascular plant data on formulations of pyroxasulfone was provided. Risk 

cannot be precluded on the basis of no data available. 

2. Risk to Terrestrial Animals and Plants 

a. Terrestrial Animals 

1. Risk following acute exposure

Birds

Technical 

The acute oral and dietary endpoints are both greater than the highest concentrations 

tested (LD50 >2250 mg a.i./kg bw and LC50 >5620 mg a.i./kg diet, respectively). There 

were no mortalities or treatment related clinical signs of toxicity in the two acute oral 

studies (bobwhite quail, MRID 47701631; zebra finch, MRID 47701632) and one of the 

two dietary studies (bobwhite quail, MRID 47701633). However, the dietary study on 

mallard duck (MRID 47701634) indicated sublethal effects statistically significant from 

the controls that led to a definitive NOAEC calculation. Nevertheless, the acute RQ 

values are not reported on account of the non-definitive LD50/LC50 values. However, 

taking the highest concentrations tested and comparing them to the T-REX generated 

EECs indicates that the lowest LOC (0.1, for listed species) is not exceeded for any of the 

application rates examined relating to corn, soybean, wheat, and non-crop uses. 

Therefore, risk to birds is not expected as a result of exposure to pyroxasulfone post-use 

on corn, soybean, wheat, and non-crop sites. 

Metabolites/degradates

No acute avian data on metabolites/degradates of pyroxasulfone was provided. Risk 

cannot be precluded on the basis of no data available. 
110

Formulations

No acute avian data on formulations of pyroxasulfone was provided. Risk cannot be 

precluded on the basis of no data available. 

Mammals 

Technical, degradates/metabolites, formulations 

The acute endpoint for mammals is greater than the limit dose (LD50 >2000 mg a.i./kg 

bw, rat, MRID 47701677) for the parent compound. There were no mortalities or 

treatment related clinical signs of toxicity in the acute oral rat study using the parent 

compound. Therefore, acute RQ values are not reported. However, taking the tested limit 

dose and comparing it to the T-REX generated EECs indicates that the lowest LOC (0.1, 

for listed species) is not exceeded for any of the application rates examined relating to 

corn, soybean, wheat, and non-crop uses. The seven degradate/metabolite (M-1, M-3, M25, I-3, I-4, I-5, M-28) acute oral rat studies had determined the same endpoint value as 

the technical grade active ingredient, however, a majority of these studies also indicated 

sublethal effects in the test animals including, but not limited to, decreased respiratory 

rate, underactivity, lethargy, and body weight loss, which could affect survival of 

individual mammals in the short term should exposure to these degradates occur. 

Furthermore, two additional studies on two pyroxasulfone formulations determined 

comparable endpoint values. However, all studies were performed on a small subset of 

organisms (either one or two groups of three to five female rats), at a limit dose, and 

without control groups. Given the comparison to T-REX generated EECs of the technical 

(as well as degradates/metabolites) and formulation based endpoints, risk to mammals is 

not expected as a result of exposure to the parent, degradates/metabolites, and 

formulations of pyroxasulfone post-use on corn, soybean, wheat, and non-crop sites. 

Terrestrial invertebrates

Honeybees 

Pyroxasulfone is classified as ‘practically non-toxic’ to honey bees on an acute contact 

basis (LD50 >100 g a.i./bee, MRID 47701637) for the technical grade active ingredient. 

Although sublethal effects were observed (i.e., lethargy, loss of equilibrium, and 

immobility) these were sporadic and not considered treatment related. In addition, the 

interim listed species LOC for terrestrial invertebrates is 0.05. To lead to LOC 

exceedances (given the toxicity value is 781.25 g a.i./g of bee, whereby the LD50 is 100 

g a.i./bee and one bee weighs approximately 0.128g), the EEC would have to equal or 

exceed 39 g a.i./g of bee (or ppm). However, the dietary-based EECs for small (36.05 

ppm) and large (4.01 ppm) insects is below this value given the highest seasonal

maximum application rate of 0.267 lbs a.i./A. Meaning, that the interim LOC is not 

exceeded at the highest application rates indicated on the labels for corn, soybean, winter 

wheat, fallow land, and non-crop sites. Thus, risk to honeybees is not expected as a result 

of direct contact with pyroxasulfone. Label language for the honeybee is, therefore, not 

required. 
111

Parasitoid wasp, predatory mite, and earthworm (Non-guideline studies) 

The two formulation (WG 85, 84.7% a.i.) studies (wasp, 48-hours long, MRID 

47889323; mite, 7-days long, MRID 47701753) indicate that this particular 

pyroxasulfone formulation is considered to lead to effects (fecundity in both studies and 

mortality in the mite study) but not in 50% of the population or greater up to the highest 

concentration tested. Both studies indicate that the ER50 and LR50 values are greater than 

the highest concentration tested (i.e., >1000 g a.i./ha = 0.892 lbs a.i./A). Given that the 

highest tested concentration is approximately 3x greater than the maximum seasonal

proposed rate (0.267 lbs a.i./A), risk to wasps and mites is not expected as a result of 

pyroxasulfone use on corn, soybean, winter wheat, fallow land, and non-crop sites. 

Given a non-guideline acute earthworm study (14-days long, MRID 47701748) using the 

technical active ingredient, pyroxasulfone is considered to be non-lethal to earthworms 

up to a concentration of 997 mg a.i./kg dry soil. Similarly, a non-guideline study (28-

days long, MRID Pending) testing earthworm growth and reproduction indicates that 

mortality and reproductive performance are not affected at soil concentrations up to 1000 

ppm (i.e., presumed units of mg a.i./kg dry soil). 

E. fetida is found in topsoil at depths of approximately 5-20cm. Given a soil depth of 20 

cm and assuming a seasonal maximum application rate (0.267 lbs a.i./A, which assumes 

a hypothetical maximum active ingredient loading rate since the seasonal rate would not 

be applied all at once), the EEC is much lower (0.114 mg/kg soil) than the concentrations 

generated in these studies. At shallower depths (5 cm), the EEC is higher (0.458 mg/kg 

soil), but still lower than maximum concentrations in the studies (997 and 1000 mg 

a.i./kg soil). Therefore, risk to earthworms is not expected as a result of pyroxasulfone 

use on corn, soybean, winter wheat, fallow land, and non-crop sites. However, given the 

persistence of pyroxasulfone in soil (i.e., anaerobic soil metabolism half life is up to 156 

days; aerobic soil metabolism half-life is up to 533 days), which is greater than the 

durations of the submitted studies, the chronic effect to earthworms and other soil 

dwelling organisms is uncertain at this time. 

2. Risk following chronic exposure

Birds

Utilizing the chronic endpoint (60 mg a.i./kg diet) from a 1-generation reproduction study 

(MRID 47701636) conducted with the mallard duck and the T-REX model v.1.4.1, the 

chronic avian dietary-based RQ (1.07) exceeds the chronic LOC of 1 for birds only for 

the short grass food item and only for the highest maximum seasonal application rate of 

0.267 lbs a.i./A found for all crop uses (corn, soybean, and winter wheat). Assuming that 

a concentration of 0.0534 lbs a.i./A is applied three days after the maximum single 

application rate (0.2136 lbs a.i./A) also leads to a chronic LOC exceedance (i.e., RQ is 

1.02) for birds for the short grass food item (Table 34). The chronic endpoint is based on 

biologically significant effects on reproductive performance (i.e., hatchability), not 

statistically significant results. According to OCSPP guidance 850.2300, normal values 
112

for hatchability for mallards are between 50 and 90%; when hatchability above 50% per 

pair was considered, it was found that in the control group, hatchability was at or above 

50% in 11 of the 15 pairs (i.e., those alive and with hatchlings; a total of 16 pairs were 

used in the study), while in the 240 and 600 mg a.i./kg-diet treatment groups only 2 and 

5, respectively, out of 13 pairs were above 50%; the 60 mg a.i./kg-diet was comparable to 

the control with 10 of 12 pairs above 50%. The means (standard deviation) for 

hatchability across the control and three test concentrations are 59% (25), 74% (19), 39% 

(21), and 28% (27), which includes pairs for which eggs were set but not hatched – this 

makes for 16 pairs in the control, 12, 14, and 14 in the respective concentrations. As a 

result, there appears to be a dose-dependent effect on hatchability, which leads to a 

NOAEC of 60 mg a.i./kg-diet and the LOAEC 240 mg a.i./kg-diet. Therefore, given the 

biologically significant effect on hatchability, the persistence of pyroxasulfone, and that 

the LOCs were exceeded for the given maximum seasonal application and multiple 

applications at potential single applications, chronic risk to birds is expected as a result of 

pyroxasulfone use on corn, soybean, and winter wheat. Reducing the maximum seasonal 

application rate would alleviate the risk concern. 

Metabolites/degradates

No chronic avian data on metabolites/degradates of pyroxasulfone was provided. Risk 

cannot be precluded on the basis of no data available. 

Formulations

No chronic avian data on formulations of pyroxasulfone was provided. Risk cannot be 

precluded on the basis of no data available. 

Mammals

Technical 

Utilizing the chronic endpoint (7.2 mg a.i./kg-bw parental toxicity for male rats; 

equivalent to 100 ppm or mg a.i./kg-diet) from a 2-generation reproduction study (MRID 

47701706) conducted with the rat and the T-REX model v.1.4.1, the chronic mammalian 

dietary-based RQs do not exceed the chronic LOC for mammals. However, the chronic 

mammalian dose-based RQs (1.17-3.86) do exceed the chronic LOC (of 1) for mammals 

for the short grass food item (in all size classes: 15, 35, and 1000g) as well as the tall 

grass and broadleaf plants/small insects categories (in the smaller two size classes: 15 and 

35 g) for a couple of maximum seasonal application rates (0.267 lbs a.i./A, 0.206 lbs 

a.i./A). LOC exceedances (i.e., RQ of 1.19-1.74) for the short grass food item (in the 

smaller two size classes: 15 and 35g) occurs for the remaining maximum seasonal 

application rates (0.120 lbs a.i./A and 0.096 lbs a.i./A). The NOAEL is based on 

decreased body weight, body weight gain, and food consumption and has implications for 

survival of the test organism in the long term. Given that LOCs were exceeded for the 

given maximum seasonal applications, chronic risk to mammals is expected as a result of 

pyroxasulfone use on corn, soybean, winter wheat, fallow land, and non-crop sites. 

Reducing the maximum seasonal application rate would alleviate the risk concern. 
113

Metabolites/degradates

No chronic mammalian data on metabolites/degradates of pyroxasulfone was provided. 

Risk cannot be precluded on the basis of no data available. 

Formulations

No chronic mammalian data on formulations of pyroxasulfone was provided. Risk cannot 

be precluded on the basis of no data available. 

b. Terrestrial Plants 

Utilizing the toxicity endpoints (MRID 47701638 - seedling emergence: monocot EC25 = 

0.0669 lbs a.i./A, NOAEC = 0.0168 lbs a.i./A and dicot EC25 = 0.2615 lbs a.i./A, 

NOAEC = 0.1338 lbs a.i./A; MRID 47701639 - vegetative vigor: monocot EC25 > 0.2676 

lbs a.i./A, NOAEC = 0.2676 lbs a.i./A, dicot EC25 = 0.0748 lbs a.i./A, NOAEC = 0.0168 

lbs a.i./A), assuming liquid ground spray (1% drift fraction) and aerial spray (5% drift 

fraction) application method, a default incorporation depth of 1 inch, and a solubility 

limit in water of 3.49 mg/L (at 25o

C), the RQ calculations (1.07-1.75), indicate that 

monocots in semi-aquatic areas (but not in dry areas or as a result of spray drift only 

areas) exposed to runoff and spray drift from either ground or aerial spray applications 

are most sensitive given that the listed species LOC (of 1) is exceeded for several 

maximum seasonal application rates (0.267 lbs a.i./A, 0.206 lbs a.i./A for ground spray 

applications and 0.120 lbs a.i./A for aerial spray applications, see Table 36). Changing 

the application rate from 0.267 to 0.2136 lbs a.i./A (the maximum single application rate) 

alters the RQ from 1.75 to 1.40 but does not change the risk conclusion for ground spray 

applications with KIH-485/Pyroxasulfone W85 formulations. The maximum seasonal

and maximum single application rate for the V-10233 Herbicide Water Dispersible 

Granules commercial label is the same (i.e., 0.206 lbs a.i./A); therefore, the RQ 

calculations and risk conclusions for ground spray applications with this formulation do 

not change. Similarly, the maximum seasonal and maximum single application rate for 

the V-10233 Herbicide label, which is the only label with proposed aerial spray 

applications, is the same (i.e., 0.120 lbs a.i./A); therefore, the RQ calculations and risk 

conclusions specifically regarding aerial spray applications with this formulation do not 

change. The terrestrial plant studies generally indicated effects on length (height) and/or 

dry weight; additional effects included chlorosis, necrosis, stem and leaf curl. Given that 

LOCs were exceeded for the given maximum seasonal as well as maximum single

applications, risk to terrestrial plants is expected as a result of pyroxasulfone use on corn, 

soybean, winter wheat, fallow land, and non-crop sites. Reducing the maximum seasonal 

application rate would alleviate the risk concern. 

Risk from contaminated irrigation water

Predicted groundwater concentrations of pyroxasulfone (equivalent to the equilibrium 

concentration taken over a 30 year period) were used to estimate the potential phytotoxic 

effects from irrigation water to plants and sensitive crops on the treated field. It is 

assumed that a one-acre field is irrigated with one inch of water containing pyroxasulfone 

at the equilibrium concentration. There are no non-listed plant LOC exceedances (on the 

basis of EEC/ EC25); however, given the estimates for the DE and WI scenarios, listed 
114

plant LOCs are exceeded (on the basis of EEC/NOAEC) with RQs of 1.12 and 2.01 for 

both monocot and dicot species. Therefore, risk to listed terrestrial plants and potentially 

sensitive crops located on the irrigated field are expected as a result of use of 

pyroxasulfone contaminated irrigation water at the estimated levels. 

3. Review of Incident Data 

With the proposed uses on corn, wheat, soybean, and non-crop sites, pyroxasulfone will 

be applied in the United States for the first time. Therefore, no incident data are available 

at this time. 

4. Endocrine Effects 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and 

are found to have the potential to interact with E, A, or T hormonal systems will proceed 

to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any 

adverse endocrine related effects caused by the substance, and establish a dose-response 

relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA is issuing test orders/data call-ins for the 

first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert 

ingredients. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

Pyroxasulfone is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data 

call-ins for all pesticide active ingredients. 

For further information on the status of the EDSP, the policies and procedures, the list of 

67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/. 
115

5. Federally Threatened and Endangered (Listed) Species 

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all 

federal agencies to consult with the National Marine Fisheries Service (NMFS) for 

marine and anadromous listed species, or the United States Fish and Wildlife Services 

(FWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that 

may affect listed species or their designated habitat. Each federal agency is required 

under the Act to insure that any action they authorize, fund, or carry out is not likely to 

jeopardize the continued existence of a listed species or result in the destruction or 

adverse modification of designated critical habitat. To jeopardize the continued existence 

of a listed species means "to engage in an action that reasonably would be expected, 

directly or indirectly, to reduce appreciably the likelihood of both the survival and 

recovery of a listed species in the wild by reducing the reproduction, numbers, or 

distribution of the species" (50 C.F.R. § 402.02). 

To facilitate compliance with the requirements of the Endangered Species Act 

(subsection (a)(2)), the Office of Pesticide Programs has established procedures to 

evaluate whether a proposed registration action may directly or indirectly reduce 

appreciably the likelihood of both the survival and recovery of a listed species in the wild 

by reducing the reproduction, numbers, or distribution of any listed species (USEPA, 

2004). After the Agency’s screening level risk assessment is conducted, if any of the 

Agency’s listed species LOCs are exceeded for either direct or indirect effects, an 

analysis is conducted to determine if any listed or candidate species may co-occur in the 

area of the proposed pesticide use or areas downstream or downwind that could be 

contaminated from drift or runoff/erosion. If listed or candidate species may be present 

in the proposed action areas, further biological assessment is undertaken. The extent to 

which listed species may be at risk then determines the need for the development of a 

more comprehensive consultation package as required by the Endangered Species Act. 

Both acute endangered species and chronic risk LOCs are considered in the screeninglevel risk assessment of pesticide risks to listed species. Endangered species acute LOCs 

are a fraction of the non-endangered species LOCs or, in the case of endangered plants, 

RQs are derived using lower toxicity endpoints than non-endangered plants. Therefore, 

concerns regarding listed species within a taxonomic group are triggered in exposure 

situations where restricted use or acute risk LOCs are triggered for the same taxonomic 

group. The risk assessment also includes an evaluation of the potential probability of 

individual effects for exposures that may occur at the established endangered species 

LOC both in the risk characterization and the endangered species sections. This 

probability is calculated using the established dose/response relationship and assumes a 

probit (probability unit) dose/response relationship. 
116

a. Action Area 

For listed species assessments, the action area is considered to be the area affected 

directly or indirectly by the Federal action and not merely the immediate area where 

pyroxasulfone is applied. At the initial Level 1 screening assessment, broadly described 

taxonomic groups are considered, and thus, conservatively assumes that listed species 

within those broad groups are co-located with the pesticide treatment area. This means 

that terrestrial plants and wildlife are assumed to be located on or adjacent to the treated 

site and aquatic organisms are assumed to be located in a surface water body adjacent to 

the treated site. The assessment also assumes that listed species are located within the 

area of highest exposure to the pesticide, and that exposure will decrease with increasing 

distance from the treated area. 

If the assumptions associated with the screening-level action area result in RQs that are 

below the listed species LOCs, a "no effect" determination conclusion is made with 

respect to listed species in that taxa, and no further refinement of the action area is 

necessary. Furthermore, RQs below the listed species LOCs for a given taxonomic group 

indicate no concern for indirect effects upon listed species that depend upon the 

taxonomic group covered by the RQ as a resource. However, in situations where the 

screening assumptions lead to RQs in excess of the listed species LOCs for a given 

taxonomic group, a potential for a "may affect" conclusion exists and may be associated 

with direct effects on listed species belonging to that taxonomic group or may extend to 

indirect effects upon listed species that depend upon that taxonomic group as a resource. 

In such cases, additional information on the biology of listed species, the locations of 

these species, and the locations of use sites could be considered along with available 

information on the fate and transport properties of the pesticide to determine the extent to 

which screening assumptions regarding an action area apply to a particular listed 

organism. These subsequent refinement steps could consider how this information would 

impact the action area for a particular listed organism and may potentially include areas 

of exposure that are downwind and downstream of the pesticide use site. 

b. Taxonomic Groups Potentially at Risk 

The preliminary risk assessment for endangered species indicates that the proposed use 

and application rate for pyroxasulfone either exceeds the Endangered Species LOCs or 

may directly affect the following taxonomic groups: 

 Terrestrial plants 

 Aquatic plants 

 Birds (as well as reptiles, terrestrial-phase amphibians) 

 Mammals 
117

Concerns For Federally Listed as Endangered and/or Threatened Species 

Table 38. Listed Species Risks Associated With Direct or Indirect Effects from Pyroxasulfone use 

Listed Taxon Direct Effects Indirect Effects

Terrestrial and semi-aquatic plants - monocots Yes Yes4

 

Terrestrial and semi-aquatic plants – dicots No Yes4

Terrestrial invertebrates No Yes4

Birds Yes (chronic) Yes4

Terrestrial-phase amphibians Yes (chronic) Yes4

Reptiles Yes (chronic) Yes4

Mammals Yes (chronic) Yes4

 Aquatic non-vascular plants Yes Yes4

Aquatic vascular plants Yes Yes4

Freshwater (FW) fish No Yes4

Aquatic-phase amphibians No Yes4

Freshwater (FW) invertebrates No Yes4

Marine/estuarine (M/E) fish No3 Yes4

Marine/estuarine (M/E) invertebrates (mollusk) No3 Yes4

1

 Results from birds used as surrogate for assessing risk to terrestrial-phase amphibians and reptiles 

2

 Results from freshwater fish used as surrogate for assessing risk to aquatic-phase amphibians 3

 Assumption of no expected risk or direct effect is made on the basis of freshwater fish and invertebrate data. 

4 From effects to mammals, birds, plants 

1. Discussion of risk quotients

The Agency’s LOCs for terrestrial and aquatic plants, mammals (chronic), and birds 

(chronic) are exceeded for the use of pyroxasulfone as outlined in previous sections. 

Should estimated exposure levels occur in proximity to listed resources, the available 

screening level information suggests a potential concern for direct effects on listed 

species within the taxonomic groups listed above associated with the uses of 

pyroxasulfone as described in Section III.A. The registrant must provide information on 

the proximity of federally listed terrestrial and aquatic plants, mammals, birds, reptiles, 

and terrestrial-phase amphibians to the pyroxasulfone use sites. This requirement may be 

satisfied in one of three ways: 1) having membership in the FIFRA Endangered Species 

Task Force (Pesticide Registration [PR] Notice 2000-2); 2) citing FIFRA Endangered 

Species Task Force data; or 3) independently producing these data, provided the 

information is of sufficient quality to meet FIFRA requirements. The information will be 

used by the OPP Endangered Species Protection Program to develop recommendations to 

avoid adverse effects to listed species. 
118

2. Probit dose response relationship

The Agency uses the probit dose response relationship as a tool for providing additional 

information on the potential for acute direct effects to aquatic and terrestrial animals 

(U.S. EPA, 2004). As part of the risk characterization, an interpretation of acute RQ for 

listed species is discussed. This interpretation is presented in terms of the chance of an 

individual event (i.e., mortality or immobilization) should exposure at the EEC actually 

occur for a species with sensitivity to pyroxasulfone on par with the acute toxicity 

endpoint selected for RQ calculation. To accomplish this interpretation, the Agency uses 

the slope of the dose response relationship available from the toxicity study used to 

establish the acute toxicity measures of effect for each taxonomic group that is relevant to 

this assessment. The individual effects probability associated with the acute RQ is based 

on the mean estimate of the slope and an assumption of a probit dose response 

relationship. In addition to a single effects probability estimate based on the mean, upper 

and lower estimates of the effects probability are also provided to account for variance in 

the slope, if available. The upper and lower bounds of the effects probability are based 

on available information on the 95% confidence interval of the slope. Studies with good 

probit fit characteristics (i.e., statistically appropriate for the data set) are associated with 

a high degree of confidence. Conversely, a low degree of confidence is associated with 

data from studies that do not statistically support a probit dose response relationship. In 

addition, confidence in the data set may be reduced by high variance in the slope (i.e., 

large 95% confidence intervals), despite good probit fit characteristics. In the event that 

dose response information is not available to estimate a slope, a default slope assumption 

of 4.5 (95% C.I.: 2 to 9) (Urban and Cook, 1986) is used. 

Individual effect probabilities are calculated based on an Excel spreadsheet tool IEC v1.1 

(Individual Effect Chance Model Version 1.1) developed by the U.S. EPA, OPP, 

Environmental Fate and Effects Division (June 22, 2004). The model allows for such 

calculations by entering the mean slope estimate (and the 95% confidence bounds of that 

estimate) as the slope parameter for the spreadsheet. In addition, the acute RQ is entered 

as the desired threshold. 

3. Data related to under-represented 

taxa

Effects data on under-represented taxonomic groups were not submitted by the 

Registrant. Effects data from other analyzed sources were either not obtained (ECOTOX 

Database, PAN Database) or were not available (publicly available ECOTOX) for this 

screening risk assessment. 

c. Indirect Effects Analysis 

In conducting a screen for indirect effects, direct effects LOCs for each taxonomic group 

are used to make inferences concerning the potential for indirect effects upon listed 

species. The listed species rely upon non-listed organisms in these taxonomic groups as 

resources critical to their life cycle. Pesticide-use scenarios, resulting in RQs that are 

below all direct effect listed species LOCs for all taxonomic groups assessed are 
119

considered of no concern for risks to listed species either by direct or indirect effects. 

However, there may be situations where a taxonomic group is not quantitatively assessed 

(e.g., some non-guideline terrestrial invertebrates), but other lines of evidence are 

sufficiently supportive of concerns for indirect effects on listed organisms that are 

dependant upon that taxonomic group. 

· Where One or More Animal Taxonomic Group RQs Exceed the LOC for 

Listed Species 

The Level I screening indirect effects analysis documents those types of dependencies 

upon non-listed organisms that could be important sources of indirect effects to listed 

organisms should effective levels of the pesticide coincide with locations of listed species 

and the biologically based resources upon which they depend. In cases where screeninglevel acute RQs for a given animal group equal or exceed the listed species acute LOC, 

the Agency uses the dose response relationship from the toxicity study used for 

calculating the RQ to estimate the probability of acute effects associated with an 

exposure equivalent to the EEC. This information serves as a guide to establish the need 

for and extent of additional analysis that may be performed using Services-provided 

“species profiles” as well as evaluations of the geographical and temporal nature of the 

exposure to ascertain if a not likely to adversely affect determination can be made. The 

degree to which additional analyses are performed is commensurate with the predicted 

probability of adverse effects from the comparison of dose response information with the 

EECs. The greater the probability that exposures will produce effects on a taxa, the 

greater the concern for potential indirect effects for listed species dependent upon that 

taxa, and therefore, the more intensive the analysis on the potential listed species of 

concern, their locations relative to the use site, and information regarding the use scenario 

(e.g., timing, frequency, and geographical extent of pesticide application). The greatest 

concerns would exist when exposure is associated with a risk higher than the effects 

probability associated with the non-listed LOC for a pesticide with an average slope of 

4.5. 

For pyroxasulfone, risks to listed species are predicted within the following taxa: 

terrestrial and aquatic plants, mammals, birds, reptiles, and terrestrial-phase amphibians. 

For example, given that the chronic LOC is exceeded for mammals, indirect effects to 

listed species (e.g., other mammals, birds, amphibians, reptiles, plants (pollination)) that 

rely on mammals as a primary food source, or on mammal burrows for shelter or 

breeding habitat, may be of concern. 

d. Critical Habitat 

In the evaluation of pesticide effects on designated critical habitat, consideration is given 

to the physical and biological features (constituent elements) of a critical habitat 

identified by the U.S Fish and Wildlife and National Marine Fisheries Services as 

essential to the conservation of a listed species and which may require special 

management considerations or protection. The evaluation of impacts for a screening 

level pesticide risk assessment focuses on the biological features that are constituent 
120

elements and is accomplished using the screening-level taxonomic analysis (risk 

quotients, RQs) and listed species levels of concern (LOCs) that are used to evaluate 

direct and indirect effects to listed organisms. 

The screening-level risk assessment has identified potential concerns for indirect effects 

on listed species for those organisms dependent upon terrestrial and aquatic plants, 

mammals, birds, reptiles, and terrestrial-phase amphibians. In light of the potential for 

indirect effects, the next step for EPA and the Service(s) is to identify which listed 

species and critical habitat are potentially implicated. Analytically, the identification of 

such species and critical habitat can occur in either of two ways. First, the agencies could 

determine whether the action area overlaps critical habitat or the occupied range of any 

listed species. If so, EPA would examine whether the pesticide's potential impacts on 

non-listed species would affect the listed species indirectly or directly affect a constituent 

element of the critical habitat. Alternatively, the agencies could determine which listed 

species depend on biological resources, or have constituent elements, that fall into the 

taxa that may be directly or indirectly impacted by the pesticide. Then EPA would 

determine whether use of the pesticide overlaps the critical habitat or the occupied range 

of those listed species. At present, the information reviewed by EPA does not permit use 

of either analytical approach to make a definitive identification of species that are 

potentially impacted indirectly or critical habitat that is potentially impacted directly by 

the use of the pesticide. EPA and the Service(s) are working together to conduct the 

necessary analysis. 

This screening-level risk assessment for critical habitat provides a listing of potential 

biological features that, if they are constituent elements of one or more critical habitats, 

would be of potential concern. These correspond to the taxonomic groups identified 

above as being of potential concern for indirect effects. This should serve as an initial 

step in problem formulation for further assessment of critical habitat impacts outlined 

above, should additional work be necessary. 

e. Co-occurrence Analysis 

The goal of the analysis for co-location is to determine whether sites of pesticide use are 

geographically associated with known locations of listed species. At the screening level, 

this analysis is accomplished using the LOCATES v. 2.13 database. The database uses 

location information for listed species at the county level and compares it to agricultural 

census data for crop production at the same county level of resolution. The product is a 

listing of federally listed species that are located within counties known to produce the 

crop upon which the pesticide will be used. 

Tables 39 and 40 below report the number of states and counties in which endangered 

species reside that have the proposed pyroxasulfone uses. The data suggest that there is 

considerable potential for exposure to a variety of endangered species (1,223 species 

total) from pyroxasulfone uses. For additional LOCATES output refer to Appendix G. 
121

Table 39. Number of Endangered Species Potentially Exposed to Pyroxasulfone with the Proposed Uses 

Mammals Amphibians Birds Reptiles Arachnids Insects Conf/Cyc Dicot Ferns Lichen Monocots 

Counties 1412 150 1469 398 15 259 8 930 51 22 553 

States 68 21 69 31 12 55 3 599 22 2 65 

Species 50 13 47 34 5 30 3 47 10 5 46 

Table 40. Number of Endangered Species Potentially Exposed to 

Pyroxasulfone with the Proposed Uses 

Bivalve Crustacean Fish Gastropod Marine Mammal 

Counties 556 75 872 57 556 

States 70 20 114 72 70 

Species 30 13 39 18 30 
122

C. Description of Assumptions, Limitations, Uncertainties, Strengths, and Data 

Gaps 

1. Assumptions, Limitations, and Uncertainties Related to 

Exposure for all Taxa 

a. Maximum Use Scenario 

The screening-level risk assessment focuses on characterizing potential ecological risks 

resulting from a maximum use scenario, which is determined from labeled statements of 

maximum application rate and number of applications with the shortest time interval 

between applications. The frequency at which actual uses approach this maximum use 

scenario may be dependant on herbicide resistance, timing of applications, cultural 

practices, and market forces. Furthermore, this assessment utilizes the maximum 

seasonal application rate for RQ calculation over the maximum single application rate for 

several reasons. The maximum seasonal application rate was used to calculate RQs given 

that the maximum single application rates were either equal or approximately equal to the 

seasonal rate. In addition, given that application intervals were not reported on the labels 

and pyroxasulfone’s persistence in water (half-lives ranging from 69 to 119 days) and 

soil (half-lives ranging from 142 to 533 days), the maximum seasonal rate was assumed 

appropriate for RQ calculations. Nevertheless, in cases where RQs exceeded LOCs, 

lower application rates were used for risk characterization. Furthermore, the seasonal 

application rate was assumed to be equivalent to annual application rate. 

2. Assumptions, Limitations, and Uncertainties Related to 

Exposure for Terrestrial Species 

a. Location of Wildlife Species 

For this screening-level terrestrial risk assessment, a generic bird or mammal was 

assumed to occupy either the treated field or adjacent areas receiving pyroxasulfone at 

the treatment rate on the field. Actual habitat requirements of any particular terrestrial 

species were not considered, and it was assumed that species occupy, exclusively and 

permanently, the modeled treatment area. Spray drift model predictions suggest that this 

assumption leads to an overestimation of exposure to species that do not occupy the 

treated field exclusively and permanently.

b. Routes of Exposure 

This screening-level assessment for ground (liquid) applications of pyroxasulfone 

considered dietary, inhalation, and drinking water exposure. Other routes of exposure that 

were not considered in the assessment are incidental soil ingestion exposure and dermal 

exposure. 
123

c. Dietary Intake and Other Limitations of Oral 

Studies in Terrestrial Species 

The avian acute oral study and the avian subacute dietary study each have limitations for 

estimating the risk to wild species exposed to pesticides in the environment. Both studies 

have a fixed exposure period and do not allow for differences in the responses of 

individuals to different durations of exposure. With the acute oral study, the chemical is 

administered in a single dose. This does not mimic wild bird exposure through multiple 

feedings. Also, it does not account for the effect of different environmental matrices on 

absorption rate into the gastrointestinal tract of the animal. With the acute dietary study, 

the endpoint is reported as the concentration mixed with food that produces a response 

rather than as the dose ingested. Although food consumption sometimes allows for 

estimation of a dose, calculations of the mg/kg/day are confounded by undocumented 

spillage of feed and how consumption is measured over the duration of the test. Usually, 

if measured at all, food consumption is estimated once at the end of the five-day exposure 

period. Group housing of birds undergoing testing allows for a measure of only the 

average consumption per day for a group, and consumption estimates can be further 

confounded if birds die within a treatment group. In addition, the dietary study utilizes 

young birds. The exponential growth of young birds complicates the estimate of the 

dose; controls often nearly double in size over the duration of the test. Since weights are 

only taken at the initiation and at the end of the exposure period, the dose per body 

weight (mg/kg) is difficult to estimate with any precision. The interpretation of this test 

can be further confounded by dietary consumption. Estimation of the acute LC50 value is 

not only a function of the intrinsic toxicity of the pesticide, but also the willingness of the 

birds to consume treated food. 

In addition to the uncertainties associated with the two toxicity studies utilized for 

estimating acute risk to birds, other factors, not normally taken into account in a 

screening level risk assessment may narrow the differences between the dose-based and 

dietary-based acute RQs for birds. The factors include differences in gross energy and 

assimilative efficiency of laboratory feed versus food items in the field, basic 

maintenance metabolic rates between wild birds and captive birds, seasonal free living 

dietary requirements for wild birds (including gorging behavior) and specific food 

avoidance behavior. These uncertainties may either overestimate or underestimate the 

risk in a screening level assessment. 

Gross Energy and Assimilative Efficiency. This screening level risk assessment does 

not allow for gross energy and assimilative efficiency differences between wildlife food 

items and laboratory feed. For example, a typical laboratory avian feed, as used, contains 

approximately 2750 kcal/ kg. The Agency’s Wildlife Exposure Factors Handbook (U.S. 

Environmental Protection Agency, 1993) presents the following dry-weight and fresh 

weight caloric contents for selected wildlife food items: 
124

Food Item Energy Dry (kcal/kg) Energy Fresh 

(kcal/kg) 

grasses 4200 1300 

broadleaf forage 4200 2200 

seeds 5100 4700 

fruits 2000 1100 

insects 5600 1600 

On gross energy content alone, direct comparison of a laboratory dietary concentrationbased effects threshold to a fresh-weight pesticide residue estimate would result in an 

underestimation of field exposure by food consumption by a factor of 1.25 - 2.5 for most 

food items. Only for seeds would the direct comparison of dietary threshold to residue 

estimate lead to an overestimate of exposure. 

Depending upon species and dietary matrix, bird assimilation of wild diet energy ranges 

from 23 - 80%, and mammal’s assimilation ranges from 41 - 85% (U.S. EPA, 1993). If it 

is assumed that laboratory chow is formulated to maximize assimilative efficiency (e.g., a 

value of 85%), a potential for underestimation of exposure may exist by assuming that 

consumption of food in the wild is comparable with consumption during laboratory 

testing. 

Metabolic Rates. In the screening process, exposure may be underestimated because 

metabolic rates are not related to food consumption. For example, the Wildlife Exposure 

Factors Handbook (U.S. EPA, 1993) includes allometric models for estimating both 

existing metabolic rate (EMR) and free living metabolic rate (FMR). EMR is the 

metabolic rate necessary for animal maintenance in captivity without body weight loss, a 

condition similar to caged test animals. FMR is the energy requirement for an organism 

in the wild. For passerine birds these relationships are as follows: 

EMR (kcal/day) = 1.572 (body weight g) 0.6210

FMR (kcal/day) = 2.123 (body weight g) 0.749 

Using a weight range for passerines of 10 - 150 g, the EMR predictions range from 6.6 to 

35.3, and the FMR ranges from 11.9 to 90.5 kcal/day. Thus, it appears that not 

accounting for increased energy demands of organisms in the wild when comparing 

dietary residues to dietary toxicity thresholds represents about a two-fold underestimation 

in exposure potential.

Free Living Metabolic Requirements. The screening procedure does not account for 

situations where the feeding rate may be above or below requirements to meet free living 

metabolic requirements. Gorging behavior is a possibility under some specific wildlife 

scenarios (e.g., bird migration) where the food intake rate may be greatly increased. 

Kirkwood (1983) has suggested that an upper-bound limit to this behavior might be the 

typical intake rate multiplied by a factor of 5. 
125

Avoidance. In contrast is the potential for avoidance, operationally defined as animals 

responding to the presence of noxious chemicals in their food by reducing consumption 

of treated dietary elements. This response is seen in nature where herbivores avoid plant 

secondary compounds. For agrochemicals, Dolbeer et al. (1994) reported that the use of 

methiocarb on fruit crops reduced depredation by birds. Of course, chemical treatment of 

food sources and any subsequent avoidance of those food sources by a species may, in 

itself, result in detrimental effects on the energetics of the species. 

d. Incidental Releases Associated with Use 

This risk assessment was based on the assumption that the entire treatment area is subject 

to pesticide application at the rates specified on the label. Uneven application of the 

pesticide through changes in calibration of application equipment, spillage, and localized 

releases at specific areas of the treated field that are associated with specifics of the type 

of application equipment were not accounted for in this assessment. 

e. Residue Levels Selection 

The Agency relies on the work of Fletcher et al. (1994) for setting the assumed pesticide 

residues in wildlife dietary items. These residue assumptions are believed to reflect a 

realistic upper-bound residue estimate, although the degree to which this assumption 

reflects a specific percentile estimate is difficult to quantify. It is important to note that 

the field measurement efforts used to develop the Fletcher estimates of exposure involve 

highly varied sampling techniques. It is entirely possible that much of these data reflects 

residues averaged over the entire above ground plants in the case of grass and forage 

sampling. Depending upon a specific wildlife species’ foraging habits, whole 

aboveground plant samples may either underestimate or overestimate actual exposure. 

f. TerrPlant Model 

At this time, the TerrPlant model cannot accurately estimate terrestrial exposure levels 

with pesticides applied with multiple applications or application intervals. The 

technology is not yet available for these types of estimations. The maximum seasonal

application rate was used to calculate RQs given that the maximum single application 

rates were either equal or approximately equal to the seasonal rate. In addition, given that 

application intervals were not reported on the labels and pyroxasulfone’s persistence in 

water (half-lives ranging from 69 to 119 days) and soil (half-lives ranging from 142 to 

533 days), the maximum seasonal rate was assumed appropriate for RQ calculations. 

Nevertheless, in cases where RQs exceeded LOCs, lower application rates were used for 

risk characterization. Furthermore, the seasonal application rate was assumed to be 

equivalent to annual application rate. 
126

3. Assumptions, Limitations, and Uncertainties Related to 

Effects Assessment 

a. Sublethal Effects 

For an acute risk assessment, the screening risk assessment relies on the acute mortality 

endpoint as well as a suite of sublethal responses to the pesticide, as determined by the 

testing of species response to chronic exposure conditions and subsequent chronic risk 

assessment. Consideration of additional sublethal data in the assessment is exercised on a 

case-by-case basis and only after careful consideration of the nature of the sublethal 

effect measured and the extent and quality of available data to support establishing a 

plausible relationship between the measure of effect (sublethal endpoint) and the 

assessment endpoints. 

 

b. Age Class and Sensitivity of Effects Thresholds 

Testing of juvenile organisms may overestimate toxicity at older age classes for pesticidal 

active ingredients that act directly (without metabolic transformation) because younger 

age classes may not have the enzymatic systems associated with detoxifying xenobiotics. 

However, the influence of age may not be uniform for all compounds, and compounds 

requiring metabolic activation may be more toxic in older age classes. The risk 

assessment uses the most sensitive life-stage information as the conservative screening 

endpoint. 

c. Use of Most Sensitive Species Tested 

Screening risk assessment relies on a selected toxicity endpoint from the most sensitive 

species tested; however, the selected toxicity endpoints do not necessarily reflect 

sensitivity of the most sensitive species in a given environment. The relative position of 

the most sensitive species tested in the distribution of all possible species is a function of 

the overall variability among species to a particular chemical. Toxicity thresholds may 

vary up to four orders of magnitude across species for some chemicals4

. Therefore, risk 

conclusions may under- or overestimate actual ecological risk for a given species. 

4. Assumptions, Limitations, Uncertainties, Strengths, and 

Data Gaps Related to the Acute and Chronic LOC’s 

The risk characterization section of the assessment document includes an evaluation of 

the potential for individual effects to listed species at an exposure level equivalent to the 

LOC. This evaluation is based on the median lethal dose estimate and dose/response 

 4

 Mayer, F.L. and M.R. Ellersieck, 1986. Manual of acute toxicity: Interpretation and data 

base for 410 chemicals of freshwater animals. Resource Publication 160. U. S. Fish and 

Wildlife Service. Department of the Interior, Washington, D.C., 579 p.
127

relationship established for the effects study corresponding to each taxonomic group for 

which the LOCs are exceeded. The slope of the probit-dose response is used to generate 

a probability of individual effects near the low end tail of the curve. Predictions based on 

low probability events are by nature highly uncertain. Moreover, for this assessment the 

dose-response curve representing a given taxa is generated from one study using one 

species. It is likely that the resulting dose-response relationship does not represent the 

response of all species within a taxa. Calculating the probability of individual effects at 

the lower and upper bounds of the slope is designed to address this source of uncertainty 

but the extent to which this captures the variability within a taxa is unknown. In some 

cases, a probit dose-response relationship cannot be calculated. In these instances, event 

probabilities are calculated based on a default slope assumption of 4.5 (Urban and Cook, 

1986). 

V. Literature Cited 

Open Literature and Other Documents

 

Arnot, J.A. and F.A.P.C. Gobas. 2004. A food web bioaccumulation model for organic 

chemicals in aquatic ecosystems. Environmental Toxicology and Chemistry, v23 

(10), 2343-2355. 

Fletcher, J.S., J.E. Nellesson, and T. G. Pfleeger. 1994. Literature review and evaluation 

of the EPA food-chain (Kenaga) nomogram, an instrument for estimating 

pesticide residues on plants. Environ. Tox. and Chem. 13(9):1383-1391. 

Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of 

representative data as a basis for estimation of their magnitude in the 

environment. IN: F. Coulston and F. Corte, eds., Environmental Quality and 

Safety: Chemistry, Toxicology and Technology. Vol 1. George Theime 

Publishers, Stuttgart, Germany. pp. 9-28. 

Urban, D.J. and N.J. Cook, 1986. Hazard Evaluation Division Standard Evaluation 

Procedure Ecological Risk Assessment. EPA 540/9-85-001. U.S. Environmental 

Protection Agency, Office of Pesticide Programs, Washington D.C. 

U.S. Environmental Protection Agency (USEPA). 1993. Wildlife Exposure Factors 

Handbook. Office of Research and Development, Washington, D.C. EPA/600/R13/187a. 

U.S. Environmental Protection Agency (USEPA) 1998. Guidelines for Ecological Risk 

Assessment. EPA/630/R-95/002F. Published in 63 FR 26846; May 14, 1998. 

U.S. Environmental Protection Agency, Washington, DC. April, 1998. 
128

U.S. Environmental Protection Agency (USEPA). 2004. Overview of the Ecological 

Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental 

Protection Agency. Endangered and Threatened Species Effects Determinations. 

Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide 

Programs, Washington, D.C. January 23, 2004. Online at: 

http://www.epa.gov/oppfead1/endanger/consultation/ecorisk-overview.pdf

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of 

Pesticide Programs. U.S. Environmental Protection Agency, Office of Prevention, 

Pesticides and Toxic Substances, Office of Pesticide Programs, Washington DC. 

January 23, 2004. 

U.S. Environmental Protection Agency (USEPA). 2008. (Terrestrial Residue EXposure 

model) Version 1.4.1 (10/09/08). Environmental Fate And Effects Division, 

Office Of Pesticide Programs, U.S. Environmental Protection Agency. 

Willis, G.H., and L.L. McDowell. 1987. Pesticide Persistence on Foliage in Reviews of 

Environmental Contamination and Toxicology. 100: 23-73. 

Fate Studies Submitted to the USEPA/Office of Pesticide Programs

Graham R. and Troth K. 2008. [14C]-KIH-485: Aerobic Soil Metabolism and 

Degradation. Covance Laboratories Ltd., Harrogate, England. Report No.: 0535/131-

D2149 August 2008. Unpublished. MRID # 47701736. 

Graham R. (2008). [14C]-KIH-485: Anaerobic Soil Metabolism and Degradation. 

Covance Laboratories Ltd., Harrogate, England. Report No. 0535/132-D2149. August 

27, 2008. Unpublished. MRID # 47701739 

Graham R. and Scholey A. (April 2007). [14C]-KIH-485: Photo-degradation on a Soil 

Surface. Covance Laboratories Europe, Harrogate, England. Report No.: 0535/142-

D2149. November 10, 2006. Unpublished. MRID # 47701735 

Graham R. (2007). [14C]-KIH-485: Aerobic Aquatic Metabolism. Covance Laboratories 

Ltd., Covance Report Number: 0535/133-D2149. December 13, 2007. Unpublished. 

MRID # 47701740 

Graham R., Scholey A. and Gilbert J. (2008). [14C]-KIH-485: Anaerobic Aquatic 

Metabolism. Covance Laboratories Ltd. Report No.: 0535/134-D2149. November 27, 

2008. Unpublished. MRID # 47701741 

Hewitt, A.J. (2009). Atomization Droplet Size Spectra for KIH-485. The University of 

Queensland, Australia. Study Number L08-001. February 23, 2009. Unpublished. MRID 

# 47701622 
129

Marin, J. E. 2008, KIH-485 field dissipation study in bare ground. PTRL West, Inc., 

California, USA. Report No.: 1505W. December 23, 2008. Unpublished. MRID # 

47701745 

Marin, J. (2008). Aquatic Field Dissipation of Residues Following Application of KIH485 WG85 to Water. PTRL West, Inc. December 17, 2008. Report 1662W. 

Unpublished. MRID # 47701747 

McKemie, T.H. and Shepler K. (2004): Soil Adsorption-Desorption of 14C-KIH-485 by 

the Batch Equilibrium Method: Adsorption/desorption on Soils. PTRL West Inc., 

Hercules, CA, USA. Report No. 1206W. January 23, 2004. Unpublished. MRID # 

47701742 

Ponte, M. and Schick, M., 2008. Aged Leaching of [14C]KIH-485 in Representative 

Agricultural Soils. PTRL West, Inc., Hercules, CA. Report No. 1629W. September 16, 

2008. Unpublished. MRID # 47701743 

Ponte, M. and Schick, M. (2008). Aerobic Soil Metabolism of [14C]-KIH-485 

(Pyroxasulfone), PTRL West, Inc., PTRL West, Inc., Hercules, CA 94547, Report 

Number 1584W. September 16, 2008 Unpublished. MRID #47701737. 

Ponte, M. December 2008. Aerobic Soil Metabolism of [14C]-KIH-485 M-1 (Major 

Metabolite of KIH-485). PTRL West, Inc., California, USA. Report No.: 1631W-1. 

Unpublished. MRID # 47701738 

Ponte, M. and Schick, M. 2008. Aged Leaching of [14C]KIH-485 M-1 (Major Metabolite 

of KIH-485) in Representative Agricultural Soils. PTRL West, Inc., Hercules, CA 

94547. Report No.: 1630W. November 11, 2008. Unpublished. MRID # 47701744 

Radunz, L. (2009). Determination of residues of AE 2196191 (pyroxasulfone) in soil 

after harvest following an application of AE 2196191 850 WG at either 125 or 150 g a.i. 

/ha at sowing. Bayer CropScience Residue Laboratory, Queensland, Australia. Report 

No. BCS-0276. 10 March 2009. Unpublished. MRID # 47701746 

Swales S. 2003. [14C]-KIH-485: Hydrolytic Stability. Covance Laboratories Europe, 

Harrogate, England. Report 535/97-D2149. May 14, 2003. Unpublished. MRID # 

47701733 

Swales S, (2004). [14C]-KIH-485: Photo-degradation in Sterile, Aqueous Solution. 

Covance Laboratories Europe, Harrogate, England. Report No.: 535/96-D2149. February 

19, 2004. Unpublished. MRID # 47701734 
130

Effects Studies Submitted to the USEPA/Office of Pesticide Programs

Blankinship, A. S., Kendall, T. Z. and Krueger, H. O. (2007) KIH-485 (pyroxasulfone as 

provisionally approved): A 96-Hour Flow-Through Acute Toxicity Test with the 

Saltwater Mysid (Americamysis bahia). Wildlife International, Ltd., Maryland, USA. 

Project Number 267A-114. May 31, 2007. Unpublished. MRID 47701625 

Blankinship, AS, Kendall, TZ, and Krueger, HO (2007) KIH-485 (pyroxasulfone as 

provisionally approved): A 96-Hour Shell Deposition Test with the Eastern Oyster 

(Crassostrea virginica). Wildlife International, Ltd., Maryland, USA. Project Number 

267A-115. December 4, 2007. Unpublished. MRID 47701624 

Bull, A. (2009) KIM-485 M-28: Acute Oral Toxicity to the Rat: (Acute Toxic Class 

Method): Final Report. Project Number: KCI0374. Unpublished study prepared by 

Huntingdon Life Sciences, Ltd. 28 p. March 31, 2009. MRID 47701755 

Desjardins, D, Kendall, TZ, and Krueger, HO (2004) KIH-485: A 96-Hour Toxicity Test 

with the Freshwater Alga, (Anabaena flos-aquae). Wildlife International, Ltd., 

Maryland, USA. Project Number 267A-107. July 12, 2004. Unpublished. MRID 

47701644 

Desjardins, D, Kendall, TZ and Krueger, HO (2004) KIH-485: A 96-Hour Toxicity Test 

with the Freshwater Diatom (Navicula pelliculosa). Wildlife International, Ltd., Easton, 

Maryland, USA. Project Number 267A-108. August 4, 2004. Unpublished. MRID 

47701645 

Desjardins, D, Kendall, TZ and Krueger, HO (2004). KIH- 485: A 96-Hour Toxicity Test 

with the Marine Diatom (Skeletonema costatum). Wildlife International, Ltd., Easton, 

Maryland, USA. Project Number 267A-109. June 7, 2004 – July 22, 2004. 

Unpublished. MRID 47701646 

Desjardins, D, Kendall, TZ and Krueger, HO (2004) KIH-485: A 7-Day Toxicity Test 

With Duckweed (Lemma gibba G3). Wildlife International, Ltd., Easton, Maryland, 

USA. Project Number 267A-110. August 4, 2004. Unpublished. MRID 47701640 

Dreher, D. (2003) KIH-485: Acute Oral Toxicity Study in the Female Rat (Acute Toxic 

Class): Final Report. Project Number: 0535/106. Unpublished study prepared by Covance 

Laboratories, Ltd. 26 p. September 1, 2003. MRID 47701677 

Durando, J. (2008) Acute Inhalation Toxicity Study in Rats – Limit Test with V-10233 

(VC 1763). Project Number: 25593, VP- 32683. Unpublished study prepared by 

Eurofins-Product Safety Laboratories. 35 p. October 31, 2008. MRID 47702107 
131

Durando, J. (2008) Acute Oral Toxicity Up and Down Procedure in Rats with V-10233 

(VC 1763). Project Number: 25591, VP-32679. Unpublished study prepared by EurofinsProduct Safety Laboratories. 27 p. November 3, 2008. MRID 47702105. 

Frey, LT, Martin, KH, Beavers, JB, and Jaber, M (2007). KIH-485 (pyroxasulfone as 

provisionally approved): A Reproduction Study with the Mallard. Wildlife International, 

Ltd., Easton, Maryland, USA. Project Number 267-122. December 21, 2007. 

Unpublished. MRID 47701636 

Frey, L.T., Martin, K.H., Beavers, J.B. and Jaber, M. (2007) KIH-485 (pyroxasulfone as 

provisionally approved): A Reproduction Study with the Northern Bobwhite. Wildlife 

International, Ltd., Easton, Maryland, USA. Project Number 267-121. October 29, 

2007. Unpublished. MRID 47701635 

Gallagher, SP and Beavers, JB (2006) Pyroxasulfone (KIH-485) TGAI: (provisionally 

approved): An Acute Oral Toxicity Study with the Northern Bobwhite. Wildlife 

International, Ltd., Easton, Maryland, USA. Project Number 267-120. October 31, 

2006. Unpublished. MRID 47701631 

Gallagher, SP, Martin, KH, and Beavers, JB (2006) KIH-485 Herbicide (TGAI): A 

Dietary LC50 Study with the Northern Bobwhite. Wildlife International, Ltd., Easton, 

Maryland, USA. Study No. 267-115. July 28, 2006. Unpublished. MRID 47701633 

Gallagher, S.P., Martin K.H., and Beavers, J.B. (2006) KIH-485 Herbicide (TGAI): A 

Dietary LC50 Study with the Mallard. Wildlife International, Ltd. Easton, Maryland, 

USA. Project Number 267-116. July 28, 2006. Unpublished. MRID 47701634 

Giannini, P. (2008) KIH-485 (Pyroxasulfone, ISO Approved) WG85: Acute Oral 

Toxicity Study in Rats: Final Report. Project Number: C00933. Unpublished study 

prepared by RCC, Ltd. 16p. September 5, 2008. MRID 47701916 

Gray, J. (2009) KIH-485 (pyroxasulfone) WG85: Acute toxicity to Typhlodromus pyri in 

the laboratory. Huntington Life Sciences Ltd., Huntingdon, Cambridgeshire, UK. Report 

No.: KCI-0366. March 5, 2009. Unpublished. MRID 47701753 

Hubbard, PM, Beavers, JB (2008) KIH-485 (pyroxasulfone provisionally approved): An 

Acute Oral Toxicity Study with the Zebra Finch (Poephila guttata). Wildlife Intl. Ltd., 

Maryland, Report No: 267-125. October 21, 2008. Unpublished. MRID 47701632 

Lewis, J.M. (2006) KIH-485TGAI: One-Generation Reproduction Study in Rats. DuPont 

Haskell Global Centers for Health and Environmental Sciences, E.I. DuPont de Nemours 

& Company, Delaware, USA. Report No. 16243. January 16, 2006. Unpublished. 

MRID 47701705 

Lewis, J. M. (2007) KIH-485TGAI (Pyroxasulfone as previously approved): 

Developmental Toxicity Study in Rabbits. Haskell Laboratory for Health and 
132

Environmental Sciences, Delaware, U.S.A. Report No.: 21678. December 18, 2007. 

Unpublished. MRID 47701704 

Mead, DC, McKenzie, J, (2004) KIH-485: Algal Inhibition Test. Safepharm Laboratories 

Ltd., Derbyshire, U.K. Project Number 131/528. February 13, 2004. Unpublished. MRID 

47701643 

Minderhout, T, Kendall, T, Krueger, H (2008) KIH-485 M-1: A 96-Hour Toxicity Test 

with the Freshwater Alga. Wildlife International, Ltd., Easton, Maryland, USA 267A119. July 1, 2008. Unpublished. MRID 47701647 

Minderhout, T., Kendall, T., Krueger, H. (2008). KIH-485 M-3: A 96-Hour Toxicity Test 

with the Freshwater Alga. Wildlife International, Ltd., Easton, Maryland, USA 267A121. July 1, 2008. Unpublished. MRID 47701648 

Minderhout, T, Kendall, TZ. and Krueger HO, (2008). KIH-485 M-1: A seven day 

static-renewal toxicity test with duckweed (Lemna gibba G3). Wildlife International, 

Ltd., Easton, Maryland, USA. Project Number 267A-120. July 1, 2008. Unpublished. 

MRID 47701641 

Minderhout, T, Kendall, TZ, and Krueger. HO, (2008). KIH-485 M-3: A seven day 

static-renewal toxicity test with duckweed (Lemna gibba G3). Wildlife International, 

Ltd., Easton, Maryland, USA. Project Number 267A – 122. July 1, 2008. Unpublished. 

MRID 47701642 

Mullaney, T. (2005) KIH-485 M-1: Acute Oral Toxicity in the Rat - Acute Toxic Class 

Method. Project Number: 131/591. Unpublished study prepared by Safepharm 

Laboratories, Ltd. 21 p. June 9, 2005. MRID 47701678 

Mullaney, T. (2004) KIH-485 M-3: Acute Oral Toxicity in the Rat - Acute Toxic Class 

Method. Project Number: 131/574. Unpublished study prepared by Safepharm 

Laboratories, Ltd. 20 p. August 5, 2004. MRID 47701679 

Munley, S. B. (2007) KIH-485TGAI (Pyroxasulfone as previously approved): 

Developmental Toxicity Study in Rats. Haskell Laboratory for Health and Environmental 

Sciences, Newark, Delaware. Study No. 20817. August 23, 2007. Unpublished. MRID 

47701702 

Munley, S.M. (2008) KIH-485TGAI: Multigeneration Reproduction Study in Rats. 

DuPont Haskell Global Centers for Health and Environmental Sciences, E.I. DuPont de 

Nemours & Company, Delaware, USA. Report No. 18827. July 11, 2008. Unpublished. 

MRID 47701706 

Palmer, SJ, Kendall, TZ, and Krueger, HO (2007) KIH-485 (pyroxasulfone as 

provisionally approved): An Early Life-Stage Toxicity Test with the Fathead Minnow 
133

(Pimephales promelas). Wildlife International, Ltd., Easton, Maryland, USA. Project 

Number 267A-118. December 4, 2007. Unpublished. MRID 47701630 

Palmer, S. K., Kendall, T. Z., and Krueger, H. O. (2007) KIH-485 (pyroxasulfone as 

provisionally approved). A 96-Hour Flow-Through Acute Toxicity Test with the 

Sheepshead Minnow (Cyprinodon variegatus). Wildlife International, Ltd. Maryland, 

USA. Project Number 267A-116. August 2, 2007. Unpublished. MRID 47701628 

Palmer, S. J., Kendall, T. Z. and Krueger H. O. (2008) KIH-485 (pyroxasulfone as 

provisionally approved): A Flow-through Life-cycle Toxicity Test with the Cladoceran 

(Daphnia magna). Wildlife International, Ltd., Maryland, USA. Project Number 267A117 February 11, 2008. Unpublished. MRID 47701629 

Porch, J.R., Krueger, H.O. (2008) Pyroxasulfone: An Acute Toxicity Study with the 

Earthworm in an Artificial Soil Substrate. Wildlife International, Ltd. Maryland, U.S.A. 

Project No.: 267-126. December 17, 2008. Unpublished. MRID 47701748 

Porch, JR, Martin, KH, and Krueger, HO (2008) KIH-485 (pyroxasulfone as 

provisionally approved): A Toxicity Test to Determine the Effects of the Test Substance 

on Seedling Emergence of Ten Species of Plants. Wildlife International, Ltd., Maryland, 

USA. Project Number 267-123. March 20, 2008. Unpublished. MRID 47701638 

Porch, JR, Martin, KH, and Krueger, HO (2008) KIH-485 (pyroxasulfone as 

provisionally approved): A Toxicity Test to Determine the Effects of the Test Substance 

on Vegetative Vigor of Ten Species of Plants. Wildlife International, Ltd., Maryland, 

USA. Project Number 267-124. March 24, 2008. Unpublished. MRID 47701639 

Rodgers, M. (2009). Pyroxasulfone: To Determine the Effects on Reproduction and 

Growth of the Earthworm, Eisenia fetida. Huntingdon Life Sciences, Cambridgeshire, 

U.K. Study No.MCW0005. November 19, 2009. Unpublished. MRID 47933801 

Sanders, A. (2007) KIH-485-I-3: Acute Oral Toxicity in the Rat - Fixed Dose Method. 

Project Number: 0131/0650. Unpublished study prepared by Safepharm Laboratories, 

Ltd. 23 p. October 19, 2007. MRID 47701681 

Sanders, A. (2007) KIH-485-I-4: Acute Oral Toxicity in the Rat - Fixed Dose Method. 

Project Number: 0131/0652. Unpublished study prepared by Safepharm Laboratories, 

Ltd. 23 p. October 22, 2007. MRID 47701682 

Sanders, A. (2007) KIH-485-I-5: Acute Oral Toxicity in the Rat - Fixed Dose Method. 

Project Number: 0131/0654. Unpublished study prepared by Safepharm Laboratories, 

Ltd. 23 p. October 19, 2007. MRID 47701683 

Schuler, D. (2008) KIH-485 (Pyroxasulfone, ISO approved) WG 85: 4- hour Acute 

Inhalation Toxicity Study in Rats: Final Report. Project Number: C01113. Unpublished 

study prepared by Harlan Laboratories, Ltd. 46 p. December 18, 2008. MRID 47701918 
134

Shepherd, N. (2004) KIH-485: Single Exposure (Nose-Only) Toxicity Study in the Rat: 

Final Report. Project Number: 0535/109. Unpublished study prepared by Covance 

Laboratories, Ltd. 65 p. March 9, 2004. MRID 47701685 

Shimizu, T., Tanetani, Y., Kaku, K., Kawai, K., Fujioka, T. (2008). Action mechanism of 

a novel herbicide, pyroxasulfone. Life Science Research Institute, Kumiai Chemical 

Industry Co., Ltd., Shizuoka 436-0011, Japan. Published: Pesticide Biochemistry and 

Physiology, Vol. 95, Issue 1, September 2009, p. 47-55. MRID 47701754 

Simon, C. (2008) KIH-485 M-25: Acute Oral Toxicity Study in Rats. Project Number: 

C08393. Unpublished study prepared by RCC, Ltd. 22 p. October 16, 2008. MRID 

47701680 

Sindermann, AB, Porch, JR, Krueger, HO (2006) KIH-485 Herbicide (TGAI): An Acute 

Contact Study with the Honey Bee. Wildlife International, Ltd., Maryland, USA. Project 

Number 267-117. August 8, 2006. Unpublished. MRID 47701637 

Taylor K. (2009) KIH-485 (pyroxasulfone) WG85: Acute toxicity to Aphidius 

rhopalosiphi in the laboratory. Huntington Life Sciences Ltd., Huntingdon, 

Cambridgeshire, UK. Report No.: MCW0001. 23 September, 2009. Unpublished. 

MRID 47889323 

Tanaka, T. (2009) Study on Recovery of Algal Growth from Effects of KIH-485. Life 

Science Research Institute, Kumiai Chemical Industry Co. Ltd, Japan. Study No. 

2009LS165. February 25, 2009. Unpublished. (Non-guideline study) MRID 47701751 

Wetton, P. M., McKenzie, J. (2003) KIH-485: Acute Toxicity to Bluegill Sunfish 

(Lepomis macrochirus). Safepharm Laboratories Ltd. Derbyshire, U.K. SPL Project 

Number: 131/527. October 30, 2003. Unpublished, MRID 47701627 

Wetton, P. M., McKenzie, J (2003) KIH-485: Acute Toxicity to Daphnia magna. 

Safepharm Laboratories Ltd. Derbyshire, U.K. SPL Project Number: 131/529. October 

28, 2003. Unpublished. MRID 47701623 

Wetton, P. M., McKenzie, J. (2003) KIH-485: Acute Toxicity to Rainbow Trout 

(Oncorhynchus mykiss). Safepharm Laboratories Ltd. Derbyshire, U.K. SPL Project 

Number: 131/526. October 28, 2003. Unpublished. MRID 47701626 

VI. List of Appendices 

APPENDIX A: Sample STIR Output 

APPENDIX B: Sample SIP Output 
135

APPENDIX C: PRZM/EXAMS Output 

APPENDIX D: Sample T-REX Output 

APPENDIX E: Structures of Degradation Products 

APPENDIX F: Risk Quotient Method 

APPENDIX G: LOCATES Output 

VII. List of Figures 

Figure 1: Potential Crop Use Areas for Pyroxasulfone........................................17 

Figure 2. Chemical Structure of Pyroxasulfone.................................................18 

Figure 3. Conceptual model depicting stressors, exposure pathways, and potential effects 

to aquatic organisms from pyroxasulfone use on corn, soybeans, wheat, fallow land, and 

non-crop areas. Dotted lines indicate exposure pathways that have a low likelihood of 

contributing to ecological risk.....................................................................27 

Figure 4. Conceptual model depicting stressors, generic exposure pathways, and potential 

effects to terrestrial organisms from pyroxasulfone use on corn, soybeans, wheat, fallow 

land, and non-crop areas. Dotted lines indicate exposure pathways that have a low 

likelihood of contributing to ecological risk...................................................28 

Figure 5. Conceptual model depicting stressors, drinking water and inhalation exposure 

pathways, and potential effects to terrestrial animals from use of pyroxasulfone on corn, 

soybeans, wheat, fallow land, and non-crop areas. Dotted lines indicate exposure 

pathways that have a low likelihood of contributing to ecological risk.....................29 

VIII.List of Tables 

Table 1. Summary of Environmental Risk Conclusions for Aquatic Animals and Plants 

from Proposed Pyroxasulfone Uses................................................................7 

Table 2. Summary of Environmental Risk Conclusions for Terrestrial Animals and 

Plants from Proposed Pyroxasulfone Uses........................................................8 

Table 3. Listed Species Risks Associated With Direct or Indirect Effects from 

Pyroxasulfone use...................................................................................15 

Table 4: Environmental Fate Properties of Pyroxasulfone....................................18 
136

Table 5. Proposed Label Pyroxasulfone Use Information.....................................20 

Table 6. Proposed Spray Drift Buffers...........................................................21 

Table 7. Pyroxasulfone use and application information based on the proposed label...21 

Table 8. Test Species Evaluated for Assessing Potential Ecological Effects of 

Pyroxasulfone and the Associated Acute Toxicity Classification............................22 

Table 9. Measures of Ecological Effects and Exposure for Pyroxasulfone................35 

Table 10. Degradation Product Identification in Laboratory Studies.......................38 

Table 11. PRZM/EXAMS Modeling Inputs for Pyroxasulfone..............................42 

Table 12. Spray Drift Fraction Used in Aquatic Exposure Modeling........................43 

Table 13: PRZM/EXAMS Simulated Application Rates, Method, and Timing According 

to Proposed Label...................................................................................44 

Table 14: Estimated Environmental Concentrations of Pyroxasulfone in Surface Water.45 

Table 15. Terrestrial Food-Item Residue Estimates for Birds with Pyroxasulfone 

Proposed Uses with a Foliar Dissipation Half-life default value of 35 Days................48 

Table 16. Terrestrial Food-Item Residue Estimates for Mammals with Pyroxasulfone 

Proposed Uses with a Foliar Dissipation Half-life default value of 35 Days...............49 

Table 17. Estimated Environmental Concentrations of Pyroxasulfone for Terrestrial 

Plants..................................................................................................50 

Table 18. PRZM GW Tier II Model Input Parameters.........................................50 

Table 19. GW Tier II Model and SCIGROW Estimated Pyroxasulfone in Groundwater 

and Estimated Concentrations in Soil from Irrigation Water..................................51 

Table 20. Freshwater Fish Acute Toxicity Data...............................................52 

Table 21. Freshwater Invertebrate Acute Toxicity Data......................................53 

Table 22. Marine/ Estuarine Fish Acute Toxicity Data.......................................54 

Table 23. Marine/ Estuarine Invertebrate Acute Toxicity Data..............................55 

Table 24. Freshwater Fish Chronic Toxicity Data.............................................57 
137

Table 25. Freshwater Invertebrate Chronic Toxicity Data....................................58 

Table 26. Aquatic Plant Toxicity Data..........................................................61 

Table 27. Aquatic Plant Toxicity Data: Non-guideline studies..............................68 

Table 28. Avian Acute Toxicity Data............................................................70 

Table 29. Mammalian Acute Toxicity Data....................................................72 

Table 30. Terrestrial Invertebrate Acute Toxicity Data.......................................80 

Table 31. Avian Chronic Toxicity Data.........................................................84 

Table 32. Mammalian Chronic Toxicity Data..................................................87 

Table 33. Terrestrial Plant Toxicity Data.......................................................90 

Table 34. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients..........98 

Table 35. Upper Bound Kenaga, Chronic Mammalian Dose-Based Risk Quotients.....99 

Table 36. RQ values for plants in dry and semi-aquatic areas exposed to Pyroxasulfone 

through runoff and/or spray drift................................................................101 

Table 37. Estimated Concentrations in Soil from Irrigation Water and RQs for Terrestrial 

Plants................................................................................................102 

Table 38. Listed Species Risks Associated With Direct or Indirect Effects from 

Pyroxasulfone use.................................................................................117 

Table 39. Number of Endangered Species Potentially Exposed to Pyroxasulfone with the 

Proposed Uses......................................................................................121 

Table 40. Number of Endangered Species Potentially Exposed to Pyroxasulfone with the 

Proposed Uses......................................................................................121