OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460



### November 5 , 2015

PC Code: 128847
DP Barcode: 428500

MEMORANDUM

SUBJECT: Difenoconazole : Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of Registration Review

FROM: Michael Lowit, Ph.D., Ecologist Faruque Khan, Ph.D., Senior Fate Scientist Sujatha Sankula , Ph.D., Branch Chief
Environmental Risk Branch I Environmental Fate and Effects Division (7507P)

TO: Maria Piansay, Chemical Review Manager
Jill Bloom , Team Leader Linda Arrington, Branch Chief Risk Management and Implementation Branch V
Pesticide Re

- evaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the environmental fate, ecological risk, endangered spec ies, and drinking water exposure assessments to be conducted as part of the Registration Review of the fungicide
difenoconazole (CAS # 119446

- 68

- 3 ). Functioning as the first stage of the risk assessment process for registration review, this problem formula tion provides an overview of what is currently known about the environmental fate and ecological effects associated with
difenoconazole and its degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing risk to non

- target species in support of the registration review of difenoconazole . This document also recommends studies that should be
inclu ded in a generic data call

- in (DCI) to address uncertainties surrounding the environmental fate and potential ecological effects of difenoconazole

.

### 2 EFED recommends the following studies to reduce uncerta inty in the risk assessment 1 

### :

• 850.4550: Cyanobacteria toxicity ( difenoconazole; TGAI) *

• 850.4100: Terrestrial plant toxicity (seedling emergence)

– (TEP) *

o Tier II testing is required for lettuce, soybean, and sugar beet. A NOAEC must be
established at the maximum single application rate (Tier 1 test) for the other seven test species (those showing no effects in the available study , MRID 48453203 ); alternatively, Tier II testing may be conducted for those species.

• 850.4150 : Terrestrial plant toxicity (vege tative vigor)

– (TEP) *

o A NOAEC must be established for all ten test species at the maximum single application rate (Tier I test). Alternatively, Tier II testing may be conducted.

• Non

- guideline: Chronic toxicity to benthic invertebrates (whole sediment; 3 test species: freshwater amphipod, freshwater midge, and estuarine/marine amphipod)

– (difenoconazole; TGAI) *

o EFED recommends that the registrant consider Agency

- wide guidelines for chronic testing of freshwater and estuarine/marine organisms 2

, 3 

### because the
OCSPP 850 series guidelines are in the process of being finalized. A protocol must be submitted for review prior to initiating the studies.

• Non

- guideline Tier I: Honeybee adult acute oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier I: Honeybee adult chronic oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier I: Honeybee larval acute and chronic oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier II: Residue in pollen and nectar (recommendation pending risks
identified in Tier I studies) (TEP)

• Non

- guideline Tier II: semi

- field testing for pollinators (tunnel and feeding studies) (recommendation pending risks identified in Tier I studies) (TEP)

• 850.3040: Tier III full

- field testing for pollinators (recommendation pending risk
ident ified in Tier II studies) (TEP)

• 850. 6 100: ILV: Independent laboratory validation report for analytical method in soil for
difenoconazole and its metabolites ( CGA

- 205375, CGA

- 142856

, and CGA

- 71019 )

.

• 850. 6 100: ECM/ILV: Environmental chemistry method and inde pendent laboratory
validation reports for analytical method in water for di fenoconazole and its metabolites ( CGA

- 205375, CGA

- 142856

, and CGA

- 71019 )

.

Toxicity data from other sources ( e.g. , other conazoles) may be used in the absence of data for
difeno cona zole. Use of surrogate data may over or underestimate risk of difenoconazole use.

1 The studies marked with an asterisk (*) were recently required as a condition of registration for a PRIA label amendment for EPA Reg. No. 100

- 739 to add new uses to the label for use on Legumes Subgroup 6C and Bushberry Subgroup 13

- 07B; Related to Petitio n #4F8231 (May 6, 2015).

2 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants
with Freshwater Invertebrates. EPA 600/R

- 99/064

3 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estu arine Sediment

- associated Contaminants with the Amphipod Leptocheirus plumulosus . EPA 600/R

- 01/020.

### 3 EFED recommends the following label changes to reduce uncertainty in the risk assessment :



### EFED requests that the registrant provide maximum annual application rates per acre (maximum lb ai/A/year) on all labels in addition to the currently labeled per

- crop or per

- season rates. Potential accumulation of difenoconazole is a concern given that it is persistent and because many crops may have multiple c rop seasons per year. In the absence of labeled maximum
annual application rates (or labeled maximum number of crop seasons/year), EFED will assume multiple crop seasons for applicable crops and make conservative assumptions about the number
of seasons ba sed on the best available information.

### 4 

# P roblem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of the Registration Review of Difeno conazole

CAS: 119446

- 68

- 3
PC Code: 12 8847

Environmental Fate and Effects Division Prepared by: Michael Lowit, Ph.D., Ecologist Faruque Khan, Ph.D., Senior Fate Scientist U.S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division
Environmental Risk Branch I 1200 Pennsylvania Ave., NW
Mail Code 7507P Washington, DC 20460 Reviewed by: Ryan Mroz, Biologist Gregory Orrick, RAPL

### 5 Table of Contents

1. Purpose

................................ ................................ ................................ ................................ ........ 6
2. Problem Formulation

................................ ................................ ................................ .................. 6 2.1. Nature of Regulatory Action

................................ ................................ ................................ 6
2.2. Previous Assessments

................................ ................................ ................................ .......... 6 2.2.1. Ecological Risk Assessments

................................ ................................ ........................ 6
2. 2.2. Drinking Water Exposure Assessments

................................ ................................ ........ 6
3. Stressor Source and Distribution

................................ ................................ ................................ 7
3.1. Mechanism of Action

................................ ................................ ................................ .......... 7
3.2. Overview of Pesticide Use and Usage

................................ ................................ ................ 7
3.3. Physical, Chemical, and Environmental Fate Properties of Difenoconazole and its Degra dates

................................ ................................ ................................ ................................ ... 8
3.4. Monitoring Data

................................ ................................ ................................ ................ 13
3.5. Clean Water Act

................................ ................................ ................................ ................ 13 4. Receptors

................................ ................................ ................................ ................................ .. 13
4.1. Toxicity of Difenoconazole

................................ ................................ .............................. 14
4.2. Toxicity of 1,2,4

- Triazole (PC 600074)

................................ ................................ ........... 18
4.3. Toxicity of Triazole Acetic Acid (PC 600082)

................................ ................................ . 19
4.4. Toxicity of CGA

- 205375

................................ ................................ ................................ .. 20
4.5. Incident Databases Review

................................ ................................ ............................... 21 5. Exposure Pathways of Concern

................................ ................................ ............................... 21 6. Analysis Plan

................................ ................................ ................................ ........................... 21
6.1. Stressors of Concern

................................ ................................ ................................ .......... 22

6. 2. Measures of Exposure

................................ ................................ ................................ ........ 23
6.3. Measures of Effect

................................ ................................ ................................ ............. 23 6.4. Integration of Exposure and Effects

................................ ................................ .................. 24 6.5. Endangered Species Assessments

................................ ................................ ...................... 24 6.6. Endocrine Disruptor Screening

................................ ................................ .......................... 25 6.7. Drinking Water Assessment

................................ ................................ .............................. 25 6.8. Preliminary Identification of Data Gaps

................................ ................................ ............ 25
6.8.1. Environmental Fate Data

................................ ................................ ............................ 25 6.8.2. Ecological Effects Data

................................ ................................ ............................... 27
7. References

................................ ................................ ................................ ................................ 33
APPENDIX A. Difenoconazole Uses

................................ ................................ .......................... 34 APPENDIX B. Names and Structures of Difenoconazole and its Major and Minor Degradates 37
APPENDIX C. ECOSAR Results

................................ ................................ ................................ 42 APPENDIX D. SIP v.1.0 Inputs and Outputs

................................ ................................ .............. 43 APPENDIX E. STIR v.1.0 Inputs and Outputs

................................ ................................ ........... 44

### 6 1. Purpose

The purpose of this problem formulation is to provide an understanding of what is known about the environmental fate, ecological effects, and currently registered uses of difeno conazole

. This document provides a plan for analyzing data relevant to difenoconazole and for conducting environmental fate, ecological risk, endangered species, and drinking water exposure assessments for its registered uses. Additionally, this problem formulation identifies data gaps, uncertainties, and potential assumptions used to addr ess those uncertainties relative to characterizing the potential ecological risk associated with the registered uses of difenoconazole

.

2. Problem Formulation

2.1. Nature of Regulatory Action

As part of the implementation of the Registration Review program 4 

### pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Agency is beginning its
evaluation of difenoconazole to determine whether it continues to meet the FIFRA standard for registration. This problem formulation in support of the R egistration R eview of difenoconazole will be posted in the initial docket which will be open to the public phase of the review process.

2.2. Previous Assessments

2.2.1. Ecological Risk Assessments

Difenoconazole was first registered in the US in 19 94 as systemic broad

- spectrum fungicide ; it is currently registered for use on a v ariety of food crops , ornamental plants, and turf

. Previous ecological risk assessments (ERA) identified risk concerns primarily for aquatic invertebrates, fish, birds, and mammals on a chronic basis and on an acute basis for
estuarine/marine invertebrates for certain uses ( most recent : USEPA, 2014a) . Risk concerns for terrestrial plants were limi ted to listed dicot species.

2.2.2. Drinking Water Exposure Assessments

The most recent drinking water assessment (DWA) in support of human health risk assessment
was conducted in 2014 to support the registration of difenoconazole on numerous uses includin g artichoke, ginseng, berry and small fruits (subgroup 13

- 07B) , legume vegetables (subgroup 6C) as well as conversion of use on stone fruit to crop group 12

- 12 and tree nuts to crop group 14

- 12 (USEPA, 2014 b )

. The estimated drinking water concentrations (EDWCs) of difenoconazole and its major degradate , CGA

- 205375 ( aka, M1), were generated using application rates of 0.46 to 0.52 lb ai/A with the Surface Water Concentration Calculator model (SWCC) for surface water and the maximum application rate of 0.52 lb ai/A with the PRZM

- GW and SCI

- GROW models for groundwater. F or surface water, the EDWCs did not exceed th os e recommended in the previous DWA for use on grapes ( see USEPA, 2013 ), which were a peak (acute) concentration of 20.0 μg/L, an annual mean (non

- cancer chronic) concentration of 13.6 μg/L

, and a 30

- year annual average concentration (cancer chronic) of 9.9 μg/L. PRZM

- GW estimated groundwater
concentrations were: acute = 1.77 μg/L and chronic = 0.66 μg/L for the maxi mum application
rate of 0.52 lb ai /A for the FL citrus scenario.

4 http://www2.epa.gov/pesticide

- reevaluation/registration

- review

- process

### 7 3. Stressor Source and Distribution

3.1. Mechanism of Action

Difenoconazole is a broad

- spectrum triazole fungicide that works by inhibiting demethylation and other processes in sterol biosynthesis. Difenoconazole is a penetrati ng systemic fungicide
which is rapidly absorb ed by leaves and is then distributed within plant tissue by translaminar

movement

.

3.2. Overview of Pesticide Use and Usage

Estimates of the actual usage of difenoconazole on agricultural crops are summarized in Table 1 (S creening Level Usage Analysis (SLUA) provided by the Biological and Economic Analysis Division (BEAD) on October 2, 2014) . Primary uses in terms of average weight of applied product of difenoconazole are wheat (seed treatment), potatoes, and sug ar beet. These data
represent usage information from 2004 to 2014.

Difenoconazole is labeled for use on a variety of food crops, ornamental plants, and turf. Most uses allow aerial and ground applications and in some cases chemigation. A summary of

pr eviously assessed uses, m aximum application rates, number of applications, and minimum application intervals is reported in Appendix A . The registration review risk assessment will be
based on current label information at the time of assessment as provide d by BEAD.

To reduce uncertai nty in the risk assessment, EFED requests that the registrant provide annual
maximum application rates per acre (maximum lb ai/A/year) on all labels in addition to the currently labeled per

- crop or per

- season rates that remain on some labels

. Potential
accumulation of difeno conazole is a concern given that it is persistent and because many crops may have multiple crop seasons per year. I n the absence of labeled maximum annual application rates (or labeled maximum number s of crop seasons/year), EFED will assume multiple crop seasons for applicable crops and make conservative assumptions about the number of seasons
based on best available information.

Table 1

. Estimated Usage of Difenoconazole on Agricultural Crops

Crop Average Annual Usage
lb ai/A Percent (%) Crop Treated

Average Maximum

Almonds 7,000 5 15

Apples 7,000 15 25

Brussels Sprouts 1 <500 Not calculated

Cabbage <500 <2.5 5

Cantaloupes <500 <2.5 <2.5

Cucumbers 3,000 5 10

Garlic <500 5 5

Grapefruit <500 <2.5 <2.5

Grapes 9,000 5 10

Onions 2,000 5 10

Oranges 1,000 <2.5 <2.5

### 8 Crop Average Annual Usage
lb ai/A Percent (%) Crop Treated

Average Maximum

Peaches <500 <1 <2.5

Pears <500 5 10

Pecans 1,000 <2.5 <2.5

Peppers <500 <2.5 5

Pistachios <500 <2.5 5

Potatoes 20,000 15 30

Pumpkins <500 <2.5 5

Squash <500 5 10

Strawberries <500 <2.5 <2.5

Sugar Beets 20,000 15 30

Tangerines 1,000 <2.5 <2.5

Tomatoes 7,000 25 40

Walnuts <500 <2.5 <2.5

Watermelons 2,000 5 10

Wheat (Seed Treatment) 40,000 10 15

1 Based on CA DPR data only (80% or more of U.S. acres grown are in California)



### 3.3. Physical, Chemical, and Environmental Fate Properties of Difeno conazole and its Degradates

Difenoconazole is a water soluble (15 mg/L) chemical. It has a relatively low vapor pressure (2.5 x 10

- 10 

### mm Hg) and Henry’s Law constant (8.9 x 10

- 12 

### atm∙m3/mol), which suggest that volatilization is not expected to be a major route of dissipation from soil and water. Select physical and chemical properties are presented in Table 2

.

Table 2

. Physical and Chemical Properties of Difenoconazole

Property Value Source

Common Name Difenoconazole

MRID 46950104 CAS Registry No. 119446

- 68

- 3

PC Code 128847

Structure

Chemical Name (CAS) 1

- {2

- [4

- (chlorophenoxy)

- 2

- chlorophenyl

- (4

- methyl

- 1,3

- dioxolan

- 2

- yl)

- methyl]}

- 1H

- 1,2,4

- triazole

### 9 Property Value Source

SMILES notation O1CC(C)OC1(Cn2ncnc2)c3c(Cl)cc(Oc4ccc(Cl)cc4)cc3 EPI Suite, v3.12
SMILES

Molecular Formula C 19 H 17 Cl 2 N 3 O 3

MRID 46950104 Molecular Weight 406.27

Physical State Red Liquid

Vapor pressure 2.5 x 10

- 10 mm Hg (25 o C) MRID 46515901

Henry’s Law constant 8.9 x 10

- 12 atm x m 3 /mol MRID 46515901

Specific Gravity/ Density 1.14g/cm 3 @ 25 o C MRID 46950104

Solubility in water 15.0 mg/L @ 25 o C MRID 46950104

log K
ow 4.4 (25 o C) MRID 46950105



### Table 3 summarizes the environmental fate data for difenoconazole. Difenoconazole was stable to hydrolysis at pH 5, 7, and 9 in aqueous buffered solutions. Aqueous photolysis half

- lives ranged from 9.2 to 228 days in sterile buffer solutions. Difenoconazole may potentially undergo relatively fast photolysis (DT 50 

### of 6 days) in natural aquatic environment s, which may be
attribut able to indirect photolysis via irradiation absorption by organic components present in the natural water. However, difenoconazole was stable to soil photolysis.

Difenoconazole is relatively stable to aerobic and anaerobic soil metabolism and aerobic and anaerobic aquatic metabolism. When applied at 0.1

- 0.23 ppm to a variety of European and
domestic aerobic soil s , difenoconazole degrade d with half

- lives ranging from 84.5 to 533 days.
At a concentration of 10 ppm in a loam soil , difenoconazole degraded w ith half

- lives of 1059 to 1600 days under aerobic conditions and 947 days under anaerobic conditions.

In aquatic environment s under aerobic conditions, difenoconazole degraded with half

- lives ranging from 315 to 565 days at c oncentrations up to 0.17 g ai /L and 860 days at a concentration of 10 mg ai/L. Under anaerobic conditions, difenoconazole degraded with half

- lives of 370 days

at a concentration of 0.04 mg ai/L and 1245 days at a concentration of 10 mg ai /L. The longer
half

- life values obtained in both terrestrial and aquatic environments with higher concentrations may imply that the rate of microbially mediated d egradation of difenoconazole may be concentration dependent.

During aqueous photolysis, difen oc onazole breaks down to 1,2,4

- triazole acetic acid ( aka,
triazole acetic acid and CGA

- 142856) and is further degr aded to triazole methanol ( aka, CGA

107069)

, and 1,2,4

- triazole ( aka

, CGA

- 71019). In aerobic soil, difenoconazole degrades slowly

to the keto ne CGA

- 205374, which in turn is reduced to the alcohol CGA

- 205375

, the cleavage product 1,2,4

- triazole , carbon dioxide

, and minor compounds. CGA

- 2 05 375 and 1,2,4

- triazole
were also identified as degradates in aerobic and anaerobic metabolism studies. CGA

- 205375 consistently reached a maximum of 4.4 % to 14.8% in biodegradation studies

. The greatest
formation of 1, 2,4

- triazole was observed in the anaerobic aquatic metabolism study ( 35.9% at

### 10 study termination; 350 days)

. T riazole acetic acid reached a m aximum of 42% at the end of the aquatic photolysis study (30 days) and CGA

- 205375 was detected at a maximum of 14% at the
end of terrestrial field stud y (580 days). T he n on

- extractable fraction (8.1 % to 48.9%) was a major sink for the applied difenoconazole, while mineralization accounted for 0.6 % to 23.4% AR in laboratory aerobic and anaerobic metabolism studies. Chemical n ame s , structure s , and
formation of major and minor degradates are reported in Appendix B

.
Submitted terrestrial field dissipation studies showed that difenoconazole and its degradates did not leach below 30 cm of soil depth except in one study where leaching was noted up to 60 cm of the cropped plot soil (under potato production c onditions in ND; MRID 469501 29).
Difenoconazole dissipated with half

- lives ranging from 136 to 462 days in the terrestrial field dissipation studies.

Difenoconazole appears to be slightly mobile to hardly mobile in soils (FAO, 2000). Freundlich adsorption coefficient ( K F( ads ) 

### ) values were 12.8 mL/g for sand soil, 63.0 mL/g for sandy loam soil, 54.8 mL/g for silt loam soil, and 47.2 mL/g for silty clay loam soil. The corresponding K Foc 

### values were 3867, 3518, 3471, and 7734 mL/g. K F(ads ) 

### values for difenoconazole are directly proportional to the soil organic carbon content. In another study, K F(ads) 

### values were 11.6, 22.9, 182, and 201 mL/g for the Madera loamy sand, Visalia sandy loam, North Dakota clay loam, and Florida sand soils, respectively; co rresponding K Foc 

### values were 3870, 4587, 4799, and 11202 mL/g. However, this study was conducted with autoclaved soil, potentially distorting the mobility characteristic s of difenoconazole.

The octanol water partition coefficient ( log Kow of 4.4 ) suggests that difenoconazole has a potential to bioaccumulate. Difenoconazole accumulated rapidly in edible and non

- edible bluegill sunfish tissues with bioconcentration factors of 170x for edible tissues, 570x for non

edible tissues, and 330x for whole b ody. Depuration was also rapid with a depuration half

- life of approximately 1 day and 96

- 98% clearance after 14 days of depuration. O ne metabolite

, CGA

205375

, was recovered f rom both edible and non

- edible tissues , accounting for 51

- 64% of the applied difenoconazole

.

Table 3. Summary of the Environmental Fate Properties of Difenoconazole

Property Value Source
Hydrolysis half

- life pH = 5 pH = 7 pH = 9 Stable
Stable
Stable MRID 42245127

Photolysis half

- life in water 6 days

– ca. 1 ppm in in natural water ca. 9.2 days

– 1mg ai/L sterile buffer
solution 228 days

– 1.52 mg ai/L in sterile buffer solution (15

- day study) Major d egradates ( m aximum % [at d ay])
CGA

- 142856 (41.8 [30d])
CGA

- 107069 (12.27 [ 30d]) 1,2,4

- triazole (12.9 [9d]) MRID 42245128

MRID 46950104
MRID 46950105

Photolysis half

- life in soil 349

- 823 days 1 No major d egradate s MRID 469501

- 06 &

- 07 3

### 11 Property Value Source

Aerobic soil metabolism half

- life 84.5 days

– at 0.1 ppm concentration 1600 days

– at 10 ppm in loam 2 1059 days

– at 10 ppm in sandy loam 2

120 days

– at 0.13 ppm; Swiss loam 104 days

– at 0.13 ppm; Swiss loam 158 days

– at 0.23 ppm; Swiss sandy loam 187 days

– at 0.23 ppm; Swiss sandy loam/loamy sand 198 days

– at 0.23 ppm; French silty clay
loam 408 days

– at ca. 0.1 ppm in CA loamy sand
at 25 o C 533 days

– at ca. 0.1 ppm in CA loamy sand
at 25 o C Major d egradates ( m aximum % [at d ay])
CGA

- 205375 (14.8 [360d] 1,2,4

- triazole (20.6 [190d])

Non

- extractable r esidue (48.9 [29 3d] ) MRID 42245131
MRID 42245132
MRID 42245133

MRID 46950109
MRID 46950110
MRID 46950111

MRID 469501

- 12 &

- 13

MRID 469501

- 14 &

- 15

Anaerobic soil metabolism half

- life 947 days

– at 10 ppm in loam 2 No major d egradate s MRID 42245132

Aerobic aquatic metabolism half

life 860 days (10 mg ai/L) 2 ; r ice p addy w ater 330 days ( 0.17 mg ai/L); Swiss pond water

silty clay loam sediment 301 days; Swiss river water

- sandy loam
sediment 565 days; water and loamy sand sediment from river near Porterville, CA Major d egradate ( m aximum % [at d ay])
CGA

- 205375 (11.6 [90d] )

Non

- extractable r esidue (8.9 [112d] ) MRID 42245134
MRID 46950116

MRID 469501

- 17 &

- 18

Anaerobic aquatic metabolism half

life 1245 days (10 mg ai/L) 2 ; r ice p addy w ater 433 days (0.04 mg ai/L); water and loamy sand sediment from river near Porterville,
CA Major d egradates ( m aximum % [at d ay])
CGA

- 205375 (12.6 [175d]
CGA

- 71019 (35.9 [350d])

Non

- extractable r esidue (8.1 [302d] ) MRID 42245134
MRID 469501

- 19 &

- 20

Terrestrial field dissipat ion half

- life 252 days

- determined in the 0

- to 3

- inch depth

– CA bare loamy sand 231 days

– GA bare loamy sand (four applications of 0.13 lb ai/A) 139 days

– CA bare plot of loam soil (four applications of 0.13 lb ai/A) 462 days

– ND bare sandy clay loam No major d egradate s MRID 42245140

MRID 46950126

MRID 46950127

MRID 46950129

### 12 Property Value Source

Soil adsorption coefficient

K F(ads) and K Foc (L/kg) K F(ads) and (1/n) soil 11.61 (0.80) Madera l oamy sand 22.94 (0.84) Visalia s andy loam 182.4 (0.86) North Dakota c lay loam 201.6 (0.91) Florida s and

K Foc (% of organic carbon) soil 3870 (0.3) Madera l oamy sand 4587 (0.5) Visalia s andy loam 4799 (3.8) North Dakota c lay loam 11202 (1.8) Florida s and MRID 469501

- 21 &

- 22

K F(ads) and (1/n) soil 12.8 (0.74) Sand 63.0 (0.76 Sandy loam 54.8 (0.85) Silt loam 47.2 (0.91) Silty clay loam

K Foc (% of organic carbon) soil 3867 (0.33) Sand 3518 (1.79) Sandy loam 3471 (1.58) Silt loam 7734 (0.61) Silty clay loam MRID 422451 35 3

CGA

- 205375

K F(ads) and (1/n) soil 9.64 (0.83) Madera l oamy sand 12.35 (0.83) Visalia s andy l oam 145.32 (0.73) North Dakota c lay loam 115.77 (0.84) Florida s and

K Foc (% of organic carbon) soil
3214 (0.3) Madera l oamy sand
2470 (0.5) Visalia s andy l oam 3824 (3.8) North Dakota c lay loam
6432 (1.8) Florida s and MRID 469501

- 23 &

- 24

B luegill sunfish ( Lepomis
macrochirus ) bioconcentration (BCF) factor

Depuration half

- life 170x in edible tissues
570x nonedible tissues 330x for whole body

1 day MRID 469501 23

1 The soil photolysis half

- life under xenon light condition s was recalculated to represent the conditions under natural sunlight intensity during 30

- day periods between June and September (104.7

- 246.9 W∙min/cm 2 ), as a result, a range of half

- lives was obtained.

2 The test application rat e was significantly higher than expected under registrant

- proposed use conditions for
difenoconazole.

3 The test soils were autoclaved prior to conducting the study which could distort the mobility characteristic of difenoconazole, thus, the study results will not be used as modeling input parameters.



### Major degradates ( CGA

- 205375

, 1,2,4 triazole, and triazole acetic acid )

There are few environmental fate studies available for the major degradates of difenoconazole

. CGA

- 205375 has the potential to be slightly more mobile (FAO, 2000) in the soil than the parent compound . Freundlich adsorption values for CGA

- 205375 are 9.6, 12.3, 145, and 116 mL/g for the Madera loamy sand, Visalia sandy loam, North Dakota clay loam, and Florida sand soils, respectively ; corresponding K Foc 

### values are 3214, 2470, 3824, and 6432 mL/g. In addition, the

K F(ads ) 

### values for CGA

- 205375 are directly proportional to soil organic carbon content.

### 13 The environmental fate properties of 1,2,4

- triazole and triazole acetic acid were provided in a recent registration review problem formulation for myclobutanil ( see USEPA, 2015). A biotic (hydrolysis half

- lives = 99 to 421 days; stable to aqueous photolysis) and biotic degradations are not major routes of 1,2,4

- triazole degradation. Mic robial degradation of 1,2,4

- triazole in aerobic soils is highly varied (half

- lives = 20 days to stable). 1,2,4

- triazole is moderately persistent in anaerobic soil (half

- life = 81 days). The major transformation products of 1,2,4

- triazole are triazole acetic acid and hydroxytriazole. Both transformation products are formed through microbial degradation in aerobic soils.

3.4. Monitoring Data

EFED is aware of monitoring data for difenoconazole. Available data from sources including
federal and state agencies will be considered in the DWA and ERA.

3.5. Clean Water Act

Difeno conazole is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 5 

### In addition, no Total Maximum Daily Loads (TMD L) have been developed

. 6 

### The Impaired Waters and Total Maximum Daily Loads website
can be consulted for more information

. 7 

### The Agency invites submission of water quality data for
difenoconazole . To the extent possible, data should conform to the quality standards in the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 8 

### , in order to ensure they can be used quantitatively or qualitatively in p esticide risk assessments.

4. Receptors

Consistent with the process described in the Overview Document (USEPA, 2004), the risk
assessment for difenoconazole relies on a surrogate species approach. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate the potential effects on a variety of species (receptors)
included under th ese taxonomic groupings.

A cute and chronic toxicity data from studies submitted by pesticide registrants along with the available open literature will be used to evaluate the potential direct and indirect effects of
difenoconazole to aquatic and terrestri al receptors. This includes toxicity on the technical grade active ingredient, degradates, and when available, formulated products ( e.g. , “Six

- Pack” studies). Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 9



### , whic h employs a literature search engine for lo cating chemical toxicity data.

A summary of available toxicity data representing non

- target organisms exposed to difenoconazole and major degradates (1,2,4

- triazole, triazole acetic acid, and CGA

- 205375) is

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

7 http://www.epa.gov/owow/t mdl/

8 http://archive.epa.gov/pesticides/ppdc/ppdc/2006/november06/session1

- sop.pdf

9 http://cfpub.epa.gov/ecotox/

### 14 provi ded in Sections 4.1

, 4.2, 4.3, and 4.4 . Ecological Structure Activity Relationship (ECOSAR) methods 10 

### were used to estimate toxicity of the major degradates in cases where data are unavailable; results are discussed below and are presented in Appendix C

. A review of ecological incidents associated with difenoconazole is provided in Section 4.5

. The ECOTOX
database will be searched when the risk assessment for difenoconazole is prepared. At that time, EFED will review the endpoints from open literature studies that are more sensitive than those from available guideline studies.

4.1. Toxicity of Difenoconazole

Table 4

. Summary of Aquatic Taxa Toxicity Endpoints for Difenoconazole

Type of Study Species Toxicity Value (μg ai/L) MRID

Acute

– Freshwater
Fish Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 = 810 (630

- 1200) 1

NOAEC = 350 LOAEC = 630 based on mortality, darkened pigmentation, and lethargy

Other sublethal effects: decreased respiration

---------------------------------------------------- 96

- hr LC 50 = 1060 (970

- 1130) 1 Slope = 16.1 (9.0

- 23.3)

NOAEC < 580 LOAEC ≤ 580 based on partial loss of equilibrium and lethargy

Other sublethal effects: darkened pigmentation 42245107

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

42245108

Bluegill Sunfish ( Lepomis macrochirus ) 96

- hr LC 50 = 1200 (900

- 1700) 1

NOAEC = 520 LOAEC = 900 based on surfacing, loss of equilibrium, fish on the bottom, and quiescence 42245109

Fathead minnow ( Pimephales promelas ) 96

- hr LC 50 = 1800 (1300

- 2600) 1

NOAEC = 660 LOAEC = 1300 based on mortality, lethargy, and loss of equilibrium

Other sublethal effects: lying on the
bottom or surface 48453201

10 ECOSAR predictive software is available publically though the Epi SuiteTM program

. http://www2.epa.gov/tsca

- screening

- tools/ecological

- structure

- activity

- relationships

- ecosar

- predictive

- model

### 15 Type of Study Species Toxicity Value (μg ai/L) MRID

Chronic

– Freshwater
Fish Fathead minnow ( Pimephales promelas ) Early Life Stage
NOAEC = 8.7
LOAEC = 19 based on reduced larval length 30

- days post

- hatch

---------------------------------------------------- Life Cycle
NOAEC = 1.9
LOAEC = 3.7 based on reduced male length of F0

- generation 12 weeks post

hatch 42245115

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

48453205

Rainbow trout ( Oncorhynchus mykiss ) NOAEC = 0.86

Value used for risk assessment. Based on

acute

- to

- chronic ratio of fathead minnow data to rainbow trout data (the most acutely sensitive species). 2 -

Acute

– Freshwater
Invertebrate Water flea ( Daphnia magna ) 48

- hr EC 50 = 770 (590

- 950) 1 Slope = 4.1 (2.5

- 5.7) 1

NOAEC < 520 LOAEC ≤ 520 based on mortality

Other sublethal effects: on bottom and quiescence 42245110

Chronic

– Freshwater
Invertebrate Water flea ( Daphnia magna ) NOAEC = 5.6
LOAEC = 13.0 based on reduced number of young/adult/reproductive day and adult length 42245114

Chronic

– Freshwater
Invertebrate (Sediment) Midge ( Chironomus riparius ) NOAEC = 5 mg ai/kg

- sediment LOAEC = 50 mg ai/kg

- sediment based on emergence rate & development rate 47648601 3

Acute

– Estuarine/Marine Fish Sheepshead minnow ( Cyprinodon variegates ) 96

- hr LC 50 = 819 (0

- infinity) 1

NOAEC = 325 LOAEC = 428 based on mortality

Other sublethal effects: lethargy and lying
on the bottom

---------------------------------------------------- 96

- hr LC 50 = 1100 (900

- 1500) 1

NOAEC = 270
LOAEC = 400 based on loss of equilibrium 42245112

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

42906702

### 16 Type of Study Species Toxicity Value (μg ai/L) MRID

Chronic

– Estuarine/Marine Fish Sheepshead minnow ( Cyprinodon variegates ) NOAEC = 0.86

Based on acute

- to

- chronic ratio of fathead minnow data to sheepshead minnow data. 4 -

Acute

– Estuarine/Marine
Mollusk Eastern oyster ( Crassostrea virginica ) 96

- hr EC 50 = 424 (333

- 539) 1

NOAEC = 180
LOAEC = 340 based on reduced shell growth

---------------------------------------------------- 96

- hr EC 50 > 300

NOAEC = 210
LOAEC = 300 based on reduced shell growth 42906701

------------------ 42245113

Acute

– Estuarine/Marine
Invertebrate Mysid shrimp ( Americamysis bahia ) 96

- hr LC 50 = 150 (125

- 193) 1 Slope = 4.7 (2.7

- 6.7) 1

NOAEC = 480 LOAEC = 730 based on mortality 42245111

Chronic

– Estuarine/Marine
Invertebrate Mysid shrimp ( Americamysis bahia ) NOAEC < 0.115 LOAEC ≤ 0.115 based on reduced number of young/adult/reproductive day

---------------------------------------------------- NOAEC < 0.31 LOAEC ≤ 0.31 based on reduced number of yo ung/adult/reproductive day and number of young/adult

---------------------------------------------------- NOAEC = 4.8 LOAEC = 10 based on reduced F0 post

pairing survival, offspring/female and time
to first brood 46950133

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

47648603

------------------ 49322901 and

49387801

Vascular Plant

– Freshwater Duckweed ( Lemna gibba ) 7

- day EC 50 = 1900 (1600

- 2400) 1,5 Slope = 1.3±0.9 6

EC 05 = 110 (59

- 190) 1

NOAEC < 110 LOAEC ≤ 110 based on reduced frond
number 46950204

### 17 Type of Study Species Toxicity Value (μg ai/L) MRID

Non

- vascular Plant Freshwater Diatom ( Navicula pelliculosa ) 96

- hr EC 50 = 98 (68

- 140) 1,5 Slope = 2.3±0.3 (poor fit) 6

NOAEC = 53
LOAEC = 150 based on reduced cell density 46950208

Freshwater Algae ( Pseudokirchneriella subcapitata) 96

- hr EC 50 = 300 (200

- 440) 1,5 Slope = 2.9±0.5 (poor fit) 6

NOAEC = 150
LOAEC = 360 based on reduced cell density 46950212

Marine Diatom ( Skeletonema costatum) 96

- hr EC 50 = 430 (300

- 630) 1,5 Slope = 2.4±0.4 6

EC 05 = 87 (39

- 190) 1

NOAEC < 6.3 LOAEC ≤ 6.3 based on reduced cell density 46950210

1 Range is 95% confidence interval.

2 Acute toxicity to fathead minnow: LC 50 = 1800 μg ai/L (MRID 48453201); acute toxicity to rainbow trout: LC 50 = 810 μg ai/L (MRID 42245107), and chronic toxicity to fathead minnow: NOAEC = 1.9 μg ai/L (MRID 48453205)

3 This is a range finding study and should not be used quantitatively for risk assessment.

4 Acute toxicity to fathead minnow: LC 50 = 1800 μg ai/L (MRID 48453201); acute toxicity to sheepshead minnow:
LC 50 = 819 μg ai/L (MRID 42245112), and chronic toxicity to fathead minnow: NOAEC = 1.9 μg ai/L (MRID 48453205)

5 Most sensitive endpoint (based on EC 50 ) is reported.

6 ± standard error



### Table 5

. Summary of Terrestrial Taxa Toxicity Endpoints for Difenoconazole
Type of Study Species Toxicity Value MRID

Acute

– Avian Oral

Dose Canary ( Serinus canaria ) LD 50 > 2000 mg ai/kg

- bw

NOAEL ≥ 2000 mg ai/kg

- bw LOAEL > 2000 mg ai/kg

- bw 48453202

Mallard duck ( Anas platyrhynchos ) LD 50 > 2150 mg/kg

- bw

NOAEL < 2150 mg/kg

- bw LOAEL ≤ 2150 mg/kg

- bw based on reduced body weight gain and feeding 42245105

Acute

– Avian Dietary Bobwhite quail ( Colinus virginianus ) LC 50 = 4760 mg/kg

- diet (4103

- 5522) 1 Slope = 1.2

NOAEC = 625 mg/kg

- diet LOAEC = 1250 mg/kg

- diet based on reduced body weight and feeding 42245103

Mallard duck ( Anas platyrhynchos ) LC 50 > 5000 mg/kg

- diet

NOAEC = 625 mg/kg

- diet LOAEC = 1250 mg/kg

- diet based mortality

Other sublethal effects: reduced body weight and feeding 42245104

Chronic

– Avian Dietary Bobwhite quail ( Colinus virginianus ) NOAEC = 21.9 mg ai/kg

- diet LOAEC = 108 mg ai/kg

- diet based on reduction in hatchling body weight 46950202

### 18 Type of Study Species Toxicity Value MRID

Chronic

– Avian Dietary Mallard duck ( Anas platyrhynchos ) NOAEC = 110.8 mg ai/kg

- diet LOAEC = 492.9 mg ai/kg

- diet based on egg shell thinning 42245106

Acute

– Mammalian
Oral Dose Laboratory rat ( Rattus norvegicus ) LD 50 = 1453 mg ai/kg

- bw 42090006

Two Generation Reproduction

– Mammalian Laboratory rat ( Rattus norvegicus ) NOAEC = 25 mg ai/kg

- diet LOAEC = 250 mg ai/kg

- diet based on reduced maternal body weight gain and reduced pup weight 42090018

Acute Contact

– Terrestrial Invertebrate Honey bee ( Apis mellifera ) LD 50 >100 μg ai/bee

NOAEL ≥ 100 μg ai/bee LOAEL > 100 μg ai/bee 42245124

Acute Contact

– Terrestrial Invertebrate Earthworm ( Eisenia fetida ) 14

- day LC 50 > 610 mg ai/kg

- dw soil

NOAEC ≥ 610 mg ai/kg

- dw soil LOAEC > 610 mg ai/kg

- dw soil 42245125

Tier I

– Terrestrial
Plants Corn, Onion, Ryegrass, Wheat, Radish, Cabbage, Lettuce, Sugar beet, Soybean, and Toma to Seedling Emergence
EC 25 > 0.111/0.112 lb ai/A 2

NOAEC < 0.111/0.112 lb ai/A 2,3
LOAEC ≤ 0.111/0.112 lb ai/A 2,3

---------------------------------------------------- Vegetative Vigor

EC 25 > 0.123 lb ai/A NOAEC ≥ 0.123 lb ai/A
LOAEC > 0.123 lb ai/A 48453203

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

48453204

1 Range is 95% confidence interval.

2 Some species were exposed to 0.111 lb ai/A and others were exposed to 0.112 lb ai/A.

3 Effects at 0.11 lb ai /A on lettuce, sugar beet, and soybean were considered biologically significant. Lettuce showed reduced emergence (21%), survival (17%), shoot length (26%), and dry weight (24%). Soybean showed reduced shoot length (23%). Sugar beet showed reduced survi val (18%).



### 4.2. Toxicity of 1,2,4

- Triazole (PC 600074)

Available guideline data for 1,2,4

- triazole are presented in Table 6 and 7 . 1,2,4

- triazole is less
toxic than difenoconazole to non

- vascular plants (green algae)

, freshwater fish (acute basis)

, and
freshw ater invertebrates ( acute basis ) . In contrast, birds are more acutely sensitive to 1,2,4

- triazole compared to difenoconazole. Finally, both 1,2,4

- triazole and difenoconazole showed chronic effects to mammals at 250 mg ai/kg

- diet; however, there is uncert ainty about the relative chronic toxicity of the two compounds because a NOAEC was established in the difenoconazole study (25 mg ai/kg

- diet) whereas the 1,2,4

- triazole study did not test below 250 mg ai/kg

- diet.

Non

- guideline, summary report data on ac ute oral toxicity to rats (MRID 45284001, 45284004, and 45284008) suggests that 1,2,4

- triazole (LD 50 

### s ranging from 1375 to 3080 mg/kg

- bw) and difenoconazole (LD 50 

### = 1453 mg ai/kg

- bw) are equally as toxic.

Table 6

. Summary of Aquatic Taxa Toxicity Endpoints for 1,2,4

- Triazole

Type of Study Species Toxicity Value (μg ai/L) MRID

Acute

– Freshwater
Fish Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 = 498,000 48474301

### 19 Type of Study Species Toxicity Value (μg ai/L) MRID

Acute

– Freshwater
Invertebrate Water flea ( Daphnia magna ) 48

- hr EC 50 > 98,100 48453206

Non

- vascular Plant Freshwater Algae ( Pseudokirchneriella subcapitata) 96

- hr EC 50 = 14,000 45880401



### Table 7

. Summary of Terrestrial Taxa Toxicity Endpoints for 1,2,4

- Triazole
Type of Study Species Toxicity Value MRID

Acute

– Avian Oral

Dose Bobwhite quail ( Colinus virginianus ) LD 50 = 770 mg ai/kg

- bw 49380701

Two Generation Reproduction

– Mammalian Laboratory rat ( Rattus norvegicus ) NOAEC < 250 mg ai/kg

- diet
LO AEC ≤ 250 mg ai/kg

- diet based on reduced body weight and body weight gain
in F1 males , reduced spleen weight in F1 females and F2 female pups, and reduced body weight, body weight gain, and brain weight in F2 pups 46467304

Subchronic (28 day adult) and reproductive (additional 28 day offspring)

– Terrestrial Invertebrate Earthworm ( Eisenia fetida ) LC 50 > 70.81 μg/kg

NOAEC ≥ 70.81 μg/kg LOAEC > 70.81 μg/kg 45880402

28 day

– Terrestrial
Invertebrate Springtails ( Folsomia candida ) 28

- day LC 50 > 10 mg ai/kg soil

NOAEC = 1.8 mg ai/kg soil LOAEC = 3.2 mg ai/kg soil based on
reduced number of juveniles 45880404



### ECOSAR methods were used to predict chronic toxicity of 1,2,4

- triazole to fish and aquatic invertebrates based on its structural similarity to chemicals for which aquatic toxicity data are known ( Appendix C ). Estimates were available for freshwater organisms but not marine/estuarine organisms. A comparison of 1,2,4

- triazole ECOSAR estimates to experimentally derived difenoconazole toxicity values suggests that 1,2,4

- triazole is much less
toxic (two orders of magnitude) than difenoconazole on a chronic basis to freshwater
invertebrates and fish. There is reasonable confidence in the ECOSAR estimates for 1,2,4

- triazole (at least for fish and non

- vascular plants 11 

### ) given that the ECOSAR estimate s are within

an order of magnitude of the available experimentally derived values

.

4.3. Toxicity of Triazole Acetic Acid (PC 600082)

Available guideline data for triazole acetic acid are presented in Table 8 and 9 . Triazole acetic acid is less acutely toxic than difenoconazole to mammals, freshwater fish, and freshwater invertebrates. It is uncertain if triazole acetic acid is more or less acutely toxic to birds than
difenoconazole because none of the available studies for either chemical showed treatment

related mortality up to the highest doses tested (ca. 2000 mg ai/kg

- bw). 12

11 There is no basis for judging confidence in the ECOSAR estimate of acute toxicity to freshwater invertebrates due

to a non

- definitive endpoint.

12 There was one mortality in the canary study (MRID 48453202) that may not have been treatment related.

### 20 Table 8

. Summary of Aquatic Taxa Toxicity Endpoints for Triazole Acetic Acid

Type of Study Species Toxicity Value (μg ai/L) MRID

Acute

– Freshwater
Fish Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 > 101,000 48453209

Acute

– Freshwater
Invertebrate Water flea ( Daphnia magna ) 48

- hr EC 50 > 108,000 48453208



### Table 9

. Summary of Terrestrial Taxa Toxicity Endpoints for Triazole Acetic Acid
Type of Study Species Toxicity Value MRID

Acute

– Avian Oral

Dose Bobwhite quail ( Colinus virginianus ) LD 50 > 1926 mg ai/kg

- bw 49412601

Acute

– Mammalian
Oral Dose Laboratory rat ( Rattus norvegicus ) LD 50 > 5000 mg ai/kg

- bw 45596802



### A comparison of triazole acetic acid ECOSAR estimates to experimentally derived difenoconazole toxicity values suggests that triazole acetic acid is much less toxic (three or more orders of magnitude) than difenoconazole to aquatic non

- vascular plants, fre shwater fish (chronic basis), and freshwater invertebrates (chronic basis) ( Appendix C ). Estimates were not available for marine/estuarine organisms. There is no basis for judging confidence in the ECOSAR
estimates because the ECOSAR estimates for acute toxicity to fish and invertebrates are substantially greater (less toxic) than the non

- definitive endpoints observed in the available acute toxicity studies.

4.4. Toxicity of CGA

- 205375

On an acute oral basis, CGA

- 205375 and difenoconazole are of similar toxici ty to mammals ( Table 5 and 10 ).

Table 10

. Summary of Terrestrial Taxa Toxicity Endpoints for CGA

- 205375
Type of Study Species Toxicity Value MRID

Acute

– Mammalian
Oral Dose Mouse LD 50 = 2309 mg ai/kg

- bw 1 46950303

1 LD 50 = 1289 mg ai/kg

- bw scaled to laboratory rat weight (350 g) based on an average mouse body weight of 34 g in this study and the following equation: mouse LD 50 * (mouse bw/rat bw) 0.25



### A comparison of CGA

- 205375 ECOSAR estimates to experimentally d erived difenoconazole toxicity values suggests that CGA

- 205375 is not more toxic than difenoconazole to aquatic organisms in general and is similar in toxicity (< 10 times difference) to aquatic non

- vascular plants, fish (acute basis), and invertebrates (acute basis) ( Appendix C ). The available information also suggests that CGA

- 205375 and difenoconazole are similar in chronic toxicity to freshwater fish and invertebrates based on ECOSAR estimates of both compounds (< 10 times difference) and to a lesser extent when based on co mparison of CGA

- 205375 ECOSAR estimates to experimentally derived difenoconazole data. Experimentally derived CGA

- 205375 data are not available to judge the level of confidence in the ECOSAR estimates.

### 21 4.5. Incident Databases Review

Reviews were conducted of t he Ecological Incident Information System (EIIS, version 2.1.1) 13



### , the Agency’s Aggregated Incidents Reports database, and the Avian Incident Monitoring System (AIMS) 14 

### on 7/16/2015

. No incidents were reported in EIIS or AIMS . Ten minor plant damage
incide nts were reported for one difenoconazole product (Revus Top) in the aggregated incident database. The Revus Top label indicates that it is a dual ai product containing mandipropamid, a fungicide, as well as difenoconazole.

The total number of actual inci dents associated with the use of difeno conazole may be higher than what is reported to the Agency. Incidents may go unreported since effects may not be immediately apparent or readily attributed to the use of a chemical. As such, the absence of
incident reports cannot be construed as the absence of incidents.

5. Exposure Pathways of Concern

The use patterns and environmental fate properties of difenoconazole indicate that exposure to

non

- target aquatic and terrestrial organisms may occur from direct spra y and off site movement via spray drift and runoff

.

An additional exposure pathway that will be considered is the consumption of contaminated fish by piscivorus animals because fate data ( log Kow ) of difenoconazole (4.4) and CGA

- 205375 (3.79; EPISUITE es timate) suggest the potential for bioaccumulation of both compounds in the aquatic food web.

Screening Imbibition Program

The Screening Imbibition Program (SIP v.1.0) 15 

### was used to calculate an upper

- bound estimate of bird and mammal exposure to difeno conazole in drinking water. Drinking water exposure alone was determined not to be a potential acute concern for birds or mammals ; h owever, the screen suggests that there is a potential chronic concern for birds and mammals

. Appendix D provides model results.

Screening Tool for Inhalation Risk

The Screening Tool for Inhalation Risk (STIR v.1.0) 15 

### was used to provide an upper

- bound estimate of exposure of birds and mammals to pesticides through inhalation of spray drift or vapor. The screening sugge sts that difeno conazole exposure is not likely significant enough for
an inhalation risk concern. Appendix E provides model results.

6. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment is
estimat ed. The use, environmental fate, and ecological effects of difenoconazole will be

13 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/technical

- overview

- ecological

- risk

assessment

- risk

14 http://www.abcbirds.org/abcpro grams/policy/toxins/aims/aims/index.cfm

15 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/models

- p esticide

- risk

- assessment

### 22 characterized and integrated to assess risk. This will be accomplished using a risk quotient ( RQ; ratio of exposure concentration to effects concentration) approach. Altho ugh risk is often defined as the likelihood and magnitude of adverse ecological effects, the risk quotient

- based approach does not provide a quantitative estimate of likelihood or magnitude of an adverse effect. However, as outlined in the Overview Docume nt (USEPA, 2004), the likelihood of effects to individual organisms from particular uses of difenoconazole will be estimated using the probit dose

- response slope and either the level of concern or actual calculated risk quotient
value.

This analysis plan will be revisited and may be revised depending upon a full review of the data available in the open literature and the information submitted by the public in response to the opening of the Registration Review docket.

6.1. Stressors of Concern

Ecological Risk Assessment

Difenoconazole and CG A

- 205375 will be considered stressors of concern in the difenoconazole
ERA. Available information suggests that CGA

- 205375 and difenoconazole are of similar
toxic ity . Equal toxicity of difenoconazole and CGA

- 205375 w ill be assumed in the absence of
data. The other two major degradates

, 1,2,4

- triazole and triazole acetic acid , will also be
considered stressors of co ncern; however, on a case by case basis. Available information suggests that they are equally as toxic as difenoconazole ( e.g. , 1,2,4

- triazole acute oral toxicity to rats), less toxic than difenoconazole ( e.g. , 1,2,4

- triazole and triazole acetic acid acute toxicity to freshwater fish and invertebrates), or more toxic than difenoconazole ( e.g. , 1,2,4

- triazol e acute oral toxicity to birds) depending on the taxonomic group and exp osure scenario. For example, 1,2,4

- triazole will be a degradate of concern for acute toxicity to mammals and birds but will not be a degradate of concern for acute toxicity to freshwa ter fish and invertebrates.

Drinking Water Assessment

Difeno conazole and CGA

- 205375 will be considered the stressor s of concern i n the
difenoconazole DWA

, consi stent with the conclusions of the Residues of Concern Knowledgebase Subcommittee ( ROCKS ) committee of the Health Effects Division (HED) ( USEPA, 2011 ). The residues of concern may be reevaluated pending receipt and review of additional environmental fate and toxicity data. It is anticipated that the other two major degradates, 1,2,4

- triazole and triazole acetic acid, will be addressed in an updated aggregate
DWA.

Aggregate Risk Assessment

Aggregate risk from two of the major degradates, 1 ,2,4

- triazole and its conjugate: triazole acetic
acid

, may be addressed in a separate ERA and DWA because they are common to the class of compounds known as triazoles ( i.e., triazole

- derivative fungicides, T

- D fungicides, or conazoles).

### 23 6.2. Measures of Exposure

Difeno conazole concentrations in aquatic and terrestrial environments will be modeled using the maximum labeled application rates, the maximum number of applications, the minimum application intervals, and application methods that have the greatest potential for off

- sit e transport.

Aquatic Exposure

There is potential for exposure to non

- target organisms through run

- off and spray drift. The
most current models will be used to estimate residues in water at the time of the risk assessment ( e.g. , SWCC ). 16 

### Bioaccumulati on potential in aquatic organisms will be estimated to assess exposure to piscivorus animals ( e.g. , Kow (based) Aquatic BioAccumulation Model (KABAM)). 16



### A total toxic residue (TTR) approach will be used to estimate exposure to aquatic organisms. Degra date CGA

- 205375 will be included in the TTR of difenoconazole because it forms greater than 10% of applied difenoconazole in available fate studies and available information suggests
that CGA

- 205375 and difenoconazole are equally toxic.

Terrestrial Expo sure

There is potential for exposure to non

- target organisms through consumption of contaminated food items ( e.g. , treated insects or vegetation and contaminated fish ), direct applic ation, runoff, or spray drift. The most current models will be used at the time of the risk assessment. Current
models include:

T

- REX (v 1.5 .2 ) 16 

### is used to estimate avian and mammal exposure residues on terrestrial food
items . For input into T

- REX, the default foliar dissipation h alf

- life of 35 days will be used in the absence of acceptable foliar dissipation rate data.

TerrPlant (v 1.2.2) 16 

### is used to calculate EECs for characterizing exposure to terres trial and semi

aquatic plants.

Terrestrial Investigation Model (TIM, v. 3.0 b eta) 16 

### is used to derive quantitative estimates of the probability (or likelihood) and magnitude of mortality to birds.

6.3. Measures of Effect

Toxicity effects data will be used as measures of direct and indirect effects to biological receptors (USEPA, 2 004). As discussed previously, data will be obtained from registrant

submitted studies and from literature studies identified in ECOTOX.

Quantitative assessment of risks will be based on study endpoints that can be directly linked to the Agency’s assessment endpoints of impaired survival, growth, and reproduction. Sub

- lethal

16 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/models

- p esticide

- risk

- assessment

### 24 effects ( e.g. , lethargy and changes in coloration) will be evaluated qualitatively. Available
incident data will be used to further characterize risk.

6.4. Integration of Ex posure and Effects

The exposure and effects data will be integrated in order to evaluate potential adverse ecological
effects on non

- target species. The risk quotient method will be used to compare exposure and measured toxicity values. EECs will be divi ded by acute and chronic toxicity values. The resulting RQs will be compared to the Agency’s Levels of Concern (LOC) (USEPA, 2004).

6.5. Endangered Species Assessments

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches de veloped to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report 17 

### outlines recommendations on specific scientific and technical issue s related to the development of pesticide risk assessments that EPA and the Services (U.S. Fish and Wildlife Service and
Nationa l Marine Fisheries ) must conduct in connection with their obligations under the ESA and
FIFRA. EPA will address concerns specif ic to difenoconazole in connection with the development of its final registration review decision for difenoconazole

.

In November 2013, EPA, the Services , and USDA released a white paper containing a summary of their joint Interim Approaches for assessi ng risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific di fferences between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper

, Interim Approaches for
National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the N ational Academy of Sciences April 2013 Report. 18



### Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habi tat, this ecological problem formulation supporting the Preliminary Work Plan for difenoconazole does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted durin g registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registration review of difenoconazole will describe the level of ESA analysis completed for this particular registration re view case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully devel oped and implemented the scientific methods necessary to complete

17 http://www.nap.edu/catalog/18344/assessing

- risks

- to

- endangered

- and

- threatened

- species

- from

- pesticides

18 http://www2.epa.gov/endangered

- species/interim

- approaches

- pesticide

- endangered

- species

- act

- assessments

based

- nas

- report

### 25 risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of difenoconazole as part of completing this registration rev iew.

6.6. Endocrine Disruptor Screening

As required by Federal Food, Drug and Cosmetic Act (FFDCA) section 408(p), difeno conazole is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP)

. 19 

### Difeno conazole is not in the first or second group of pesticide active ingredients to be
screened under the EDSP.

6.7. Drinking Water Assessment

A DWA will be conducted, if warranted, to support future human health dietary risk assessments
of difenoconazole. The resid ues of concern will be difenoconazole and CGA

- 205375 as recommended by the ROCKS committee (USEPA, 2011). The residues of concern may be reevaluated pending receipt and review of additional environmental fate and toxicity data.
Concentrations in surface and groundwater will be estimated using current exposure models. 20 

### Additionally, EFED may update the previously conducted aggregate drinking water exposure assessment for 1,2,4

- triazole and its conjugates

.

6.8. Preliminary Identification of Data Gaps

Avail able studies submitted to fulfill environmental fate and ecological effects guideline requirements, as well as outstanding data gaps for difeno conazole are defined in Sections 6.8.1
and 6.8.2 , respectively. Studies are i dentified that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support the
risk assessment.

6.8.1. Environmental Fate Data

Environmental fate data gaps for difeno conazole are indicated in the table below ( Table 11 )

.

EFED recommends requesting the following studies to reduce uncertainty in the risk assessment :

• 850.7100: ILV: Independent laboratory validation report for analytical method in soil for
dif enoconazole and its metabolites (CGA

- 205375, CGA

- 142856

, and CGA

- 71019)

.

• 850.7100: ECM/ILV: Environmental chemistry methods and independent laboratory
validation in water for dif enoconazole and its metabolites (CGA

- 205375, CGA

- 142856

, and CGA

- 71019)

.

Major degradate (CGA

- 205375)

There are no environmental fate studies available for CGA

- 205375 ex cept for a soil batch equilibrium study (MRID 469501

- 23/24 ) . In the absence of CGA

- 205375 environmental fate
studies

, needed physio chemical and environmental fate properties will be estima ted using EPI

19 http://www2.epa.gov/endocrine

- disruption

20 http://www2.epa.gov/pesticide

- science

- and

- assessing

- pesticide

- risks/models

- p esticide

- risk

- assessment

### 26 Suite. 21 

### Study

- sourced environmental fate and physicochemical properties of CGA

- 205375 may reduce the uncertainties in the aquatic exposure and drinking water assessments.

T able 11 . Environmental Fate Data and Data Gaps for Difeno conazole

Guideline Description MRID Classification Data Gap? Comments

835.2120 Hydrolysis 42245127 Acceptable No

-- 835.2240 Aqueous photolysis 42245128
46950104
46950105 Supplemental No

--

835.2410 Soil photolysis 46950106 Supplemental No

-- 835.4100 Aerobic soil
metabolism 42245131
42245132
42245133
46950109
46950110
46950111
469501

- 12 &

- 13
469501

- 14 &

- 15 Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental No

--

835.4200 Anaerobic soil
metabolism 42245132
42245133 Supplemental Supplemental No Two an aerobic soil metabolism
stud ies ha ve already been
submitted and are classified as supplemental. Additional data are required under 40 CFR Part 158
for terrestrial outdoor uses.
Predicted DT 50s suggest that
difenoconazole is stable under
anaerobic condition s . Additional
data are considered to have a low potential to add value to exposure assessments for the ecological risk and drinking water.

835.4300 Aerobic aquatic
metabolism 42245134
46950116
46950117 Supplemental Supplemental Supplemental No

--

835.4400 Anaerobic aquatic
metabolism 42245134
46950119 Supplemental Supplemental No

--

835.1230
835.1240 Adsorption/ desorption and leaching 42245135
42245136
46950121 Supplemental Supplemental

Acceptable No

--

835.1410 Volatility

– laboratory -- -- No Difenoconazole is not expected
to be volatile under normal use conditions based on low vapor pressure and Henry’s Law
Constant

21 Estimation Programs Interface (EPI) SuiteTM is comprised of a set of programs that estimate fate and physical properties. It was developed b y the EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC).

### 27 Guideline Description MRID Classification Data Gap? Comments

835.6100 Terrestrial field dissipation 42245140
46950126
46950127
46950129 Supplemental Acceptable Acceptable No

---

850.6100 Analytical
method in soil 46950128 (ECM) Not applicable Yes Independent laboratory validations (ILV) is required for
difenoconazole and its degradates

. Analytical
method in water -- -- Yes Environmental chemistry method (ECM) and independent laboratory validations (ILV) are required for difenoconazole and its degradates

. 850.1730 Fish

bioconcentration 42245142 Acceptable No

---

BOLD = Recommended Studies



### 6.8.2. Ecological Effects Data

D ata gaps for difenoconazole remain ( Tables 12
, 1 3 , and 1 4 ) ; however, some of these studies are anticipated to have little impact on the risk assessment and are not recommended for a data

call in (DCI)

. EFED recommends requesting the following studies to r educe uncertainty in the
risk assessment: 22



### • 850.4550: Cyanobacteria toxicity ( difenoconazole; TGAI) *

• 850.4100: Terrestrial plant toxicity (seedling emergence)

– (TEP) *

o Tier II testing is required for lettuce, soybean, and sugar beet. A NOAEC must be established at the maximum single application rate (Tier 1 test) for the other seven test species (those showing no effects in the available study , MRID 48453203 ); alternatively, Tier II testing may be conducted for those species.

• 850.4150 : Terrestrial plant toxicity (vegetative vigor)

– (TEP) *

o A NOAEC must be established for all ten test species at the maximum single application rate (Tier I test). Alternatively, Tier II testing may be conducted.

• Non

- guideline: Chronic toxicity to benthic invertebrates (whole sediment; 3 test species: freshwater amphipod, freshwater midge, and estuarine/marine amphipod)

– (difenoconazole; TGAI) *

o EFED recommends that the registrant consider Agency

- wide guidelines for chronic testing of freshwater and estuarine/marine org anisms 23

, 24 

### because the
OCSPP 850 series guidelines are in the process of being finalized. A protocol must be submitted for review prior to initiating the studies.

22 The studies marked with an asterisk (*) were recently required as a condition of registration for a PRIA label amendment for EPA Reg. No. 100

- 739 to add new uses to the label for use on Legumes Subgroup 6C and Bushberry Subgroup 13

- 07B; Related to Petition #4F8231 (May 6, 2015).

23 USEPA 2000. Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants
with Freshwater Invertebrates. EPA 600/R

- 99/064

24 USEPA 2001. Methods for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- associated Contaminants with the Amphipod Leptocheirus plumulosus . EPA 600/R

- 01/020.

### 28 • Non

- guideline Tier I: Honeybee adult acute oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier I: Honeybee adult chronic oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier I: Honeybee larval acute and chronic oral exposure (difenoconazole; TGAI)

• Non

- guideline Tier II: Residue in pollen and nectar (recommendation pending risks
identified i n Tier I studies) (TEP)

• Non

- guideline Tier II: semi

- field testing for pollinators (tunnel and feeding studies) (recommendation pending risks identified in Tier I studies) (TEP)

• 850.3040: Tier III full

- field testing for pollinators (recommendation pending r isk identified in Tier II studies) (TEP)

Toxicity data from other sources ( e.g. , other conazoles) may be used in the absence of data for difenoconazole. Use of surrogate data may over or underestimate risk of difenoconazole use.

Major degradate s (CGA

- 20 5375 , 1,2,4

- triazole, and t riazole acetic acid )

D ata submission for CGA

- 205375 , 1,2,4

- triazole, and t riazole acetic acid chronic toxicity would
be welcomed and may reduce uncertainty in the risk assessment ; however, EFED is not recommending degradate toxicity data at this time given that it is not anticipated that data would substantially change risk conclusions

. Nonetheless, chronic toxicity data may be useful for refining risk concerns for birds, fish, and aquatic invertebrates. ECOSAR estimates s uggest that
CGA

- 205375 and difenoconazole are equally toxic to aquatic organisms (less than an order of magnitude difference in toxicity) ; therefore, e qual toxicity will be assumed in the absence of
data

. ECOSAR estimates of 1,2,4

- triazole and triazole ac etic acid suggest that they are less toxic on a chronic basis than difenoconazole to aquatic organisms ; thus, empirical data would be useful to confirm this assumption. Data indicate that 1,2,4

- triazole is more acutely toxic to birds than difenoconazole, suggesting chronic toxicity of 1,2,4

- triazole may be greater than
difenoconazole as well. A lthough a chronic risk concern is expected for birds based on difenoconazole alone, 1,2,4

- triazole data would be useful to confirm the assumption of greater
toxicit y and better characterize risk from difenoconazole use.

Table 12 . Ecological Effects Data Requirements (TGAI) for Aquatic Organisms Exposed

to Difeno conazole and Data Gaps A

Guideline Description MRID Classification Data Gap? Comments

850.1075 Acute freshwater fish toxicity (cold water species) 42245107
42245108 Acceptable 1 Acceptable 1 No 1 In some cases an older
classification scheme was reported in the DER.
Studies classified as “core” are equivalent to “acceptable”.

2 Upgraded to acceptable
wi th submission of MRID
46950132. Acute freshwater fish toxicity (warm water

species) 42245109
48453201 Acceptable 1 Acceptable No

Acute estuarine/ marine fish toxicity 42245112
42906702 Acceptable 1 Acceptable 1 No

### 29 Guideline Description MRID Classification Data Gap? Comments

850.1010 Acute toxicity to
freshwater
invertebrates 42245110 Acceptable 1 No 3 A definitive endpoint was
established in MRID
49322901/49387801 but at a higher concentration than those showing effects in the two previously conducted studies (MRID 46950133 and 47648603). Given the
available informatio n, additional testing is unlikely
to add substantial value to
the risk assessment (conclusions) and is therefore not requested at this time. However, additional testing could be
recommended in the future if it appears that it would impact the risk assessm ent ( see detailed discussion in USEPA, 2014 a ).

4 There is some uncertainty
in the results of the available early life stage study. A new study is not
recommended because risk can be assessed using the acceptable life cycle study (MRID 48453205)

.

5 Although a study
submission would be welcomed, EFED is not recommending a study at
this time. Toxicity can be estimated using an acute

- to

chronic ratio if data are not
available. Available acute data suggest similar toxicity
of difenoconazole to freshwa ter and
marine/estuarine fish ; thus, it is assumed that toxicity is
similar on a chronic

- basis
too. It is assumed that the freshwater study is protective of marine

estuarine fish. 850.1025 Acute estuarine/
marine mollusk toxicity 42245113
42906701 Acceptable 1 Acceptable 1 No

850.1035 Acute estuarine/
marine invertebrate toxicity 42245111 Acceptable 1 No

850.1300 Freshwater
invertebrate life cycle 42245114 Acceptable 2 No

850.1350 Saltwater
invertebrate life cycle 46950133
47648603
49322901/49387801 Supplemental Supplemental

Acceptable No 3

850.1400 Freshwater fish early life stage 42245115 Supplemental Yes 4

Saltwater fish early life stage - - Yes

850.1500 Freshwater fish life cycle 48453205 Acceptable No

Saltwater fish life cycle - - Yes 5

850.1735 Whole sediment

acute to xicity,

freshwater
invertebrates 47648601 Supplemental No 6

850.1740 Whole sediment
chronic toxicity,
marine invertebrates - - No

- Whole sediment chronic toxicity,
freshwater
invertebrates - - Yes 7

- Whole sediment chronic toxicity,
marine

- estuarine

invertebrates - - Yes 7

850.5400 B Aquatic plant growth (freshwater green alga) 46950212 Acceptable No

Aquatic plant growth (freshwater diatom) 46950208 Acceptable No

### 30 Guideline Description MRID Classification Data Gap? Comments

Aquatic plant growth (saltwater diatom) 46950210 Acceptable No 6 The available study is a

non

- guideline range finding study that does not fill the data requirement for 850.1735. However, there is not a data gap because an acute study is not re quired.

7 Data are recommended
because t here is uncertainty
associated with chronic risk
to benthic invertebrates given that pore water EECs
are similar to water column
EECs and the chronic LOC (1.0) is exceeded for aquatic
invertebrates based on comparison of water column species tox icity data to pore
water EECs. Sediment
chron ic toxicity testing with three species is
recommended: freshwater midge, freshwater amphipod, and marine/estuarine amphipod.

8 Testing with a TEP is typically recommended; however, TGAI testing is preferred to be consistent
with available
difenoconazole t oxicity data for other aquatic plants.

9 A study is not
recommended at this time as additional data are unlikely to have substantial impact
on the risk assessment. 850.5400 B Aquatic plant growth (Cyanobacteria) 46950206 Invalid Yes 8

850.4400 B Aquatic plant growth (vascular plants) 46950204 Supplemental Yes 9

A An invalid early life stage (ELS) stud y w as previously submitted for freshwater fish (MRID 45137502) but was subsequently replaced with a supplemental ELS study and an acceptable life cycle study

. B As of July 2012 the new guideline numbers are 850.4500 (Algal toxicity) and 850.4550 (Cyanobacteria toxicity)
BOLD = Recommende d Studies

### 31 Table 1 3 . Ecological Effects Data Requirements (TGAI) for Terrestrial Animals Exposed

to Difenoconazole and Data Gaps A

Guideline Description MRID Classification Data Gap? Comments

850.2100 Avian acute oral toxicity (upland game or
waterfowl species) 42245105 Acceptable 1 No 2 1 In some cases an older
classification scheme was reported in the DER. Studies
classified as “core” are equivalent to “acceptable”.

2 Non

- definitive endpoints were reported

. Additional data are not
needed nor recommended at this time. However, if the risk picture changes ( e.g. , risk concerns cannot be precluded
based on the available data due to greater exposure than is expected
at this time based on current uses) then addi tional data could
be recommended in the future.

3 Upgraded to acceptable with
submission of MRID 46950201.

4 Data are needed to assess risk because an exposure pathway exists, some of the registered uses are pollinator attractive crops (USDA, 2015), and incidental residues may occur on other flowering plants ( e.g. weeds) on or near the treatment
site.

5 If Tier 1 screening risks are identified based on Tier I toxicity
studies then Tier II studies (residue in pollen and nectar and
850.3040 semi

- field test ing for pollinators) could be
recommended and if risks are
identified based on Tier II
assessment then Tier III studies
could be recommended (850.3040 full

- field testing for pollinators). Avian acute oral toxicity (passerine species) 48453202 Acceptable No 2

850.2200 Avian dietary toxicity (upland game species) 42245103 Acceptable 1 No

Avian dietary toxicity

(waterfowl species) 42245104 Acceptable 1 No 2

850.2300 Avian reproduction (upland game species) 46950202 Acceptable No

Avian reproduction (waterfowl species) 42245106 Acceptable 3 No

850.3020 Adult honeybee acute contact toxicity (Tier 1) 42245124 Acceptable 1 No 2

Non

guideline Adult honeybee acute oral toxicity (Tier 1) 42245123 Invalid Yes

Non

guideline Adult honeybee
chronic oral toxicity (Tier 1) - - Yes 4,5

Non

guideline Larval honeybee acute
and chronic oral toxicity (Tier 1) - - Yes 4,5

A In some cases invalid studies were submitted [avian reproduction with an upland game species (MRID 42280601) and adult honeybee acute contact toxicity (MRID 42245123)] but were subsequently replaced with valid studies.
BOLD = Recommended Studies

### 32 Table 1 4 . Ecological Effects Data Requirements (TEP) for Plants Exposed to
Difenoconazole and Data Gaps

Guideline Description MRID Classification Data Gap? Comments

850.4100 A Terrestrial plant toxicity (Tier I or Tier II seedling emergence) 48453203 Supplemental Yes 1 ,2 1 The available Tier I study is supplemental because there were biologically significant effects
observed in dicots at the limit
test concentration which is below the maximum labeled single application rate (turf; 0.26 lb ai/A). Tier II testing is required for the dicot species that showed effects in the available study (lettuce, soybean, and sugar beet). Furthermore, a NOAEC
must be established at the maximum single application rate (Tier 1 test) for the other seven test species (those showing no
effects in the available study) to meet the data requirement; alternatively, Tier II testing may be conducted for those species.

2 It is EFEDs understanding that
0.26 lb ai/A is the maximum single application rate for all currently registered uses. The registran t should confirm the maximum registered rate prior to conducting any Tier I studies.

3 The available Tier I study is supplemental because the limit
test concentration is below the maximum labeled single application rate (turf; 0.26 lb ai/A). To meet the data requirement, a NOAEC must be established for all ten test species at the maximum single application rate (Tier I test). Alternatively, Tier II testing may
be conducted. 850.4150 B Terrestrial plant toxicity (Tier I or Tier

II vegetative vigor) 48453204 Supplemental Yes 2 ,3

A As of July 2012 the Final Guideline 850.4100 contains both Tier I and Tier II test guidance.

B As of July 2012 the Final Guideline 850.4150 contains both Tier I and Tier II test guidance.
BOLD = Recommended Studies

### 33 7. References

FAO

. 2000. Appendix 2. Parameters of pesticides that influence processes in the soil. In FAO Information Division Editorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil
Contamination. A Reference Manual. Rome: Food & Agriculture Organization of the United Nations (FAO). http://www.fao.org/docrep/003/x2570e/x2570e00.htm

USDA. 2015. Attractiveness of Agricultural Crops to Pollinating Bees for the Collection of
Nectar and/or Pollen.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Pro grams, Washington DC. January 23, 2004.

USEPA. 2011. Difenoconazole: Report of the Residues of Concern Knowledgebase Sub

committee (ROCKS). Health Effects Division, Office of Chemical Safety and Pollution Prevention. U. S. Environmental Protection Agen cy. DP 391350.

USEPA

. 2013. Drinking Water Exposure Assessment in support of the new use registration of difenoconazole formulated product Inspire on Canola/Oilseed Subgroup 20A. Environmental Fate and Effects Division, Office of Chemical Safety and Po llution
Prevention. U. S. E nvironmental Protection Agency. D P 412614

.

USEPA

. 2014 a. Difenoconazole: Ecological Risk Assessment for Numerous Proposed New Uses and Changes to Registered Uses (Application Rate, Crop Groupings, and Additions to New Products) . DP 417610 +



### .

USEPA. 2014b. Drinking Water Exposure Assessment in support of the new use registration of multiple difenoconazole formulated products on Artichoke, Berry Bushb erry Subgroup
13

- 07B, Ginseng, and Bean and Pea, Dried Shelled (except Soybean) Subgroup 6C as
well as Conversion of St one Fruit Crop Group 12

- 12 and Tree Nuts Crop Group 14

- 12. Environmental Fate and Effects Division, Office of Chemical Safety and Pollution Prevention. U. S. Environmental Protection Agency. DP 421092.

USEPA. 2015. Myclobutanil Problem Formulation for Registration Review. DP 421959.

### 34 

## APPENDIX A. Difenoconazole Uses

Previous assessments are listed in Table A

- 1

. The purpose of this table is to capture the
historical range of assessed uses and rates an d is not intended to constitute a comprehensive up

to

- date list of currently registered uses and rates. Most uses allow aerial and ground applications and in some cases chemigation. In some cases a different mode of action fungicide should be
alternated after a specified number of applications of difenoconazole containing products

. The registration review risk assessment will be based on current label information at the time of assessment as provided by BEAD.

Table A

- 1. Previous Actions and Assessed Us es for Difenoconazole

Crop Maximum Application Rate (lb ai/A) Number of Applic ations ( Minimum Application Interval (d ays) ) Action
DP Barcode ( Date ) Single Seasonal/
Annual

Ornamentals 0.13 0.52 /year (outdoor) or /crop (indoor) 4 (7) ERA 417610, 418014, 418502, 421513, 421518, 421519,
and 421523 (12/19/2014)

DWA
421092 (11/13/2014) Berry and small fruit; bushberry subgroup 13

- 07B Brassica (cole) leafy vegetables Bulb vegetables (green onion limited to 3 applications or 0.345 lb ai/A/year (outdoor crop) or per crop (indoor crop) Cucurbit vegetables Ginseng Legume vegetables; dried shelled pea and bean (except soybean) subgroup 6C Stone fruit (crop group 12

- 12) 0.115 0.46 /year (outdoor ; all uses) or /crop (indoor; Brassica,
bulb vegetables

, and cucurbit vegetables) 4 (7)

Artichoke Tree nuts (crop group 14

- 12) 0.115 0.46 4 (14)

Cucurbit vegetables 0.114 +
0.064 0.52 4 +1 (7)

C ucumber (greenhouse grown) 0.114 0.46 4 (7)

Fruiting vegetables (except tomato) 0.113 0.45 /year (outdoor) or /crop (indoor) 4 (7)

Tomato 0.0656 0.385 /year (outdoor) or /crop (indoor) 6 (7)

Pome fruit (crop group 11

- 10) Post

- harvest treatment (dip, drench, flood, or spray)

### 35 Crop Maximum Application Rate (lb ai/A) Number of Applic ations ( Minimum Application Interval (d ays) ) Action
DP Barcode ( Date ) Single Seasonal/
Annual

Canola and oilseed subgroup
20A 0.113 N S (assumed 0.113) N S (assumed 1 application/year) ERA
409484 and 409488 ( 11/08/2013 )

DWA
412614 ( 8/14/2013 ) Potato (seed treatment) 0.062 N A N A ERA
402993 and 404403 ( 8/29/ 20 12 )

Citrus 0.125 0.50 4 (7) DWA

- revised
395784 (12/20/2011) Fruiting vegetable Low growing berry subgroup (except cranberry) Vegetable, tuberous and corm subgroup 0.114 0.46 4 (7)

Pome fruit 0.07 0.35 5 (7)

Carrot Chickpea Strawberry 0.114 0.46 4 (7) ERA
378927 and 384074 (2/22/ 20 11)

DWA
378946 (9/27/2010)

* Seed treatments were not
included in the DWA. Soybean 0.114 0.46 4 (7

- 14 depending on the formulation)

Stone f ruit (group 12) 0.114 0.46 4 (7

- 10 depending on the formulation) Oat (s eed treatment ) 0.023 N A N A Rye (s eed treatment ) 0.034 N A N A

Golf course t urf 0.26 0.52 2 (14) ERA
377719 ( 7/28/ 20 10 )

DWA
371044 ( 6/ 1/2010 )

Citrus fruit 0.125 0.5 0 4 (7) ERA
361251 (8/26/2009)

DWA
361398 ( 5/28/2009 )

DWA

- revised
398836 (2/23/2012) Bulb vegetables (green onion) 0.114 0.34 3 (7) Brassica (cole) leafy vegetables Bulb vegetables (dry bulb) Cucurbit vegetables 0.114 0.46 4 (7)

Grapes 0.114 0.46 4 (10)

Almonds
Filberts

Pecans
Pistachios

Tree nuts 0.114 0.46 4 (14)

Watermelon 0.114 0.228 2 Emergency Exemption for
Indiana
353502 ( 7/3/ 20 08 )

### 36 Crop Maximum Application Rate (lb ai/A) Number of Applic ations ( Minimum Application Interval (d ays) ) Action
DP Barcode ( Date ) Single Seasonal/
Annual

Cucurbits

- watermelons, cantaloupes, cucumbers 0.114 0.46 4 Emergency Exemption for Georgia
351238 ( 5/15/ 20 08 )

Almonds 0.11 N/A 2 Emergency Exemption for
California
351716 ( 5/15/ 20 08 )

Ornamental s (carnations, gladiolus, irises, and roses) 0.13 0.56 1 NS (7) ERA
333319 and 340041 (7/12/2007)

DWA
333319 and 340041 ( 5/1/2007 and 6/19/2007 ) Fruiting vegetables Sugar beet Vegetables, tuberous and corm subgroup 0.11 0.44 NS (7)

Pome fruit 0.07 0.35 NS (7)

Barley (seed t reatment)
Corn , sweet (seed t reatment) Cotton (s eed t reatment) 0.024
0.008
0.006 NA
NA
NA NA
NA
NA ERA
316708

, 316620 , and
316707 ( 9/21/ 20 05 ) Wheat (seed treatment) 0.044 NA NA DWA
307166 (5/2/2005)

Canola (seed treatment) 0.0 0192 NA NA ERA and DWA
252640 ( 5/30/ 20 01 ) Canola (seed treatment) 0.0013 NA NA Emergency Exemption for
North Dakota
260762 ( 12/20/ 19 99 ) Wheat (seed treatment) 0.031 NA NA DWA
252509 (2/9/1999)
Wheat (seed treatment) 0.01 5 NA NA DWA
Unknown DP (10/27/1998)

W heat (seed treatment)

B arley (seed treatment ) 0.010 NA NA ERA 194836, 194830, 194872
and 194874 ( 3/29/1994 )

Wheat (seed treatment) 1 oz per 100
lb seed NA NA Emergency Exemption for
Idaho
194787 ( 9/29/ 19 93 )

N A = Not applicable NS = Not specified

1 The 2007 ERA and DWA seem to have erroneously reported the annual rate as 0.56 lb ai/A. The correct rate is
0.52 lb ai/A

### 37 

## APPENDIX B. Names and Structure s of Difenoconazole and its Major and Minor Degradates

Table B

- 1

Code Name ( Synonym ) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)

PARENT

Difenoconazole (CGA

- 169374) IUPAC Name: 3

- Chloro

- 4

- [(2RS,4RS;2RS,4SR)

- 4

- methyl

- 2

- (1H

- 1,2,4

- triazol

- 1

- ylmethyl)

- 1,3

- dioxolan

- 2

- yl]phenyl 4

- chlorophenyl ether.
CAS Name: 1

- [2

- [2

- Chloro

- 4

- (4

- chlorophenoxy)phenyl]

- 4

- methyl

- 1,3

- dioxolan

- 2

- ylmethyl]

- 1H

- 1,2,4

- triazole.
CAS Number: 119446

- 68

- 3
Formula: C 19 H 17 C l2 N 3 O 3 MW: 406.3
SMILES: O1CC(C)OC1(Cn2ncnc2)c3c(Cl)cc(Oc4ccc(Cl)cc4)cc3 Hydrolysis pH 5

42245127

Not applicable stable

Hydrolysis pH 7 stable

Hydrolysis pH 9 stable

Aqueous Photolysis 42245128 2.50 (30 days)

46950104 1.21 ± 0.5 (30 days)

46950105 94.1 (15 days)

Soil Photolysis 46950106
46950107 91.4 (30 days)

Aerobic
Soil
Metabolism 4695 0 109 18.4 ± 0.1 (293 days)

46950110 14.1 (293 days)

46950111 38.7 (228 days)

46950112
46950113 57.6 (360 days)

46950114
46950115 59.6 (372 days)

Aerobic Aquatic
Metabolism 46950116 71.2 (183 days)

46950117
46950118 81.53 ± 3.22 (112 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 42.72 ± 0.88 (350 days)

### 38 Code Name ( Synonym ) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)

Difenoconazole (CGA

- 169374) Terrestrial
Field Dissipation 46950126 Not applicable 44 ppb (531 days)

46950127 14 ppb (535 days)

46950129 302 ppb (422 days)
MAJOR (>10%) TRANSFORMATION PRODUCTS

CGA

- 205375 (CGA

- 179500,
CGA

- 211391

, and M1) CAS Name: alpha

- [2

- Chloro

- 4

- (4

- chlorophenoxy)phenyl]

- 1H

- 1,2,4

- triazole

- 1

- ethanol.

1

- [2

- Chloro

- 4

- (4

- chlorophenoxy)phenyl]

- 2

- [1,2,4]

- triazol

- 1

- yl

- ethanol.
CAS Number: 117018

- 19

- 6 Aqueous Photolysis 42245128 2.9 (5 days) 0.1 (30 days)

46950104 2.04 (14 days) 0.96 (30 days)

46950105 NA NA

Aerobic
Soil
metabolism 46950109 5.1 ± 1.4 (84 days) 3.7 ± 0.1 (293 days)

46950110 4.6 ± 0.1 (56 days) 3.7 ± 0.5 (293 days)

46950111 4.4 ± 1.6 (120 days) 2.7 (293 days)

46950112
46950113 14.8 ± 1.8 (360 days) 14.8 ± 1.8 (360 days)

4695 0 114
4695 0 115 9.4 ± 0.1 (372 day s ) 9.4 ± 0.1 (372 day s )

Aerobic Aquatic
Metabolism 46950116 6.2 (183 days) 6.2 (183 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 12.60 ± 0.42 (175 days) 6.2 ± 0.76 (350 days)

Terrestrial
Field Dissipation 46950126 11 ppb (358 days) 6.2ppb (531 days)

46950127 12 ppb (123 days) 5.6 ppb (531 days)

46950129 18ppb (364 days) 12.0 2ppb (535 days) N

N N Cl O

Cl

O H

### 39 Code Name ( Synonym ) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)
1,2,4

- triazole
( CGA

- 71019 ) CAS Name: 1H

- 1,2,4

- Triazole
CAS Number: 288

- 88

- 0 Aqueous Photolysis 42245128 13.4 (9 days) 10.9 (30 days)

46950104 12.27 ± 0.7 (30 days) 12.27 ± 0.7 (30 days)

46950105 NA NA

Aerobic
Soil
Metabolism 4695 0 110 20.6 (190 day s ) 17.8 ± 2.8 ( 293 day s )

4695 0 111 1.6 ± 0.4 (120 day s ) 0.9 (228 day s )

4695 0 114
4695 0 115 7.8 ± 0.1 (372 day s ) 7.8 ± 0.1 (372 day s )

Anaerobic Aquatic
Metabolism 46950119
46950120 35.92 ± 0.71 (350 day s ) 35.92 ± 0.71 (350 day s )

Terrestrial
Field Dissipation 46950129 3.5 ppb (36 days) < LOQ (535 days)

1,2,4

- triazole
acetic acid ( CGA

- 142856 ) CAS Name: 1H

- 1,2,4

- Triazole

- 1

- acetic acid
CAS Number: 28711

- 29

- 7 Aqueous Photolysis 46950104 41.83 ± 0.9 (30 days) 41.83 ± 0.9 (30 days)

Terrestrial
Field Dissipation 46950126 <LOQ 11 ppb (358 days)

CGA

- 107069 CAS Name: 1H

- 1,2,4

- Triazole

- 1

- methanol
CAS Number: 74205

- 82

- 6 Aqueous Photolysis 46950104 Reported as combined residue
with 1,2,4

- triazole

Carbon dioxide CAS Number : 124

- 38

- 9
Formula: CO 2 MW: 44.1 g/mol Aqueous Photolysis 46950104 2.01 (30 day s ) 2.01 ± 2.5 (30 days)

46950105 0.01 (3 days) <0.1 (15 days)

Soil Photolysis 46950106
46950107 0.02 (21 days) <0.2 (30 days)

Aerobic
Soil
Metabolism 46950109 23.4 ± 1.9 (293 days) 23.4 ± 1.9 (293 days)

46950110 4.5 ± 2.4 (293 days) 4.5 ± 2.4 (293 days) O H

O N

N N

C H 2 N

N N O H



## C O O

### 40 Code Name ( Synonym ) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)

Carbon dioxide Aerobic
Soil
Metabolism 46950111 19.2 (228 days) 19.2 (228 days)

46950112
46950113 15.0 ± 1.3 (360 days) 15.0 ± 1.3 (360 days)

46950114
46950115 4.2 ± 0.1 (372 days) 4.2 ± 0.1 (372 days)

Aerobic Aquatic
Metabolism 46950116 3.0 (183 days) 3.0 (183 days)

46950117
46950118 0.59 ± 0.28 (98 days) 0.29 ± 0.03 (112 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 0.55 ± 0.33 (245 days) 0.25 ± 0.02 (350 days)

Non

- extractable
Residues Not identified Not identified Aerobic
Soil
Metabolism 4695 0 109 38.0 ± 1.3 (293 days) 38.0 ± 1.3 (293 days)

46950110 48.9 ± 0.6 (293 days) 48.9 ± 0.6 (293 days)

46950111 22.9 (228 days) 22.9 (228 days)

46950112
46950113 14.4 ± 1.0 (360 days) 14.4 ± 1.0 (360 days)

46950114
46950115 18.4 ± 1.0 (360 days) 14.4 ± 1.0 (372 days)

Aerobic Aquatic
Metabolism 46950116 13.9 (183 days) 13.9 (183 days)

46950117
46950118 8.87 ± 3.04 (112 days) 8.87 ± 3.04 (112 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 8.06 ± 1.24 (302 days) 7.11 ± 0.32 (350 days)

Unidentified 1

Unknowns Not identified Not identified Aqueous Photolysis 42245128 20.0 (15 days) 6.5 (30 days)

46950104 29.02 ± 2.9 (30 days) 29.02 ± 2.9 (30 days)

46950105 16.7 (15 days) 11.1 (15 days)

### 41 Code Name ( Synonym ) Chemical Name Chemical Structure Study Type MRID Maximum %AR (day) Final %AR (study length)

Unidentified 1

Unknowns Aerobic
Soil
Metabolism 4695 0 111 0.4 (228 days) 0.4 (228 days)

MINOR (<10%) TRANSFORMATION PRODUCTS

CGA

- 205374 (CGA

- 176459) CAS Name: 1

- [2

- Chloro

- 4

- (4

- chlorophenoxy)phenyl ]

- 2

- (1H

- 1,2,4

- triazol

- 1

- yl)

- ethanone.
CAS Number: 136815

- 80

- 0 Aqueous Photolysis 42245128 1.5 (0 day) < LOQ (30 days)

46950104 1.11 ± 0.11 (14 days) 0.13 ± 0.1 (30 days)

46950105 NA NA

Aerobic
Soil
Metabolism 46950114
46950115 2.1 ± 0.4 (272 days) 1.4 ± 0.1 (293 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 0.77± 0.23 (245 day) LOQ (350 days)

M2 Not identified Not identified Aerobic
Soil
Metabolism 46950109 1.5 (28 days) 1.4 ± 0.1 (293 days)

46950110 2.1 ± 1.81 (293 days) 2.1 ± 1.81 (293 days)

46950111 1.5 (228 days) 1.5 (228 days)

Anaerobic Aquatic
Metabolism 46950119
46950120 5.79 ± 1.42 (245 days) < LOQ (350 days)

M4 Not identified Not identified Aerobic
Soil
Metabolism 46950109 1.2 (190 days) 1.0 ± 0.4 (293 days)

NA = Not Analyzed LOQ = Limit of Quantitation (1ppb)

1 Unidentified unknowns consist of M4, M5, M6

, and several unidentifie d components ranging from 0.5% to 9.7% of the applied radioactivity at study
termination. O N

N N Cl O

Cl

### 42 

## APPENDIX C

. ECOSAR Results

Table C

- 1. Comparative Aquatic Toxicity of Difenoconazole and Major Degradation Products

Compound FW fish
96

- hr

acute
LC 50 (mg/L) FW fish
chronic
NOAEC (mg/L) 1 FW
invertebrate
48

- hr acute
EC 50 (mg/L) FW
invertebrate
chronic
NOAEC (mg/L) 1 ME fish
96

- hr
acute LC 50

(mg/L) ME fish
chronic
NOAEC (mg/L) 1 ME
invertebrate
96

- hr acute
LC 50 (mg/L) ME
invertebrate
chronic
NOAEC (mg/L) 1 Non

vascular plant 96

- hr
EC 50 (mg/L)

Difenoconazole 0.87 ( 0.81 ) 0.007 ( 0.0009 ) 0.95 ( 0.77 ) 0.030 ( 0.006 ) ( 0.82 ) ( 0.0009 ) ( 0.15 ) (< 0.000115 ) 0.51 ( 0.30 ) 2

1,2,4

- triazole 722.0 ( 498.0 ) 2.2 3166.2 (> 98.0 ) 29.2

- - - - 35.7 ( 14.0 ) 2

Triazole acetic
acid 51322.1 (> 101.0 ) 132.3 281000.0 (> 108.0 ) 2132.3

- - - - 1716.9

CGA

- 205375 2.79 0.022 2.6 0.179 8.36 3 0.099 0.870 0.252 1.33

1 ECOSAR estimated chronic value is defined as the geometric mean of the no observed effect concentration (NOEC) and the lowest observed effect concentration (LOEC).

2 Green algae

3 Endpoint exceeds predicted water solubility of compound.
BOLD values are ECOSAR (v1.00) toxicity estimates (lowest toxicity value if multiple ECOSAR classes are available

, i.e. , the most toxic).
Italic values are from submitted toxicity studies (most sensitive endpoint if multiple are available)
FW = freshwater and ME = marine/estuarine

### 43 

## APPENDIX D . SIP v.1.0 Inputs and Outputs

Table D

- 1. Inputs

Parameter Value
Chemical name Difeno conazole Solubility (in water at 25 o C; mg/L) 15

Mammalian LD 50 (mg/kg

- bw) 1453

Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 1.25 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2150

Avian test species Mallard duck Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 110.8 Bobwhite quail NOAEC (mg/kg

- diet) 21.9 NOAEC (mg/kg

- diet) for other bird species 0 Body weight (g) of other avian species 0 NOAEC (mg/kg

- diet) for 2nd other bird species 0 Body weight (g) of 2nd other avian species 0



### Table D

- 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 2.5800 2.5800 Adjusted toxicity value (mg/kg

- bw) 1117.5903 0.9615 Ratio of exposure to toxicity 0.0023 2.6834

Conclusion* Drinking water exposure alone is NOT a potential

concern for mammals Exposure through drinking water alone is a potential concern for
mammals



### Table D

- 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 12.1500 12.1500 Adjusted toxicity value (mg/kg

- bw) 1116.3346 2.3279 Ratio of exposure to acute toxicity 0.0109 5.2192

Conclusion* Drinking water exposure alone is NOT a potential
concern for birds Exposure through drinking water alone is a potential concern for
birds

* Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.

### 44 

## APPENDIX E . STIR v.1.0 Inputs and Outputs

Table E

- 1 . Input

Application and Chemical Information

Enter Chemical Name Difenoconazole

Enter Chemical Use turf Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 406.27 Enter Chemical Vapor Pressure (mmHg) 2.50E

- 10 Enter Application Rate (lb ai/acre) 0.26

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 (mg/kg

- bw) 2150 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg

- bw) 1453

Enter Lowest Rat Inhalation LC 50 (mg/L) >3.3 1

Durat ion of Rat Inhalation Study (hr ) 4 Enter Rat Weight (kg) 0.35

1 MRID 42090008



### Table E

- 2 . Output

Results Avian (0.020 kg )
Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 5.47E

- 06

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 6.87E

- 07

Adjusted Inhalation LD 50 1.96E+01

Ratio of Vapor Dose to Adjusted Inhalation LD 50 3.50E

- 08 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 2.75E

- 02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 1.40E

- 03 Exposure not Likely Significant

Results Mammalian (0.015 kg )
Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 5.47E

- 06

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 8.64E

- 07

Adjusted Inhalation LD 50 1.96E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 4.40E

- 09 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.45E

- 02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 1.76E

- 04 Exposure not Likely Significant