## NEW CHEMICAL REGISTRATION
(Section 3) 

## ECOLOGICAL RISK ASSESSMENT Pyroxasulfone: Herbicide

USEPA PC # 090099

Chemical Name(s) : 3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1 H-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 (acetolacta se 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 T echnical (99.2% a.i.; EPA Reg No. 63588-xx) for formulation only into registered en d-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 cor n, soybeans, winter wheat;

b field corn, soybean, fallow land, non-crop ar eas 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 Division3 

### 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 ........................................................................................... 514 (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

...............................................................................................1225 1. Assumptions, Limitations, and Uncerta inties Related to Exposure For All

Taxa.................. ........................................................................122
a. Maximum UseScenario............................................................122 2. Assumptions, Limitations and Uncertainti es Related to Exposure for Terrestrial Species .................................................................................................................... 12 2 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........................................................................1356 I. Executive Summary

A. Nature of the Chemical Stressor

Pyroxasulfone is a new pesticide active ingr edient 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, or chards 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 sulfonyli oxazoline (acetolactase syntha se, ALS inhibitor). What is known is that the chemical inhibits biosynthe sis 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-ch ain 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 sp ecies such as barnyard millet and Italian ryegrass, but also rice were determined to be sensitive to pyroxasul fone; 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 pyroxa sulfone is 0.2136 lbs ai/A with a seasonal maximum rate of 0.267 lbs ai/A. Pyroxasulf one 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% fl umioxazin) water dispersibl e granule; Pyroxasulfone Technical (99.2% a.i.; EPA Re g No. 63588-xx) for formulation only into registered enduse herbicide products.

B. Potential Risks to No n-target Organisms

The results of this screening-level assessm ent indicate a potential for direct adverse effects to non-target aq uatic (non-vascular and va scular RQs of 1.03-22.07) and terrestrial plants (monocots in semi-aqua tic 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, bi rds, and mammals associated with the application of pyroxasulfone on corn, soybean, winter wheat, and non-crop sites, i ndirect effects may7 consequently affect other aquatic and terrestrial species. Data were not submitted for the
marine/estuarine fish and invertebrates via ch ronic 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 or ganisms are, which implies that risk to estuarine/marine organisms from chronic e xposure to pyroxasulfone is not expected. Metabolite/degradate data were submitted only for non-vascular and vascular aquatic plants and mammals (acute or al studies). With the excepti on of two terrestrial plant studies and two non-guideline terr estrial 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 conc lusions made on the technical grade active ingredient and metabolite s (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

count 1 , cell density 2 ) Risk is expected (from the technical grade active ingredient, but not the metabolites).

* Consult ‘Risk Description’ section for further details. Al so, risk in this table implies risk to technical grade active ingredient unless otherwise specified that meta bolites and/or formulations were assessed as well.

1 Vascular plants

2 Non-vascular plants8 Table 2. Summary of Environmental Risk Conclusion s for Terrestrial Animals an d 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 e xpected (from technical grade active ingredient). Acute and chronic 1 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 meta bolites 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 (K
oc = 57-119 L/kg) and persistent (t 1/2 = 142 to 533 days) in terrestrial and aquatic environmen ts. The major routes of di ssipation are expected to be associated with microbial-mediated degradation, leaching, and runoff. Pyroxasulfone is stable to hydrolysis and photodegr adation 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 bi oaccumulation 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 (t 1/2 = 4 to 35 days) of pyroxasulfone. Degradation of pyroxasulfone was identified as a potential route of dissipation in field studies. Leaching also wa s 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 t 1/2 ~ 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 applie d radioactivity) of pyroxasulfone are:

 3-(5-Difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-yl methanesulfonyl)-4,5- dihydro-5,5-dimethylisoxazole (M5),

 3-(5-difluoromethoxy-1-methyl-3-t rifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-dihydro-5,5-di methylisoxazol-4-ol (M6),

 (5-difluoromethoxy-1-methyl-3-trifluoromet hyl-1H-pyrazol-4-yl) methanol (M8),9  5-difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-carboxy lic 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-methylis oxazol-5-yl] methanol (M11).

The Residue of Concern Knowledgebase S ubcommittee (ROCKS) in the Office of Pesticide Programs (OPP) identified pyroxasulf one, M1, and M3 as residues of concern
in the human health risk assessment.

Additionally, there was a high pe rcentage of applied radio activity (8-25% of applied radioactivity) in “unextracted” soil/sedim ent residues. Because the extraction of pyroxasulfone residues was conducted using only acetonitrile/water without the use of sequentially harsher extractan ts, there is uncertainty regarding the identity and availability of the une xtracted so il residues.

D. Ecological Effects Summary

Aquatic Animals

Acute
Freshwater and marine/estuarine fish were tested on the tec hnical grade active ingredient and did not show (sub)lethal e ffects at limit concentrations (2.2 mg a.i./L for rainbow trout, MRID 47701626; 2.8 mg a.i./L for blue gill sunfish, MRID 47701627) or up to the highest concentration tested (3.3 mg a. i./L for sheepshead minnow, MRID 47701628);

LC 50 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); EC 50 values indicate that pyroxasulfone is at most moderately toxic to
freshwater and marine/est uarine invertebrates.

Chronic Unlike the acute toxicity study which lead to a non-definitive endpoint, the chronic toxicity study using the techni cal grade active ingredient on freshwater fish determined a definitive endpoint (28-da y NOAEC of 2.0 mg a.i./L for fathead minnow, MRID 47701630) on the basis of wet weight and lengt h (growth endpoints) reductions at the highest concentration test ed (3.9 mg a.i./L).

A chronic freshwater invertebrate study us ing the technical grade active ingredient determined a non-definitive endpoint (NOAEC ≥ 1.9 mg a.i./L for water flea, MRID10 47701629) given that differences between tr eatment groups and controls were not statistically significant and s ublethal effects (discoloration, injury, and lethargy) were infrequent, comparable to controls, a nd 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 tech nical yielded a definitive endpoint (7-day EC 50 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 meta bolites (M-1, M-3) in dicated that none of the endpoints of interest (frond count, bioma ss, growth rate) were affected leading to a non-definitive endpoint for both studies (7-day EC 50 > 123 mg a.i./L, NOAEC ≥ 123 mg a.i./L, MRIDs 47701641, 47701642). Chlorosis and n ecrosis were consistently observed
in all three studies.

On the other hand, three non-vascular aquatic pl ant studies on the freshwater green algae yielded definitive endpoints for the technical (96-hr EC 50 of 0.00038 mg a.i./L, NOAEC of 0.0001 mg a.i./L, MRID 47701643), metabolite M-1 (96-hr EC 50 of 56 mg a.i./L, NOAEC of 31 mg a.i./L, MRID 47701647), and metabolite M-3 (96-hr EC 50 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 grow th rate) were affected, with cell density generally being the most sens itive 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 EC 50 of 0.66 mg a.i./L, NOAEC of 0.14 mg a.i./L, MRID 47701646), though all three endpoints of in terest were affected and cel l 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 EC 50 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 sensitiv e and biomass less so (NOAEC 1.6 mg a.i./L). Cell aggregation and long chains were obser ved in all treatment levels and controls. Finally, the freshwater diatom indicated no sensitivity to the technical whereby the cell density, biomass, and growth rate endpoi nts were all non-definitive (96-hr EC 50 >3.2 mg a.i./L, NOAEC ≥ 3.2 mg a.i./L, MRID 47701645) and ce ll aggregation was observed in
all treatment levels and controls.

Terrestrial Animals

Acute Upland, waterfowl, and passerine birds we re tested on the technical grade active ingredient. The acute oral stud ies did not show (sub)lethal e ffects 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); LD 50 values indicate that pyroxasulfone is pr actically non-toxic to birds on an acute oral basis. An acute dietary study determined a non-definitive endpoint (8-day LC 50 > 5620 mg a.i./kgdiet and NOAEC ≥ 5620 mg a.i./kg-diet for north ern bobwhite quail, MRID 47701633)11 given that the study indicated no mortalities, ov ert 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 dr oop) were not considered treatment related. A second acute dietary study determined a non-definitive endpoint (8-day LC 50 > 5620 mg a.i./kg-diet for mallard duck, MRID 47701634) given that the study indicated no mortalities, overt signs of t oxicity, 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 calcu lation) and a 5-day NOAEC of 1000 mg a.i./kg-diet (APVMA calculation). The LC 50 values from the acute dietary studies indicate that pyroxasulfone is practically non -toxic to birds on an acute
oral basis

Eight acute oral studi es were conducted on female ra ts to satisfy OCSPP guidance 870.1100 (OECD 425) – one technical and seve n degradate/metabolite (M-1, M-3, M-25, I-3, I-4, I-5, M-28). All of the studies were d eemed acceptable and indicated that the test compound was practically non-toxi c with toxicity category I II. 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 th e study design. The singl e active ingredient product tested (MRID 47701916) is at most slig htly toxic (category III), while the coformulated product (MRID 47702105) is practi cally non-toxic (cat egory IV) at the respective limit doses. No deat hs or sublethal effects were observed in either study.

Terrestrial Invertebrates A 48-hour acute contact study us ing the technical grade activ e 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 c onsidered practically non-toxic to honey

bees on the basis of a no n-definitive endpoint (LD 50 > 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 ER 50 and LR 50 >0.892 lbs a.i./A, MRID 47889323) as well as mortality and fecundity that di d reach a 50% reduction but was not deemed dose dependent (overall eggs produced per female predatory mite per day, 7-day ER 50 and LR 50 >0.892 lbs a.i./A, MRID 47701753).

Another couple of non-guideline studies using the technical grade activ e ingredient on the
earthworm indicated no effects at the con centrations tested which resulted in nondefinitive endpoints for the 14-day study (LC 50 > 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 st udies 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 th e northern bobwhite quail (NOAEC ≥ 1000 mg a.i./kg diet on the basis of no apparent treat ment related effects on adult or offspring body weight, reproductive performance, a nd eggshell thickness, MRID 47701635).

Out of four chronic mammalian studies av ailable all on the t echnical grade active ingredient, the 2-generation re production study on the rat yielded the most sensitive endpoint (NOAEL of 7.2 mg/kg-bw/day for ma les 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 submitte d 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 gr owth to monocots grown for 6-7 days from
seed at concentrations on the order of 10 -7 – 10 -5 M (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 exte nt at these concentrations for corn (less than 20% inhibition). The c oncentrations in solution 10 -7 , 10 -6 , and 10 -5 M 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 *10 3 mg/g) and 40, 400, and 4000  g/L [ppb]. However, these concentrations exceed the aquatic EEC s (maximum concentration calculated in

PRZM/EXAMS is 8.4  g/L, see Table 14) by at leas t an order of magnitude. The
concentrations in solution 10 -7 , 10 -6 , and 10 -5 M 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 H 2 O * 367 g/mol *10 3 mg/g *20 g H 2 O/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 c oncentrations (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 applic ation 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 th ese 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 terr estrial plant EEC of 0.018 lbs a.i./A, a value comparable to the lo west concentration in the mode of actionstudy (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 sp ray applications and the aerial application for one of the formula tions, an effect on shoot growth is possible on target weeds Italian ryegrass, barnyard mille t, but also on rice and potentially other nontarget monocots. Furthermore, the seed ling 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 sta tistically significant at 0.0168, 0.0334, 0.0669, 0.1338, and 0.2676 lbs a.i./A con centrations, respectively. This indicates that the study may not capture what it was intended to captu re as there was high variability in the raw data. However, for wheat , this still implies that sublethal effects13 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 variab ility in the raw data) in detecting plant sensitivity to pyroxasulfone, the seedling em ergence study led to identification of the most sensitive monocot (onion, EC 25 of 0.0669 lbs a.i./A and NOAEC of 0.0168 lbs a.i./A) and dicot species (kidney bean, EC 25 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), in dicated that monocots, overall, did not exhibit signs of treatment-rela ted 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 EC 25 of the monocots for which the endpoint was available. However, the EC

x ’s for onion (as well as most monocot data) did not indicate convergence whereby an algor ithm was not plotted against the data indicating clear inhibition with increasing concentration. As a result, for onion the EC 25 > 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 (EC 25 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 equilibriu m concentration taken over a 30 year period) were used to estimate th e potential phytotoxic e ffects 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 pr edicted 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 expe cted. In addition, risk to li sted terrestrial plants and potentially sensitive crops located on the irriga ted/treated field are expected as a result of use of pyroxasulfone contaminated irriga tion water at the estimated levels. The pyroxasulfone degradates, M-1 and M-3, are no t considered degradates of concern for duckweed (vascular aquatic plant) or freshwat er green algae (non-vasc ular 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 form ulations WG85 (84.7% a.i.) and V-10233 (42.2% pyroxasulfone; 33.6% flum ioxazin) 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-gui deline) terrestrial invertebrate s (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 unc ertainty in the environmental fate data is the identification and availability of unextracted residues in soil and aquatic
metabolism studies. These residues acc ount for a high percentage of applied radioactivity (8-25% of applied radioac tivity). 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 th e potential to accumulate in groundwater.

 Prospective ground wate r monitoring study.

2. Ecological Effects Data

The submitted ecotoxicity database is inco mplete. For a list of submitted ecological effects studies for pyroxasulfone see Secti on 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 fi sh study is not required.

 Chronic: Fish early-l ife 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 require d 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 sugg ests 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. Theref ore, a chronic marine/estuari ne invertebrate study is not required.

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

TGAI

Fish Bioaccumulation Study A bioaccumulation in fish study was not s ubmitted to support the proposed registration. According to CFR 40 Part 158, this data is conditionally re quired and although pyroxasulfone is mobile and persistent, the low octanal:water partitioning coefficient (log

K
ow = 2.39) is expected to limit bioconcentra tion and bioaccumulation of pyroxasulfone. Based on the log K
ow of 2.39, the expected BCF assuming no metabolism and 5% lipids would be approximately 12 L/kg wet weight ( i.e., 10 2.39 * 0.05). This low BCF combined with the low acute toxicity to birds and ma mmals 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 a ssociated with either direct or indirect effects following application of pyr oxasulfone for the proposed uses.

Concerns For Federally Listed as Endangered and/or Threatened Species

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

Listed Taxon Direct Effects Indirect Effects
Terrestrial and semi-aquatic plants - monocots Yes Yes 4

Terrestrial and semi-aquatic plants – dicots No Yes 4

Terrestrial invertebrates No Yes 4
Birds Yes (chronic) Yes 4

Terrestrial-phase amphibians 1 Yes (chronic) Yes 4
Reptiles 1 Yes (chronic) Yes 4

Mammals Yes (chronic) Yes 4

Aquatic non-vascular plants Yes Yes 4

Aquatic vascular plants Yes Yes 4
Freshwater (FW) fish No Yes 4

Aquatic-phase amphibians 2 No Yes 4
Freshwater (FW) invertebrates No Yes 4
Marine/estuarine (M/E) fish No 3 Yes 4

Marine/estuarine (M/E) invertebrates (mollusk) No 3 Yes 4

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, plants16 II. Problem Formulation

The purpose of this problem formulation is to provide the foundation for the ecological risk assessment being conducted for the herbic ide pyroxasulfone. As such, it articulates the purpose and objectives of the risk assessmen t, 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 ingr edient 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, or chards and vineyards and to maintain bare ground on non-crop areas). As a new ac tive ingredient submitted for registration, there are no previously prepared ecologi cal risk assessments by the Agency for pyroxasulfone uses. However, the chemical is undergoing a global review in which Australian Pesticides and Veterinary Medi cines 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, fi eld, popcorn), soybean, and winter wheat. Additionally, non-crop use sites include fa llow land and non-crop areas around farms, orchards, and vineyards. Fallow land and crop use treatment requires consideration of rotation intervals because of the persiste nce 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 bean s, canola, 11 months for alfalfa, barley, canola, and 12 months for all other crops. The extent of potentia l 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 th e use pattern as well as the lack of adequate GIS overlays for non-crop use areas.

A) Corn17 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 st ructure of pyroxasulfone. Table 4 identifies the physical and chemical properties of pyr oxasulfone 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 Numbe r 44739-55-5

Molecular Wei g ht ( g rams/mole) 367 g /mole

A q ueous solubilit y ( at 25  C ) 3.49 m g /L

Va p or Pressure 1.8 x 10 -8 tor r Henr y ’s Law Constant 2.65 x 10 -9 atm m 3 /mol Octanol Partitioning Coefficient (log K
ow ) @ 25 o C 2.39

Environmental Fate Properties

H y drol y sis half life (pH 4, pH 7, pH 9) Stable Aqueous photol y sis half life 119 da y s Soil photol y sis half life Stable (>30 da y s)

Aerobic soil metabolism half-lives 142-533 da y s Anaerobic soil metabolism half-lives 145 -156 da y s Aerobic aquatic metabolism half-lives ( ) 108 -109 days* Anaerobic aquatic metabolism half-lives 69-70 days*
Soil-water distribution coefficient (K
oc ) 57-119

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

p hases of a g iven test s y stem.19 Proposed End-use Products : Pyroxasulfone 85 WG (85% a.i.; EPA Reg.No.63588-xx); V-10233 Herbicide (42.5% pyroxasulfone; 33.5% flum ioxazin) 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 pyraz ole class; also considered an oxazole, K-3 herbicide, and a sulfonyliox azoline (acetolactase synthase, ALS inhibitor). What is known is that the chemical inhibits biosynthe sis 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-ch ain 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 sp ecies such as barnyard millet and Italian ryegrass, but also rice were determined to be sensitive to pyroxasul fone; 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 (K
oc = 57-119 L/kg) and persistent (t 1/2 = 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 photod egradation 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-m 3 /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 (t 1/2 = 4 to 35 days) of pyroxasulfone. The presence of degradates (see Appendix E for structures) in the terrestrial field dissipation st udies indicated that degrada tion was a potential route of pyroxasulfone dissipation in field studies. Leaching also was identified as a route of dissipation for the metabolite 5-difluoromet hoxy-1H-pyrazol-4-yl) methanesulfonic acid (M1). This degradation product was very persistent (extrapolate t 1/2 ~ 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 applie d radioactivity) of pyroxasulfone are:

 3-(5-Difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-yl methanesulfonyl)-4,5- dihydro-5,5-dimethylisoxazole (M5),

 3-(5-difluoromethoxy-1-methyl-3-t rifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-dihydro-5,5-di methylisoxazol-4-ol (M6),

 (5-difluoromethoxy-1-methyl-3-trifluoromet hyl-1H-pyrazol-4-yl) methanol (M8),20  5-difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-carboxy lic 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-methylis oxazol-5-yl] methanol (M11).

Additionally, there was a high pe rcentage of applied radio activity (8-25% of applied radioactivity) in unextracted soil/sedimen t residues. Because the extraction of pyroxasulfone residues was conducted using only acetonitrile/water without the use of sequentially harsher extractan ts, there is uncertainty regarding the identity and availability of the une xtracted so il 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 pyroxasulf one 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 mixtur e 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 met hyl, norfurazon, oryzalin, pendimethalin, picloram, pramitol, simazine, sulfometur on methyl, tebuthiuron, and triclopyr.

Table 5. Proposed Label Py roxasulfone 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 SoilIncorporatedGround 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 SoilIncorporatedGround 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 SoilIncorporatedGround 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 SoilIncorporatedGround /Aerial Spray 0.080-0.120 0.12021 Two of the pyroxasulfone labe ls have standard runoff a nd ground water label advisory statements for uses on corn, soybean, fallow land, and non-crop areas. Additionally, required spray drift buffer distances ar e stated on theV 10233 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 wint er 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, wetla nds, marshes, lakes, reservoirs)

The maximum single application rate of pyroxasulfone is 0.2136 lbs ai/A for corn, soybean and winter wheat with a seas onal maximum rate of 0.267 lbs ai/A ( Table 7 ). Pyroxasulfone can be applied using broadcas t or banded ground spray as well as aerial spray. Application timing is pre- and early post emergent. Other recommended applications include fall treatment (b efore 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 specifiedCorn, 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 stre ssor (EPA, 1998). Based on the proposed uses for pyroxasulfone, it is e xpected that the aquatic and terrestrial receptors will include freshwater fish and invertebrates, marine/estuarine fish and invertebrates, aquatic plants, terrestria l plants, birds, mammals, and terrestrial
invertebrates.22 Consistent with the process described in th e Overview Document (EPA, 2004), this risk assessment uses a surrogate species appro ach in its evaluatio n of pyroxasulfone. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are us ed to extrapolate to potential effects on a variety of species (receptors) incl uded 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 wh en 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 e ffects of pesticides to these non-target taxonomic groups. In addition, the table provid es a preliminary overview of the potential acute toxicity of pyroxasulfone by providi ng the acute toxicity classifications.

Table 8. Test Species Evaluated for Assessing Pote ntial Ecological Effects of Pyroxasulfone and the Associated Acute Toxicity Classification

Taxonomic Group Surrogate Species Acute Toxicity Classification

Birds 1 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 fish 2 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 plants 3 Monocots – most sensitive species Dicots – most sensitive species No Classification

Aquatic plants and algae Duckweed ( Lemna gibba ) Cyanobacteria/blu e-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 terrest rial-phase amphibians and reptiles.

2 Freshwater fish may be surrogate s 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 sc ope, and as a result it may not be possible to identify specific ecosystems during the deve lopment of a baseline risk assessment. However, in general terms, terrestrial ecosy stems potentially at ri sk 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 grassla nds, 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 fr om, the treated field and might include impounded bodies such as ponds, lakes and rese rvoirs, or flowing waterways such as
streams or rivers. For uses in coastal ar eas, aquatic habitat also includes marine ecosystems, including estuaries.

D. Assessment Endpoints

Assessment endpoints represent the actual enviro nmental value that is to be protected, defined by an ecological entity (species, comm unity, or other entity) and its attribute or characteristics (EPA, 1998). Generally, the eco logical entities may include the following:
freshwater as well as marine/estuarine fish and invertebrates, a quatic and terrestrial plants, birds, reptiles, amphi bians, mammals, and non-target insects. The attributes for each of these entities may include gr owth, reproduction, and survival.

E. Conceptual Model

A conceptual model provides a written desc ription and visual re presentation of the predicted relationships between pyroxasulfone residues, potential rout es of exposure, and the predicted effects for the assessment endpoint. A conceptual model consists of two major components: risk hypothesis a nd 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 environmen t from the application site to non-target organisms. The evaluation of the ecologica l exposure pathways in this assessment includes an examination of the source and pot ential 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 th e potential to reduce survival, reproduction, and/or growth in non-target aquatic plants ( non-vascular and vascula r), terrestrial plants, birds, reptiles, amphibians, and mammals wh en used in accordance with the proposed labels. These non-target organisms incl ude 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 sect ion. It is assumed that pyroxasu lfone 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 a nd 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 e ffects. Direct effect s 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 potenti al for these effects to occur within the surrogate taxa with the intent to extrapolate to actual e ffects within the environment.

In order for an exposure pathway to be co mplete, it must have a source, a release mechanism, an environmental transpor t medium for pyroxasulfone and/or its transformation products, a point of exposure fo r ecological receptors, and a feasible route of exposure. The assessment of these path ways 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 pha se is not considered as a dominant route of exposure. Atmospheric transport is repr esented by dotted lines given the low likelihood of volatilization of pyr oxasulfone (i.e. vapor pressure = 1.8 x 10 -8 torr, MRID 47701752; and, Henry’s law constant at 25 o C of 2.65 x 10 -9 atm m 3 /mol).

Bioaccumulation potential This screening-level assessment for ground and aerial spray applicatio ns of pyroxsulfone considered dietary exposure (Figures 3 and 4). Log K
ow (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 th at were not considered quantitativ ely in the assessment are incidental soil ingest ion exposure and dermal exposure.

Partitioning to sediment The partitioning properties of pyroxasulfone (K
oc 57-119) indicate that exposure to benthic (sediment-dwelling) inve rtebrates is not an exposure r oute of concern relative to exposure through the water column.25 Dermal exposure The dermal route of exposure for terrestrial w ildlife can be divided into a few sub-routes. These include organisms exposed:

 In the treated field at the tim e 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 tr eated or drift-impacted areas whereby exposure may occur via cont act with dislodgeable resi dues of the pesticide on treated vegetation.

 To the pesticide deposited on soil pa rticles 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 th at is dissolved in puddle water on the treated field or in areas imp acted by drift and run-off.

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

At the present time, the Agency does not ha ve a method to quantif y 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 impingeme nt of applied foliar sprays and from
incidental contact with disl odgeable foliar pesticide resi dues from treated or driftimpacted vegetation.

Inhalation exposure
The S creening T ool for I nhalation R isk (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 applic ation 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 LD 50 >2000 mg a.i./kgbw, MRID 47701677; and, acute inhalation LC 50 > 6.56 mg a.i./L, a te st duration of 4.5 hours MRID 47701685) as well as the most sens itive acute oral avian toxicity endpoint (acute oral LD 50 >2250 mg a.i./kg-bw for the nort hern bobwhite quail, MRID 47701631). Based on the results of the STIR model, inha lation 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 dr ift and vapor-phase of the pe sticide 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, respectiv ely) 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 inhala tion route in STIR does not consider that aggregation with other26 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 ro utes of exposure in situations where data indicate that pesticide exposures through ot her routes may be potentially significant contributors to wildlife risk (USEPA, 2004). The risk characteriza tion section, discusses the impact of consideration of other routes of exposure, particularly ingestion, that have been identified as potentially important a nd 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, irri gation equipment (e.g., drip irrigation in grape cultivation), dew deposited on treated plants, and off-field surface
water exposures.

The S creening I mbibition P rogram (SIP v.1.0, Released June 15, 2010) was used to calculate an upper bound estim ate of exposure using pyroxa sulfone’s solubility (3.49 mg/L at 25 o C), the most sensitive acute (LD 50 >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 (LD 50 > 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 a ppear to be of concern, this does not take into account that when aggregated w ith other exposure pathways (dietary food sources, dermal, inhalation) drinking water ma y 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 scen arios not triggering a SIP 1.0 concern would contribute significantly to aggregate risks from water pl us 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 stress ors, exposure pathways, and potential effects to aquatic organisms from pyroxa sulfone use on corn, soybeans, wheat, fallow land, and non-crop areas. Dotted lines indica te 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

A quatic Plants
Non-vascular
Vascula r Uptake/cell, roots, leaves Riparian plants
terrestrial

exposure pathways see Figure 428 Figure 4. Conceptual model depicting stressor s, generic exposure pathways, and potential effects to terrestrial organism s 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 inhala tion exposure pathways for terrestrial vert ebrates 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 S p ra y 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
Groundwate r Irrigation

water29 Figure 5. Conceptual model depicting stressors, drinking water and inhalation exposure pathways, and potential effects to terrestria l animals from use of pyroxasulfone on corn, soybeans, wheat, fallow land, and non-crop areas. Dotted lines indicate exposure pathways that have a lo w likelihood of contribut ing 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 th e Overview Document (U.S. EPA, 2004).

1. Conclusions from Previous Risk Assessments

There are no previous Agency ecological ri sk assessments because this is the first registration petition for pyroxasulfone fo r 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 S p ra y 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

trans p ort

Receptors Puddles (formed
on treated fields )

Ingestion Inhalation Ai r30 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 unc ertainty in the environmental fate data is the identification and availability of unextracted residues in soil and aquatic
metabolism studies. These residues acc ount for a high percentage of applied radioactivity (8-25% of applied radioac tivity). 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 th e potential to accumulate in groundwater.

 Prospective ground wate r monitoring study.

Ecotoxicity The submitted ecotoxicity database is inco mplete. For a list of submitted ecological effects studies for pyroxasulfone see Secti on 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 fi sh study is not required.

 Chronic: Fish early-l ife 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 require d 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 sugg ests 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. Theref ore, a chronic marine/estuari ne invertebrate study is not required.

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

TGAI

Fish Bioaccumulation Study A bioaccumulation in fish study was not s ubmitted to support the proposed registration. According to CFR 40 Part 158, this data is conditionally re quired and although pyroxasulfone is mobile and persistent, the low octanal:water partitioning coefficient (log

K
ow = 2.39) is expected to limit bioconcentra tion and bioaccumulation of pyroxasulfone. Based on the log K
ow of 2.39, the expected BCF assuming no metabolism and 5% lipids would be approximately 12 L/kg wet weight ( i.e., 10 2.39 * 0.05). This low BCF combined with the low acute toxicity to birds and ma mmals 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 e xposure modeling to asse ss ecological risk following a registered applicati on of that pesticide. This tiered system is designed to minimize the amount of analysis which is requir ed to register any given chemical. Each of the tiers is designed to sc reen out pesticides by requiri ng 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 EXAMS 2 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 envi ronmental fate studies and proposed product labels submitted by the petitioner to s upport 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 esti mates is for birds (also acting as surrogate for reptiles and terrestrial-phase amphibian s) and mammals with an exposure route emphasis on uptake through the diet. The residu es in or on potential dietary sources for mammals and birds (e.g., vegetation, insects, a nd seeds) were estimated using the Tier I model T-REX (Version 1.4.1, 2008). In this Ti er 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 pres ented in the Risk
Characterization section of this doc ument 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 pyroxa sulfone. Upper-bound exposure levels were calculated for spray applica tions 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 associat ed 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 pr esent on a given food item. Food item residue levels are then linearly adjusted based on applicati on rate. The upper-bound estimates are used to estimate risks since these values represent th e high-end exposure that may be encountered for terrestrial species that consume food items that have received la bel-specified pesticide application. Although these re present 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 (terrest rial 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 gra nule version. However, these labels are multi-active ingredient products ( i.e. , containing 42.2% pyr oxasulfone 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 additi on to incorporating the relationship between application rate and food ite m residue concentrations, accoun ts for pesticide degradation
in the estimation of terrestrial EECs. T-REX calculates pesticide re sidues on each type of food item on a daily interval for one year. A fi rst-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 f ood item concentration on any gi ven day is the sum of all residues up to that day, taking into account the first-order degradation. The initial33 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 measur e of exposure (EEC) used to calculate risk quotients (RQs).

The foliar dissipation half-life and residue dec line studies can be important in estimating exposure because they essentially determine how long the pesticide remains in or on food items after application. In ma ny cases, neither empirically de termined foliar dissipation nor residue decline half-life (w ith a day 0 residue) values ar e 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 ei ther equal or approximately equal to the seasonal rate. In addition, given that application intervals we re not reported on the labels and pyroxasulfone’s persistence in water (h alf-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 applica tion rate was assumed to be equivalent to a nnual application rate.

In cases where RQs exceeded LOCs at the maximum seasonal rate, two applications (that totaled the maximum seasonal rate) were mode led and used for risk characterization. TREX does not currently allow for variable a pplication rates/applic ations or different application intervals between applications. Therefore, to account for the variable application rates described on the proposed la bels for corn, soybean, and winter wheat, the EECs for the different potential food ite ms 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 lb s 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 cal culate RQ values (Table 32).

TERRPLANT Model

The TerrPlant (Ver.1.2.2) model is used to predict EECs from te rrestrial uses for terrestrial plants located in dry and semi-a quatic areas adjacent to the treated field or treated water body. A semi-aquatic area is defi ned 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 depicti ng dry and semi-aquatic areas of terrestrial habitats. For both models, a non-target area is adjacent to the ta rget 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-targ et area (1:1 ratio of areas). In the sheet runoff scenario, the treated area generating runo ff 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 e xposure is estimated as channel runoff.34 Channel runoff is the amount of pesticide that ru ns 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 a pplication rate being deposited on soil with emerging or emerge d seedlings. The magnitude of runoff is assumed to be dependent on the water solubil ity 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 select ed 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 seedli ng emergence studies. In addition, RQs are derived for plants with consideration for sp ray drift exposures. For monocots and for dicots, TerrPlant compares estimated spra y drift deposition, wit hout 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 a ddition, given that applic ation 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 cal culations. Nevertheless, in cases where RQs exceeded LOCs, lower application rate s 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 pes ticides with phytotoxic effects.

To estimate exposure to plants when gr oundwater contaminated by pyroxsulfone is applied to crops, the following method was us ed. 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 pr ocess in OPP. The model provides ground concentration as predicted through the Pe sticide 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 Effect 1,2 Measures of Exposure

Birds 3 Survival Bobwhite Quail acute oral LD 50 , subacute dietary LC 50 Mallard Duck subacute dietary

LC 50 Zebra Finch acute oral LD 50

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 LD 50 Reproduction and growth Laboratory rat reproduction and development NOAEL/LOAEL Rabbit development
NOAEL/LOAEL

Freshwater fish 4 Survival Rainbow trout 96-hr LC 50 Bluegill sunfish 96-hr LC 50 Peak EEC 5

Reproduction and growth Fathead minnow
NOAEC/LOAEC 60-day average EEC 5

Freshwater invertebrates Survival Water flea 48-hr EC 50 Peak EEC 5
Reproduction and growth Water flea NOAEC/LOAEC 21-day average EEC 5
Marine/estuarine fish Survival Sheepshead minnow 96-hr LC 50 Peak EEC 5
Reproduction and growth No study available 60-day average EEC 5

Marine/estuarine
invertebrates Survival Eastern oyster 96-hr EC 50 Saltwater mysid 96-hr LC 50 Peak EEC 5

Reproduction and growth Saltwater mysid NOAEC/LOAEC 21-day average EEC 5
Terrestrial plants 6 Survival and growth Monocot Seedling emergence

EC 25 , NOAEC or EC 05 Monocot Vegetative Vigor

EC 25 , NOAEC or EC 05 Dicot Seedling emergence

EC 25 , NOAEC or EC 05 Dicot Vegetative Vigor

EC 25 , NOAEC or EC 05 Estimates of runoff and spray drift to non-target areas

Terrestrial invertebrates Survival Honey bee acute contact 48-hr

LD 50 , Parasitoid wasp & predatory mite ER 50 /LR 50 , Earthworm 14-day LC 50 , 28-day

NOAEC Maximum application rate

Aquatic plants and algae Survival and growth Duckweed 7-day EC 50 , NOAEC Freshwater green algae 96-hr

EC 50 , NOAEC Freshwater blue-green algae 96-hr

EC 50 , NOAEC
Freshwater diatom 96-hr EC 50 , NOAEC
Marine diatom 96-hr EC 50 , NOAEC Peak EEC 5

1 LD 50 = Lethal dose to 50% of the test populat ion; NOAEC = No observed adverse effect con centration; LOAEC = Lowest observed adverse effect concentration; LC 50 = Lethal concentration to 50% of the test population; EC 50 /EC 25 = Effect concentration to 50%/25% of the test population.

2 Species listed in this table represent the most commonly enc ountered species from registrant-s ubmitted studies, risk assessmen t guidance indicates the most sensitive species tested within each ta xonomic group are to be used for baseline risk assessments.

3 Birds represent surrogates for amphibi ans (terrestrial phase) and reptiles.

4 Freshwater fish may be surroga tes for amphibians (aquatic phase).

5 One in 10-year return frequency.

6 Four species of two families of monocots - one is corn, six spec ies of at least four dicot families, of which one is soybeans.36 III. Analysis

A. Use Characterization

Pyroxasulfone is a new herbicide in the pyraz ole class; also considered an oxazole, K-3 herbicide, and a sulfonyliox azoline (acetolactase synthase, ALS inhibitor). What is known is that the chemical inhibits biosynthe sis 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-ch ain 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 sp ecies such as barnyard millet and Italian ryegrass, but also rice were determined to be sensitive to pyroxasul fone; 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 pyroxa sulfone is 0.2136 lbs ai/A with a seasonal maximum rate of 0.267 lbs ai/A. Pyroxasulf one 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 degrad ation products with these crop uses.

B. Exposure Characterization
1. Environmental Fate and Transport Summary

Pyroxasulfone is mobile (K
oc = 57-119 L/kg) and persistent (t 1/2 = 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 photod egradation 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 (t 1/2 = 4 to 35 days) of pyroxasulfone. The presence of degradates (see Appendix E for structures) in the terrestrial field dissipation st udies indicated that degrada tion was a potential route of pyroxasulfone dissipation in field studies. Leaching also was identified as a route of dissipation for the metabolite 5-difluoromet hoxy-1H-pyrazol-4-yl) methanesulfonic acid (M1). This degradation product was very persistent (extrapolate t 1/2 ~ 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 applie d radioactivity) of pyroxasulfone are:

 3-(5-Difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-yl methanesulfonyl)-4,5- dihydro-5,5-dimethylisoxazole (M5),

 3-(5-difluoromethoxy-1-methyl-3-t rifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-dihydro-5,5-di methylisoxazol-4-ol (M6),

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

 5-difluoromethoxy-3-trifluoromethyl-1 H-pyrazol-4-carboxy lic 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-methylis oxazol-5-yl] methanol (M11).

Additionally, there was a high pe rcentage of applied radio activity (8-25% of applied radioactivity) in unextracted soil/sedimen t residues. Because the extraction of pyroxasulfone residues was conducted using only acetonitrile/water without the use of sequentially harsher extractan ts, there is uncertainty regarding the identity and availability of the une xtracted so il residues.

In Tier II PRZM/EXAMS modeling the post-pl ant application of pyroxasulfone in the MS corn scenario produced the highest esti mated exposure concentrations (EECs). The maximum 1 in 10 year for pyroxasulfone wa s 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 m odeling because of th e persistence of pyroxasulfone. In addition, surface water m odeling for total residues (parent+M1+M3) showed a small difference in exposure concen trations when compared with modeling for the parent.

Persistence

Pyroxasulfone was stable to abiotic hydrolys is 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 rangi ng 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 st andard deviation of 119.9 days. In two anaerobic soils, pyroxasulf one 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 se diment 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 ace tonitrile/water (2:1 v:v) extractable residues from water, soil, and sediment. Major metabolites ( ≥ 10% of applied radioactivity) of pyroxasu lfone in laboratory metabolism studies were 5- difluoromethoxy-1H-pyrazol-4-yl) methanesulf onic acid (M1) and 5-difluoro methoxy-1- methyl-3-trifluoromethyl-1H-pyraz ol-4- carboxylic acid (M3).

Minor metabolites (<10% of applied radi oactivity) were 3-(5-Difluoromethoxy-3- trifluoromehyl-1H-pyrazol-4-yl methanesul fonyl)-4,5-dihydro-5,5-dimethylisoxazole (M5), 3-(5-difluoromethoxy-1-methyl -3-trifluoromethyl-1H-pyrazol-4-yl methanesulfonyl)-4,5-dihydro-5,5-dimethylis oxazol-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. B ound soil/sediment residues (post a cetonitrile/water extraction)
account for 8 to 25% of the a pplied radioactivity.

Table 10 shows the maximum concentration of each degradation product in each laboratory environmental fate study.

Table 10. Degradation Product Iden tification 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) 4770174039 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) 4770174140 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 fo r pyroxasulfone was 1.93 L/kg (1/n=1; K
oc =104) in sandy clay loam, 1.93 L/kg (1/n=0.9880; K
oc =99) in clay loam, 1.59 L/kg (1/n=0.9898;

K
oc =119), and 2.00 L/kg (1/n=1; K
oc =57) in loam. The Freund lich desorption coefficient was 4.10 L/kg (1/n=0.9590; K
oc =216) in sandy clay loam, 7.44 L/kg (1/n=0.9289;

K
oc =169) in clay loam, 3.16 L/kg (1/n=0.9208; K
oc =226), and 4.16 L/kg (1/n=0.9650;

K
oc =119) in loam. Pyroxasulfone was leac hed through packed so il columns; 42.5 to 90.3% of applied radioactivity was detect ed in the soil column leachate. The radioactivity in leachate samples were id entified as pyroxasulfone (72.6 to 84% of applied dose), M1 (7.5 to 18.6% of applied dos e), M3 (2.6 to 4.2% of applied dose), and M6 (1.1 to 6.7% of applied dose). The column K d 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 K d 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 WG 85) 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 s ite. 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 af ter 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 dept h 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 WG 85P) 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 draine d after 130 to152 days after application. Samples were taken to repres ent sediment, flood water, and soil after flooding. The dissipation DT50 for pyroxasulfon e in surface sediment (0-6 inches) was41 77 days in CA and 64.8 days in AR. The dissipation DT50 for pyroxasulfone in water was 16 days at both sites. Pyroxasulfone wa s 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 subm itted to support the proposed registration. Although the pyroxasulfone is mobile and persis tent, the low octanal:water partitioning coefficient (log K
ow = 2.39) is expected to limit bioc oncentration and bioaccumulation of pyroxasulfone. Based on the log K
ow of 2.39, the expected BCF assuming no metabolism and 5% lipids would be appr oximately 12 L/kg wet weight ( i.e., 10 2.39 * 0.05). This low BCF combined with the low acute toxicity to birds and mammals indicates that risks to piscivorous wildlife woul d 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 surf ace 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 pyroxasu lfone that may occur in surface water bodies adjacent to applica tion sites receiving pyroxasulfone through runoff and spray drift for specific scenarios. PRZM simu lates pesticide application, movement and transformation on an agricultural field and the resultant pesticide loadings to a receiving water body via runoff, erosion and spray drif t. EXAMS simulates the fate of the pesticide and resulting concentrations in th e water body. The standard scenario used for ecological pesticide assessments assumes app lication to a 10-hectar e agricultural field that drains into an adjacent 1-hect are water body, 2-meters deep (20,000 m 3 volume) with
no outlet. PRZM/EXAMS was used to esti mate screening-level exposure of aquatic organisms to pyroxasulfone residues. The meas ure 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 expos ures of direct effect s to aquatic organisms as well as indirect effects. The 1-in-10-y ear 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. De gradation products were not considered in the exposure modeling because of the persistence of pyroxasulfone. In addition, surface water modeling for total re sidues (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 sel ected from the physical/chemical properties and environmental fate data submitted by the petitioner to su pport registration of pyroxasulfone ( Table 11 ). Input parameters were selected in accordance with US EPAOPP EFED water model parameter selecti on guidelines, Guidance for Selecting Input Parameters in Modeling the Environmental Fa te 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 90 t h percentile of
confidence bound of
the mean

N=10 Mean=343.8 days SD=119.8 days 47701736

47701737

Organic Carbon Partition Coefficient (K

oc ) (mL/ g

oc ) 94.75 Average (104, 99, 119, 57) 47701742

Aerobic Aquatic Half-Life (days) 146.74 90 t h 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 90 t h 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-m 3 /mol) 2.65E-9 Calculated 47701752

Water Solubility @ 25°C (mg/L) 3.49 47701752

Vapor Pressure (torr) 1.8E-8 4770175243 Spray drift fractions were estimated to acc ount 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 es timate the impact of spray drift buffers
on drift fractions. It is im portant to recognize that the de fault aerial spra y drift fraction (0.05) is greater than the adjusted spray frac tion for the label recommended drift buffers. The edge-of-pond AgDrift model drift frac tion 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, util izing 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 focuse d 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 surroga te scenarios for pyroxasulfone application on corn and soybeans. Agronomic practices in cluding application rate, application timing, number of applications, application interv al, and application method were modeled to represent proposed label practices. Fallowla nd use of pyroxasulfone was not explicitly
modeled because the standard PRZM/EXAMS scen arios are associated with crops. Some proposed pyroxasulfone labels allow applic ation 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 nur sery, PA apple, and NY grapes. It is anticipated the EECs for fallowl and 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 sp ecified, 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 3.75546 Uncertainty There is a high percentage of applied radioactivity (8-25% of applied radioactivity)
identified as unextracted soil/sediment resi dues. Because the extraction of pyroxasulfone residues was conducted using only acetonitrile/water without the use of sequentially harsher soil extractants, there is uncertainty re garding the identity a nd availability of the
unextracted soil residues. The uncertainty with identification of unextracted residues is not expected to alter the exposure assessm ent 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 co ntaminant because of the fate properties.

The aquatic exposure modeling was not conduc ted on fallow land use of pyroxasulfone. This modeling approach was taken because the PRZM/EXAMS standard scenarios represent scenarios with crops. It is antic ipated the EECs for fallow land uses will be adequately represented by the exposure s cenario for crops and non-crops uses.

b. Aquatic Exposure Monitoring and Field Data

Because pyroxasulfone is a new pesticide, th ere are no monitoring data in surface water and ground water.

c. Aquatic Bioaccumulation Assessment

Available data on the octanol-w ater partition coefficient (K
ow ) for pyroxasulfone indicates that this pesticide has a low bio accumulation potential in aquatic food webs. Because the log K
ow is < 4.0, KABAM v.1.0 was not used to estimate concentrations of pyroxasulfone in tissues of aquatic or ganisms 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 lo cation and behavior of those species. OPP’s terrestrial exposure model ge nerates exposure estimates a ssuming that the animal is present on the use site at the time that pe sticide levels are highest. The upper-bound pesticide residue concentration on food items is calculated from both initial applications and any additional applications, taking in to account pesticide degradation between applications. Although this approach is conser vative, 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 le vels 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 ar e 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-depende nt, 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 spri ng, hence uses of pyroxasulfone ar e likely to occur in spring and perhaps summer depending on the region. Spring and early summer are typically seasons of active migrating, feeding, and re production for many wildlife species. The increased energy demands associated with th ese activities (as opposed to hibernation, for example) can increase the potential for e xposure to pesticide-c ontaminated food items since agricultural areas can represent a concen trated source of relativ ely easily obtained, high-energy food items. In this assessment, the spatial extent of exposure for terrestrial animal species is limited to the use ar ea only and the area imme diately surrounding the

use area.

Currently, the Agency does not require toxic ity studies on reptiles and amphibians in support of pesticide registrations. To accomm odate this data gap, birds are used as surrogates for terrestrial-phase amphibians a nd 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 rela tive 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 bird s, reptiles, terrestrial amphibians,
and mammals obtained from T- REX simulations for the prop osed 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-BasedEECs (mg/kgbw) 1 Maximum
Dose-BasedEECs (mg/kgbw) 2 Maximum
Dose-BasedEECs (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

2 Based 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 Pyrox asulfone 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 Gr anules 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-1023 3 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 Estimate s for Mammals with Py roxasulfone Proposed Uses with a Foliar Dissipation Ha lf-life default value of 35 Days

.

Crop Food Item Maximum
Dose-BasedEECs (mg/kgbw) 1 Maximum
Dose-BasedEECs (mg/kgbw) 2 Maximum
Dose-BasedEECs (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

2 Based 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 Pyrox asulfone 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 Gr anules 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-1023 3 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 pl ants are most likely to occu r as a result of spray drift and/or runoff from ground applications. Thes e are important factors in characterizing the risk of pyroxasulfone to non-target plants, wh ich is assumed to reach off-site soil. The TerrPlant (Ver.1.2.2) model predicts EECs for te rrestrial 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 a nd drift characteristic s. 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 appl ication rate. An incor poration depth was not referenced in the label, which meant set ting 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 characteri zed as “sheet runoff”50 (one treated acre to an ad jacent acre; a 1:1 ratio) and inhabiting semi-aquatic areas adjacent to a field is characterized as “channeli zed 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 Concentrat ions 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 groundw ater contaminated by pyroxasulfone is applied to crops, the following method was us ed. Predicted groundwater concentrations of pyroxasulfone (equivalent to the equilibrium concentration taken over a 30 year period) were used to estimate the potentia l phytotoxic effects from irrigation water to plants and sensitive cr ops on the treated field

. It is assumed that a one-acre field is irrigated with one inch of water cont aining pyroxasulfone at the equilibrium concentration. Pyroxasulfone concentrations we re 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 In p ut Parameters

In p ut Parameter Value Source Application Rate 0.267 lbs ai/A LabelHydrolysis Halflife Stable 47701733

Soil Half-life 369 days 47701736

47701737

Koc 94.75 4770174251 Table 19. GW Tier II Model and SCIGROW Es timated 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-definiti ve, 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/degra dates 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 patter n, 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 LC 50 /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 LC 50 > 2.2 2 mg a.i./L

NOAEC ≥ 2.2 mg a.i./L

Endpoint(s) affected: None.

Sublethal effects: None. 47701626 Acceptable

At most moderately toxic 1

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 LC 50 > 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 toxic 1

1 Based on LC 50 (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 usef ul for RQ calculations, but can contribute to risk description.

Freshwater Invertebrates –Metabolites / Degradates
There are no acute data on metabolites/d egradates 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 fre shwater invertebrates at the limit of solubility, toxicity data on formul ations (Technical End Use Products) would not be required.53 Table 21. Freshwater Invertebrate Acute Toxicity Data

Common

Name %AI Study parameters EC 50 /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),

4.4 3 mg a.i./L 48-hr EC 50 > 4.4 2 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
toxic 1

1 Based on EC 50 (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 EC 50 > 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 mari ne/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 Fi sh Acute Toxicity Data

Common Name %AI Study parameters LC 50 /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 LC 50 > 3.3 2 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 toxic 1

1 Based on LC 50 (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 invertebra te 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 EC 50 > 3.6 mg a.i./L because no
treatment related effects were observed at the highest test concentra tion. As the endpoints are non-definitive, they are not useful for RQ calculations, but can contribute to risk description. However, only one replicate wa s 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 treatmen t and in each control. An EC 50 and NOAEC are not calculable since linear regression indicates no dose-response and estimation of any parameter using this method w ould likely be an under-estima tion (i.e., less protective or conservative estimate) of true sensitivity.

The marine/estuarine invertebrate study usi ng 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. Neve rtheless, juveniles (28-45 hours old) were used for testing. Current guidance suggests using juveniles <2 4 hours old or young adults 5-6 days old, depending on range-finding test results. Juve niles used in this test yielded a NOAEC ≥ 1.4 mg a.i./L and an LC 50 >1.4 mg a.i./L. As the endpoint s are non-definitive, they are not useful for RQ calculations, but ca n contribute to risk description.55 Marine/Estuarine Invertebrates – Metabolites/Degradates There are no acute data on metabolites/degra dates for marine/estua rine 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 Inve rtebrate Acute Toxicity Data

Common

Name %AI Study parameters EC 50 /LC 50 /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

3.6 3 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 EC 50 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 EC 50 > 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
toxic 156 Table 23. Marine/ Estuarine Inve rtebrate Acute Toxicity Data

Common

Name %AI Study parameters EC 50 /LC 50 /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 LC 50 > 1.4 2 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
toxic 1

1 Based on EC 50 (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 tes t 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 endpoint s (wet weight and length) of surviving fish (which were used in the study since <24 hour s old) at the end of the exposure period (28-days) indicated statisti cally significant reduc tions (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 gr oups and was at 99-100% for al l 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 significan tly different (Dunnett’s test, p = 0.05; MSD 3 value of 9.1%) relative

3 MSD = minimum significant difference57 to the negative control, but was not consider ed treatment related as higher concentrations
did not exhibit similar or increas ing effects to the test compound.

Most organisms appeared normal in the c ontrol 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 ap pear to differ greatly from the controls.

Freshwater Fish and Aquatic-Phase Amphibians –Metabolites / Degradates There are no chronic data on metabolites/deg radates 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

3.9 2 mg a.i./L 28-day NOAEC: 2.0 1 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 (lik ely 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. Statis tically analyzed endpoints (Dunnett’s test, p>0.05) including first-generation Daphnid surv ival, reproduction (number of live young produced per reproductive day), and growth (l ength and dry weight at day 21), indicated no statistically significant difference from pool ed control, negative control, and solvent control. As the endpoints are non-definitive, th ey 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 ≥ 1.9 1 mg a.i./L LOAEC > 1.9 mg a.i./L

Endpoint(s) affected: None. Endpoint(s) considered: 1 st 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 invertebra te 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 majo r guideline deviation. A small amount of test material (0.0405  g a.i./L) was detected in the solvent control at test in itiation, 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 determ ined between only the negative control and the treatment groups, which implies that endpoint calculations would not be affected as a result. Indeed, endpoint calculati ons indicate that st atistically significan t 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

EC 50 is 6.0  g a.i./L based on frond count.

Vascular Aquatic Plants – Metabolites/ Degradates The two metabolite vascular aquatic pl ant 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 relati ve to the negative control for either study lead ing to a 7-day NOAEC of ≥ 123 mg a.i./L and 7-day EC 50 of >123 mg a.i./L. As the endpoints are non-de finitive, they are not useful for RQ calculations, but can contribu te to risk description.

Vascular Aquatic Plants – Formulations
There are no data on formulations for vascul ar aquatic plants, as these data are not required.

Non-vascular Aquatic Plants - Technical The non-vascular aquatic plant st udy on freshwater green algae Pseudokirchneriella subcapitata (MRID 47701643) is classified as suppl emental (but upgradable) on account of high variability in analytic recovery of test samples, which were attributed to chromatographic interference. As a result, nomin al concentrations were used to determine the endpoints (96-hour EC 50 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 ‘Verifica tion of Test Concentrations’ where it is indicated that the presence of algae significantly affected the test ch emical recovery), then the study can be upgraded. The raw data would serve as a re cord to confirm the expected nominal
concentrations in addition to analytical results at levels above where interference affects analytical detection. In addi tion, random assignment of treat ments and test vessels were not reported in the test protocol; this inform ation would also be re quired for the study to be upgradable.60 The non-vascular aquatic plan t study on freshwater blue-g reen algae/cyanobacteria Anabaena flos-aquae (MRID 47701644) is classified as acceptable. All three endpoints (cell density, biomass, and gr owth rate) yielded a 96-hour EC 50 >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. A ll three endpoints (cell density, biomass, and growth rate) yielded a 96-hour EC 50 > 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 plan t study on marine diatom Skeletonema costatum (MRID 47701646) is classified as supplemental. Th e reason being that after 96 hours, the increase in cell density was approximately 14 times, resulting in a cell density of ~ 1.1 ×

10 6 cells/mL in the controls. This is slightly less than the OPPTS 850.5400 guideline requirement that cell density should reach 1.5 × 10 6 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 requ ired and inhibition of algal growth was demonstrated during the exposure to pyroxasulf one. However, due to the growth in the controls not being fully exponential some uncerta inty exists to the accuracy of the results obtained. All three endpoints (cell density, biomass, grow th rate) yielded a NOAEC of 0.14 mg a.i./L; the most sensit ive endpoint on the basis of EC 50 (= 0.66 mg a.i./L) is cell density.

Non-vascular Aquatic Plants – Metabolites / Degradates The non-vascular aquatic plant st udy 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 va lues 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) fo r the control and all concentrations except the highe st concentration, which had th e 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 EC 50 (= 56 mg a.i./L) is cell density.

Similarly, the non-vascular aquatic pl ant 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 sp ecifically, the pH values were above and below the guideline recomm ended value (7.5 ± 0.1) for P. subcapitata. The values were higher at test termination (8.5-8.9) than they were at test initiat ion (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 two61 observation times (initiation, termination, resp ectively). All three e ndpoints (cell density, biomass, growth rate) yielded a NOAEC of 15 mg a.i./L; the most sensitive endpoint on
the basis of EC 50 (= 38 mg a.i./L) is cell density.

Non-vascular Aquatic Plants – Formulations
There are no data on formulations for non-vasc ular aquatic plants, as these data are not required.

Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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 EC 50 : 6.0 1 (4.9-7.3)  g a.i./L 7-day NOAEC: 0.18 3  g a.i./L

Biomass 7-day EC 50 : 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 EC 50 : 16 (15-17)  g a.i./L 7-day NOAEC: 1.0  g a.i./L

Most sensitive endpoint: frond
count based on EC 50 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/ Degradates62 Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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 EC 50 > 123 2 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 Acceptable63 Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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 EC 50 > 123 2 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 Plants64 Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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 EC 50 : 0.00038 1 (0.00035-0.00041) mg a.i./L
96-hr NOAEC: 0.0001 3 mg a.i./L

Biomass:
96-hr EC 50 > 0.0008 mg a.i./L 96-hr NOAEC: 0.00005 mg
a.i./L

Growth rate
96-hr EC 50 : 0.00077 (0.00073- 0.00082) mg a.i./L 96-hr NOAEC: 0.0002 mg
a.i./L

Most sensitive endpoint: Cell density (EC 50 ), 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 EC 50 /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 EC 50 >3.5 mg a.i./L 96-hr NOAEC: 0.16 mg a.i./L

Growth rate
96-hr EC 50 > 3.5 mg a.i./L 96-hr NOAEC: 0.16 mg a.i./L

Biomass:
96-hr EC 50 > 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 EC 50 > 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 Acceptable66 Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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 EC 50 : 0.66 (0.4-1.1) mg
a.i./L 96-hr NOAEC: 0.14 mg a.i./L

Biomass:
96-hr EC 50 > 2.9 mg a.i./L 96-hr NOAEC: 0.14 mg a.i./L

Growth rate
96-hr EC 50 > 2.9 mg a.i./L 96-hr NOAEC: 0.14 mg a.i./L

Most sensitive endpoint: Cell density (based on EC 50 )

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 Plants67 Table 26. Aquatic Plant Toxicity Data

Species %A.I. Study Parameters EC 50 /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

EC 50 : 56 1 (47-67) mg a.i./L

NOAEC: 31 3 mg a.i./L

Growth rate

EC 50 : 78 (68-89) mg a.i./L NOAEC: 31 mg a.i./L

Biomass

EC 50 > 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

EC 50 : 38 1 (2.2-670) mg a.i./L

NOAEC: 15 3 mg a.i./L

Growth rate

EC 50 : 40 ( 3.6x 10 -21 – 4.4x10 23 ) mg a.i./L NOAEC: 15 mg a.i./L

Biomass

EC 50 > 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/EC 50 2 Bold value used in risk description for non-listed (EC 50 value) and listed (NOAEC value) plant species

3 Bold value used in risk quotient calculation for listed plant species whereby RQ = EEC/NOAEC68 Non-vascular Aquatic Plants (Non-guideline study) – Technical

The non-vascular aquatic plant st udy on freshwater green algae Pseudokirchneriella subcapitata (MRID 47701751) on technical grade pyroxasu lfone (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 c oncentration. It is also unclear from the study protocol why a test concentration (nominal) of 2  g a.i./L was used in the st udy. 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 primar y reviewer (APVMA) re-calculations of growth rate the effect of pyroxasulfone on green algae ( P. subcapitata ) was algistatic rather than algicidal at th e tested concentration (2.13  g a.i./L).

Table 27. Aquatic Plant Toxici ty 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 cl assified as acceptable. KIH-485 Technical was administered to the birds via gavage (singl e dose of test substan ce 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-day69 acute oral LD 50 from both studies was >2250 mg a i/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 contribu te to risk description. The quail study indicated no mortalities, overt signs of toxicity, or treatment-relate d effects on body weight or food consumption at the dosage levels tested. Th e finch study indicated no mortalities or overt signs of toxicity in the single treatment gr oup tested, there were no apparent treatmentrelated effects upon body weight, and the es timated food consump tion over the duration of the study was not reported. KIH-485 Techni cal (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 clas sified as acceptable. KIH-485 Technical was
administered to the birds in the diet at nom inal concentrations of 0 (negative control), 562, 1000, 1780, 3160, and 5620 mg a.i./kg-diet . The 8-day acute dietary LC 50 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 usef ul for RQ calculations, but can contribute to risk description. The quail study indicated no mortalities, overt si gns of toxicity, or treatment-related effects on body weight or food consumption at the dosage levels tested. The 8-day acute dietary LC 50 is also >5620 mg a.i./kg diet for the duck study. However,
relative to the contro l, 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 cha nge in body weight from day 0 to day 8. The APVMA primary reviewer calc ulated 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 exam ple, 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 t oxicity, or treatment-related effects on food consumption at the dosage levels tested.

Bird – Metabolites/Degradates
There are no acute data on me tabolites/degradates for birds.

Bird – Formulations
There are no acute data on formulations fo r birds, as these data are not required.70 Table 28. Avian Acute Toxicity Data

Common Name %AI Study parameters LD 50 /LC 50 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 LD 50 > 2250 3 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-toxic 1

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 LD 50 > 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-toxic 171 Table 28. Avian Acute Toxicity Data

Common Name %AI Study parameters LD 50 /LC 50 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 LC 50 > 5620 3 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-toxic 2

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 LC 50 > 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 theother 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-toxic 272 Table 28. Avian Acute Toxicity Data

Common Name %AI Study parameters LD 50 /LC 50 NOAEL/

LOAEL MRID Classification /Category

1 Based on LD 50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately toxic; 501-2000 slightly toxic; >2000 practically nontoxic

2 Based on LC 50 (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 studi es were conducted on female ra ts to satisfy OCSPP guidance 870.1100 (OECD 425) – one technical and seve n degradate/metabolite (M-1, M-3, M-25, I-3, I-4, I-5, M-28). All of the studies were d eemed acceptable and indicated that the test compound was practically non-toxi c with toxicity category I II. 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 th e study design. The singl e active ingredient product tested (MRID 47701916) is at most slig htly toxic (category III), while the coformulated product (MRID 47702105) is practi cally non-toxic (cat egory IV) at the respective limit doses. No deat hs or sublethal effects were observed in either study.

Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ >2000 2 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-toxic 1

Toxicity category III73 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ > 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 hunchedposture, 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-toxic 1

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 LD 50 ♀ > 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-toxic 1

Toxicity category III74 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ > 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-toxic 1

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 LD 50 ♀ > 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-toxic 1

Toxicity category III75 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ > 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-toxic 1

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 LD 50 ♀ > 2000 mg a.i./kg bw

NOAEL: No NOAEL

LOAEL: No LOAEL

Endpoint(s) affected: None.

(Sub)lethal effects: None. 47701683 Acceptable/
Practically
non-toxic 1

Toxicity category III76 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ > 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-toxic 1

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 LD 50 ♀ > 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 toxic 1

Toxicity category III77 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 ♀ > 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-toxic 1

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 LC 50 ♂ > 6.56 mg a.i./L

LC 50 ♀ > 6.56 mg a.i./L

LC 50 Combined > 6.56 3 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 IV78 Table 29. Mammalian Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LC 50 ♂ > 4.93 mg a.i./L

LC 50 ♀ > 4.93 mg a.i./L

LC 50 Combined > 4.93 mg
a.i./L

Endpoint(s) affected: None.

(Sub)lethal effects : None. 47701918 Acceptable / Toxicity Category IV

Rat,
albinoSpragueDawley 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 LC 50 ♂ > 0.86 mg a.i./L

LC 50 ♀ > 0.86 mg a.i./L

LC 50 Combined > 0.86 mg
a.i./L

Endpoint(s) affected: None.

(Sub)lethal effects : None. 47702107 Acceptable / Toxicity Category IV

1 Based on LD 50 (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 effect s (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, so lvent 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 LD 50 > 100  g a.i./bee (the highest concentration tested). For the positive control (dimethoate) nominal test79 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 a pparently not treatment-related, but include lethargy, loss of equilibrium, and immobility. More specifically, there were sporadic occurrences of lethargy (two cases duri ng the first half hour in the 9.4 and 100  g a.i./L concentration; one cas e 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 perf ormed 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 f ecundity which showed a significant decrease in the reproduction parameter ( i.e., mean number of parasitized aphids per female) at the two highest test c oncentrations. However, the primary reviewer noted that the application of KIH-485 (pyr oxasulfone) WG85 to th e parasitoid wasp resulted in up to 45% reduction in fecund ity. As 50% reduction in fecundity was not reached at any level of expos ure to pyroxasulfone, an ER 50 was not calculated from the data available and was thus considered as gr eater 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 be ing a non-guideline study. The review and toxicity calculations were performed by APVMA; the st udy was considered valid and received a ‘fully reliable’ rating. Fisher’s ex act 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 da ys of exposure. Corrected mortality for KIH485 (pyroxasulfone) WG85 applied at rate s 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 LR 50 was > 1000 g a.i./ha. There were statistically significant reductions in fecundity in a ll the KIH-485 (pyroxasu lfone) WG85 treated groups compared to the control group. Th e 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. Howeve r, the response was not dose dependent. Therefore, based on nominal concentration, the 7-day LR 50 of KIH-485 (pyroxasulfone)

WG85 to Typhlodromus pyri was >1000 g a.i./ha.

A terrestrial invertebra te 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 re view and toxicity calculations were performed by APVMA; the study received a ‘fully reliable’ rating. There were no80 mortalities in the control group or any of th e 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 we ight loss did not appear to be dose responsive. Treatment-related e ffects were not observed in the test. All earthworms in the control group and treatment groups were nor mal 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 LC 50 and NOAEC were determined by visual exam ination of the mortality and clinical

observation data.

A terrestrial invertebra te study on earthworm ( E. fetida , MRID 47933801) testing growth and reproduction and using the pyroxasulfone technical (99.21% purit y) 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 a ny of the treatments or controls. Adult bodyweight increases were similar in treated groups to the contro l. 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 (p resumably mg a.i./kg dry soil).

Table 30. Terrestrial Invertebrate Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 LD 50 > 100 2  g ai/bee

NOAEC: 100 μ g a.i./bee

LOAEC > 100 μ g 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-toxic 1

Non-guideline studies – Technical and Formulation81 Table 30. Terrestrial Invertebrate Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /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 ER 50 / LR 50 4 > 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 Supplemental 3

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 ER 50 / LR 50 4 > 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 Supplemental 3

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 LC 50 > 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 Supplemental 382 Table 30. Terrestrial Invertebrate Acute Toxicity Data

Common

Name %AI Study parameters LD 50 /NOAEL MRID Classification /Category

Earthworm

Eisenia fetida 99.21 4 week exposure period of adults; 2 nd 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 ppm 5

Endpoint(s) affected: None. Endpoint(s) considered: mortality, bodywt loss, juvenile

counts

Sublethal effects : None. 47933801 Supplemental 3

1 Based on acute contact LD 50 (  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 ER 50 : effect level corresponds to fecundity calculation; LR 50 : 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), 9 7.1, 295.5, 1004.5 mg a.i./kg-diet, respectively. There were no apparent treatment-relate d effects upon adult body weight, reproductive performance, eggshell thickness, or offspri ng 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 wa s administered to the bird s in the diet at nominal concentrations of 0 (control), 60, 240, a nd 600 mg a.i./kg-diet. Mean-measured concentrations were <25 (control), 60.9, 243, a nd 621.5 mg a.i./kg-diet, respectively. At the 600 mg a.i./kg-diet nominal test concentr ation, there was a slight, treatment related decrease in adult body weight during the peri od from week 4 to week 8. There were no apparent treatment related effects on egg shel l thickness at any concentration tested. At83 the 600 mg a.i./kg-diet nominal test concentra tion, there were treatm ent-related decreases in body weight of both hatchling and 14-day old survivors that were statistically significant. For the nominal co ncentrations 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 hatchl ings hatched out of the number of eggs set, above 70% per pair was considered, it was found that in th e control group, hatchability was above 70% in 9 of 15 pairs ( i.e. , those alive and with hatchlings; a total of 16 pairs we re 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 comparab le 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 cont rol 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, re spectively, 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 hatc hability across the control and three test concentrations are 59% (25), 74% (19), 39% (21), and 28% (2 7), 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 concentra tions. As a result, there appe ars to be a dose-dependent effect on hatchability. Therefore, on a bi ological 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 me tabolites/degradates for birds.

Bird – Formulations
There are no chronic data on formulations fo r 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 andone 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 Acceptable85 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: 60 1 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 the60 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) toxici ty is 5000 mg a.i./kg-diet (equivalent to 339/383 mg/kg-bw/day in males/females, resp ectively) 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 decr eased 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 o ffspring toxicity is 5000 mg a.i./kg-diet (equivalent to 339/383 mg/kg-bw/day in males/ females, respectively) based on decreased86 body weight gains in the P males and female s 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, respectivel y). The LOAEL for reproductive toxicity was not observed. The NOAEL for reproductive toxicity is 5000 mg a.i./kg-di et (equivalent to 339/383 mg/kg-bw/day in males/females, respecti vely), the highest concentration tested.

A rat 2-generation reproduction study (MRI D 47701706) was classified as acceptable. The LOAEL for parental toxicity is 2000 mg a.i./kg-diet (equiva lent to 144/165 mg/kgbw/day in males/females, respectively) based on decr eased body weights, body weight gains, and food consumption. The NOAEL is 100 mg a.i./kg-diet (equ ivalent to 7.2/8.4 mg/kg-bw/day in males/females, respectivel y). 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/d ay in males/females, respectively). The LOAEL for reproductive toxi city was not observed. The NOAEL for reproductive toxicity is 2000 mg a.i./kg-di et (equivalent to 144/165 mg/ kg-bw/day in males/females, respectively), the highest dose tested.

A rat developmental toxicity study (MRID 4770 1702) was classified as acceptable. The maternal and developmental LOAELs we re not observed. The maternal and developmental NOAELs are 1000 mg/kg/day (limit dose).

A rabbit developmental toxic ity study (MRID 47701704) was cl assified 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 de velopmental 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

NOAEL 2 (M/F): 16/20 mg/kg bw/day

LOAEL 3 (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/day 4

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, 100 1 , 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):

7.2 1 /8.4 mg/kg bw/day

LOAEL 5 (M/F): 144/165 mg/kg bw/day

Offspring Toxicity NOAEL (M/F): 7.2/8.4 mg/kg bw/day

LOAEL 6 (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 /
Guideline88 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 Maternal 7
NOAEL: 1000 mg a.i./kg-bw/day
LOAEL: not attained

Developmental NOAEL: 500 mg a.i./kg-bw/day

LOAEL 8 : 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 delaye d 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 pr ior to scheduled necropsy, 3 due to premat ure abortion and 4 becau se of intubation inju ry. One abortion occurred at 250 mg a.i./kg-bw/day and two occurred at 1000 mg a.i./kg-bw/day. However, there we re no test-substance related deaths or su blethal effects in dams at any level tested.

8 Based on reduced fetal weight and increased fetal re sorptions (total and early) at 1000 mg a.i./kg-bw/dayb. 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 st udy 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. Ho wever, 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 si gnificant. 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 sta tistically significant at 0.0168, 0.0334, 0.0669, 0.1338, and 0.2676 lbs a.i./A con centrations, respectively. This indicates that the study may not capture what it was intended to captu re as there was high variability in the raw data. For wheat, this implies that sublethal effects may be observed below maximum application leve ls and below the lowest test ed concentration. The most sensitive monocot was the onion ( Allium cepa ) with an EC 25 of 0.0669 lbs a.i./A and
NOAEC of 0.0168 lbs a.i./A based on the obs erved 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 EC 25 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), how ever, is classified as acceptable because it is scientifically sound and satisfies th e data requirement for a Tier II vegetative vigor toxicity study. Monocots, overall, did not exhibit signs of treat ment-related toxicity, whereas dicots did. However, there is some un certainty 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 EC 25 of the monocots for which the endpoint was available. However, the EC

x ’s for onion (as well as most monocot data) did not indicate convergence whereby an algorithm was not plotted against the data indicating clear inhibi tion with increasing concentration. As a result, for onion the EC 25 > 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 EC 25 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 EC 05 /EC 25 /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

EC 05 : 0.1044 (0.024-0.45)
lbs a.i./A

EC 25 : 0.2615 (0.17-0.41)
lbs a.i./A

EC 50 : 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

EC 05 : 0.0048 (0.0003- 0.08) lbs a.i./A

EC 25 : 0.0669 (0.02-0.19)
lbs a.i./A

EC 50 : 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 Supplemental91 Table 33. Terrestrial Plant Toxicity Data

Study Type %AI Study Parameters EC 05 /EC 25 /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

EC 05 : 0.0071 (0.001-0.05)
lbs a.i./A

EC 25 : 0.0748 (0.03-0.17)
lbs a.i./A

EC 50 : 0.3834 (0.20-0.72)
lbs a.i./A

NOAEC: 0.0168 lbs
a.i./A

Most sensitive monocot
Onion 1 ( Allium cepa ; Liliaceae) – length

EC 05 : 0.2626 (0.25-0.27)
lbs a.i./A

EC 25 >0.2676 lbs a.i./A

EC 50 >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 concen tration. As most monocot data had similar re sults, the onion was chosen on the basis of
the lowest EC 25 of the monocots for which the endpoint was available.

2 Bold values used to calculate risk quotients and/or in risk descriptionIV. Risk Characterization

A. Risk Estimation –Integration of Exposure and Effects Data

A quantitative estimation of risk integrates EECs and toxicity estimates and
evaluates the likeli hood of adverse ecological effect s to non-target species. In a deterministic approach, an exposure estimat e is divided by a single point estimate of toxicity to calculate a risk quo tient (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 regul atory 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 yi elded non-definitive endpoints but presented sublethal effects, endpoints were used in risk description, however, RQs were not calculated; this includes chronic data for fres hwater invertebrates a nd 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 th e registrant; although
acute data on these taxa indica te no effect at the highest te sted concentrations, risk to these taxa on a chronic basis cannot be pr ecluded. However, equivalent toxicity to
freshwater fish and invertebrates is as sumed for the estuarine/marine fish and invertebrates, thereby negating the risk conclu sion. It is important to note that discussion
of corn scenarios in the a quatic 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 fo r pre-emergent, pre-pl ant, pre-plant (soil incorporated), post-plant, and fall applications; winter wheat scenario includes ND wheat for fall pre-plant applications, and non-crop sc enarios include TN nur sery, PA apple, and NY grapes.

a. Aquatic Animals
1. Risk following acute exposure

Freshwater Fish and A quatic-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 eff ects. However, taking the lowest limit dose (rainbow trout, MRID 47701626) value and comparing it to the EEC s for the corn scenarios (IA, IL, OH, MS), wheat and non-crop uses indicates that the lowest LO C (0.05, for listed species) is
not exceeded.93 Freshwater Invertebrates

The acute aquatic RQs for freshwater inverteb rates 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 scenario s (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 fi sh were not calculated on the basis of a non-definitive endpoint with no sublethal effects observed in the provided study. However, taking the highest concentrati on tested (sheepshead minnow, MRID 47701628) and comparing it to the EECs for the corn/s oybean 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 i nvertebrates were not calculated on the basis of a non-definitive endpoint with no sublethal effects obs erved in the provided study. However, taking the highest concentration tested (saltwater mysid, MRID 47701625) and comparing it to the EECs for the corn/soyb ean 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 A quatic-Phase Amphibians

The chronic aquatic RQs (all <0.01) for freshw ater fish and aquatic -phase amphibians did not exceed the chronic LOC for any of the us es analyzed (the corn, soybean, winter wheat and non-crop uses).

Freshwater Invertebrates

The chronic aquatic RQs for freshwater invert ebrates were not calculated on the basis of a non-definitive endpoint observed in the pr ovided 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 c onducted. Chronic risk to marine/estuarine94 fish cannot be precluded on this basis alone. However, both freshwater and marine/estuarine acute data indicate that pyroxa sulfone is at most, moderately toxic to the tested organisms ( i.e. , no effects were observed at comp arable concentrations) suggesting that a comparison between freshw ater and marine/estuarine fish may be appropriate in the particular case of pyroxasulfone. Furthermor e, comparison of EEC values with acute endpoints for freshwater and ma rine/estuarine fish, respectiv ely, 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 invertebrate s cannot be precluded on this basis alone. However, both
freshwater and marine/estuari ne acute data indicate that pyroxasulfone is at most, moderately toxic to the tested organisms ( i.e. , no effects were obser ved at the highest concentrations tested) suggesting that a comparison between freshwater and
marine/estuarine invertebrates may be appropriate in the part icular case of pyroxasulfone. Furthermore, comparison of EEC values with acute endpoints for freshwater and marine/estuarine invertebrates, respec tively, as well as chronic RQs (<0.01) for
freshwater invertebrates suggest that chronic risk to mari ne/estuarine invertebrates is not expected.

b. Aquatic Plants

Vascular plants

The RQ calculations (1.03-1.4) based on a duckweed study (EC 50 : 0.006 mg a.i./L based on frond count, MRID 47701640) using technical gr ade 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, fa ll application), ND wh eat (fall) but not the IA corn scenario, ND wheat (pre-plant) scen ario, 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 LO C 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 meta bolites (M-1, M-3) were not ca lculated 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 concentrati on 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 (EC 50 : 0.00038 mg a.i./L based on cell density, MR ID 47701643) using tech nical grade active ingredient indicate aquatic non-listed pl ant 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 scen arios, and non-crop uses. Similarly, the RQ calculations (15.08 – 83.88) based on the sa me study (NOAEC 0.0001 mg a.i./L based on cell density) indicates aquatic listed pl ant LOC exceedances for all corn/soybean scenarios (IA/IL/OH/MS: pre-emergence, pre- plant, pre-plant soil incorporated, postplant, and fall applications), ND wh eat scenarios, and non-crop uses.

The RQ calculations (all <0.01) based on a freshwater green algae study (EC 50 : 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 lis ted or non-listed plant LOC exceedances for the other metabolite (M-3) tested on the freshwater green algae (EC 50 : 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-targ et birds and mammals, EECs and acute and chronic RQs for residues on various forage cate gories (short grass, tall grass, broadleaf plants/small insects, fruits/pods /large insects, and seeds) we re 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 propo sed 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 di ssipation. In this case, one application of 0.267 a.i./A was used to addres s corn, soybean, winter wheat (per the KIH485 W85 and Pyroxasulfone 85W labels), 0.096 lb s 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 dissi pation half-life of 35 days was used.

For birds, acute RQs are derived using dos e-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-ba sed chronic toxicity value and a dietarybased chronic toxicity value using the st andard FDA laboratory rat conversion value provided in the T-REX model. Dietary-based RQs are calc ulated using EECs expressed
in terms of residue concentration for the va rious forage categories and toxicity values (LC 50 or NOAEC) expressed in units of dietar y concentration. Dose-based RQs are calculated using a body weight-adjusted LD 50 and consumption-wei ghted equivalent dose96 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 (LD 50 >2250 mg a.i./kg bw and LC 50 >5620 mg a.i./kg diet, respectively). There
were no mortalities or treatment related clinic al signs of toxicity in the two acute oral studies (bobwhite quail, MRID 47701631; zeb ra finch, MRID 47701632) and one of the two dietary studies (bobwh ite quail, MRID 47701633). Howeve r, the dietary study on mallard duck (MRID 47701634) indicated subletha l effects statistica lly significant from
the controls that led to a definitive NOAE C calculation. Nevertheless, the acute RQ values are not reported on account of the non-definitive LD 50 /LC 50 values. However, taking the highest concentrati ons 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 c onsiders exposure via consumption of fish contaminated with pyroxasulfone residue s. However, given that the log K
ow for pyroxasulfone is below the 4-8 range require d 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 K
ow of pyroxasulfone (2.39).

Mammals

The acute endpoint for mammals is greater than the limit dose (LD 50 >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 or al 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 generate d 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 se ven 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 resi dues. However, given that the log K
ow for pyroxasulfone is below the 4-8 range require d 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 K
ow of pyroxasulfone (2.39).

Terrestrial invertebrates Honeybee Pyroxasulfone is classified as ‘practically non-toxic’ to honey bees on an acute contact basis (LD 50 >100  g a.i./bee, MRID 47701637) for the tec hnical grade active ingredient. In addition, the interim listed species LOC for terres trial invertebrates is 0.05. To lead to LOC exceedances (given the toxicity value is 781.25  g a.i./g of bee, whereby the LD 50 is

100  g a.i./bee and one bee weighs approximate ly 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 applicati on 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 th is 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 ER 50 and LR 50 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-le thal to earthworms up to a concentration of 997 mg a.i./kg dr y soil. Similarly, a non-guideline study (28- days long, MRID Pending) testing earthworm growth and reproduction indicates that mortality and reproductive perf ormance 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 earth worms 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 malla rd 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 RQs 1,2,3

Short Grass Tall Grass Broadleaf Plants/
Small Insects Fruits/Pods/
Seeds/ Large Insects

EEC RQ EEC RQ EEC RQ EEC RQ

60 a 64.08 1.07 4 29.37 0.49 36.05 0.60 4.01 0.07

60 b 49.44 0.82 22.66 0.38 27.81 0.46 3.09 0.05

60 c 28.80 0.48 13.20 0.22 16.20 0.27 1.80 0.03

60 d 23.04 0.38 10.56 0.18 12.96 0.22 1.44 0.02

60 e 61.20 1.02 4 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 Gr anules 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-da y 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 c onsiders exposure via consumption of fish contaminated with pyroxasulfone residue s. However, given that the log K
ow for pyroxasulfone is below the 4-8 range re quired 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 K
ow of pyroxasulfone (2.39).

Mammals

Utilizing the chronic endpoint (7.2 mg a.i./k g-bw parental toxicity for male rats; equivalent to 100 mg a.i./kg-diet) from a 2-generation repr oduction 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 fo r 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 smalle r two size classes: 15 and 35 g) for a couple of maximum seasonal applic ation 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 seas onal 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 RQs 1,2, 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

15 a 15.82 61.10 3.86 4 28.00 1.77 34.37 2.17 3.82 0.24 0.85 0.05

35 a 12.80 42.23 3.30 19.35 1.51 23.75 1.86 2.64 0.21 0.59 0.05

1000 a 5.54 9.79 1.77 4.49 0.81 5.51 0.99 0.61 0.11 0.14 0.02

15 b 15.82 47.14 2.98 21.60 1.37 26.51 1.68 2.95 0.19 0.65 0.04

35 b 12.80 32.58 2.54 14.93 1.17 18.33 1.43 2.04 0.16 0.45 0.04

1000 b 5.54 7.55 1.36 3.46 0.63 4.25 0.77 0.47 0.09 0.10 0.02

15 c 15.82 27.46 1.74 12.59 0.80 15.45 0.98 1.72 0.11 0.38 0.02

35 c 12.80 18.98 1.48 8.70 0.68 10.67 0.83 1.19 0.09 0.26 0.02

1000 c 5.54 4.40 0.79 2.02 0.36 2.48 0.45 0.28 0.05 0.06 0.01

15 d 15.82 21.97 1.39 10.07 0.64 12.36 0.78 1.37 0.09 0.31 0.02

35 d 12.80 15.18 1.19 6.96 0.54 8.54 0.67 0.95 0.07 0.21 0.02

1000 d 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 seas onal rate of 0.267 lbs a.i./A for co rn, soybean, and wint er wheat (KIH-485 W85 and Pyroxasulfone 85W labels)

b Single application at the maximum s easonal 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 s easonal 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 resi dues. However, given that the log K
ow for pyroxasulfone is below the 4-8 range re quired 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 K
ow of pyroxasulfone (2.39).

b. Terrestrial Plants

Utilizing the toxicity endpoints (MRI D 47701638 - seedling emergence: monocot EC 25 = 0.0669 lbs a.i./A, NOAEC = 0.0168 lbs a.i./A and dicot EC 25 = 0.2615 lbs a.i./A, NOAEC = 0.1338 lbs a.i./A; MRID 47701639 - vegetative vigor: monocot EC 25 > 0.2676 lbs a.i./A, NOAEC = 0.2676 lbs a.i./A and dicot EC 25 = 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 inco rporation depth of 1 inch, and a solubility limit in water of 3.49 mg/L (at 25 o C), the RQ calculations indi cate that monocots in semiaquatic areas exposed to runoff and spra y drift from either ground or aerial spray applications are most sensitive given that th e 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 comm ercial label is the same ( i.e. , 0.206 lbs a.i./A); therefore, the RQ calculations and risk conclusions for gr ound spray applications with
this formulation do not cha nge. Similarly, the maximum seasonal and maximum single application rate for the V-10233 Herbicide labe l, which is the only label with proposed aerial spray applications, is the same ( i.e. , 0.120 lbs a.i./A); therefor e, the RQ calculations and risk conclusions specifically regarding aeri al 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 drift 1,2

Plant Type Listed Status Dry Semi-Aquatic Spray Drift Ground spray (1% drift fraction)

Monocot a non-listed <0.1 0.44 <0.1

Monocot a listed 0.32 1.75 3 0.16

Dicot a non-listed <0.1 0.11 <0.1

Dicot a listed <0.1 0.22 0.16

Monocot b non-listed <0.1 0.34 <0.1

Monocot b listed 0.25 1.35 3 0.12

Dicot b non-listed <0.1 <0.1 <0.1

Dicot b listed <0.1 0.17 0.12

Monocot c non-listed <0.1 0.20 <0.1

Monocot c listed 0.14 0.79 <0.1

Dicot c non-listed <0.1 <0.1 <0.1

Dicot c listed <0.1 <0.1 <0.1

Monocot d non-listed <0.1 0.16 <0.1

Monocot d listed 0.11 0.63 <0.1

Dicot d non-listed <0.1 <0.1 <0.1

Dicot d listed <0.1 <0.1 <0.1 Aerial Spray (5% drift fraction)

Monocot c non-listed 0.11 0.27 <0.1

Monocot c listed 0.43 1.07 3 0.36

Dicot c non-listed <0.1 <0.1 <0.1

Dicot c listed <0.1 0.13 0.36

1 Risk Quotients are calculated using the following formula: EEC / NOAEC or EC 05 (listed); EEC / EC 25 (non-listed)

2 Chronic risk LOC = 1. If RQ > 1. 0, the LOC is exceeded, resulting in pot ential for risk to that plant group.

3 Bolded values exceed LOC

a Single application at the maximum seas onal rate of 0.267 lbs a.i./A for co rn, soybean, and wint er wheat (KIH-485 W85 and Pyroxasulfone 85W labels)

b Single application at the maximum s easonal 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 s easonal 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 pyr oxasulfone (equivalent to the equilibrium concentration taken over a 30 year period) we re 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 calcu lations obtained given
the estimated concentrations. There are no non-listed plant LOC exceedances (on the
basis of EEC/ EC 25 ); 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 fr om Irrigation Water and RQs for Terrestrial

Plants

Scenario Post Breakthrough Average (ppb) EECs (lbs a.i./A) 1 Monocot
non-listed RQ 2 Dicot
non-listed RQ 2 Monocot &
Dicot listed RQ 4

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 1.12 5

NC Cotton 43.4 0.010 0.15 0.13 0.59

WI Corn 149 0.034 0.50 0.45 2.01 5

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 EC 25 = 0.0669 lbs a.i./A

3 Based on vegetative vigor study (MRID 47701639) most sensitive dicot, pumpkin EC 25 = 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 pr edicted 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 an d M-3, are not considered degradates of concern for duckweed (vascular aquatic plant) or freshwater green algae (non-vascular aquatic plant). The pyroxasulfone degrad ates, M-1, M-3, M-25, I-3, I-4, I-5, M-28, are not considered degradates of concern for ma mmals (on an acute basis). The formulations WG85 (84.7% a.i.) and V-10233 (42.2% pyroxasu lfone; 33.6% flumioxazin) are not considered to pose a risk to mammals (on an acute basis). The fo rmulation WG85 (84.7% a.i.) is considered to not pose a risk to (non-guideline) terrest rial invertebrates (parasitoid wasp, predatory mite).103 1. Risk to Aquatic Animals and Plants

a. Aquatic Animals
1. Risk following acute exposure

Freshwater Fish and A quatic-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 effect s. However, taking the lowest limit dose (2.2 mg a.i./L for rainbow trout, MRID 47701626) value and co mparing it to the EECs for the corn scenarios (IA, IL, OH, MS), wheat and non-cr op uses indicates that the lowest LOC (0.05, for listed species) is not exceeded. The pyroxasulfone lim it of water solubility is reported as 3.49 mg/L at 25 o C. 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. Ho wever, according to the model estimated EECs (0.002 - 0.008 mg/L, which includes pyroxasulfone only residues), levels of pyroxasulfone at the so lubility limit are not expected to occur in surface water given the proposed corn, soyb ean, wheat, and non-crop uses. Therefore,
acute risk to freshwater fish a nd 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 prec luded on the basis of no data available.

Formulations No acute data on formulations of pyroxasulf one for freshwater fish and aquatic-phase amphibians was provided. Risk cannot be prec luded on the basis of no data available.

Freshwater Invertebrates

Technical The acute aquatic RQs for freshwater inverteb rates 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 scen arios (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 25 o C. However, for the particular study and on account of poor so lubility, column elution methodology was
utilized to achieve saturation at the limit dos e, 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 the104 environment reach the solubility limit, the eff ect of the technical grade active ingredient
on freshwater invertebrates is likely to be low. Accordi ng to the model estimated EECs (0.002 - 0.008 mg/L, which includes pyroxa sulfone only residues), levels of pyroxasulfone at the solubility limit are not expected to occu r in surface water given the proposed corn, wheat, and non-crop uses. Th erefore, acute risk to freshwater
invertebrates is not expected as a result of pyroxasul fone use on corn, soybean, wheat, and non-crop sites given the results from th e 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 basi s of no data available.

Formulations No acute data on formulations of pyroxas ulfone 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 fi sh 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 fo r the corn scenarios (IA, IL, OH, MS), wheat and non-crop uses indica tes that the lowest LOC ( 0.05, for listed species) is not exceeded. The pyroxasulfone limit of wa ter solubility is reported as 3.49 mg/L at 25 o C. Given this study and assuming that pyroxasu lfone concentrations in the environment reach the solubility limit, the effect of the technical grade active ingredient on
marine/estuarine fish is likel y to be low. According to the model estimated EECs (0.002 - 0.008 mg/L, which includes pyroxasulfone only re sidues), levels of pyroxasulfone at the solubility limit or at the highe st 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 basi s of no data available.

Formulations No acute data on formulations of pyroxasulf one 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 i nvertebrates were not calculated on the basis of a non-definitive endpoints with no sublet hal 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 25 o C. Given this study and assuming that pyroxasulfone concentrations in the environmen t reach the solubility limit, the effect of the technical grade active ingredient on marine/e stuarine 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 pyroxasu lfone at the solubility limit or at the highest concentration tested ar e not expected to occur in su rface 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 us e 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 inve rtebrates was provided. Risk cannot be precluded on the basis of no data available.

Formulations No acute data on formulations of pyroxasulf one 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 A quatic-Phase Amphibians

The chronic aquatic RQs for freshwater fish and aquatic-phase amphibians did not exceed the chronic LOC for any of the uses analy zed (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 wa s a significant re duction in percent
survival relative to the contro ls in the second lowest mean-m easured concentration tested (0.58 mg a.i./L) but was not considered treatm ent related. Sublethal effects were observed in the study such as weakness, small size, a nd a curled/crooked spin e, 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 25 o 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 durati on 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, which106 includes pyroxasulfone only residues) , levels of pyroxasulfone at the solubility limit or at the highest concentration tested are not e xpected 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 re sults from the fathead minnow study using technical grade active ingredient.

Metabolites/Degradates No chronic data on metabolites/degradate s for freshwater fish and aquatic-phase amphibians was provided. Risk cannot be prec luded on the basis of no data available.

Formulations No acute data on formulations of pyroxasulf one for freshwater fish and aquatic-phase amphibians was provided. Risk cannot be prec luded on the basis of no data available.

Freshwater Invertebrates

The chronic aquatic RQs for freshwater invert ebrates were not calculated on the basis of a non-definitive endpoint observed in the pr ovided study. However, sublethal effects were observed such as pale discoloration, in jury, and lethargy, which were infrequent, comparable to controls, and not consider ed 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 25 o 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 da ys (per aerobic aquati c 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 freshwat er 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 solubi lity limit or at the highest concentration tested are not expected to o ccur in surface water gi ven the proposed corn, wheat, and non-crop uses. Therefore, chronic risk to freshwater invertebrates is not expected as a result of pyroxasulfone us e on corn, soybean, wheat , and non-crop sites given the results from the Daphnia study using technical gr ade 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 pyroxas ulfone 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 c onducted. Chronic risk to marine/estuarine fish cannot be precluded on the basis of no da ta available for the technical grade active ingredient, metabolite/degradate, or formulation. However, both freshwater and marine/estuarine acute data indicate that pyroxa sulfone is at most, moderately toxic to the tested organisms ( i.e. , no effects were observed at comp arable concentrations) suggesting that a comparison between freshw ater 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 appr oximately equal sensitivity to pyroxasulfone as freshwater organisms are, chronic ri sk to marine/estuarine fish is not expected as a result of pyroxasulfone (TGAI) use on co rn, 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 invertebrate s cannot be precluded on the ba sis of no data available for the technical grade active ingredient, metabolite/degradate, or formulation. However,
both freshwater and marine/est uarine acute data indicate th at pyroxasulfone is at most, moderately toxic to the tested organisms ( i.e. , no effects were obser ved at the highest concentrations tested) suggesting that a comparison between freshwater and
marine/estuarine invertebrates may be appropriate in the part icular case of pyroxasulfone. Therefore, given the results of the freshwater invertebrate analysis ( Daphnia study using technical grade active ingredient), and assumi ng that marine/estuarine organisms are of approximately equal sensitivity to pyroxasulf one 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 (EC 50 : 0.006 mg a.i./L based on frond count, MRID 47701640) using technical gr ade 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, fa ll application), ND wh eat (fall) but not the IA corn scenario, ND wheat (pre-plant) scen ario, 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 LO C exceedances for all of the corn/soybean scenarios (IA/IL/OH/MS), all wheat scenarios (ND pre-plant and ND fall), as well as all108 non-crop scenarios (TN nursery, PA apple, a nd NY grapes). Biomass and growth rate were also affected in the study and subl ethal effects were noted including root destruction, curled fronds, small fronds, ch lorotic and necrotic plants. Given the sensitivity of aquatic vascular plants to pyroxasulfone and expected surface water concentrations, risk to aq uatic listed and non- listed vascular plants is expected as a result of pyroxasulfone use on corn, soybeans, wh eat, and non-crop uses (listed species).

Metabolites/Degradates The vascular plant RQs for meta bolites (M-1, M-3) were not ca lculated 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. Taki ng the highest concentration tested (123 mg a.i./L) and comparing it to the EECs for th e 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 wa s not provided by the re gistrant. However, surface water modeling for total residues (p arent+M1+M3) showed small difference in exposure concentrations when compared w ith modeling for the parent and EPISuite
calculations indicate th at 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 a nd non-listed vascul ar plants is not expected as a result of exposure to metabolites of pyroxasulfone pos t-use on corn, soybean, wheat, and non-crop
sites.

Formulations No aquatic vascular plant data on formul ations of pyroxasulfone was provided. Risk cannot be precluded on the basi s of no data available.

Non-vascular plants

Technical The RQ calculations (3.97- 22.07) based on a freshwater green algae study (EC 50 : 0.00038 mg a.i./L for cell density, MRID 47701643) using technical grade active ingredient indicate non-listed aquatic pl ant 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 sa me study (NOAEC 0.0001 mg a.i./L based on cell density) indicates aquatic listed pl ant 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 s cenarios, and non-crop uses. Given the sensitivity of aquatic non-vascular plants to pyroxasulfone and expected surface water concentrations, risk to listed and non-liste d 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 (EC 50 : 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 lis ted or non-listed plant LOC exceedances for the other metabolite (M-3) tested on the freshwater green algae (EC 50 : 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 wa s not provided by the re gistrant. However, surface water modeling for total residues (p arent+M1+M3) showed small difference in exposure concentrations when compared w ith modeling for the parent and EPISuite
calculations indicate th at 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 co rn, soybean, wheat, and non-crop sites.

Formulations No aquatic non-vascular plant data on form ulations of pyroxasulfone was provided. Risk cannot be precluded on the basi s 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 (LD 50 >2250 mg a.i./kg bw and LC 50 >5620 mg a.i./kg diet, respectively). There
were no mortalities or treatment related clinic al signs of toxicity in the two acute oral studies (bobwhite quail, MRID 47701631; zeb ra finch, MRID 47701632) and one of the two dietary studies (bobwh ite quail, MRID 47701633). Howeve r, the dietary study on mallard duck (MRID 47701634) indicated subletha l effects statistica lly significant from
the controls that led to a definitive NOAE C calculation. Nevertheless, the acute RQ values are not reported on account of the non-definitive LD 50 /LC 50 values. However, taking the highest concentrati ons 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 e xposure 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 basi s 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/met abolites, formulations The acute endpoint for mammals is greater than the limit dose (LD 50 >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 or al 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 generate d 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 limite d to, decreased respiratory rate, underactivity, lethargy, and body weight loss, which could affect survival of
individual mammals in the short term s hould exposure to these degradates occur. Furthermore, two additional studies on two pyroxasulfone formulations determined comparable endpoint values. However, all st udies 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 formul ation 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 (LD 50 >100  g a.i./bee, MRID 47701637) for the tec hnical grade active ingredient. Although sublethal effects were observed ( i.e. , lethargy, loss of equilibrium, and immobility) these were sporadic and not cons idered treatment rela ted. 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 LD 50 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 applica tion rates indicated on the labe ls 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 honeyb ee 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 th is 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 ER 50 and LR 50 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 concentrat ion is approximately 3x greater than the maximum seasonal proposed rate (0.267 lbs a.i./A), ri sk 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-le thal to earthworms up to a concentration of 997 mg a.i./kg dr y soil. Similarly, a non-guideline study (28- days long, MRID Pending) testing earthworm growth and reproduction indicates that mortality and reproductive perf ormance 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 appr oximately 5-20cm. Given a soil depth of 20 cm and assuming a seasonal maximum application rate (0.26 7 lbs a.i./A, which assumes a hypothetical maximum active ingredient loadin g rate since the seasonal rate would not be applied all at once), the EEC is much lowe r (0.114 mg/kg soil) than the concentrations generated in these studies. At shallower de pths (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 la nd, and non-crop sites. However, given the persistence of pyroxa sulfone 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 chr onic 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 malla rd duck and the T-REX model v.1.4.1, the chronic avian dietary-based RQ (1.07) exceed s 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 appl ied 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 (T able 34). The chronic endpoint is based on biologically significant effects on reproductive performance ( i.e. , hatchability), not statistically significant re sults. According to OCSPP guidance 850.2300, normal values112 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 cont rol, 12, 14, and 14 in the resp ective 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 2 40 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 applicati ons, chronic risk to birds is expected as a result of pyroxasulfone use on corn, soybean, and wint er wheat. Reducing the maximum seasonal application rate would alle viate the risk concern.

Metabolites/degradates No chronic avian data on metabolites/deg radates of pyroxasulfone was provided. Risk cannot be precluded on the basi s 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./k g-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 fo r 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 cl asses: 15, 35, and 1000g) as well as the tall grass and broadleaf plants/small insects categories (in the sma ller two size classes: 15 and 35 g) for a couple of maximum seasonal a pplication 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) occu rs 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 alle viate the risk concern.113 Metabolites/degradates
No chronic mammalian data on metabolites/d egradates of pyroxa sulfone 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 (MRI D 47701638 - seedling emergence: monocot EC 25 = 0.0669 lbs a.i./A, NOAEC = 0.0168 lbs a.i./A and dicot EC 25 = 0.2615 lbs a.i./A, NOAEC = 0.1338 lbs a.i./A; MRID 47701639 - vegetative vigor: monocot EC 25 > 0.2676 lbs a.i./A, NOAEC = 0.2676 lbs a.i./A, dicot EC 25 = 0.0748 lbs a.i./A, NOAEC = 0.0168 lbs a.i./A), assuming liquid ground spray (1% drift fraction) and aer ial spray (5% drift fraction) application method, a default incor poration depth of 1 inch, and a solubility limit in water of 3.49 mg/L (at 25 o 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 sp ecies 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/Pyroxasulf one W85 formulations. The maximum seasonal and maximum single application rate fo r the V-10233 Herbicide Water Dispersible Granules commercial label is the same ( i.e. , 0.206 lbs a.i./A); th erefore, the RQ calculations and risk conclusions for ground sp ray applications with this formulation do not change. Similarly, the maximum seasonal and maximum single application rate for the V-10233 Herbicide label, which is th e 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 regardi ng 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 l eaf 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-cr op sites. Reducing the maximum seasonal application rate would alle viate the risk concern.

Risk from contaminated irrigation water Predicted groundwater concentrations of pyr oxasulfone (equivalent to the equilibrium concentration taken over a 30 year period) we re 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 ar e no non-listed plant LOC exceedances (on the
basis of EEC/ EC 25 ); however, given the estimates for the DE and WI scenarios, listed114 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 th e irrigated field are expected as a result of use of pyroxasulfone contaminated irrigati on 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), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whet her 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 em ploys a two-tiered approach to making the statutorily required determinations. Tier 1 cons ists of a battery of 11 screening assays to identify the potential of a chemical substan ce to interact with th e estrogen, androgen, or thyroid (E, A, or T) hormona l 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. Ti er 2 testing is designed to identify any adverse endocrine related effects caused by th e substance, and esta blish a dose-response relationship between the dose a nd 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 wa ter, residential activity, and certain postapplication agricultural s cenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Pyroxasulfone is not among the group of 58 pest icide 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 anticip ates issuing future EDSP test orders/data call-ins for all pesticide active ingredients.

For further information on the status of the ED SP, 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 Nati onal Marine Fisheries Service (NMFS) for marine and anadromous listed species, or th e United States Fish and Wildlife Services (FWS) for listed wildlife and freshwater organism s, 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 a ny action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a liste d species or result in the destruction or adverse modification of designated critical habi tat. To jeopardize th e continued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably the likeli hood 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 requir ements of the Endangered Species Act (subsection (a)(2)), the Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may dir ectly 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 dist ribution of any list ed species (USEPA, 2004). After the Agency’s screening level ri sk assessment is conducted, if any of the Agency’s listed species LOCs are exceeded fo r either direct or indirect effects, an analysis is conducted to determ ine 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, fu rther biological assessment is undertaken. The extent to which listed species may be at risk then de termines the need for the development of a more comprehensive consultation package as required by the Enda ngered Species Act.

Both acute endangered species and chronic ri sk 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 LO Cs or, in the case of endangered plants, RQs are derived using lower toxicity endpoint s than non-endangered plants. Therefore, concerns regarding listed species within a taxonomic group are triggered in exposure
situations where restricted use or acute ri sk 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 establishe d dose/response relationship and assumes a probit (probability unit) dos e/response relationship.116 a. Action Area

For listed species assessments, the action area is considered to be the area affected directly or indirectly by th e Federal action and not merely the immediate area where pyroxasulfone is applied. At the initial Le vel 1 screening assessment, broadly described taxonomic groups are considered, and thus, cons ervatively 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 assume s that listed species are located within the area of highest exposure to the pesticide, a nd that exposure will de crease with increasing
distance from the treated area.

If the assumptions associated with the screen ing-level action area resu lt 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 list ed species LOCs for a given taxonomic group
indicate no concern for indirect effect s upon listed species that depend upon the taxonomic group covered by the RQ as a resour ce. However, in situations where the screening assumptions lead to RQs in exce ss 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 belongi ng to that taxonomic group or may extend to indirect effects upon listed species that depe nd upon that taxonomic group as a resource. In such cases, additional information on the biology of listed speci es, the locations of these species, and the locations of use site s 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 step s 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 dow nstream of the pesticide use site.

b. Taxonomic Groups Potentially at Risk

The preliminary risk assessment for endangere d species indicates that the proposed use and application rate for pyroxa sulfone 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)

 Mammals117 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 Yes 4

Terrestrial and semi-aquatic plants – dicots No Yes 4

Terrestrial invertebrates No Yes 4
Birds Yes (chronic) Yes 4

Terrestrial-phase amphibians Yes (chronic) Yes 4
Reptiles Yes (chronic) Yes 4

Mammals Yes (chronic) Yes 4

Aquatic non-vascular plants Yes Yes 4

Aquatic vascular plants Yes Yes 4
Freshwater (FW) fish No Yes 4

Aquatic-phase amphibians No Yes 4
Freshwater (FW) invertebrates No Yes 4
Marine/estuarine (M/E) fish No 3 Yes 4

Marine/estuarine (M/E) invertebrates (mollusk) No 3 Yes 4

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 a quatic plants, mammals (chronic), and birds (chronic) are exceeded for the use of pyroxasu lfone as outlined in previous sections. Should estimated exposure levels occur in pr oximity to listed resources, the available screening level information suggests a poten tial concern for dire ct effects on listed species within the taxonomic groups listed above a ssociated with the uses of pyroxasulfone as described in Section III.A. The registrant must provide information on the proximity of federally liste d terrestrial and aq uatic plants, mammals, birds, reptiles, and terrestrial-phase amphibians to the pyroxasu lfone use sites. This requirement may be satisfied in one of three ways: 1) having me mbership in the FIFRA Endangered Species Task Force (Pesticide Registration [PR] Notice 2000-2); 2) citing FIFRA Endangered Species Task Force data; or 3) independe ntly producing these data, provided the information is of sufficient quality to meet FIFRA requirements. The information will be used by the OPP Endangered Species Protec tion Program to develop recommendations to avoid adverse effects to listed species.118 2. Probit dose response relationship

The Agency uses the probit dose response rela tionship 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 charac terization, an interpreta tion of acute RQ for listed species is discussed. This interpretati on is presented in term s of the chance of an individual event (i.e., mortality or immobili zation) should exposure at the EEC actually occur for a species with sensitivity to pyr oxasulfone 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 av ailable from the toxicity study used to establish the acute toxicity measures of eff ect for each taxonomic group that is relevant to this assessment. The individual effects probabi lity 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 es timate 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 lowe r 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 appr opriate for the data set) are associated with a high degree of confidence. Conversely, a lo w 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 prob it 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) (Urb an and Cook, 1986) is used.

Individual effect probabilitie s 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 (J une 22, 2004). The model allows for such calculations by entering the mean slope estima te (and the 95% confidence bounds of that estimate) as the slope parameter for the spread sheet. In addition, the acute RQ is entered
as the desired threshold.

3. Data related to under-represented

taxa

Effects data on under-represented taxono mic groups were not submitted by the Registrant. Effects data from other analyzed sources were either not obtained (ECOTOX Database, PAN Database) or were not availa ble (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 th e potential for indire ct effects upon listed species. The listed species re ly upon non-listed organisms in these taxonomic groups as
resources critical to their lif e cycle. Pesticide-use scenar ios, resulting in RQs that are below all direct effect listed species LOCs for all taxonomic groups assessed are119 considered of no concern for risks to listed speci es either by direct or indirect effects. However, there may be situations where a taxonomic group is not qua ntitatively assessed (e.g., some non-guideline terrestr ial invertebrates), but other lines of evidence are sufficiently supportive of concerns for indi rect 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 anal ysis 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 pestic ide 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 equa l or exceed the listed species acute LOC, the Agency uses the dose response relati onship from the toxicity study used for calculating the RQ to estimate the probabil ity of acute effects associated with an exposure equivalent to the EEC. This informa tion 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 anal yses are performed is commen surate with the predicted probability of adverse effects from the comparison of dose response information with the EECs. The greater the probability that e xposures will produce effects on a taxa, the greater the concern for potent ial indirect effects for liste d 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 informa tion regarding the use scenario (e.g., timing, frequency, and geogr aphical extent of pesticide application). The greatest concerns would exist when exposure is associ ated 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, amphi bians, 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 ha bitat, consideration is given to the physical and biological features (c onstituent 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 liste d 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 constituent120 elements and is accomplished using the sc reening-level taxonomic analysis (risk quotients, RQs) and listed species levels of concern (LOCs) that are used to evaluate
direct and indirect effect s to listed organisms.

The screening-level risk assessment has identif ied potential concerns for indirect effects on listed species for those organisms depende nt upon terrestrial and aquatic plants, mammals, birds, reptiles, and terrestrial-phase amphibians. In light of the potential for indirect effects, the next st ep for EPA and the Service(s) is to identify which listed species and critical habitat are potentially im plicated. Analytically, the identification of such species and critical habita t can occur in either of two wa ys. First, the agencies could determine whether the action area overlaps criti cal habitat or the o ccupied 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. Alternativ ely, 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 revi ewed by EPA does not permit use of either analytical approach to make a de finitive identification of species that are potentially impacted indirectly or critical habi tat that is potentially impacted directly by the use of the pesticide. EPA and the Serv ice(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 constituen t elements of one or more critical habitats, would be of potential concern. These corr espond to the taxonomi c groups identified above as being of potential concern for indire ct 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 site s of pesticide use are geographically associated with known locations of listed species. At the screening level, this analysis is accomplished using the LO CATES v. 2.13 database. The database uses
location information for listed species at the count y level and compares it to agricultural census data for crop production at the same county level of resolu tion. The product is a listing of federally listed sp ecies 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 va riety 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 30122 C. Description of Assumptions, Limitation s, 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 poten tial ecological risks resulting from a maximum use scenario, which is determined from labeled statements of maximum application rate and number of app lications with the shortest time interval between applications. The frequency at whic h actual uses approach this maximum use scenario may be dependant on herbicide re sistance, timing of applications, cultural practices, and market forces. Furthermore, this assessment utilizes the maximum

seasonal application rate for RQ cal culation over the maximum si ngle 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 we re not reported on the labels and pyroxasulfone’s persistence in water (h alf-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. Neverthe less, in cases where RQs exceeded LOCs, lower application rates were used for risk characterizati on. Furthermore, the seasonal application rate was assumed to be e quivalent 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 recei ving pyroxasulfone at
the treatment rate on the field. Actual habita t requirements of any particular terrestrial species were not considered, and it was a ssumed that species occupy, exclusively and permanently, the modeled treatment area. Spra y drift model predictions suggest that this assumption leads to an overestimation of exposure to species th at 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 wate r exposure. Other routes of exposure that
were not considered in the assessment are in cidental soil ingesti on 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 sub acute 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 allo w for differences in the responses of
individuals to different durati ons 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 eff ect of different environmental matrices on absorption rate into the gastro intestinal tract of the animal. With the acute dietary study, the endpoint is reported as the concentrati on mixed with food that produces a response rather than as the dose ingested. Alth ough 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 esti mated once at the end of the five-day exposure period. Group housing of birds undergoing te sting 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 th e estimate of the dose; controls often nearly doubl e in size over the duration of the test. Since weights are only taken at the initiation and at the end of the e xposure period, the dose per body weight (mg/kg) is difficult to estimate with any precision. The interp retation of this test can be further confounded by dietary consumption. Estimation of the acute LC 50 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 fact ors, not normally taken into account in a screening level risk assessment may narrow th e differences between the dose-based and dietary-based acute RQs for birds. The fact ors include differences in gross energy and assimilative efficiency of laboratory feed versus food items in the field, basic
maintenance metabolic rates between wild bird s and captive birds, se asonal free living dietary requirements for wild birds (inc luding gorging behavior) and specific food
avoidance behavior. These uncertainties ma y 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 e fficiency differences between wildlife food items and laboratory feed. For example, a typi cal laboratory avian f eed, as used, contains approximately 2750 kcal/ kg. The Agency’s Wildlife Exposure Factors Handbook (U.S. Environmental Protection Agency, 1993) pres ents 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 compar ison of a laboratory dietary concentrationbased effects threshold to a fresh-weight pes ticide residue estimate would result in an underestimation of field exposure by food cons umption 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 comp arable with consumption during laboratory testing.

Metabolic Rates. In the screening process, exposure may be underestimated because
metabolic rates are not related to food consum ption. 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 maintena nce in captivity without body weight loss, a condition similar to caged test animals. FM R is the energy requirement for an organism in the wild. For passerine birds th ese 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 k cal/day. Thus, it appears that not accounting for increased energy demands of organisms in the wild when comparing dietary residues to dietary toxicity threshol ds 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 so me specific wildlife scenarios (e.g., bird migration) where the f ood intake rate may be greatly increased. Kirkwood (1983) has suggested that an upper-b ound limit to this behavior might be the typical intake rate multiplied by a factor of 5.125 Avoidance. In contrast is the potential for a voidance, operationally defined as animals responding to the presence of noxious chemi cals 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 assumpti on that the entire treatment area is subject to pesticide application at the rates specifi ed on the label. Uneven application of the pesticide through changes in ca libration of application equipm ent, spillage, and localized releases at specific areas of the treated field th at 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 it ems. These residue assumptions are believed to reflect a realistic upper-bound residue estimate, alt hough 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 devel op 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 wild life species’ foragi ng habits, whole aboveground plant samples may either underes timate or overestimate actual exposure.

f. TerrPlant Model

At this time, the TerrPlant model cannot accurately estimate terrestrial exposure levels with pesticides applied with multiple appl ications or application intervals. The technology is not yet available for thes e types of estimations. The maximum seasonal application rate was used to calculate RQ s 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 th e 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 LO Cs, lower application rates were used for risk characterization. Furthermore, the seas onal 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 respon ses to the pesticide, as determined by the testing of species response to chronic expos ure conditions and subsequent chronic risk
assessment. Consideration of additional subletha l data in the assessment is exercised on a case-by-case basis and only after careful cons ideration of the nature of the sublethal
effect measured and the exte nt 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 ma y overestimate toxicity at older age classes for pesticidal active ingredients that act di rectly (without metabolic transformation) because younger age classes may not have the enzymatic system s 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 relie s on a selected toxicity endpo int from the most sensitive species tested; however, the selected toxi city 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 distri bution of all possible species is a function of the overall variability among species to a par ticular chemical. Toxicity thresholds may vary up to four orders of magnitude across species for some chemicals 4 . Therefore, risk conclusions may under- or overestimate actual ecological risk fo r 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 a ssessment document includes an evaluation of the potential for individual effect s to listed species at an exposure level equivalent to the
LOC. This evaluation is ba sed on the median lethal dose estimate and dose/response

4 Mayer, F.L. and M.R. Ellersieck, 1986. Manu al of acute toxicity: Interpretation and data

base for 410 chemicals of freshwater animal s. Resource Publication 160. U. S. Fish and Wildlife Service. Department of th e 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 individua l effects near the low end tail of the curve. Predictions based on low probability events are by nature highly unc ertain. Moreover, for this assessment the dose-response curve representing a given ta xa is generated fro m one study using one species. It is likely that the resulting dos e-response relationship does not represent the response of all species within a taxa. Calculating the probabi lity 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 defa ult 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. Envi ronmental Toxicology and Chemistry, v23 (10), 2343-2355

.

Fletcher, J.S., J.E. Nellesson, and T. G. Pfl eeger. 1994. Literature review and evaluation of the EPA food-chain (Kenaga) nom ogram, an instrument for estimating pesticide residues on plants. E nviron. Tox. and Chem. 13(9):1383-1391.

Hoerger, F. and E.E. Kenaga. 1972. Pes ticide residues on plan ts: 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 Ev aluation Division Standard Evaluation Procedure Ecological Risk Assessment. EPA 540/9-85-001. U.S. Environmental Protection Agency, Office of Pes ticide Programs, Washington D.C.

U.S. Environmental Protection Agency (U SEPA). 1993. Wildlife Exposure Factors
Handbook. Office of Research and Devel opment, Washington, D.C. EPA/600/R13/187a.

U.S. Environmental Protection Agency (U SEPA) 1998. Guidelines for Ecological Risk
Assessment. EPA/630/R-95/002F. Pub lished 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 Threat ened Species Effects Determinations. Office of Prevention, Pesticides and T oxic 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 Ri sk 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). Environm ental 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. [ 14 C]-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). [ 14 C]-KIH-485: Anaerobic Soil Me tabolism 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). [ 14 C]-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). [ 14 C]-KIH-485: Aerobic Aquatic Me tabolism. Covance Laboratories Ltd., Covance Report Number: 0535/133-D2149. December 13, 2007. Unpublished.

MRID # 47701740

Graham R., Scholey A. and Gilbert J. (2008). [ 14 C]-KIH-485: Anaerobic Aquatic
Metabolism. Covance Laboratories Lt d. Report No.: 0535/134-D2149. November 27, 2008. Unpublished. MRID # 47701741

Hewitt, A.J. (2009). Atomization Droplet Si ze Spectra for KIH-485. The University of Queensland, Australia. Study Number L08-001. February 23, 2009. Unpublished. MRID

# 47701622129 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 Dissipati on 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 14 C-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 [ 14 C]KIH-485 in Representative Agricultural Soils. PTRL West, Inc., Herc ules, CA. Report No. 1629W. September 16, 2008. Unpublished. MRID # 47701743

Ponte, M. and Schick, M. (2008) . Aerobic Soil Metabolism of [ 14 C]-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 [ 14 C]-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 [ 14 C]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). Determin ation 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. [ 14 C]-KIH-485: Hydrolytic Stabilit y. Covance Laboratories Europe, Harrogate, England. Report 535/97-D2149. May 14, 2003. Unpublished. MRID #

47701733

Swales S, (2004). [ 14 C]-KIH-485: Photo-degradation in Sterile, Aqueous Solution. Covance Laboratories Europe, Harrogate, E ngland. Report No.: 535/96-D2149. February 19, 2004. Unpublished. MRID # 47701734130 Effects Studies Submitted to the USEPA/Office of Pesticide Programs

Blankinship, A. S., Kendall, T. Z. and Krue ger, 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 Krue ger, HO (2007) KIH-485 (pyroxasulfone as provisionally approved): A 96-Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica) . Wildlife Inte rnational, 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-H our Toxicity Test with the Freshwater Alga, ( Anabaena flos-aquae) . Wildlife Inte rnational, Ltd., Maryland, USA. Project Number 267A-107. July 12, 2004. Unpublished. MRID

47701644

Desjardins, D, Kendall, TZ a nd Krueger, HO (2004) KIH-485: A 96-Hour Toxicity Test
with the Freshwater Diatom (Navicula pelliculosa ). Wildlife Intern ational, Ltd., Easton, Maryland, USA. Project Number 267A- 108. August 4, 2004. Unpublished. MRID

47701645

Desjardins, D, Kendall, TZ a nd 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 Internationa l, Ltd., Easton, Maryland, USA. Project Number 267A-110. August 4, 2004. Unpublished. MRID 47701640

Dreher, D. (2003) KIH-485: Acut e 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 Laborator ies. 35 p. October 31, 2008. MRID 47702107131 Durando, J. (2008) Acute Oral Toxicity Up and Down Procedure in Rats with V-10233 (VC 1763). Project Number: 25591, VP-32679. U npublished study prepared by EurofinsProduct Safety Laboratories. 27 p. November 3, 2008. MRID 47702105.

Frey, LT, Martin, KH, Beavers, JB, and Ja ber, M (2007). KIH-485 (pyroxasulfone as provisionally approved): A Re production Study with the Mallard. Wildlife International, Ltd., Easton, Maryland, USA. Proj ect Number 267-122. December 21, 2007. Unpublished. MRID 47701636

Frey, L.T., Martin, K.H., Beavers, J.B. a nd Jaber, M. (2007) KIH-485 (pyroxasulfone as provisionally approved): A Reproduction Study with the Northern Bobwhite. Wildlife International, Ltd., Easton, Maryland, US A. Project Number 267-121. October 29, 2007. Unpublished. MRID 47701635

Gallagher, SP and Beavers, JB (2006) Pyroxa sulfone (KIH-485) TGAI: (provisionally approved): An Acute Oral Toxicity St udy with the Northern Bobwhite. Wildlife International, Ltd., Easton, Maryland, US A. Project Number 267-120. October 31, 2006. Unpublished. MRID 47701631

Gallagher, SP, Martin, KH, and Beavers, JB (2006) KIH-485 Herbicide (TGAI): A Dietary LC 50 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 LC 50 Study with the Mallard . Wildlife Internationa l, Ltd. Easton, Maryland, USA. Project Number 267-116. July 28, 2006. Unpublished. MRID 47701634

Giannini, P. (2008) KIH-485 (Pyroxasulf one, 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 (pyroxasu lfone) 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 Stu dy with the Zebra Finch ( Poephila guttata) . Wildlife Intl. Ltd., Maryland, Report No: 267-125. Octo ber 21, 2008. Unpublished. MRID 47701632

Lewis, J.M. (2006) KIH-485TGAI: One-Genera tion Reproduction Study in Rats. DuPont
Haskell Global Centers for Health and Envir onmental Sciences, E.I. DuPont de Nemours & Company, Delaware, USA. Report No. 16243. January 16, 2006. Unpublished.

MRID 47701705

Lewis, J. M. (2007) KIH-485TGAI (Pyroxa sulfone as previously approved): Developmental Toxicity Study in Rabbits . Haskell Laboratory for Health and132 Environmental Sciences, Delaware, U.S. A. Report No.: 21678. December 18, 2007. Unpublished. MRID 47701704

Mead, DC, McKenzie, J, (2004) KIH-485: Alga l 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 Inte rnational, Ltd., East on, 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 Inte rnational, Ltd., East on, Maryland, USA 267A121. July 1, 2008. Unpublished. MRID 47701648

Minderhout, T, Kendall, TZ. and Kruege r 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 Numb er 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. Unpublis hed 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. Unpublis hed study prepared by Safepharm Laboratories, Ltd. 20 p. August 5, 2004. MRID 47701679

Munley, S. B. (2007) KIH-485TGAI (Pyroxa sulfone as previously approved): Developmental Toxicity Study in Rats. Haske ll Laboratory for Health and Environmental Sciences, Newark, Delaware. Study No. 20817. August 23, 2007. Unpublished. MRID

47701702

Munley, S.M. (2008) KIH-485TGAI: Multig eneration Reproduction Study in Rats.
DuPont Haskell Global Centers for Health a nd 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 Minnow133 ( 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 Kruege r H. O. (2008) KIH-485 (pyroxasulfone as provisionally approved): A Fl ow-through Life-cycle Toxicity Test with the Cladoceran ( Daphnia magna ). Wildlife International, Ltd., Ma ryland, USA. Project Number 267A117 February 11, 2008. Unpublished. MRID 47701629

Porch, J.R., Krueger, H.O. (2008) Pyroxasulf one: 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 Toxic ity Test to Determine the Effects of the Test Substance on Seedling Emergence of Ten Species of Plan ts. Wildlife Internat ional, 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 Toxic ity 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 De termine the Effects on Reproduction and Growth of the Earthworm, Eisenia fetida . Huntingdon Life Sciences, Cambridgeshire, U.K. Study No.MCW0005. Novemb er 19, 2009. Unpublished. MRID 47933801

Sanders, A. (2007) KIH-485-I-3: Acute Oral To xicity 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 To xicity 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 To xicity 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 Numb er: C01113. Unpublished study prepared by Harlan Laboratorie s, Ltd. 46 p. December 18, 2008. MRID 47701918134 Shepherd, N. (2004) KIH-485: Single Exposur e (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 Scien ce 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 B ee. Wildlife International, Ltd., Maryland, USA. Project Number 267-117. August 8, 2006. Unpublished. MRID 47701637

Taylor K. (2009) KIH-485 (pyroxasu lfone) 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 Al gal Growth from Effects of KIH-485. Life Science Research Institute, Kumiai Ch emical Industry Co. Ltd, Japan. Study No. 2009LS165. February 25, 2009. Unpublishe d. (Non-guideline study) MRID 47701751

Wetton, P. M., McKenzie, J. (2003) KIH-485: Acute Toxicity to Bluegill Sunfish ( Lepomis macrochirus) . Safepharm Laboratories Ltd. De rbyshire, 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 Proj ect 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. De rbyshire, 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 Output135 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 Us e Areas for Pyroxasulfone........................................17

Figure 2. Chemical Structure of Pyroxasulfone.................................................18

Figure 3. Conceptual model depicting stressor s, exposure pathways, and potential effects to aquatic organisms from pyroxasulfone us e 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 stressor s, generic exposure pathways, and potential effects to terrestrial organi sms from pyroxasulfone use on co rn, soybeans, wheat, fallow land, and non-crop areas. Dotted lines indica te 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 terrestria l animals from use of pyroxasulfone on corn, soybeans, wheat, fallow land, and non-crop areas. Dotted lines indicate exposure pathways that have a lo w likelihood of contributi ng to ecological risk.....................29

VIII. List of Tables

Table 1. Summary of Environmental Risk C onclusions 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....................................18136 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 A ssessing Potential Ecological Effects of Pyroxasulfone and the Associated Acute Toxicity Classification............................22

Table 9. Measures of Ecological Eff ects and Exposure for Pyroxasulfone................35

Table 10. Degradation Product Identi fication in Labor atory 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 Applicat ion Rates, Method, and Timing According to Proposed Label...................................................................................44

Table 14: Estimated Environmental Concentrat ions 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 Es timates for Mammals with Pyroxasulfone Proposed Uses with a Foliar Dissipation Half-life default value of 35 Days...............49

Table 17. Estimated Environmental Concentr ations 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 Inverteb rate Acute Toxicity Data......................................53

Table 22. Marine/ Estuarine Fi sh Acute Toxicity Data.......................................54

Table 23. Marine/ Estuarine Invert ebrate Acute Toxicity Data..............................55

Table 24. Freshwater Fish Chronic Toxicity Data.............................................57137 Table 25. Freshwater Invertebra te Chronic Toxicity Data....................................58

Table 26. Aquatic Plant Toxicity Data..........................................................61

Table 27. Aquatic Plant Toxic ity Data: Non-guideline studies..............................68

Table 28. Avian Acute Toxicity Data............................................................70

Table 29. Mammalian Acute Toxicity Data....................................................72

Table 30. Terrestrial Inverteb rate 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 Av ian Dietary Based Risk Quotients..........98

Table 35. Upper Bound Kenaga, Chronic Ma mmalian 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 fr om 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 Pote ntially Exposed to Pyroxasulfone with the Proposed Uses......................................................................................121

Table 40. Number of Endangered Species Pote ntially Exposed to Pyroxasulfone with the Proposed Uses......................................................................................121