### 1 The results of this scree ning

- level risk

assessment indicate that the combination of isofetamid and its degradates of concern pose potential risks to mammals (various sizes and dietary categories; highest RQ = 2.56) for the proposed almond, grapes,

low

- growing berries, and turf us es for isofetamid from chronic exposure. Isofetamid and its degradates of concern also pose potential risks to birds (and, thus,

terrestrial

- phase amphibians and reptiles) that eat short grass (all sizes) (highest RQ = 1.41) for the proposed almond, grapes , and

turf uses for isofetamid from chronic exposure. Additionally, there are

exceedances of the chronic level of concern for fish from the proposed wet

- harvested cranberry use (RQs range from 0.07 to 2.29), and exceedances of the endangered species level of concern for estuarine/marine invertebrates (acute exposure) from the proposed low

- growing berry (including wet

- harvested cranberry) and grape uses (RQs range from 0.01 to 0.47). There are no risks expected for aquatic plants, and there are no risks

exp ected for any aquatic taxa from the proposed lettuce or rapeseed uses.



# Ecological Risk

Assessment for the Section 3 Registration of

the New Chemical

Isofetamid

Melissa Panger, Ph.D. and Melanie Biscoe

### 2 OFFICE OF
CHEMICAL SAFETY AND
POLLUTION PREVEN TION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

PC Code : 270000

DP Barcod e : 409629



### MEMORANDUM

DATE: April 29, 2015

SUBJECT: Ecological Risk Assessment for the Section 3 Registration of the New

Chemical Isofetamid.

TO: Cynthia Giles

- Parker, Chief

Fungicide Branch Registration Division

THROUGH: Dana Spatz, Branch Chief

Environmental Risk Branch III

Envir onmental F ate and Effects Division

FROM: Melissa Panger, Ph.D., Senior Scientist

Melanie Biscoe, Physical Scientist

Environmental Risk Branch III

Environmental F ate and Effects Division

PEER REVIEW: James Hetrick, Ph.D., Senior Advisor

Rosanna Louie

- Juzwiak, RAPL

Environmental Risk Branch III

Environmental Fate and Effects Division

The Environmental Fate and Effects Division (EFED) has completed the e cological risk

assessment f

or the Section 3 registration decision on the new broad

- spectrum, syste mic fungicide isofetamid (IKF

- 5411) (PC Code 2 70000 )

. Isofetamid is being proposed for

use on almond, lettuce, grapes (Subgroup 13

- 07F), low growing berries (Subgroup 13

- 07G), rapeseed (Subgroup 20A), and turf (commercial and residential). One technical product (EPA File Symbol 71512

- ER) and two end

- use products [Isofetamid 400SC Fungicide (EPA File Symbol 71512

- EE) and Isofetamid Turf Fungicide (EPA File Symbol 71512

- EG)] are being proposed for registration in the United States. The

### 3

maximum proposed sin gle application rate is 0.5 72 lb a.i./acre (grapes) and the maximum annual application rate proposed is 3.65 lb a.i./acre (turf)

. Application methods include ground spray, aerial spray, and chemigation. Two degradates of isofetamid, 4HP and PPA, are expe cted to have toxicity characteristics similar to isofetamid based on their chemical structures. These two degradates, along with isofetamid, are considered in the Total Toxic Residues (TTR) approach used in this assessment.

The results of this screening

- l evel risk assessment indicate that the combination of isofetamid and its degradates of concern pose potential risks to mammals (various sizes and dietary categories; highest RQ = 2.56) for the proposed almond, grapes, low

- growing berries, and turf uses for isofetamid from chronic exposure. Isofetamid and its degradates

of concern also pose potential risks to birds (and, thus, terrestrial

- phase amphibians and reptiles) that eat short grass (all sizes) (highest RQ = 1. 41 ) for the proposed almond, grapes, and turf uses for isofetamid from chronic exposure. Additionally, there are

exceedances of the chronic level of concern for fish from the proposed wet

- harvested cranberry use (RQs range from 0.07 to 2.29), and exceedances of the endangered species

level of co ncern f

or estuarine/marine invertebrates (acute exposure) from the proposed

low

- growing berry (including wet

- harvested cranberry) and grape use s (RQs range from

0.0 1 to 0. 47 )

. There are no risks expected for aquatic plants, and t here are no risks expected for any aquatic taxa from the proposed lettuce or rapeseed uses.

There are a few notable uncertainties in the risk conclusions described above. C urrently

, no acute data are available for the freshwater fish species used in the chronic study ( i.e

., fathea d minnow), therefore, there is uncertainty regarding the chr onic freshwater fish endpoint. However, a dditional data would not be expected to alter the risk conclusions for the proposed uses ( i.e ., minimal risk to fish from chronic exposure , except for the proposed wet

- harvested cranberry use ) because of the relatively low toxicity of isofetamid to fish and the low estimated environmental concentrations (EECs) for the proposed non

- flooded crop uses for isofetamid

. Additionally, data are currently only

avail able for three, instead of four, species of non

- vascular aquatic plant. Due to the toxicity profile of the chemical, additional plant data are not expected to change the

current risk conclusions.

Another uncertainty involves the risk conclusions for aq uatic invertebrates. The only

chronic toxicity data currently available for isofetamid and an aquatic invertebrate are for the waterflea ( Daphnia magna ). In the waterflea study there was reduced length at all test concentrations resulting in a NOAEC of < 0.39 mg a.i./L

. At 0.39 mg a.i./L, no chronic risk is expected. However, b ecause the 0.39 mg a.i./L is only 2 times the highest

21

- day average EEC for the uses modeled (wet

- harvested cranberry), t here is uncertainty regarding the potential risk to aquati c invertebrates from chronic exposure to isofetamid

and the wet

- harvested cranberry use

. A definitive NOAEC w ould help address this uncertainty

.

T he Agency has issued guidance for assessing the potential risks of pesticides to bees and
the data needed to support such assessments (USEPA et al. , 2014). Th e guidance

document indicates that if exposure of bees to a pesticide is expected, a Tier I screening

level risk assessment is conducted . The Tier I assessment is intended to be sufficiently

### 4

conservative that chemicals that pass the screen are considered to represent a relatively

low ris k for potential adverse effects to bees. Tier I toxicity data that are needed to complete screening

- level risk assessments include a suite of laboratory

- based studies of

i ndividual bees and include the following tests: chronic oral toxicity to adult honey bees, and acute and chronic oral toxicity to honey bee larvae. If risk concerns are identified in the screening

- level assessment, the assessment may be refined using data that further define exposure or through additional toxicity data from Tier II semi

- field or Tier III full

field studies conducted with whole colonies. Below is the suite of honey bee toxicity and

residues studies:

Tier I D ata

 A cute oral toxicity to larval honey bees (Non

- guideline, OECD TG 237)

 C hronic oral toxicity to adult honey bees (Non

- guideline)

 Chronic oral toxicity to larval honey bees (Non

- guideline)

Tier II Data

 Field trial of residues in pollen and nectar (Non

- guideline)

 Semi

- field testing for pollinator (Non

- guideline, OECD Guidance 75)

Tier III Data

 Field testing for pollinators (Guideline 850.3040)

Labeling Recommendations

According to the Label Review Manual, the following label statements are

recommended:

Environmental Hazards

 “For te rrestrial uses: Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. Do not contaminate water when disposing of equipment washwater or rinsate.”

### 5

TABLE OF CONTENTS

Labeling Recommendations

................................ ................................ ............................. 4
LIST OF FIGURES

................................ ................................ ................................ .......... 7
LIST OF TABLES

................................ ................................ ................................ ............ 7
LIST OF APPENDICES

................................ ................................ ................................ .. 8
I. EXECUTIVE SUMMARY

................................ ................................ .......................... 9
A. Nature of Chemical Stressor

................................ ................................ .... 9
B. Conclusions

- Exposure Characterization

................................ .............. 9
C. Conclusions

- Effects Characterization

................................ ................. 10
D. Potential Risks to Non

- target Organisms

................................ ............. 10
E. Uncertainties

................................ ................................ ............................ 11
II PROBLEM FOR MULATION

................................ ................................ ................. 13

A. Stressor Source and Distribution

................................ .......................... 13 1. Source and Intensity

................................ ................................ ... 13 2. Physical/Chemical/Fate and Transport Properties

.................. 13 3. Pesticide Type, Class, and Mode of Action

............................... 13

4. Overview of Pesticide Usage

................................ ...................... 13 B. Receptors

................................ ................................ ................................ . 14

1. Aquatic and Terrestrial Effects

................................ ................. 14 2. Ecosystems Potentially at Risk

................................ .................. 14
C. Assessment Endpoints

................................ ................................ ............ 14 D. Conceptual M odel

................................ ................................ ................... 15 1. Risk Hypotheses

................................ ................................ .......... 15 2. Diagram

................................ ................................ ....................... 15

1. Uncertainties

................................ ................................ ................ 18 2. Measures to Evaluate Risk Hypotheses and Conceptual Model

................................ ................................ ................................ ....... 19 a. Measures of Exposure

................................ ..................... 19

b. Measures of Effect

................................ .......................... 21

III. ANALYSIS

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

A. Use Characteriza tion

................................ ................................ .............. 22 B. Exposure Characterization

................................ ................................ ..... 25

1. Environmental Fate and Transport Characterization

............ 25 2. Measures of Aquatic Exposure

................................ .................. 29

a. Aquatic Exposure Modeling

................................ .......... 29

b. Aquatic Exposure Monitoring and Field Data

............. 34 3. Measures of Terrestrial Exposure

................................ ............. 34

a. Terrestrial Exposure Modeling

................................ ..... 34 C. Ecological Effects Characterization

................................ ......................... 36 1. Aquatic Effects Characterization

................................ .................. 39 a. Aquatic Animals

................................ ................................ .. 39

b. Aquatic Plants

................................ ................................ . 44
2. Terrestrial Effects Characterization

................................ ............. 45

a. Terrestrial Animals

................................ ............................. 45

b. Terrestrial Plants

................................ ............................ 48

### 6

IV. Risk Characterization

................................ ................................ .......................... 50

A. Risk Estimation

- Integration of Exposure and Effects Data

................. 50

1. Non

- target Aquatic Animals and Plants

................................ ....... 50

2. Non

- target Terrestrial Animals

................................ ..................... 54

3. Non

- target Terrestrial and Semi

- aquatic Plants

.......................... 57 B. Risk Description

................................ ................................ ......................... 57 1. Risks to Aquatic Organisms

................................ ........................ 58

a. Animals

................................ ................................ ............ 58

a. Plants

................................ ................................ ................ 58 2. Risks to Terrestrial Organisms

................................ ................... 58

a. Animals

................................ ................................ ............ 58

b. Plants

................................ ................................ ................ 63

3. Review of Incident Data

................................ ................................ . 63
V. REFERENCES

................................ ................................ ................................ ........... 64

### 7

LIST OF FIGURES

Figure 1: Conceptual model depicting stressors, exposure pathways, and potential effects to aquatic organisms from the proposed uses of isofetamid. Dotted lines indicate exposure pathways that are hypothesized to have a low likelihood of contributing to ecological risk.

................................ ................................ ................................ .................. 16 Figure 2: Conceptual model depicting stressors, exposure pathways, and potentia l effects to terrestrial organisms from the proposed uses of isofetamid. Dotted lines indicate exposure pathways that are hypothesized to have a low likelihood of contributing to ecological risk.

................................ ................................ ................................ .................. 17 Figure 3 . Potential Degradation Pathway of Isofetamid

................................ .................. 29

LIST OF TABLES

Table 1 Typical Taxonomic Groups and Test Species Evaluated for Ecological Effects in Screening

- Level Risk Assessments.

................................ ................................ ................. 14

Table 2

. Acute and Chronic Measures of Effect.

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

Table 3

. Application Information from the Proposed Isofetamid Labels 1



### . ...................... 23

Table 4. SWCC: Summary of application input parameters used in aquatic modeling for

total toxic residues.

................................ ................................ ................................ ........... 30

Table 5. SWCC: summary of environmental fate input parameters used in aquatic modeling for total toxic residues of Isofetamid.

................................ ............................... 31

Table 6. PFAM input parameters for isofetamid total toxic residues for use on wet

harvested cranberry

................................ ................................ ................................ ........... 31

Table 7. Calculated EECs for the use of isofetamid on proposed uses based on proposed application rates and intervals.

................................ ................................ .......................... 33

Table 8 . EECs on Potential Food Items Following Label

- Specified Applications of Isofetamid Using the T

- REX Model (ppm) (the default 35

- day foliar half

- life was used in modeling).

................................ ................................ ................................ ......................... 35

Table 9. EECs on Plants Following Label

- Specified Ground and Aerial Applications of Isofetamid Using the TerrPlant Model (lbs a.i./A).

................................ .......................... 36

Table 10 . Summary of Specific Assessment Endpoints for Animals and Plants Considered in this Assessment for Estimating Risks to Non

- target Taxa.

....................... 37

Table 11 . Submitted Toxicity Data for Isofetamid and Aquatic Anima ls.

...................... 40

Table 12. Submitted Toxicity Data for Isofetamid and Aquatic Plants.

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

Table 13. Submitted Toxicity Data for Isofetamid an d Birds.

................................ ......... 45

Table 14. Submitted Toxicity Data for Isofetamid and Terrestrial Plants.

...................... 49

Table 15. Agency Levels of Concern (LOC).

................................ ................................ .. 50

Table 16. RQs for Aquatic Animals and Isofetamid.

................................ ....................... 52

Table 17. RQs for Aquatic Plants and Isofetamid.

................................ ........................... 53

Table 18 . Chronic Dietary

- Based RQs for Birds and Isofetamid Using the T

- REX Model (the default 35

- day foliar half

- life was used in modeling).

................................ .............. 54

Table 19. Chronic Dose

- Based RQs for Mammals and Isofetamid Using the T

- REX Model (the default 35

- day foliar half

- life was used in modeling).

................................ ... 55

### 8

Table 20. Chronic Dietary

- Based RQs for Birds and Isof etamid Using the T

- REX Model: Comparing the 35

- day and 16

- day foliar half

- life results.

................................ ................ 60

Table 21. Chronic Dose

- Based RQs for Mammals and Isofetamid Using the T

- REX Model: Comparing the 35

- da y and 16

- day foliar half

- life results.

................................ ... 62

LIST OF APPENDICES

Appendix A. Sample Screening Tool for Inhalation Risk (STIR v. 1.0) Inputs and Outputs for the Propose d Uses of Isofetamid.

................................ ................................ .. 71 Appendix B. Isofetamid Total Toxic Residues Aquatic Modeling Results

. ..................... 72 Appendix C. Sample T

- REX Inputs and Outputs for the Proposed Uses of Isofetamid.

. 74 Appendix D. SAMPLE TerrPlant Inputs and Outputs for the Proposed Isofetamid Uses.

................................ ................................ ................................ ................................ ........... 79 Appendix E Fate Data for Isofetamid Parent and Degradates and QSAR Analyses for

4HP and PPA.

................................ ................................ ................................ ................... 80

### 9

I. EXECUTIVE SUMMARY

A. Nature of Chemical Stressor

Isofetamid is a new broad

- spectrum, systemic fungicide that is proposed for registration by the applicant ISK BIOSCIENCES CORPORATION (a subsidiary of ISHIHARA SANGYO KAISHA, LTD.) for use on almond, lettuce, grapes (Subgroup 13

- 07F), low growing berries (Subgroup 13

- 07G), rapeseed (Subgroup 20A), and turf (co mmercial and residential)

. One technical product (EPA File Symbol 71512

- ER) and two end

- use products [Isofetamid 400SC Fungicide (EPA File Symbol 71512

- EE) and Isofetamid Turf Fungicide (EPA File Symbol 71512

- EG)] are being proposed for registration in th e United States

. Both proposed e nd

- use products have a single ac tive ingredient (a.i.) (36% isofetamid). For the non

- turf uses, isofetamid would be applied as a foliar spray (ground or aerial) or via chemigation with a maximum proposed single application rate of 0.572

lb a.i./acre and a maximum annual application rate of 2.28 lb a.i./acre

. For turf , the proposed single maxi mum application rate is 0.568 lb a.i./acre and the proposed maximum annual application rate is 3.65 lb a.i./acre

.

Isofetamid is a ph enyl

- oxo

- ethyl thiophene amide and is a succinate dehydrogenase inhibitor (SDHI)

. Other fungicides that also target this site (complex II:succinate

dehydro

- genase) include, but are not limited to, carboxin, fluopyra m , sedaxane, and

boscalid

.

Two enviro nmental degradates of isofetamid, 4HP and PPA, are expected to have toxicity

characteristics similar to isofetamid based on their structural similarity and preliminary QSAR runs (using EPIS uite v. 4.1; see A PPENDIX E , Table E 1 for structures ). These

two de gradates, along with isofetamid, are considered in the Total Toxic Resi dues (TTR) approach used in the aquatic assessment. Additionally, a metabolite of isofetamid, N

- [l ,1

– dimethyl

- 2

- (4

- β

- D

- glucopyranosyloxy

- 2

- methylphenyl)

- 2

- oxoethyl]

- 3

- methyl

- 2

- thiophenecarboxamide (GPTC) , was found in some of the available plant metabolism studies and the terrestrial field dissipation studies conducted on turf. It is assumed that

G PTC has similar toxicity as parent based on its structure. Therefore, for the terrestrial assessment both environmental degradates, 4HP and PPA, and the metabolite GPTC are considered and will be assessed using a TTR.

B . Conclusions

- Exposure Characterization

Isofetamid is moderately mobile in soil (K F oc 

### values are 2 74 to 6 03 mL/g

- organic carbon) and is not expected to volatilize under field conditions ( vapor pressure of 4.4 ×10 - 11 

### t orr)

. Major routes of degradation for isofetamid include ph otolytic degradation in water (half

life 1.4

- 1.8 days), as well as degradation in soil and water from aerobic metabolic processes (aerobic soil metabolism half

- lives range from 25

- 66 days, aerobic aqueous

half

- lives range from 47 to 173 days). Isofetamid is stable in anaerobic environments.

I sofetamid ’s environmental degradates of concern (4HP and PPA) are mobile to moderately mobile and may enter surface water through runoff and groundwater via

### 10

leaching ( 4HP K F oc 

### values 11 0

- 355 mL/g

- organic carbon , PPA EPISuite v.4.1 K
oc 

### values

121

- 180 mL/g

- organic carbon )

. EPISuite v. 4.1 estimates indicate that 4HP and PPA

have vapor pressures lower than 9.98 x 10 - 7 

### torr and are therefore are not expected to

volatilize under field conditions.

Isofetamid and its deg radates are very persistent in anaerobic soil and water, with

estimated half

- lives above 1,000 days. Isofetamid and its degradates are persistent in aerobic aqueous environments, with half

- lives ranging from 173 to 361 days. I sofetamid and its degradates are less persistent in aerobic soil, with a erobic soil metabolism half

lives ranging from 25 to 65 days

. R esults from terrestrial field dissipation studies suggest

that isofetamid parent may accumulate in the soil from year to year in fields where the

che mical is routinely applied; this is not expected to be the case for 4HP or PPA

. Major routes of degradation for isofetamid residues include photolytic degradation in water, as well as degradation in soil and water from aerobic metabolic processes.

C. Conclusions

- Effects Characterization

Based on the available data, isofetamid is classified as moderately toxic to freshwater fish and invertebrates, no more than moderately toxic to estuarine/marine fish, highly toxic to

estu arine/marine invertebrates (specifically oysters)

, and practically non

- toxic to birds,

mammals , and terrestrial invertebrates on an acute exposure basis. Chronic exposure resulted in reduced growth in freshwater fish at 0.086 mg a.i./L. In freshwater

inv ertebrates, isofetamid resulted in effect s (reduced length) at all of the concentrations tested, resulting in a NOAEC value <0.39 mg a.i./L. Chronic toxicity data are not available for estuarine/marine fish or invertebrates. Chronic exposure in birds res ulted in reduced egg shell thickness at 928 mg a.i./kg

- diet (NOAEC = 276 mg a.i./kg

- diet). In mammals, chronic exposure resulted in reduced body weights and reduced weight gain and slightly delayed sex maturation in females (NOAEL = 1,000 mg a.i./kg

- diet)

.

For terrestrial plants, t he most sensitive monocot in the seedling emergence study was ryegrass based on dry weight, with NOAEC and EC 25 

### values of 8 3.7 and 576 lb ai/A, respectively. The most sensitive dicot was tomato, based on dry weight, with NOAE C

and EC 25 

### values of 2 .6 and 10.3 lb ai/A, respectively. In the vegetative vigor study, the

most sensitive monocot was determined to be corn with NOAEC and EC 25 

### values of 1.07 and 1.3 lb ai/A, respectively. The most sensitive dicot was determined to be s oybean

with NOAEC and EC 25 

### values of 1.07 and 1.26 lb ai/A. The most sensitive aquatic plant

tested was the marine diatom Skeletonema costatu m with an EC 50 

### value of > 4.1 mg a.i./L

and a NOAEC value of 4.1 mg a.i./L based on a reduction in yield.

D. Potential Risks to Non

- target Organisms

The results of this screening

- level risk assessment indicate that none of the proposed isofetamid uses are expected to pose a direct risk to freshwater aquatic invertebrates, vascular aquatic plants, or terrest rial plants

. A d ditionally, risks to birds (and, thus,

terrestrial

- phase amphibians and reptiles) or mammals are not expected from acute

### 11

exposure to isofetamid from the proposed uses. Regarding chronic exposure , the proposed lettuce and rapeseed uses are not expected to pose a risk to birds or mammals.

With the exception of low

- growing berries (including wet

- harvested cranberry) and

grapes, none of acute RQs for non

- listed species exceed the Agency’s LOC for

estuarine/marine invertebrates [the highest R Q for estuarine/marine invertebrates is 0. 46 6 ( wet

- harvested cranberry )]

.

The RQs for chronic risk exceed the Agency’s LOC for birds that eat short grass (for the proposed almond, grapes, and turf uses). The chronic RQs for birds that eat short grass

and these uses range from 1.03 to 1.41

. For mammals, t he chronic dose

- based RQs for several of the proposed uses (almond, grapes, low

- growing berries, and turf) , dietary categories, and size classes exceed the Agency’s LOC of 1 for chronic risk (RQs range

fr om 0.01 to 2.56 ). None of the chronic dietary

- based RQs exceed the Agency’s LOC for

mammals

.

Isofetamid is classified as ‘practically nontoxic’ to non

- target terrestrial invertebrates on an acute exposure basis (both oral and contact) . Based on the avai lable data, precautionary label language for bees does not appear necessary for the proposed

isofetamid uses

.

E. Uncertainties

With regard to environmental fate data, there are only anaerobic soil metabolism data from one soil for isofetamid pare nt. However, g iven the compound’s persistence in the single anaerobic soil, as well as its persistence in anaerobic aquatic test systems,

additional anaerobic soil metabolism data are not expected to alter the risk conclusions

.

Limited environmental fa te data are available for isofetamid degradates. Only one laboratory study was conducted for one degradate (adsorption/desorption for 4HP) which is of limited value due to deficiencies in study design, execution, and data recording

. In the soil photolysi s and metabolism studies conducted for isofetamid parent, 4HP and PPA did not consistently peak and decline by the end of each study (see A PPENDIX E
, Table

E 3 ). This introduces some uncertainty in the representative half

- lives calculated for

isofetamid TT R ; however, the aquatic EECs are not expected to substantially change

.

Toxicity data are not available for the isofetamid degradates. However, based on structural similarity and preliminary QSAR runs (using EPISUITE v. 4.1 ), 4HP and PPA

are assumed to ha ve similar toxicity as parent isofetamid.

There is currently only one chronic study available for fish and isofetamid. Because there are currently no acute data available for the species used in the chronic study ( i.e

., fathead minnow), there is uncerta inty regarding the chronic endpoint ( i.e ., it is not clear

whether or not fathead minnow are more or less sensitive than rainbow trout

– the most sensitive freshwater fish tested on an acute exposure

- basis). However, because of the relatively low toxicity of isofetamid to fish and the low estimated environmental

### 12

concentrations (EECs) for the proposed isofetamid uses, additional data are not expected

to alter the risk conclusions ( i.e ., minimal risk to fish from chronic exposure).

The only chronic toxicity data currently available for isofetamid and an aquatic invertebrate are for the waterflea ( Daphnia magna ). In the waterflea study there was reduced length at all test concentrations resulting in a NOAEC of <0.39 mg a.i./L

. At 0.39 mg a.i./L, no chronic risk is expected. However, because the 0.39 mg a.i./L is only 2

times the highest 21

- day average EEC for the uses modeled (wet

- harvested cranberry), there is uncertainty regarding the potential risk to aquatic invertebrates from chronic exposure to isofet amid and the wet

- harvested cranberry use. A definitive NOAEC would help address this uncertainty

.

Data are currently available for three species of non

- vascular plant (data on four species is generally required). However, because of the toxicity prof ile of the chemical, additional data are not expected to alter risk conclusions.

T he Agency has issued guidance for assessing the potential risks of pesticides to bees and

the data needed to support such assessments (USEPA et al. , 2014). Th e guidance

docu ment indicates that if exposure of bees to a pesticide is expected, a Tier I screening

level risk assessment is conducted . The Tier I assessment is intended to be sufficiently conservative that chemicals that pass the screen are considered to represent a r elatively

low ris k for potential adverse effects to bees. Tier I toxicity data that are needed to complete screening

- level risk assessments include a suite of laboratory

- based studies of individual bees and include the following tests: chronic oral toxicit y to adult honey bees, and acute and chronic oral toxicity to honey bee larvae. If risk concerns are identified in the screening

- level assessment, the assessment may be refined using data that further define exposure or through additional toxicity data fro m Tier II semi

- field or Tier III full

field studies conducted with whole colonies.

### 13

II

. PROBLEM FORMULATION

The purpose of this assessment is to evaluate the ecological risks for the registration of

the new chemical isofetamid ( N

- [1,1

- dimethyl

- 2

- [2

- methy l

- 4

- (1

- methylethoxy)phenyl]

- 2

- oxoethyl]

- 3

- methyl

- 2

- thiophenecarboxamide ) (PC Code: 2 70000 ).

A. Stressor Source and Distribution

1. Source and Intensity

Isofetamid is a new fungicide that is undergoing registration (as th e active ingredient in

o ne manufacturing product and two end

- use product s ) by the applicant ISK BIOSCIENCES CORPORATION (a subsidiary of ISHIHARA SANGYO KAISHA, LTD.) . The isofetamid end

- use product s being proposed for registration in the United

States ar e Isofetamid 400SC Agricultural Fungicide (36.0 % isofetamid) and Isofetamid Turf Fungicide (36.0% isofetamid). Both of the proposed end

- use products are formulated as a flowable suspension concentrate. According to the proposed label s
, isofetamid is a br oad

- spectrum fungicide with preventative, systemic, and curative properties for foliar and soil

- borne diseases. T he turf product (Isofetamid Turf Fungicide) would be used to control dollar spot on turfgrasses

. The Isofetamid 400SC product would be used t o treat a variety of fungal diseases in almond, lettuce, grapes,

low

- growing berries, and rapeseed

. The proposed application methods of i sofetamid include ground application to turf as a foliar spray or via chemigation , or by ground or

aerial application for all of the other proposed non

- turf uses

.

2. Physical/Chemical/Fate and Transport Properties

Physical, chemical, and fate and transport properties of isofetamid parent and, to the extent possible, isofetamid degradates , are summarized in the tables in APPENDIX E

and discussed further in the ANALYSIS section of this assessment.

3. Pesticide Type, Class, and Mode of Action

Isofetamid is a phenyl

- oxo

- ethyl thiophene amide and is a succinate dehydrogenase inhibitor (SDHI)

. SD is an enz yme linked to the mitochondrial electron transport chain. Other fungicides that also target this site (complex II:succinate

- dehydrogenase) include, but are not limited to, carboxin, fluopyra m , sedaxane, and boscalid. Isofetamid is a systemic pesticide as noted on the proposed labels

.

4. Overview of Pesticide Usage

Since this is a new chemical, the Agency do es not have any usage information for

Isofetamid . The proposed registration is for use on almond, lettuce, grapes, low

- growing berries, rapeseed, and t urf

.

### 14 B. Receptors

1. Aquatic and Terrestrial Effects

Table 1 gives examples of taxonomic groups and species tested to help understand potential ecological effects of pesticides to non

- target organisms. Within each of these

v ery broad taxonomic groups, a measure of effect from chronic and/or acute exposure is

selected from the available test data.

Table 1

. Typical Taxonomic Groups and Test Species Evaluated for Ecological Effect s in Screening

- Level Risk A ssessments.

Taxonomic Group Example(s) of Representative Species

Birds 1 Passerine Mallard duck (

Anas platyrhynchos ) , or Bobwhite quail ( Colinus virginianus )

Mammals Laboratory rat ( Rattus norvegicus )

Terrestrial invertebrates Honey bee ( Apis mellifera L. )

Freshwater fish 2 Bluegill sunfish ( Lepomis macrochirus )

Rainbow trout ( Oncorhynchus mykiss )

Freshwater invertebrates Water flea ( Daphnia magna )

Estuarine/marine fish Sheepshead minnow ( Cyprinodon variegatus )

Estuarine/marine invertebra tes Mysid ( Americamysis bahia) Eastern oyster ( Crassostrea virginica ) Terrestrial plants 3 Monocots

– corn ( Zea mays )

Dicots

– soybean ( Glycine max ) Aquatic plants and algae Duckweed ( Lemna gibba ) Green algae ( Pseudokirchneriella subcapitata )

1 Birds represent surrogates for amphibians (terrestrial phase) and reptiles.

2 Freshwater fish may be surrogates for amphibians (aquatic phase).

3 Four spe cies of two families of monocots, of which one is corn; six species of at least four dicot families, of which one is soybeans.



### 2. Ecosystems Potentially at Risk

The ecosystems potentially at risk include the areas adjacent t o the application sites and water bodies adjacent to the application sites and downstream. In addition

, organisms that use the application site as part of their habitat ( e.g., birds foraging for insects within application areas) are also considered to be part of the ecosystems potentially at risk.

C. Assessment Endpoints

FIFRA Part 158 guideline toxicity tests (CFR 40 §158. 630, 2009 ) are intended to determine pesticidal effects on a variety of organisms, including birds, mammals, fish, terrestrial and aquat ic invertebrates, and plants. These tests include both short

- term and long

- term exposure periods and evaluate the survival, reproduction, and/or growth of laboratory species. The studies, when available, are used to evaluate the potential of a pesticide to cause adverse effects, to determine whether further testing is required, and to determine the need for precautionary label statements to minimize the potential adverse

effects to non

- target ani mals and plants (CFR 40 §158.630, 2009 ).

### 15 D. Concept ual Model

The conceptual model used to depict the potential ecological risk associated with

isofetamid is fairly generic and assumes that as a fungicide

, isofetamid is capable of affecting terrestrial and aquatic organisms (animals a nd plants) provided environmental concentrations are sufficiently elevated as a result of proposed label uses. Therefore, we will consider potential exposure as a result of direct applications, spray drift, and runoff.

1. Risk Hypotheses

For this assessment, the risk to non

- target organisms is based on potential effects from the application of isofetamid to the environment. The Agency presume s the following risk hypothesis for this screening level assessment:

B ased on mo de of action , the proposed use patterns, and the sensitivity of non

target aquatic and terrestrial species, the proposed uses of isofetamid have the potential to reduce survival, reproduction, and/or growth in terrestrial and aquatic animals and plants thr ough direct application, spray drift and/or runoff.

In order for a chemical to pose an ecological risk, it must reach non

- target organisms at concentrations found to cause adverse effects. The assessment of ecological exposure pathways in this assessment includes an examination of the source and potential migration pathways to isofetamid exposure, and the determination of potential adverse

effects on non

- target species.

2. Diagram

Application methods for isofetamid involve foliar spray applications via ground and

aerial equipment . Ecological receptors that may potentially be exposed to isofetamid

include terrestrial and semi

- aquatic wildlife ( i.e. , mammals, birds, amphibians, terrestrial invertebrates, and reptiles) and pla nts. In addition, aquatic receptors ( e.g ., freshwater and estuarine/marine fish and invertebrates, amphibians, and plants) may also be exposed as a result of potential movement of isofetamid via spray drift and/or runoff from the site of application to aq uatic environments. The assessment following the process depicted in Figure 1 (aquatic exposure) and Figure 2 (terrestrial exposure) forms the basis for identifying potential endpoints, stressors, and ecological effects associated with

isofetamid use.

Si nce volatility of isofetamid does not appear to be an issue, t his assessment does not take into account atmospheric transport in estimating environmental concentrations . Exposure to terrestrial animals is based primarily on dietary consumption of foliar r esidues while aquatic assessments assume that all major potential routes of direct exposure are

accounted for.

### 16

Figure 1 : Conceptual model depicting stressors, exposure pathways, and potential effects to aquatic organisms from the proposed uses of isofetamid

. Dotted lines indicate exposure pathways that are hypothesized to have a low likelihood of contributing to ecological risk.

### 17

Figure 2 : Conceptual model depicting stressors, exposure pathways, and potential effects to terrestrial organisms from the proposed uses of isofetamid . Dotted lines indicate exposure pathways that are hypothesized to have a low likelihood of contributing to ecological risk.

### 18

E. Analysis Plan

Thi s document characterizes the environmental fate of isofetamid to assess whether proposed

label uses of isofetamid on almond, lettuce, grapes, low

- growing berries, rapeseed, and turf provide a means of exposure to non

- target species. Additionally, the toxi city of isofetamid is characterized, then both potential exposure and effects are integrated to estimate the likelihood of adverse effects (risk) to non

- target animals and plants

.

The maximum proposed label application rates for use of isofetamid on almon d, lettuce, grapes,

low

- growing berries, rapeseed, and turf were selected for modeling environmental concentrations for this screening

- level deterministic (risk

- quotient based) assessment. The most sensitive toxicity endpoints from surrogate test species are used to estimate treatment

- related effects on growth, and survival. The aquatic e stimated environmental concentrations (EECs) are based on

the parent and t he two degradates of concern, 4HP and PPA , using a total toxic residue (TTR) approach

. E ven tho ugh only the parent chemical is modeled in the terrestrial modeling, the terrestrial EECs are expected to acco unt for the parent and all residues of conce rn , including 4HP, PPA, and the metabolite, GPTC

, b ecause a default 35

- day foliar half

- life is used (d ue to a
lack of available data to calculate foliar half

- lives)

.

In the following sections, we characterize the use, environmental fate, and ecological effects of

isofetamid and, using a risk quotient (ratio of exposure concentration to effects concentrati on) approach, we estimate the potential for adverse effects on non

- target terrestrial and aquatic animals and plants.

1. Uncertainties

The following uncertainties were identified in this risk assessment:

Environmental Fate:

Environmental f

at e data were not submitted for isofetamid’s ecological residues of concern, 4HP and PPA, with the exception of a 4HP adsorption/desorption study of limited value (MRID

49011980 )

. This introduces uncertainties into this risk assessment, as is described in t he following paragraphs.

The adsorption/desorption study conducted for 4HP did not use radiolabelled test chemical or a control. It also only measured 4HP in supernatant, rather than measuring it in both the soil and
supernatant. These are noteworthy def iciencies in the study that introduce uncertainty into our understanding of the mobility of 4HP

. However, because the estimated K F 

### s and K F oc 

### s suggest
that 4HP is mobile to moderately mobile (K F oc 

### s range from 110 to 355 mL/g

- organic carbon) , it is not expec ted that an additional adsorption/desorption study for 4HP would substantially change the conclusions in this risk assessment (FAO 2000)

.

With regard to adsorption/desorption of PPA, EPISuite v.4.1 estimates that K
oc 

### values would range fr o m 121 to 180 m L/g

- organic carbon, and would be classified as being mobile to moderately mobile (FAO 2000). Without a PPA adsorption/desorption study for these estimates

cannot be confirmed. While this introduces uncertainty into exposure calculations, it is not

### 19

expected to change the conclusions in this risk assessment because isofetamid degrades to PPA primarily in aquatic (as opposed to terrestrial) environments.

Although 4HP and PPA were observed in most degradation studies conducted for the parent compound, the stud y durations were often not long enough to show formation and decline of both compounds. The lack of complete formation and degradation data in the aerobic metabolism studies has the potential to impact half

- lives calculated for modeling, particularly for t he aerobic aquatic metabolism study. In the aerobic soil metabolism studies, both 4HP and PPA began declining by study termination in three of the four soils tested, so additional data may not result in major differences in the half

- lives calculated and us ed in modeling. Lack of degradate formation/decline data is not expected to impact conclusions concerning the anaerobic metabolism and soil photolysis studies, as isofetamid and isofetamid degradates were stable in

these studies. Overall, while additional information on degradate formation and decline would be helpful, it is not expected to substantially alter the conclusions in this risk assessment.

Ecological Effects:

There is currently only one chronic study available for fish and isofetamid. Because there are currently no acute data available for the species used in the chronic study ( i.e ., fathead minnow), there is uncertainty regarding the chronic endpoint ( i.e ., it is not clear whether or not fathead

minnow are more or less sensitive than rainbow trout

– the most sensitive freshwater fish tested
on an acute exposure

- basis).

The only chronic exposure data currently available for isofetamid and an aquatic invertebrate are for the waterflea ( Daphnia magna ). In this study there was reduced length a t all of the concentrations tested resulting in a non

- definitive NOAEC of <0.39 mg a.i./L. Therefore, there is uncertainty regarding how low isofetamid concentrations would need to be to no longer elicit an adverse effect in aquatic invertebrates after ch ronic exposure.

Data are currently only available for three, instead of four, non

- vascular aquatic plant species. Toxicity tests using nonvascular aquatic plants resulted in 96

- hour EC 50 

### values ≥ 4.1 mg a.i./L. NOAEC values ranged from 0.412 mg a.i./L in a freshwater diatom ( Navicula pelliculosa ) to 4.1 mg a.i./L in a marine diatom ( Skeletonema costatum ).

There are currently no ecotoxicity data available for the isofetamid degradates , 4HP and P PA

. Additionally there are uncertainties associated with estimating dietary exposures to birds and mammals from contaminated feed items with systemic pesticides since our current model (T

REX) is based on exposure via residues on the surface of food items (and not on residues that may be translocated within plant material).

2. Measures to Evaluate Risk Hypotheses and Conceptual Model

a. Measures of Exposure

In order to estimate risks of isofetamid exposures in aquatic and terrestrial env ironments, all exposure modeling and resulting risk conclusions will be made based on maximum proposed

### 20

application rates as discussed in Section III.B.2.a . Measures of exposure are based on aquatic

and terrestrial models that estimate environmental concen trations of isofetamid and its residues

of concern using maximum proposed labeled application rates and application methods that have the greatest potential for off

- site transport of the chemical. The Surface Water Concentration

Calculator (SWCC version 1

. 10 6 ) model and the Pesticide Flooded Application Model (PFAM version 0.70) was used to generate aquatic EEC s . The model used to produce terrestrial EECs on

food items is T

- REX. The model used to derive EECs relevant to terrestrial and wetland plants

is TerrPlant. These models are parameterized using relevant reviewed registrant

- submitted

environmental fate data. Additionally, the Screening Tool for Inhalation Risk ( STIR ) was used

to determine if inhalation , is potentially a significant route of concern for terrestrial animals.

The SWCC generates daily expos ures and 1

- in

- 10

- year EECs of isofetamid that may occur in surface water bodies adjacent t o application sites receiving isofetamid through runoff and spray

drift. SWCC simulates pesticide applicati on, movement and transformation on an agricultural field and the resultant pesticide loadings to a receiving water body via runoff, erosion, and spray

drift , and then simulates the fate of the pesticide and resulting concentrations in the water body.

The standard watershed geometry used for ecological pesticide assessments assumes application

to a 10

- hectare agricultural field that drains into an adjacent 1

- hectare water body that is 2 meters deep (20,000 m 3 

### volume) with no outlet. The SWCC is used to est imate screening

- level

exp osure of aquatic organisms to isofetamid TTR . The measure of exposure for aquatic species

is the 1

- in

- 10

- year peak or rolling mean concentration. The 1

- in

- 10

- year peak is used for estimating acute exposures of direct effects to a quatic organisms. The 1

- in

- 10

- year 60

- day mean is used for assessing the effects to fish and aquatic

- phase amphibians from chronic exposure.

The 1

- in

- 10

- year 21

- day mean is used for assessing the effects on aquatic invertebrates from chronic exposure.

F or the wet

- harvested cranberry use, EECs were generated using the Pesticide Flooded Application Model (PFAM version 0.70) instead of the SWCC

. PFAM was developed as a flooded agriculture model for use in pesticide regulatory work. This model has been devel oped under USEPA Guidance, and external independent evaluations have been positive (USEPA 2009; Luo 2011)

.

PFAM includes both hydrological processes and chemical processes. The water body depth may change due to precipitation, refill, drainage, evapor ation, and weir

- height changes. The model consists of two regions: a water column and a benthic region. Each individual region is completely mixed and at equilibrium with all phases within the individual region, and equilibrium within each region follows a linear isotherm (USEPA 2004b) . The two regions are coupled by a first

- order mass transfer process. Equations for chemical processes (i.e., 

### hydrolysis, bacterial metabolism, photolysis, and sorption) within each region are similar to the EXAMS

model. The model accounts for plant growth, metabolism, hydrolysis, photolysis, and metabolism in water, sediment, and soil (when no water is present), sorption, and volatilization. Water, sediment, and pesticide may flow out of the field. Changes in water body cond itions (temperature, water levels, wind speed, etc

. ) 

### and the resulting changes in degradation rates occur on a daily time step. Pesticide application and flooding sequences are mapped onto the time

series in 1

- year cycles for the length of the simulation. For instance, a typical exposure assessment assumes the pesticide is used every year for 30 years (the length of most EFED

### 21

meteorological files). Output is delivered as released mass of pesticide as well as a daily time

series of concentrations.

PFAM est imates exposure in the field effluent, which is even tually mixed with surface water. Mixing of paddy water with other surface water will result in dilution of the paddy water and

reductions in EECs . In order to account for this, PFAM was set up to flow (ma ss and volume)

into the standard farm pond , the standard water body used by EFED to estimate surface water

EECs using the varying volume pon d model (FIFRA SAP 2004) . This portion of the model is still under development and evaluation, so the derived estima tes using PFAM with the index reservoir are considered provisional.

Two environmental degradates of isofetamid, 4HP and PPA, are assumed to be equatoxic with the parent based on structural similarities and a QSAR analysis. They form at roughly 10% of

th e parent in some of the environmental fate studies, and are expected to metabolize quickly in humans. For these reasons, they are not considered in the drinking water assessment conducted

for HED (D411110)

. They were, however, included in the aquatic env ironmental assessment because the rapid metabolism could not be assumed for all taxa ; therefore, they we re assessed in the aquatic risk assessment using the total toxic residues approach. This approach was used to

determine the e nvironmental fate data par ameters for modeling in conjunction with the Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides

, Version 2. 1, October 22, 2009 and the draft Guidance for Modeling Pesticides Total Toxic Residues (TTR) May 20, 2009.

b. Measures of Effect

Measures of effect are obtained from a suite of registrant

- submitted guideline studies conducted with a limited number of surrogate species. The acute measures of effect routinely used f or listed and non

- listed animals in screening level assessments are the LD 50 

### , LC 50 

### or EC 50 

### , depending on taxa (see Table 3 ). Endpoints for chronic measures of exposure for listed and non

listed animals are the NOAEL or NOAEC. For non

- listed plants, only acute exposures are assessed ( i.e ., EC 25 

### for terrestrial plants and EC 50 

### for aquatic plants). For listed terrestrial plants the Agency use s the EC 5 

### or NOAEC (see Table 3 ).

### 22

Table 2

. Acute and Chronic Measures of Effect

.

TAXA ASSESSMENT MEASURE OF EFFECT

Aquatic Animals ( Freshwater fish

and inverts. and estuarine/marine fish and inverts. ) Acute Lowest tested EC 50 or LC 50 (acute toxicity tests)

Chronic Lowest NOAEC ( early life

- stage or full life

- cycle tests)

Terrestrial Animals

Birds Acute /Sub

- acute Lowest LD 50 (single oral dose) and LC 50 (subacute dietary)

Chronic Lowest NOAEC (21

- week reproduction test)

Terrestrial Animals

Mammals Acute Lowest LD 50 (single oral dose test)

Chronic Lowest NOAEC (two

- generation reproduction test)

Plants

Terrestrial non

- listed (monocots and dicots) Acute /Chronic Lowest EC 25 (seedling emergence and vegetative vigor)

Plants

Terrestrial listed (monocots and dicots) Acute /Chronic EC 0 5 or NOAEC associated with the lowest EC 25 (seedling emergence and vegetative vigor)

Plants Aquatic non

- listed (vascular and

non

- vascular

) Acute /Chronic Lowest EC 50

Plants Aquatic listed (vascular and algae) Acute/Chronic EC 05 or NOAEC associated with th e lowest EC 50



### III. ANALYSIS

A. Use Characterization

The proposed isofetamid registration being assessed here is for almond, lettuce, grapes, low

growing berries (including wet

- harvested cranberry) , rapeseed, and turf (commercial and residential)

. The refore, potential isofetamid use sites are found throughout much of the US.

Isofetamid i s applied as a foliar spray via ground or aerial equipment or via chemigation

. There

are two iso fetamid end

- use product s being proposed for registration in the Unit ed States: Isofetamid 400SC Agricultural Fungicide ( flowable suspension concentrate ; 36.0 % isofetamid ; the product does not contain any other active ingredients); and Isofetamid Turf F u ngicide (flowable suspension concentrate; 36.0% isofetamid; the product does not contain any other active ingredients)

. According to the proposed label s
, isofetamid can be applied at a single maximum application rate of 0.572 lb a.i./acre ( grapes ) and a yearly maximum application rate

of 3.65 lb a.i./acre ( turf

) (see Table 4 ). At most, it can be applied eight times per year (turf).

The minimum application interval is 7 or 14 days , depending on the proposed use

. For all of the proposed uses, except turf, isofetamid can be applied via chemigation and ground or aerial spray. Isofetamid can only be applied to turf via ground spray. For resistance management, both

### 23

proposed labels stipulate that no more than two sequential applications of isofetamid can be

made to use sites.

Table 3

. Application Informa tion from the Proposed Isofetamid Labels 1



### .

Crop Maximum

Individual Application

Rate
lb a.i./A Number of

Applications/

year Minimum

Application

Interval (days) Max Annual

Application

Rate i n lb a.i./A/year Application

Method Comments

Almond 0.442 4 2 7 wi th 14 days between

second and

third applications 1.77 Ground

Aerial Chemigation 3 - Do not apply

after first

cover.

- Do not make

more than two sequential applications of

isofetamid.

- Do not apply

the third application within 14 days

of the second applicat ion.

Lettuce (head and leaf) 0.3 20 2 14 0. 64 Ground

Aerial Chemigation 3 - on direct

seeded lettuce

make first application

after

emergence, thinning or prior to onset

of disease development; on transplanted

lettuce make application immediately

after
transp lanting or prior to

disease development;

make a second application if

conditions

continue to

favor disease development.

- Do not make

more than two sequential applications of

isofetamid.

Grapes (Crop Subgroup

13

- 07F) 4 0.572 3 2 7 with 28 days between

secon d and

third applications 1.72 Ground

Aerial Chemigation 3 - Do not make

more than two sequential applications of

isofetamid.

- Do not apply

the third application

### 24

Crop Maximum

Individual Application

Rate
lb a.i./A Number of

Applications/

year Minimum

Application

Interval (days) Max Annual

Application

Rate i n lb a.i./A/year Application

Method Comments

within 28 days

of the second application.

Low growing

berries (Crop Subgroup

13

- 07G) 5 0.4 00 3 applications

of 0.4 lb

a.i./acre and a

fourth application of

0.2 lb a.i./acre 2 14 with 28

days between

second and

third applications 1.4 Ground

Aerial Chemigation 3 - Do not make

more than two sequential applications of

isofetamid.

- Do not apply

the third application within 28 days

of the second application. Rapeseed (Canola) (Crop Subgroup 20A) 6 0.312 2 14 0.63 Ground

Aerial Chemigation 3 - Initiate

applications at

20

- 40% flowering or prior to disease development.

A second application may be made

near th e end of flowering.

- Do not make

more than two sequential applications of

isofetamid.

Turf 7 0.56 7 8 applications

are allowed at

0.452 lb a.i./acre/applic

ation

6 applications

are allowed at

0.56 7 lb a.i./acre/applic

ation in

addition to 1 application of

0.248 lb a.i./acre/applic

ation 8 14 days

between a one pair of applications, 28 days

between two pairs of applications 3.65 Ground

- Do not apply by air or through any type of irrigation
system

- Do not make

more than two sequential applications of

isof etamid.

- Do not apply

the next application of

isofetamid within 28 days of the previous

two
consecutive

isofetamid applications

1 There is 3.33 lb a.i. ( isofetamid ) in one gallon of the isofetamid products

. 2 This is not specified on the label; it is assumed by dividing the maximum application rate allowed/year by the maximum single application rate.

### 25 3 Only center pivot, motorized lateral move, traveling gun, solid set or portable (wheel move, side roll, end tow, or hand move) irrigation systems.

4 Inc ludes amur river grape. Gooseberry, grape (wine, table, raisin, and juice), kiwifruit (hardy), maypop, schisandra berry, and cultivars, varieties, and/or hybrids of these.

5 Includes bearberry, bilberry, blueberry (low bush), cloudberry, cranberry, lingon berry, muntries, partri d geberry, strawberry, and cultivars, varieties, and/or hybrids of these.

6 Includes borage, crambe, cuphea, echium, flax seed, gold of pleasure, hare’s ear mustard, lesquerella, lunaria, meadowfoam, milkweed, mustard seed, oil radish , poppy seed, rapeseed, sesame, sweet rocket, and cultivars, varieties, and/or hybrids of these.

7 Turf areas associated with golf courses (greens, tees and fairways), sod farms, seed farms, college and professional sports fields, residential and commercia l lawns. Application by homeowners to residential turf is prohibited.

8 Eight applications of 0.452 lb a.i./acre would result in the maximum annual rate of 3.65 lb a.i./acre. However, the maximum single application rate specified on the label is 0.567 lb a.i./acre. To fully account for uses at this higher single application rate, the number of applications per year is also reported in this table as six applications at the maximum single application rate in addition to a seventh application at a lower sin gle application rate of 0.2 48 lb

a.i./acre

.



### B. Exposure Characterization

1. Environmental Fate and Transport Characterization

a. Degradation

Isofetamid parent rapidly degrades as a result of aqueous photolysis, and degradation is also expected t o occur as a result of aerobic metabolism in soil and water

. In the aqueous photolysis study, isofetamid parent degraded to half its initial concentration within two days (1.4

- 1.8 days at pH 7). H alf

- lives calculated for isofetamid parent in the aerobi c soil metabolism studies ranged from 25 to 66 days, with comparable DT 50 

### s. H alf

- lives calculated for isofetamid parent

in the aerobic aqueous metabolism study ranged from 108 to 173 days.

Laboratory studies indicate that isofetamid parent is stable to hydrolysis and soil photolysis, and very persistent in anaerobic environments. No degradation of isofetamid parent occurred in the hydrolysis study. The half

- lives for soil photolysis ranged from 294 days for dry soil to 354 days

for moist soil. The ha lf

- life calculated for the anaerobic soil metabolism study was 572 days,

while the half

- lives calculated for anaerobic aquatic metabolism exceeded 1,000 days.

4HP and PPA formation was not observed in the aqueous photolysis study. Similar to isofetamid
parent, a erobic soil metabolism half

- lives for isofetamid and its residues of concern range from

25 to 65 days

, with comparable DT 50 

### s. The aerobic aquatic metabolism half

- lives range from

173 to 361 days. There is some uncertainty with regard to the aer obic metabolism half

- life

values calculated for isofetamid total toxic residues, as 4HP and PPA did not consistently reach

their maximum concentration and begin their subsequent decline by the end of the study period

. This is discussed further in the A PPE NDIX E Table E3 footnotes.

The soil photolysis half

- lives for isofetamid and its degradates ranged from 2 30 days for moist

soil to 296 days for dry soil. The half

- life calculated for the anaerobic soil metabolism study was

700 days, while the half

- live s calculated for anaerobic aquatic metabolism exceeded 1 ,000 days.

Based on these half

- life estimates, the modeling conducted in this assessment assumes that

isofetamid residues do not degrade in anaerobic environments.

### 26

Figure 3 in the Degradates section illustrates the proposed degradation pathways for isofetamid.

b. Mobility and Transport

Isofetamid parent and degradates are expected to be mobile to moderately mobile and may enter surface water through runoff and groundwater via leaching.

Isofetami d’s vapor pressure ( 4.4 ×10 - 11 

### Torr ) and Henry’s Law Constant ( 1.2×10 - 5 

### Pa

- m 3 

### /mol) indicate that volatilization is not a likely dissipation pathway. EPISuite v.4.1 estimates indicate that 4HP and PPA have vapor pressures lower than 9.98 x 10 - 7 

### torr and ar e therefore are not expected to volatilize under field conditions.

Adsorption/desorption testing for isofetamid was conducted on two US soils, two UK soils, and one Japanese soil (volcanic ash). For these five soils, the K d 

### values range f rom 6.59 to 19 .43 mL/g, while K F 

### values range from 6.64 to 20.79 with 1 

### /

n 

### values ranging from 0.873 to 0.991

. K
oc 

### values range from 281 to 615 mL/g

- organic carbon and K F oc 

### values range from 274 to 603 mL/g

organic carbon

. Results from this study are also summarized in A PPENDIX E
, Table E2

.

The adsorption/desorption study results indicate that soil sorption of isofetamid is influenced by soil organic carbon content. The coefficient of variance is lower for the K
oc 

### ’ s and K F oc 

### ’ s than for

the K d 

### ’ s and K F 

### ’ s indicating a correlation between isofetamid soil sorption and soil organic carbon content; however, a regression analysis of percent organic carbon versus K F 

### for the five soils did not find this relationship to be statistically significant. A dsorption and desorption b oth decreased slightly with increasing concentration in the study. Based on its K F oc 

### values, isofetamid would be classified as moderately mobile ( FAO, 2000 )

.

Both 4HP and PPA are expected to be mobile to moderately mobile in soil. Adsorption/desorption testing for 4HP was conducted on two US soils, two UK soils, and one Japanese soil (volcanic ash). For these five soils, the K F 

### values range from 3 .9 ( 1 

### /

n 

### = 0.93) to

8.58 mL/g ( 1 

### /

n 

### = 0.86) and the K F oc 

### values range from 110 to 3 55 mL/g

- organic carbon (MRID 49011980)

. Study results indicate that 4HP is more mobile than expected, as EPISuite v. 4.1 estimates that 4HP is moderately mobile to slightly mo bile with Koc values ranging from 766.4 to 2041 mL/g

- organic carbon. An adsorption/desorption study as not conducted for PPA, but

EPISuite v. 4.1 indicates that K
oc 

### values for PPA range from 121

- 180 mL/g

- organic carbon, making it mobile to moderately mobil e (FAO 2000).

Based on their K F oc 

### and K
oc 

### values, isofetamid and its degradates are expected to remain moderately mobile in aquatic environments rather than bind to sediment; however, this is dependent on the sediment’s organic matter content and the wa terbody’s pesticide load as a

result of runoff.

c. Field Studies

Several terrestrial field dissipation studies have been completed for isofetamid (MRIDs 49011993, 49018438, 49018441 , 49011992, 49018442)

. Results from these studies are

summarized in APPE NDIX E
, Table E4

. Three studies were co nducted on bare ground sites in

### 27

both the US (North Dakota, California) and Canada (Saskatchewan), and two studies were

conducte d on turf in the US (North Carolina, Arkansas). Several applications of isofetamid were

made at each site. The single application rate s in each study ranged between 5 00 and 800 g a.i./ha, which are comparable to the proposed application rate for isofetamid

.

Isofetamid parent d issipation half

- lives calculated for the whole soil profile ran ged from 38 to 47 days for four of the five studies. The half

- life for the Aberdeen, Saskatchewan study was 2 4 7 days, and this longer half

- life was attributed to a prolonged winter

. With the exception of the Saskatchewan study, DT 50 

### s in the terrestrial f ield dissipation studies were generally consistent

with the half

- lives calculated for the aerobic soil metabolism studies. However, the carryover percentages in some of the terrestrial field dissipation studies are indicative of higher persistence

in surf ace soils.

At all sites

, isofetamid parent residues were observed in the top 15 cm; however, isofetamid was observed up to a depth of 30 cm in the California and North Carolina studies. Carryover of

isofetamid residues at the end of the sampling period r anged from 3 to 46 %, indicating that it has the potential to accumulate in soil over multiple applications and from year to year.

4HP was a major degradate in the isofetamid aerobic soil metabolism studies and was therefore

monitored in the terrestrial fi eld dissipation studies. Although PPA was a major degradate in the aerobic aquatic metabolism study, PPA was not a major degradate in the aerobic soil metabolism

studies and was therefore not considered in the terrestrial field dissipation studies.

4HP w as observed in all but one field study in the top 0

- 15 cm of soil. The highest concentration of 4HP was 0.025 mg/kg

- soil (0

- 15 cm soil depth) observed in the Saskatchewan study. Y ear

- to

year accumulation of 4HP is not expected to occur, as no carryover o f 4HP occurred after approximately one year in the North Dakota, Saskatchewan, and California studies and 120 days in the Arkansas study. 38% carryover of 4HP was observed in the North Carolina study at 119 days after application (0

- 8 cm soil depth)

GPTC is an isofetamid metabolite produced only in plants. Because this metabolite was observed in residue field trials, it was also included in terrestrial field dissipation studies conducted for turf use sites. In the terrestrial field dissipation studies, it was observed at a maximum of 0.0045 ppm in the North Carolina study and below the limit of quantitation in all turf thatch collected in the Arkansas study.

c. Degradates

Identification information and structures for isofetamid degradates are summarized in

A PPENDIX E, Table E 1

. A s ummary of maximum amount of transformation products

observed in the laboratory fate studies is in APPENDIX E, Table E5

.

4HP and PPA are the isofetamid environmental degradates that have structural similarity to isofetamid par ent, and are both considered residues of concern in this assessment (aquatic)

. Additionally, the metabolite, GPTC, is also considered in the terrestrial assessment.

### 28

4HP was observed as a major degradate ( > 10% Applied Radioactivity (AR)) in the aerobic an d

an aerobic soil metabolism studies. 4HP reached a peak of 10.4% AR in one of the four soils studied for the aerobic test (a North Dakota sandy loam, day 30) and was a minor degradate (<10% AR) in the other three soils. 4HP reached a maximum of 10.3% AR in the soil studied for the anaerobic test (a North Dakota sandy loam, day 150). 4HP was also observed as a minor degradate in the soil photolysis, aerobic aquatic, and anaerobic aquatic studies, reaching maxima

of 3.7 %AR ( moist soil, day 21), 7.6 %AR ( S wiss Lake system, day 100) and 2.5 %AR ( Golden Lake system, day 365), respectively. As noted in the previous section, 4HP was observed in the terrestrial field dissipation studies in the 0

- 15 cm soil layers. 4HP formation was not observed in the hydrolys is or aqueous photolysis studies.

PPA was observed as a major degradate in the aerobic aquatic metabolism study, where it reached a peak of 11.8 %AR (Calwich Abbey system, day 100)

. PPA remained a minor degradate in the soil photolysis, aerobic soil me tabolism, anaerobic soil metabolism, and anaerobic aquatic metabolism studies, reaching maxima of 2.0 %AR ( moist soil, day 30), 4.4% AR ( a United King d om sand, day 30), 2.0 % AR ( a North Dakota sandy loam, day 150 ), and 3.3% AR ( Golden Lake system, day 365 ), respectively. PPA formation was not observed in as a result of hydrolysis

, aqueous photolysis , or photodegradation on dry soil.

Two other degradates, 2

- methyl

- 4

- (2

- propyloxy)benzoic acid ( IBA ) and an unidentified polar compound, were present at levels above 10% AR in the aqueous photolysis study. Even t hough IBA and the polar compound reached maxima of 80.8% AR (day 10) and 66.8% AR (day 20), respectively, they are not considered residues of concern in this assessment. IBA retains only the

benzene ri ng from the isofetamid parent, and is therefore considered less toxic than isofetamid parent. The study author was able to determine that high levels of polar compound in natural water consisted of several degradates accounting for less than 10% AR. In b uffered solution, the thiophene radiolabel had a “single component” that constituted 20 .9 % of the polar compound , or 13 .3 % AR ; for the benzene label, the polar compound was comprised of several compounds that were individually less than 10% AR. The molecu lar weight and structure of the polar compound components are unknown. Given this information and the correlation between IBA formation

and the polar compound components, it seems likely that the “single component” in particular and perhaps other componen ts of the polar compound contain only the thiophene ring and are therefore not structurally similar to isofetamid parent.

Minor degradates observed in the laboratory fate studies include 3

- methyl

- 2

- thiophenecarboxamide (3

- MTCAM) and 3

- methyl

- 2

- thiophene carboxylic acid ( 3

- MTCA) , which were observed at 5.5% AR (soil photolysis, day 14) and 2.4%AR (aerobic soil metabolism, day 59), respectively. 3

- MTCAM and 3

- MTCA retain only the thiophene ring from the original isofetamid structure, and are therefore not expected to be as toxic as parent

isofetamid.

U nknowns were observed in all laboratory fate studies

. Unknowns collectively exceeded 10%

AR for aerobic and anaerobic soil metabolism studies, as well as the aqueous photolysis study, but individually the un knowns were less than 10% AR.

### 29

GPTC was observed in magnitude of residue studies f or primary and rotational crops and, as previously mentioned, was observed in turf thatch collected in the terrestrial field dissipation

studies. GPTC was not observed in an y laboratory fate studies or in soil samples collected in the terrestrial field dissipation studies

.

Figure 3 shows the applicant’s depiction of the potential degradation pathways of isofetamid in soil, water, and air based on chemical structures and observed transformation products in the fate studies. This figure does not take into consideration the potential for numerous degradation products that may form from isofetamid degradates prior to mineralization.

Figure 3

. Potential Degradation Pathway of Isofetamid



### 2. Measures of Aquatic Exposure

a. Aquatic Exposure Modeling

The pesticide application assumptions used for modeling total toxic residues using the SWCC

are summariz ed in Table 4

, and the environmental fate properties used for SWCC modeling are

summarized in Table 5 . Application, environmental fate, and flooding assumptions used for

mo deling the wet

- harvested cranberry use in PFAM are summarized in Table 6

.

Detailed description, documentation, and direct links for running models used for estimating aquatic environmental concentrations can be found at : http://www.epa.gov/oppefed1/models/water/index.htm

### 30

Table 4

. S WCC: S ummary of application input parameters used in aquatic modeling for total toxic

residues

.

Model Input

Parameter Input Value and Unit
Source/

Comment

Turf Low

- Growing

Berries Subgroup Almonds Grapes Subgroup Lettuce Rapeseed Subgroup

SWCC

Scenarios 5 FL Turf

PA Turf CA Strawberry

(RLF) FL Strawberry 1
OR Berries (OP) CA

Almond 1 CA Grapes 1

CA Fruit 1
NY Grapes CA Lettuc e

FL Cabbage ND Canola

ND Wheat

OR Wheat (OP) See

Footnote 2.

Maximum Single Application

Rate 6

applications

of 0.635 kg

a

. i

. /ha

1 application

of 0. 278 kg

a

. i

. /ha 0.4 48 kg ai/ha 0.495 kg

ai/ha 0.641 kg ai/ha 0.358 kg ai/ha 0.349 kg ai/ha See

Footnote 2.

Maximum

Number of Applications 7 3 applications of 0.448 kg a.i./ha

and a fourth application of 0.224 kg a.i./ha 4 3 2 2 See

Footnote 2.

Method of Application Ground Aerial and

Ground Aerial and

Airblast Aerial and

Ground (NY Grapes) Aerial Aerial See

Fo otnote 3.

Application Efficiency 0.99 0.95 and

0.99 0.95 and

0.99 0.95 and

0.99 0.95 0.95 December

2013

EFED Spray Drift

Guidance

Spray Drift

Fraction 0.062 0.125 and

0.062 0.125 and

0.042 0.125 and

0.062 0.125 0.125 December

2013

EFED Spray Drift

Gui dance

Type of Application Foliar See

Footnote 2

Initial Date of Application 5
(month/day) FL Turf: 2/1

PA Turf: 4/1 CA Strawberry

(RLF): 1/1

FL Straw b erry: 10/1

OR Berries (OP):

4/1 CA

Almond:

1/16 CA Grapes:

2/1

CA Fruit:

1/16

NY Grapes:

6/1 CA Lett uce:

2/16

FL Cabbage:

10/16 ND Canola

and

ND Wheat:

5/16

OR Wheat (OP): 9/1 See

Footnote 4.

Minimum

Interval

between Applications 14 days

between a one pair of applications, 28 days

between two pairs of applications 14 days with 28

days between the

se cond and third application 7 days

with 14 days

between

the second

and third application 7 days with

28 days

between the

second and

third application 14 days 14 days See

Footnote 2.

1 Crop scenario includes irrigation

2 Proposed End

- Use Labels (EPA File Sy mbols 71512

- EE and 71512

- EG)

3 The label allows ground application and chemigation use of isofetamid on Turf (except chemigation)

, Low

- growing Berries Subgroup, Almonds, Grapes, Lettuce, and Rapeseed Subgroup. Only Aerial was considered for Lettuce and Ra peseed Subgroup, as model results for the aerial applications are expected to be protective of ground and chemigation applications.

### 31 4 Initial application dates were assumed to occur on the crop emergence dates listed in scenario metadata, with the exceptio n of Rapeseed Subgroup. For Rapeseed Subgroup, the proposed label states that applications should be initiated at 20

- 40% flowering or prior to disease development. Therefore, the Rapeseed Subgroup application date is estimated to be 60 days after crop em ergence.

5 With regard to SWCC scenario names, RLF is the acronym for Red

- Legged Frog and OP is the acronym for Organophosphate.



### Table 5

. S WCC: s ummary of environmental fate input parameters used in aquatic modeling for total

toxi c residues of Isofetamid

. Model Input Parameter Input Value and Unit Source/Comments

Foliar Half

- life Stable Assumption based on Input Parameter Guidance

Soil Partition Coefficient K F oc 4 91 mL/g

oc MRID 49011979

Mean of isofetamid K F oc's calculated for f ive

soils 2

. Hydrolysis Stable MRID 49011976

Aerobic Soil Metabolism Half

life (20°C) 66.62 days 1 MRIDs 49011981 and 49011982 The 90th percentile confidence bound on the

mean of four soil half

- lives.

Anaerobic Soil Metabolism Half

life (20°C) Stable 1 M RID 49011985

Aerobic Aquatic Metabolism

Half

- life (20°C) 556 .30 days 1 MRID 49011986 The 90th percentile confidence bound on the mean of two test system half

- lives.

Anaerobic Aquatic Metabolism

Half

- life (20°C) Stable 1 MRID 49011987

Aqueous Photolysis

H alf

- life 1.8 days MRID 49011977 The longer half

- life of the two half

- lives calculated in the study. Aqueous Photolysis did

not produce 4HP and PPA

Vapor pressure (25°C) 4.4 ×10

- 11 Torr MRID 49011905 Vapor pressure for parent isofetamid
Solubility in w ater (20 o C) 5.33 mg/L MRID 49011905 Solubility for parent isofetamid
Molecular Weight 359.48 g/mole Molecular Weight of parent isofetamid

1 Based on half

- lives inclusive of isofetamid parent and degradates 4HP and PPA.

2 Based on data for isofetamid p arent ; although this K F oc was expected to result in lower EECs than the K

oc s for

4HP and PPA reported in this assessment, a sensitivity analysis demonstrated that using the K F oc for isofetamid parent did not reduce EECs. Additionally, the K F oc for isofeta mid parent is based on more reliable data than the reported K

oc s for 4HP and PPA.



### Table 6

. PFAM i nput parameters for i sofetamid total toxic residues for u se on wet

- h arvested c ranberry

. Input Parameter Value Comments Source

Water column half

- life (d) at

20 °C 556.3 1 Represents the 90th percentile

confidence bound on the mean of two test system half

- lives. MRID 49011986

Benthic Compartment

half

- life at 20 °C (d) 100,000 (default) 1 Represents no biodegradation under

anaerobic condi tions. MRID 49011985

Unflooded half

- life at 20 °C (d) 66.62 1 Represents the 90th percentile

confidence bound on the mean of

four soil half

- lives. MRIDs 49011981

and 49011982

### 32

Input Parameter Value Comments Source

Aqueous photolysis half

life at 40° Latitude (d) 1.8 The longer half

- life of the two half

lives calculated in the study. Aqueous Photolysis did not produce

4HP and PPA MRID 49011977

Hydrolysis half

- life (d) 100,000 (default) Represents no hydrolysis. MRID 49011976

Organic Carbon Partition Coefficient (K OC ) (L/kg OC ) 180 For parent, the mean of isofetamid

K F oc's calculated for five soils. For
TTR, lowest K

oc value for TTR in all submitted data and EpiSuite 4.1 estimates using the K

ow method 2 . 180 L/kg OC is the estimate for PPA. Parent: MRID

49011979

TTR: Estimated

Molecular weight (g/mol) 359.48 Product chemistry data (Calculated)

Vapor pressure at 20 °C (torr) 4.4 x 10 - 11 Product chemistry data MRID 49011905

Water solubility at 20 °C (mg/L) 5.33 Product chemistry data MRID 49011905

Heat of Henry at 25 °C (J/mol) 54872.4 Equals 8.314 × enthalpy of salvation (6,600 K) estimated by HenryWin

v3.20. (Calculated)

Application Date & Rate (kg a.i./ha) 5/31: 0.448

6/14: 0.448

7/12: 0.448

7/26: 0.224 Maximum proposed single application rate and maximum number of applications. Minimum

re

- application intervals (14 days) applied, in addition to 28 day interval

for label

- specified resistance

management measures. Proposed label and likely application

timeframes for
Wisconsin, New Jersey, and

Massachusetts (BEAD)
Slow Release (1/day) 0 for ea ch application Estimated (Estimated)

Meteorology data location (metfile code) La Crosse, WI (w14920) Atlantic City, NJ (w14734) Boston, MA (w14739) Meteorological file for a location near cranberry agriculture. CEAM, 2011

Flood Events Starting on 10/1, 2 events 3 days apart Estimated (Estimated)

Fill level (m) 10/1: 0.305

10/4: 0 Minimum flood depth and release depth. (Estimated)

Wier level (m) 10/1: 0.458

10/4: 0 Estimated wier heights. (Estimated)

Min. Level (m) 0 for each event Estimated minimum wat er level (Estimated)
Turn Over (1/day) 0 for each event Estimated turn over (Estimated)

Crop zero height

reference May 1 Estimated value (Estimated)

Days from zero to full height 120 Estimated value (Estimated)

Days from zero height to

removal 153 Esti mated value (Estimated)

Max. aerial coverage 0.2 Value from OR berries PE scenario (Estimated)

### 33

Input Parameter Value Comments Source

Area of application (m 2 ) 100,000 Parent: Represents 10x the area of the

Index Reservoir TTR: Represents 10 ha application

area that drains to the Farm Pond (Ca lculated)

Area of watershed (m 2 ) 0 Parent: Area of the Index Reservoir

watershed TTR: No surrounding watershed

considered USEPA, 2010 a

Watershed curve number 84 Value for fallow conditions in OR

berries and other PE scenarios (Estimated)

Base flow (m 3 /s ec) 0 Value based on conceptual models

for Index Reservoir and Farm Pond (Estimated)

1 Based on half

- lives inclusive of isofetamid parent and degradates 4HP and PPA.

2 491 L/kg OC was used for surface water modeling using the SWCC because a sensitivity ana lysis demonstrated that using the K Foc for isofetamid parent did not reduce EECs in the SWCC. This is not the case for PFAM.



### The aquatic EECs for the various scenarios and application practices are listed Table 7

. See
APPENDIX B for output from the SWCC scenario resulting in the highest EECs for non

flooded agricultural crops , the CA Stra wberry (RLF) aerial application , as well as for output

from the PFAM scenario resulting in the highest EECs for wet

- harvested cranberry (which were the highest EECs over all), LaCrosse, Wisconsin. For non

- flooded agricultural crops, p eak 1

- in

10 year EECs ranged from 6.36

- 30.2 μg/L. For wet

- harvested cranberry, peak 1

- in

- 10 year EECs ranged from 158

- 205 μg/L

.

Table 7

. Calculated EECs for the prop osed use s of i sofetamid based on proposed application rates and

intervals

.

Crop/Site Crop Scenario

or Weather File Application

Method Initial

Application

Date Peak 1

-

in

- 10

Year

EEC 21

- day

1

- in

- 10

Year

EEC 60

- day

1

- in

- 10

Year

EEC
μg/L

Turf FLturfSTD Ground 1

- Feb 13.2 12.1 11.2

PAturfSTD 1

- Apr 20.3 18.7 18

Low

- growing Berries (Crop Subgroup 13

- 07G)
except Wet

Harvested Cranberry CAStrawberry

noplasticRLF_V2 Aerial 1

- Jan 30.2 29.1 27.3

Ground 26.3 25.4 23.8

FLstrawberry_ WirrigSTD Aerial 1

- Oct 19.3 17.6 16.3

Ground 16.3 14.5 13.1

ORberriesOP Aerial 1

- Apr 11.4 10.7 10

Ground 6.36 6.02 5.59

Wet

- Harvested Cranberry LaCrosse, WI 20% Aerial

coverage 31

- May 205 200 197

Atlantic City, NJ 158 151 146

Bost on, MA 167 160 153

Almond Caalmond_WirrigSTD Aerial 16

- Jan 21.2 19.2 16.8

Airblast 12.7 11.4 9.81

Grapes (Crop CAgrapes_WirrigSTD Aerial 1

- Feb 15.5 14.1 13.3

### 34

Crop/Site Crop Scenario

or Weather File Application

Method Initial

Application

Date Peak 1

-

in

- 10

Year

EEC 21

- day

1

- in

- 10

Year

EEC 60

- day

1

- in

- 10

Year

EEC
μg/L
Subgroup 13

- 07F) Ground 9.62 8.67 8.27

CAfruit_WirrigSTD Aerial 16

- Jan 16.7 15 .6 14.5

Ground 10.8 10.1 9.56

NYGrapesSTD Aerial 1

- Jun 26 24.6 23.4

Ground 19.8 18.6 18.1

Lettuce (head and leaf) CA Lettuce Aerial 16

- Feb 14.5 13.1 11.1

FL Cabbage 16

- Oct 10.8 9.6 10.8

Rapeseed (Canola) (Crop Subgroup 20A) ND Canol a

Aerial 16

- May 10.9 10.1 9.5

ND Wheat 16

- May 10.7 10.1 9.4

OR Wheat (OP) 1

- Sep 9.4 9 8.6



### b. Aquatic Exposure Monitoring and Field Data

Isofetamid is a new chemical, for which no monitoring data are available.

3. Measures of Terrestrial Exposure

a. Terrestrial Exposure Modeling

The application method for the proposed isofetamid use s is limited to foliar spray via ground equipment , aerial equipment (except turf), and via chemigation (except turf) . T herefore, for th is terrestrial exposure assessment, we consider only foliar applications.

We derive terrestrial estimated environmental concentrations ( Table s 8 and 9 ) for animals and

isofetamid using the maximum annual application rate s and the maximum proposed single application rates for the plant analyses . Terrestrial exposure estimates for avian and mammalian

risk assessments were derived us ing the T

- REX model (version 1.5.2

, June 6, 2013 ). The default

35

- day foliar half

- life value was used for modeling EECs on t errestrial food items. A 35

- day

half

- life is expected to incorporate (and be protective of) any transformation product that is not
more toxic than the parent ( i.e ., 4HP, PPA, and GPTC)

. A complete description of the input parameters and output is contain ed in A PPENDIX C

.

### 35

Table 8

. EECs on Potential Food I tems Following Label

- Specified Applications of Isofetamid U sing the

T

- REX M odel (ppm ) (the default 35

- day foliar half

- life was used in modeling)

.

USE DIETARY

- BASED

EECs KENAG A

VALUES Upper Bound (ppm)

Almond (4 applications of 0.442 lb a.i./acre; 7

- day application interval with 14 days between the

2 nd and 3 rd applications) Short Grass 329.34

Tall Grass 150.95

Broadleaf Plants 185.25

Fruits/Pods/Seeds 20.58 Arthropods 128.99

Lettuce (2 applications of 0.320 lb a.i./acre; 14

- day application interval) Short Grass 1 35

Tall Grass 62

Broadleaf Plants 76

Fruits/Pods/Seeds 8 Arthropods 53
Grapes (3 applications of 0.572 lb a.i./acre; 7

- day application

interval with 28 days between 2 nd

and 3 rd applications) Short Grass 284.77

Tall Grass 130.52

Broadleaf Plants 160.18

Fruits/Pods/Seeds 17.80 Arthropods 111.53 Low growing berries ( 3 applications of 0.40 lb a.i./acre and 1 application of 0.20 lb

a.i./acre ; 14

- da y application interval with 28 days between 2 nd

and 3 rd applications) Short Grass 194.21

Tall Grass 89.01

Broadleaf Plants 109.24

Fruits/Pods/Seeds 12.14

Arthropods 76.07

Rapeseed (2 application of 0.312 lb a.i./acre; 14

- day application interval) Short Grass 140

Tall Grass 64

Broadleaf Plants 79

Fruits/Pods/Seeds 9 Arthropods 55

Turf (6.4 applications of 0.567 lb a.i./acre; 14

- day interval between two sequential applications, 28 days between pairs of applications ) 1 Short Grass 388.65

Tal l Grass 178.13

Broadleaf Plants 218.62

Fruits/Pods/Seeds 24.29

Arthropods 152.22

1 T he ‘6.4’ applications is calculated by dividing the maximum annual application rate by the single maximum application rate. This was modeled using 6 applications at 0.567 lb a.i./acre and 1 application at 0.227 lb a.i./acre.



### Exposure to upland and wetland plants is estim ated using the TerrPlant (v1.2.2 ) screening model. TerrPlant estimates potential exposure from a single application using default assumptions for

r unoff (1% given solubility is <10 ppm) and spray drift (1% given a ground application of a liquid formulation ; and 5% for aerial applications ) ( Table 9 ). Se e APPENDIX D for more information.

### 36

Table 9

. EECs on Plants Following Lab el

- Specified Ground and Aerial Applications of

Isofetamid Using the TerrPlant M odel (lb a

. i

. /A)

.

USE RATE SPRAY

DRIFT ONLY (lb a.i./A) TOTAL

FOR DRY

AREAS (lb a.i./A) TOTAL FOR

SEMI

AQUATIC

AREAS (lb a.i./A) Almond (ground) 0.442 lb a.i./acre 0.004 0.009 0.049
Almond (aerial) 0.442 lb a.i./acre 0.022 0.027 0.066
Lettuce (ground) 0.320 lb a.i./acre 0.00 3 0.00 6 0.03 5
Lettuce (aerial) 0.320 lb a.i./acre 0.01 6 0.0 19 0.0 48
Grapes (ground) 0.572 lb a.i./acre 0.006 0.011 0.063
Grapes (aerial) 0.572 lb a.i./a cre 0.029 0.034 0.086
Low growing berries (ground) 0.4 00 lb a.i./acre 0.004 0.008 0.04 4
Low growing berries (aerial) 0.4 00 lb a.i./acre 0 .020 0.02 4 0.06 0
Rapeseed (ground) 0.312 lb a.i./acre 0.003 0.006 0.034
Rapeseed (aerial) 0.312 lb a.i./acre 0.016 0.019 0.047
Turf (ground) 0.567 lb a.i./acre 0.006 0.011 0.062



### C. Ecological Effects Characterization

Based on the available data, isofetamid is classified as moderately toxic to freshwater fish and invertebrates, no more than moderately toxic to estuarine/marine fish, highly toxic to estuarine/marine invertebrates (specifically oysters)

, and practically non

- toxic to birds, mammals, and terrestrial invertebrates on an acute exposure basis

. Chronic exposure resulted in

reduced growth in freshwater fish at 0.086 mg a.i./L

. In freshwater invertebrates, isofetamid

resulted in effect s (reduced length) at all of the concentrations tested, resulting in a NOAEC

value of <0.39 mg a.i./L. Chronic toxicity data are not available for est uarine/marine fish or invertebrates

. Chronic exposure in birds resulted in slightly reduced egg shell thickness at 928 mg a.i./kg

- diet in mallard ducks (0.324 mm versus 0.345 mm in the controls) (NOAEC = 276 mg a.i./kg

- diet). In mammals, c hronic exposure resulted in reduced body weights and reduced weight gain and slightly delayed sex maturation in females (NOAEL = 1,000 mg a.i./kg

- diet )

.

For terrestrial plants, t he most sensitive monocot in the seedling emergence study was ryegrass based on dry weight , with NOAEC and EC 25 

### values of 83.675 and 576 lb a

. i

. /A, respectively. The most sensitive dicot was tomato, based on dry weight, with NOAEC and EC 25 

### values of

2.615 and 10.3 lb a

. i

. /A, respectively. In the vegetative vigor study, the most sensitive mono cot
was determined to be corn with NOAEC and EC 25 

### values of 1.07 and 1.3 lb a

. i

. /A, respectively. The most sensitive dicot was determined to be soybean with NOAEC and EC 25 

### values of 1.07

and 1.26 lb a

. i

. /A.

The most sensitive aquatic plant tested was the marine diatom Skeletonema costatu m with an

EC 50 

### value of >4.1 mg a.i./L and a NOAEC value of 4.1 mg a.i./L based on a reduction in yield

. See Table 10 for the most sensitive measurement endpoints considered in this assessment for estimating risks to non

- target taxa

.

### 37

Table 10

. Summary of S pecific A ssessment Endpoints for Animals and Plants Considered in this

A ssessment for Estimating Risks to Non

- target Taxa

. TAXA MEASURE OF EFFECT Survival, growth

and/ or reproduction of: Species Toxicity Endpoint MRID/ Study

Classification

Freshwater Fish Acute

Oncorhynchus mykiss

Rainbow trout LC 50 = 2.27 mg a.i. /L Mortality 49018402 / Acceptable

Chronic Pimephales promelas

Fathead minnow NOAEC = 0.086 mg a.i./L Red uced growth 49018406/ Acceptable

Freshwater

Invertebrates Acute

Daphnia magna

Waterflea EC 50 = 4.7 mg a.i. /L Mortality/ immobility 490119 9 5/ Acceptable

Chronic

Daphnia magna

Waterflea NOAEC < 0. 39 mg a.i. /L

LOAEC = 0.39 mg a.i./L Reduced offspring

production; reduced parental growth 49018405/

Supplemental

Estuarine/Marine

Fish Acute

Cyprinodon variegates Sheepshead minnow LC 50 > 2.8 mg a.i. ./L None (no effects at the highest

concent ration tested) 49018404/ Acceptable

Chronic

No data submitted N/A N/A N/A

Estuarine/Marine

Invertebrates Acute

Crassostrea virginica Eastern oyster EC 50 = 0.44 mg a.i./L Shell deposition 49011997/ Acceptable Americamysis bahi a Mysid LC 50 = 1.5 1 mg a.i. /L Mortality 49011998/ Acceptable

Chronic

Not Available

Aquatic Plants Acute

Lemna gibba

Duckweed EC 50 >4.9 mg a.i./L None (no effects at the highest concentration tested) 49018417/ Acceptable

Listed

Lemna gibba

Duckweed NOAEC = 4.9 mg a.i./L None (no effects at

the highest concentration tested) 49018417/ Acceptable

Acute

Skeletonema

costatum
Marine diatom EC 50 = >4.1 mg a.i./L Reduction in yield 49018421/ Supplemental

Listed

Skeletonema

co statum
Marine diatom NOAEC = 4.1 mg

a.i./L Reduction in yield 49018421/ Supplemental

Birds Acute

/Sub

- Acute

Colinus virginianus

Northern bobwhite quail LC 50 = >5,180 mg a.i. /kg

- diet ; LD 50 = >2,000 mg

a.i. /kg

- bw Mortality 49018411/ Acceptable ; 49018408/ Acceptable

### 38

TAXA MEASURE OF EFFECT Survival, growth

and/ or reproduction of: Species Toxicity Endpoint MRID/ Study

Classification

Chronic Colinus virginianus

Northern bobwhite quail NOAEC = 276 mg a.i./kg

- diet No effects noted 49018413/ Acceptable

Mammals Acute

Rattus Norvegicus Norway Rat LD 50 >2,000 mg a.i./kg

- bw No eff ects noted 49011907/

Acceptable

Chronic

Rattus Norvegicus Norway Rat NOAEL = 1,000 mg a.i./kg

- diet [65.8 mg/kg

- bw/day(males); 76.6 mg/kg

- bw/day (females)] Based on decreased

pup weight and weight gain (both generations) and slight ly delayed sex

maturation in F 1 females. 49011940/

Acceptable

Terrestrial

Invertebrates Acute

Apis mellifera Honey Bee LD 50 = 100 μg a.i. /bee (contact)

L D 50 > 30 μg a.i. /bee (oral) Mortality 49018426/ Acceptable

Terrestrial Plants Non

- listed (Seedling Emergence)

Monocot : corn ( Zea

mays ) ; onion (

Allium

cepa ) ; ryegrass ( Lolium perenne ) ; and wheat, ( Triticum

aestivum ) EC 25 = 576 lb a.i./acre Reduced dry weight 49018415/ Acceptable

Dicot : sugarbee t ( Beta vulgaris) ; radish ( Raphanus sativus) ; lettuce ( Lactuca sativa ) ; flax ( Linum usitatissimum) ; soybean ( Glycine

max ) ; and tomato ( Lycopersicon

esculentum ) EC 25 = 10.3 lb a.i./acre Reduced dry weight 49018415/Acce ptable

Listed (Seedling Emergence)

Monocot : corn ( Zea

mays ) ; and wheat

, ( Triticum aestivum ) NOAEC = 83.7

a.i./acre Reduced dry weight 49018415/Acce ptable

Dicot : sugarbee t ( Beta vulgaris) ; radish ( Raphanus sativus) ; lettuce ( Lactuca sativa ) ; flax ( Linum usitatissimum) ; soybean ( Glycine NOAEC = 2.6 lb

a.i./ acre Reduced dry weight 49018415/Acce ptable

### 39

TAXA MEASURE OF EFFECT Survival, growth

and/ or reproduction of: Species Toxicity Endpoint MRID/ Study

Classification

max ) ; and tomato ( Lycopersicon
esculen tum )

Non

- listed (Vegetative vigor)

Monocot : corn ( Zea

mays ) ; onion (

Allium

cepa ) ; ryegrass ( Lolium perenne ), and wheat, ( Triticum

aestivum ) EC 25 = 1.3 lbs a.i./ acre Reduced dry weight 49018416/Acce ptable

Dicot : sugarbeet ( Beta vulgaris) ; radish ( Raphanus sativus) ; lettuce ( Lactuca sativa ); flax ( Linum usitatissimum) ; soybean ( Glycine

max ) ; and tomato ( Lycopersicon

esculentum ) EC 25 = 1.3 lbs a.i./ acre Reduced dry weight 49018416/Acce

p table

Listed (Vegetative vigor)

Monocot : corn ( Zea

mays ) ; onion (

Allium

cepa ) ; ryegrass ( Lolium perenne ), and wheat, ( Triticum

aestivum ) NOAEC = 1.1 lbs

a.i./A Reduced dry weight 49018416/Acce ptable

Dicot : sugarbeet ( Beta vulgaris) ; radish ( Raphanus sativus) ; lettuce ( Lactuca sativa ); flax ( Linum usitatissimum) ; soybean ( Glycine

max ) ; and tomato ( Lycopersicon

esculentum ) NOAEC = 1.1 lbs

a.i./A Reduced dry weight 49018416/Acce ptable

1 N/A = not applicable



### 1. Aquatic Effects Characterization

a. Aquatic Animals

Toxicity s tudies were sub mitted for four freshwater fish, i.e

., rainbow trout ( Oncorhy n chus mykiss ), bluegill sunfish ( Lepomis macrochirus ), common carp ( Cyprinus carpio ), and fathead minnow ( Pimephales promelas ); two freshwater invert ebrate s, i.e ., waterfleas ( Daphnia magna ) and chironomids ( Chironomus riparius ); one estuarine/marine fish

, i.e

., sheepshead minnow

### 40

( Cyprinodon variegates ), one estuarine/marine mollusk

, i.e

., Eastern oyster ( Crassostrea virginica ), and one estuarine/marin e crustacean

, i.e

., mysid shrimp ( Americamysis bahia ), all exposed to technical grade isofetamid (see Table 1 1 )

. Acute toxici ty data for one freshwater fish (common carp) is also available for the formulated product, 400SC.

Table 11

. Submitted Toxicity Data for Isofetamid and Aquatic Animals.

TAXON ENDPOINT FORMULATION MRID STUDY

CLASS

IFICATION COMMENTS

FRESHWATER FISH

Acute

Rainbow trout ( Oncorhynchus mykiss ) 96

- hr LC 50 2.27

mg a.i./L TGAI ( 96.7 % a.i.) 49018402 Acceptable NOAE C = 0.528 based on mortality and sublethal

effects ; a probit slope could

not be calculated Bluegill sunfish ( Lepomis

macrochirus ) 96

- hr LC 50 > 3.2

mg a.i./L TGAI ( 96.7 % a.i.) 49018403 Acceptable NOAEC = 3.2 mg a.i./L (the highest concentration tested)

Co mmon carp ( Cyprinus carpio ) 96

- hr LC 50 > 6.8

mg a.i./L TGAI (96.7% a.i.) 49011999 Acceptable NOAEC = 2.4 mg a.i./L based

on sublethal effects

Common carp ( Cyprinus carpio ) 96

- hr LC 50 = 35

mg a.i./L 400SC (36.5% a.i.) 49018 401 Supplemental (qualitative) NO AEC < 5.5 mg a.i./L based

on sublethal effects); classified as supplemental due to precipitate noted in all test

concentrations

Chronic

Fathead

minnow ( Pimephales promelas ) NOAEC: 0.086

mg a

. i

. /L

LOAEC: 0.18

mg a

. i

. /L TGAI ( 96.7 % a.i.) 49018406 Accept able The LOAEC is based on reduced length.

ESTUARINE/MARINE FISH

Acute Sheepshead

minnow ( Cyprinodon variegatus ) 96

- hr LC 50 > 2.8

mg a.i./L TGAI ( 96.7 % a.i.) 49018404 Acceptable The NOAEC was 2.8 mg a.i./L (the highest concentration tested)

Chronic

No data available

FRESHWATER INVERTEBRATES

Acute

Water flea ( Daphnia

magna ) 48

- hr EC 50 =

4.7 mg a.i./L TGAI ( 96.7 % a.i.) 49011995 Acceptable NOAEC = 3.5 mg a.i./L based

on sublethal effects ; probit slope = 10.8

Chronic

Water flea ( Daphnia

magna ) NOAEC < 0.39

mg a.i./L

LOAEC = 0.39 mg a.i.?l TGAI ( 96.7 % a.i.) 49018405 Supplemental The most sensitive endpoint was reduced length (at all test concentrations); the study is supplemental because it failed

to establish a NOAEC

Chironomid ( Chironomus riparius ) 28

- day

NOAEC = 483 mg a.i./kg TGAI (99.9% a.i.) 49018407 Supplemental (qualitative) LOAEC is based on reduced

emergence success; classified as supplemental because no

### 41

TAXON ENDPOINT FORMULATION MRID STUDY

CLASS

IFICATION COMMENTS

(sediment)

LOAEC = 993 mg a.i./kg (sediment) data on growth endpoints were provided and the concentrations of the pore water or overlying water were not provided.

ESTUARINE/MARINE INVERTEBRATES Mysid ( Americamysis

bahia ) 96

- hr LC 50 =

1.5 1 mg a.i./L TGAI ( 96.7 % a.i.) 49011998 Acceptable NOAEC < 0.31 mg a.i./L based on mortality.

Eastern oyster ( Crassostrea virginica ) 96

- hr EC 50 =

0.44 mg a.i./L (shell deposition) TGAI ( 96.7 % a.i.) 49011997 Acceptable NOAEC = 0.030 mg a.i./L based on shell deposition

Chronic

No data available



### Freshwater Fish:

Acute toxicity data for isofetamid have been subm itted for the following freshwater fish species: Rainbow trout ( Oncorhynchus mykiss )

, b luegill sunfish ( Lepomis macrochirus ) , and c ommon carp ( Cyprinus carpio ) . The rainbow trout study, conducted with TGAI, resulted in a 96

- hr LC 50 

### of 2.27 mg a.i./L (mea n

- measured) (MRID 49018402). There was 10, 40, and 90% mortality in

the mean

- measured 1.07, 2.18, and 3.82 mg a.i./L treatment groups, respectively. There were no mortalities in the controls or 0.130, 0.238, or 0.528 mg a.i./L treatment groups. Subletha l effects included hyperventilation, loss of coordination, fish overturned and immobile at the base of the tank, increase in mucus production, darkened coloration, and quiescence at all treatment levels ≥ 1.07 mg a.i./L. The LOAEC and N OAEC values in this study were 1.07 mg a.i./L and 0.528 mg

a.i./L based on sublethal effects and mortality ( Table 11 1 )

.

In the acute bluegill sunfish study with isofetamid (TGAI), the 96

- hr LC 50 

### is > 3.2 mg a.i./L (mean

- measured), t he highest concentration tested due to the limit of solubility (MRID 49018403). There was 5, 5, 0, 10, 0, and 5% mortality in the solvent control, 0.28, 0.60, 1.2, 2.1, and 3.2 mg a.i./L mean

- measured treatment groups, respectively. The mortalities were not concentration dependent or associated with signs of toxicity, therefore, they were not considered

treatment

- related. There were no sublethal effects noted in the study. There fore, there were no compound

- related effects on survival or sublethal effect s noted in the study, resulting in a NOAEC of 3.2 mg a.i./L.

Acute toxicity data for the common carp are available for TGAI and the 400SC formulation. In the TGAI study the 96

- hr LC 50 

### is >6.8 mg a.i./L (MRID 49011999). There was one mortality in the hig hest treatment group ( i.e ., 6.8 mg a.i./L, mean

- measured). There were no other mortalities noted in the study. At concentrations ≥3.4 mg a.i./L, the following sublethal effects were noted: fish swimming at the surface, loss of equilibrium, curved bodies , exophthalmia, hemorrhaging, and reduced activity. This resulted in a NOAEC and LOAEC of 2.4 and 3.4 mg a.i./L, respectively, based on sublethal effects. In the study conducted with the formulated product

### 42

(400SC, 36.5% a.i.), the LC 50 

### for common carp is 35 mg a.i./L (MRID 49018401). There were sublethal effects noted in all concentrations tested (the lowest concentration tested was 5.5 mg a.i./L, mean

- measured), so a NOAEC could not be determined. Sublethal effects at the lowest

concentration tested in cluded muscle spasms. Other sublethal effects noted in the study included loss of equilibrium, curved body, hemorrhage, light body color, and rapid respiration. This study was classified as supplemental (qualitative) due to uncertainty regarding the conc entration of a.i. the fish were actually exposed to during the study (because of the presence of precipitate at all test concentrations).

A freshwater fish early life stage on fathead minnow ( Pimephales promelas ) and isofetamid (TGAI) resulted in N OAEC an d L OAEC values of 0.086 and 0.18 mg a.i./ L, respectively (MRID

49018406 ). The LOAEC was based on reduced growth (length), the most sensitive endpoint. Although the percent of the reduction in length was small compared to the nega tive control (0.39%), it was statistically significant and the reductions in length followed a dose

- response trend

. There were no significant effects on hatching success or larval surviv al at any

concentration tested. This is the only chronic study available for fish and isofeta mid. Because there are currently no acute data available for the species used in the chronic study ( i.e ., fathead minnow), there is uncertainty regarding the chronic endpoint ( i.e ., it is not clear whether or not

fathead minnow ar e more or less sensitive than rainbow trout

– the most sensitive freshwater fish tested on an acute exposure

- basis).

Based on the available data, an LC 50 

### of 2.27 mg a.i./L and a NOAEC of 0.086 mg a.i./L will be

used to assess risks to freshwater fish from acute and chronic exposu re , respectively, to
isofetamid

.

Estuarine/Marine Fish:

Acute toxicity data for estuarine/marine fish and isofetamid are available for one species, i.e

., sheepshead minnow ( Cyprinodon variegatus ). Th e sheepshead minnow study resulted in a 96

- hr

LC 50 

### v alue >2.8 mg a.i./L (mean

- measured) (the highest concentration tested due to the solubility limit of the compound) (MRID 49018404). There were no mortalities or sublethal effects noted in the study, therefore, the NOAEC is 2.8 mg a.i./L. There are curren tly no chronic toxicity data available for estuarine/marine fish. Because estuarine/marine fish do not appear more sensitive than freshwater fish based on an acute exposure

- basis, the chronic endpoint from freshwater fish ( i.e ., NOAEC of 0.086 mg a.i./L) is expected to be protective of estuarine/marine species. Therefore, a NOAEC value of 0.086 mg a.i./L will be used to assess risks to estuarine/marine fish from chronic exposure to isofetamid.

Freshwater Invertebrates :

Acute toxicity data for freshw ater invertebrates and isofetamid are available for one species, i.e

., waterfleas ( Daphnia magna ). The waterflea study with TGAI resulted in a 48

- hr EC 50 

### value of

4.7 mg a.i./L (mean

- measured) , with a probit slope of 10.8 (MRID 4901 1995 ). Sublethal effec ts included lethargy observed at concentrations ≥4.6 mg a.i./L resulting in a NOAEC value of 3.5 mg a.i./L.

### 43

A 21

- chronic toxicity test was conducted with waterfleas and isofetamid (TGAI) (MRID 49018405). There were statistically significant treatment

- re lated effects on terminal body lengths at all of the concentrations tested, resulting in a NOAEC value of <0.39 mg a.i./L. The reductions in length at the 0.39 mg a .i./L concentration were slight when compared to the

controls (4.85 mm vs 4.92 mm, respectiv ely) , but the effect followed a treatment

- related dose

response. No effects on adult survival were noted at any test concentration. There were reductions in the number of young produced and dry weight at concentrations equal to and greater than 1.7 mg a. i./L. This study is classified as supplemental because it failed to establish a

NOAEC.

A 28

- day study (spiked sediment) with the freshwater dipteran Chironomus riparius was conducted with isofetamid (TGAI) (MRID 49018407) . The emergence success was red uced at the highest concentration tested (993 mg a.i./kg

- sediment). The resulting EC 50 

### for emergence was >993 mg a.i./kg

- sediment. There were no effects to development rate or sex ratios in the treated groups. Th e refore, the NOAEC was 483 mg a.i./kg

- sed iment, based on reduced emergence. The study is classified as supplemental (not suitable for quantitative analysis) due to the fact that no data were provided for growth endpoints. Additionally, data on the

concentrations of the test chemical measured in the overlying water and pore water were not provided (beyond a percent recovered relative to the sediment concentration).

Based on the available data, an EC 50 

### of 4.7 mg a.i./L and a NOAEC of <0.39 mg a.i./L will be

used to assess risks to freshwater in vertebrates from acute and chronic exposure, respectively, to

isofetamid.

Estuarine/Marine Invertebrates:

Acute toxicity data for isofetamid have been submitted for the following estuarine/marine invertebrate species: saltwater mysid ( Americamysis bahi a ) and Eastern oyster ( Crassostrea virginica ) . In the mysid study with isofetamid (TGAI), the 96

- hr LC 50 

### is 1.5 1 mg a.i./L (based

on mean

- measured values) (MRID 49011998 )

. Percent mor t a lity in the 0.31, 0.64, 1.2, 2.1, and 4.1 mg a.i./L (mean

- measured) t est concentrations was 25, 0, 40, 45, and 100%, respectively (there were no mortalities in the negative or solvent control groups). Sublethal effects included lethargy, seen at the 1.2 mg a.i./L concentration. Therefore, the NOAEC for this study is <0. 31 mg a.i./L (the lowest concentration tested) based on mortality.

For Eastern oyster exposed to isofetamid (TGAI), the 96

- hr EC 50 

### is 0.44 mg a.i./L, based on

mean

- measured values and shell deposition (MRID 49011997). There were no mortalities noted

in the study, and the NOAEC, based on shell deposition, is 0.030 mg a.i./L. All of the oysters in the controls, 0.030, 0.088, and 0.23 mg a.i./L concentration groups appeared normal throughout

the 96

- hr exposure period. At 96

- hr, some or all of the oysters (de pending on the concentration) did not appear to be open or feeding at concentrations ≥0.64 mg a.i./L.

There are currently no chronic data available for estuarine/marine invertebrates , and an acute

- to

chronic ratio (A CR ) could not be calculated because a definitive NOAEC value is no t available

for the freshwater invertebrate.

### 44 b. Aquatic Plants

Acceptable or supplemental s tudies were submitted for a freshwater vascular plant [ i.e

., duckweed ( Lemna gibba )], and three aquatic non

- vascular plant species: a green algae ( Pseudokirchneriell a subcapitata formerly known as Selenastrum capricornutum ), a freshwater diatom ( Navicula pelliculosa ), and a marine diatom ( Skeletonema costatum ) exposed to technical grade isofetamid (see Table 1 2 ).

Table 12

. Submitted Toxicity Data for Isofetamid and Aquatic Plants.

TAXON ENDPOINT FORMULATION MRID STUDY

CLASS

IFICATION COMMENTS

AQUATIC VASCULAR PLANTS

Duckweed ( Lemna gibba ) EC 50 >4.9 mg

a.i./L

NOAEC = 4.9 mg a.i./L TGAI ( 96.7 % a.i.) 49018417 Acceptable LOAEC > 4.9 mg a.i./L (the highest concentration tested)

AQUATIC NON

- VASCULAR PLANTS

Green Algae ( Pseudokirchne

riella subcapitata ) EC 50 >4.1 mg

a.i./L

NOAEC = 1.2 mg a.i./L TGAI ( 96.7 % a.i.) 49018419 Acceptable LOAEC = 2.8 mg a.i./L [based

on reduced cell density and yield (based on cell density)]

Marine Diatom ( Skeletonema

costatum ) EC 50 >4.1 mg

a.i./L

NOAEC = 4.1 mg a.i./L TGAI ( 96.7 % a.i.) 49018421 Supplemental The study is classified as ’supplemental’ because there appeared to be effects from the

solvent at 96

- hrs. Th erefore,

the results from 72

- hrs are reported here.

Freshwater

Diatom ( Navicula pelliculosa ) EC 50 >4.8 mg

a.i./L

NOAEC =

0.41 2 mg a.i./L TGAI ( 96.7 % a.i.) 49018420 Acceptable LOAEC = 1.4 mg a.i./L (based

on cell density, yield , and growth rate )



### There were no effects noted in the duckweed 7

- day toxicity study , resulting in an EC 50 

### value >4.9 mg a.i/L and a NOAEC of 4.9 mg a.i./L (the highest concentration tested) (MRID

49018417 ). Therefore, an EC 50 

### value of >4.9 mg a.i./L and a NOAEC of 4.9 mg a .i./L will be

used to assess the risk of isofetamid to vascular aquatic plants ( macrophytes )

.

Toxicity tests using nonvascular aquatic plants resulted in 96

- hour EC 50 

### values ≥ 4.1 mg a.i./ L

. NOAEC values ranged from 0.412 mg a .i./L in a freshwater diatom ( Navicula pelliculosa ) based on reductions in cell density, yield, and growth rate (MRID 49018420 ) to 4.1 mg a.i./L in a

marine diatom ( Skeletonema costatum ) based on no effec ts at the highest treatment concentration

tested (MRID 49018421 ).

### 45

2. Terrestrial Effects Characterization

a. Terrestrial Animals

Birds

Based on the LD 50 

### values for the northern bobwhite quail ( Colinus virginianus ) and c anary ( Serenus canaria ) of >2,000 mg a.i. /kg

- bw, isofetamid is characterized as “practically nontoxic" to avian species on an acute oral

- exposure basis (MRIDs 49018408 and 49018410, respectively) (see Table 1 3 ). Isofetamid is no more than “slightly toxic” to avian species on a sub

- acute dietary

- exposure basis, with LC 50 

### values of > 5,180 mg/kg

- diet reported for northern bobwhite quail (MRID 49018411 ) and 4,930 mg a.i./kg

- diet for mallard ducks (MRID 49018412 )

, respectively

.

Table 13

. Submitted Toxicity Data for Isofetamid and Birds.

TAXON ENDPOINT FORMULATION MRID STUDY

CLASS

IFICATION COMMENTS

Acute Oral

Bobwhite quail ( Colinus virginianus ) 14

- day LD 50

>2,000 mg a.i./kg

- bw TGAI ( 96.7 % a.i.) 49018408 Acceptable The NOAEL < 500 mg a.i./kg

bw, based on reduced weight gain (in females); there were

no treatment

- related mortalities noted in the study.

Canary ( Serenus

canaria ) 14

- day LD 50

>2,000 mg a.i./kg

- bw TGAI ( 96.7 % a.i.) 49018410 Acceptable There were no treatment

related mortali ties or sublethal effects noted in the study.

Sub

- Acute Dietary

Bobwhite quail ( Colinus virginianus ) 8

- day LC 50

> 5180 mg ai/kg

- diet TGAI ( 96.7 % a.i.) 49018411 Acceptable Body weight gain was reduced at the highest concentration tested (5180 mg a. i./kg

- diet) over Days 0 to 5, but was comparable to controls following the removal of the treated diet; there were no

treatment

- related mortalities

or other sublethal effects noted in the study.

Mallard duck ( Anas platyrhynchos ) 8

- day LC 50

>4 930 mg

a

. i

. / kg

- diet TGAI ( 96.7 % a.i.) 49018412 Acceptable There were no treatment

related mortalities or sublethal effects noted in the study.

### 46 Chronic

Bobwhite quail ( Colinus virginianus ) NOAEC = 276

mg a.i./kg

- diet

LOAEC >276 mg a.i./kg

- diet TGAI ( 96.7 % a .i.) 49018413 Acceptable While the study author and reviewer both detected a slight (5%) significant (p<0.05)

reduction in the ratio of hatchlings to live embryos at the highest treatment level, relative to the negative control, there were no subsequent re ductions on hatchling survivorship or any other endpoint

Mallard duck ( Anas platyrhynchos ) NOAEC = 285

mg a.i./kg

- diet

LOAEC 928 mg a.i./kg

- diet TGAI ( 96.7 % a.i.) 49018414 Acceptable The LOAEC is based on reduced egg

- shell thickness



### In all of the avian acute and sub

- acute toxicity studies submitted, there were no treatment

- related mortalities at the highest treatment levels tested ( i.e ., all of the LD 50 

### and LC 50 

### endpoints are ‘greater than’ values), therefore, these endpoints are not used to calculate R Q values here. They are, however, used to help characterize risk in the ‘Risk Description’ section of this assessment.

Frank sublethal effects ( i.e., reduced weight gain) were noted in the acute oral and sub

- acute dietary studies for bobwhite quail. I n the acute oral study with bobwhite quail (MRID 49018408) n o mortality was observed, and all birds remained in apparent good health following dosing. Body weight gain (0

- 7 days) was significantly reduced at the 1

, 000 mg a.i. /kg

- bw and higher dosage level for male s and 500 mg a.i. /kg

- bw and higher dosage level for female birds. A reduction in feed consumption was observed in the 1

, 000 and 2

, 000 mg a.i./kg

- diet treatment groups during the first week following treatment.

In the sub

- acute dietary study w ith bobwhite quail (MRID 49018411) b odyweight gain was reduced in the 5180 mg a.i./kg treatment group over Days 0 to 5. Following removal of treated diet, the group bodyweight increased and was comparable to the control group. There were no
apparent treatm ent

- related effects for feed consumption and n o clinical signs of toxicity were

observed. There were no treatment

- related mortalities or sublethal effects noted in the acute oral study with the canary (MRID 49018410) or the sub

- acute dietary study with ma llard ducks (MRID 49018412).

Although frank sublethal effects were noted in these studies, the highest concentrations tested are

> 2 x the estimated environmental concentration (based on the highest application rate on the proposed label s : 6. 4 applications at 0.567 lb a.i./acre, 14

- day application interval). Th e ‘2 x’

factor is based on the current acute non

- listed species LOC for birds and mammals ( i.e ., RQ >

0.5 or 1/ 2 the acute/sub

- acute endpoint value). Therefore, a definitive LD 50 

### or LC 50 

### value is not

needed at this time to fully assess risks to non

- listed birds.

Avian reproduction studies were performed for isofetamid in two species, northern bobwhite quail and mallard duck

. In bobwhite quail, the NOAEC was 276 mg a.i./kg

- diet (MRID 49018413). For mallard ducks, the NOAEC is 285 mg a.i./kg

- diet (MRID 49018414) based on

### 47

egg

- shell thickness. At 928 mg a.i./kg

- diet (the LOAEC) , the overall mean eggshell thickness was slightly but significantly ( p <0.05) lower than that for control s (0.324 mm versus 0.345 mm in the controls)

. There were no treatment

- related effects on adult clinical signs, bodyweight or food consumption in adults or ducklings

. With the exception of e ggshell thickness, the reproductive parameters of all treated grou ps were statistically similar to the control.

For the purposes of this risk assessment, a NOAEC of 276 mg a.i. /kg

- diet serves as the toxicological endpoint for evaluating chronic effects in birds ( Table 10 )

.

Mammals

Based on the LD 50 

### value for the Norway rat ( Rattus norvegicus ) of >2 ,000 mg a.i./kg

- bw,

isofetamid is characterized as “practically nontoxic" to mammalian species on an acute oral

exposure basis (MRID 49011940 ; the study is classified as ‘acceptable’) (see Table 10 )

. There were no mortalities or sublethal effects noted in the study. In this assessment, an LD 50 

### value of

>2 ,000 mg a.i./kg

- will be used to assess the acute risk of isofetamid to mammals.

A 2

- generation study was performed for isof etamid in R. n orvegicus . The lowest NOAEC was 1,000 mg a.i./kg

- diet [65.8 mg a.i./kg

- bw/day (males) and 76.6 mg a.i./kg

- bw/day (females)]

based on decreased pup body weight and weight gain in both sexes and generations and slightly delayed sexual maturati on in F 1 

### females (MRID 49011940 ; this study is classified as ‘acceptable’). The LOAEC is 10,000 mg a.i./kg

- diet [679 mg a.i./kg

- bw/day (males) and 775 mg a.i./kg

- bw/day (females)]. The NOAEC for reproductive effects was 10,000 mg a.i./kg

- diet (the highes t concentration tested) . For the purposes of this risk assessment, 1,000 mg a.i./kg

- diet serves as the toxicological endpoint for evaluating chronic effects in mammals

.

Terrestrial Invertebrates

The registrant submitted two acute contact and oral toxici ty studies with young, adult honey bee s ( Apis mellifera ) ; one with TGAI and one with the formulated product, IKF

- 5411 400SC

. The TGAI study resulted in LD 50 

### values of 100 μg a.i./bee (contact) and >30 μg a.i./bee (oral) (MRID 49018426). In the TGAI study the contact LD 50 

### value was statistically estimated to be >100 ug a.i./bee with 95% confidence interval of 75.2

- 411 ug a.i./bee ; however, since there was 52% mortality at the end of the study in the 100 ug a.i./bee treatment group and there was such a

wi de confidence interval, the LD 50 

### value (contact) in this study is considered to be 100 ug

a.i./bee

. The NOAEL was 20.66 ug a.i./bee based on mortality. There were n o other abnormal effects reported in either the oral or contact portions of the study

. The contact portion of this study is classified as acceptable and the oral portion of the study is classified as supplemental (since it is currently a non

- guideline study).

The study with the formulat ed product (400SC) resulted in LD 50 

### values >100 μg a.i./be e for both the contact and oral portions of the study (MRID 49018425). There were no effects noted in the study. The contact portion of this study is classified as acceptable and the oral portion of the study is classified as supplemental (since it is cu rrently a non

- guideline study).

### 48

Therefore, isofetamid is classified as ‘practically nontoxic’ to honey bees on an acute contact and

oral exposure basis.

There were three other non

- guideline studies submitted for isofetamid [earthworms ( Eisenia fetida ), predatory mite ( Typhylodromus pyri ), and parasitic wasp ( Aphidius rhopalosiphi )]. In

the 14

- day earthworm study with TGAI, the LC 50 

### value (based on mortality) was >1,000 mg a.i./kg

- soil (MRID 49018422). The worms did show a reduction in body weight at t he 556 mg a.i./kg

- soil concentration resulting in a NOAEC of 309 mg a.i./kg

- soil. There were no other effects noted in the study. In the predatory mite study, conducted with a f ormulated product (IKF

- 5411 400 SC), the LD 50 

### value was > 1,000 g a.i./ha ( 0.8 9 lb a.i./acre) and the NOAEC was 250 g a.i./ha ( 0.22 lb a.i./acre) based on mortality (MRID 49018423). In the parasitic wasp study

with a formulated product (400 SC) there wer e no effects noted in the study resulting i n an LD 50 

### of >1,000 g a.i./ha ( >0.89 lb a.i./acre) and a NOAEC of 1,000 g a.i./ha ( 0.89 lb a.i./acre) (MRID 49018424).

b. Terrestrial Plants

The effects of the proposed isofetamid formulation, IKF

- 5411 400 SC

, were tested on various

monocots and dicots in Tier I I seedling emergence and vegetati ve vigor studies (MRID s 49018415 and 49018416, respectively )

. Both studies are classified as acceptable.

Seedling Emergence:

In the seedling emergence study, a ll plants that emerged survived, therefore the results for emergence and survival are the same

. The rates used in the seedling emergence study were very high (up to 669.4 lb a.i./acre). It is unclear why the study included such high application rates, but the rates were confirmed by the applicant

. There was a significant decrease in emergence

an d survival compared to the negative control for corn of 8, 13 and 23% at the 167.4, 334.7 and

699.4 lb a

. i ./acre test levels; and in tomato of 41 and 50% at the 334.7 and 669.4 lb a.i./acre test levels. There were no significant reductions in emergence or survival for any other species at any treatment level compared to the negative control (see Table 1 4 ).

Height in cabbage, cucumber, lettuce, oat, onion, and ryegrass were significantly reduced by up to 16, 13, 20, 8, 18, and 7%, respectively; however t he responses were not dose

- dependent. Cucumber, lettuce and onion each showed a plateaued response, with similar reductions at all test levels. Tomato height was significantly reduced by 17% beginning at 20.919 lb ai/A, and up

to 50% at the 669.4 lb ai/A test level; the response was dose

- dependent.

Dry weight in cabbage and oat were significantly reduced by up to 35 and 13%, respectively;

however the res ponses were not dose

- dependent . There were dose

- dependent reductions for cucumber, ryegrass and tomat o of up to 21 , 32 and 62% beginning at 41.8, 167.4 and 5.2 lb

a

. i ./acre test levels, respectively.

The most sensitive monocot was ryegrass based on dry weight, with NOAEC and EC 25 

### values of

83.7 and 576 lb ai/A, respectively. The most sensitive dicot wa s tomato, based on dry weight,

with NOAEC and EC 25 

### values of 2.615 and 10.3 lb a

. i ./acre , respectively.

### 49

Vegetative Vigor :

In the vegetative vigor study, t here were no significant reductions in survival for any species at any treatment level compared to th e negative control. Likewise, there were no significant reductions in dry weight or height for any species at any treatment level compared to the negative control.

EC 25 

### values were generated for corn and soybean dry weight; although, these values range d higher than the highest test level. Inhibition of corn dry weight did not exceed 3% at the highest test level and the ECx values for this species should be cautiously interpreted. However, inhibition in soybean dry weight at the two highest doses was 14 and 16% of the negative control

response. Based on these results, the most sensitive monocot was determined to be corn with

NOAEC and EC 25 

### values of 1.07 and 1.3 lb a

. i ./acre , respectively. The most sensitive dicot was determined to be soybean with NOAE C and EC 25 

### values of 1.07 and 1.26 lb a

. i ./acre

.

Table 14

. Submitted Toxicity Data for Isofetamid and Terrestrial Plants.

TAXON ENDPOINT FORMULATION MRID STUDY

CLASS

IFICATION COMMENTS

Terrestrial plants (seedling emergence) Monoc ot : ryegrass

EC 25 = 576 lbs

a.i./acre

NOEC = 83.7 lbs

a.i./acre

Dicot : Tomato

EC 25 = 10.3 lbs

a.i./acre

NOEC = 2.6 lbs

a.i./acre IKF

- 5411 400 SC 49018415 Acceptable The most sensitive endpoint was dry weight

for both monocots and

dicots

Terrestrial pl ants (vegetative vigor) Monocot : corn

EC 25 = 1.3 lbs a.i./acre

NOEC = 1.1 lbs

a.i./acre

Dicot : soybean

EC 25 = 1.3 lbs a.i./acre

NOEC = 1.1 lbs

a.i./acre IKF

- 5411 400 SC 49018416 Acceptable The most sensitive endpoint was dry weight

for both monocots an d

dicots

### 50

IV. Risk Characterization

A. Risk Estimation

- Integration of Exposure and Effects Data

Toxicity data and exposure estimates are used to evaluate the potential for adverse ecological

effects on non

- target species. For this screening

- level assessment of isofetamid , the deterministic risk quotient (RQ) method is used to provide a metric of potential risks. The RQ is a comparison of exposure estimates to toxicity endpoints; estimated exposure concentrations are divided by acute and chr onic toxicity values. The resulting unitless RQs are compared to the Agency’s levels of concern ( LOCs ) (see Table 1 5 )

, which are the Agency’s interpretive policy such that when LOCs are exceeded, the need for regulatory action may be considered. These

cr iteria are used to indicate when the use of a pesticide, as directed on the label, has the potential

to cause adverse effects on non

- target organisms.

Table 15

. Agency Levels of Concern (LOC)

.

Risk Description RQ Taxa

Acute Potential for acute risk to non

- target organisms

which may warrant regulatory action in addition

to restricted use classification acute RQ > 0.5 aquatic animals, mammals, birds

Acute Restricted

Use Potent ial for acute risk to non

- target organisms,

but may be mitigated through restricted use

classification acute RQ > 0.1 aquatic animals

acute RQ > 0.2 mammals and

birds

Acute Listed Species Listed species may be potentially affected by

use acute RQ > 0.0 5 aquatic animals

acute RQ > 0.1 mammals and

birds

Chronic Potential for chronic risk may warrant

regulatory action, listed species may potentially be affected through chronic exposure chronic RQ > 1 all animals

Non

- Listed and

Listed Plant Potential for effects in non

- listed and listed

plants RQ > 1 all plants



### 1. Non

- target Aquatic Animals and Plants

Aquatic Organisms

Isofetamid is classified as moderately toxic to freshwater fish and invertebrates, no more than moderately toxic to estuarine/m arine fish, and highly toxic to estuarine/marine invertebrates (specifically oysters), on an acute exposure basis

. Since there are no definitive acute endpoints

available for estuarine/marine fish ( i.e ., all of the available LC 50 

### /EC 50 

### values are ‘greater than’ values and there were no effects noted at the highest concentrations tested), acute RQs for

estuarine/marine fish are not calculated here. Additionally, because a definitive chronic endpoint is not available for freshwater invertebrates (there were e ffects noted at all test concentrations), and chronic data are not available for any other aquatic invertebrate, chronic RQs for aquatic

### 51

invertebrates are not calculated here. The RQ for non

- listed aquatic vascular plants is also not calculated here, since the EC 50 

### value in the Lemna study was non

- definitive. For these taxa, estimated exposure values will be compared to the available endpoints in the Risk Description

section of this document.

For freshwater fish, none of the acute RQs for any of the uses exceed an Agency LOC [the acute RQs range from 0. 00 3 ( low

- growing berries ) to 0.0 9 ( wet

- harvested cranberries )

. T he only chronic RQ exceedances for freshwater (and estuarine/marine) fish were for wet

- harvested cranberry [the chronic RQ s range from 0. 07 ( lo w

- growing berries ) to 2.29 ( wet

- harvested

cranberries )]. N one of the acute RQs for any of the proposed uses exceed an Agency LOC for freshwater invertebrates [RQs range from 0.00 1 ( low

- growing berries ) to 0.0 44 ( wet

- harvested

cranberries )]. For estuarine /marine invertebrates, none of the acute RQs for non

- listed species exceed the Agency’s LOC, however, the RQs for low

- growing berries (including wet

- harvested cranberries)

, and grapes do exceed the acute LOC for listed species [RQs for estuarine/marine

inv ertebrates range from 0.0 1 ( low

- growing berries ) to 0. 47 ( wet

- harvested cranberries )]

. 6 ).

For aquatic vascular and non

- vascular plants, none of the RQs exceed a listed or non

- listed Agency LOC (RQs for aquatic plants range from 0.001 to 0.05) (see T able 17 )

.

### 52

Table 16

. RQs for Aquatic Animals and Isofetamid

.

Use Scenario

or Weather File Application

Method 1

- in

- 10 Year EECs

(μg/L) FW Fish RQ 1 FW

Invertebrate RQ 2 E/M

Invertebrate RQ 3, 4

Peak 21

-

day 60

- day Acute Chro nic Acute Acute

Turf FLturfSTD Ground 13.2 12.1 11.

2 0.01 0. 1 3 0.00 0.03

PAturfSTD 20.3 18.7 18 0.01 0.21 0.00 0.05

Low

growing

Berries (Crop Subgrou p 13

- 07G)
except
Wet

Harvest

- ed

Cranber

ry CAStrawber

ry

noplasticRL F_V2 Aerial 30 .2 29.1 27.

3 0.01 0.32 0.01 0.07

Ground 26.3 25.4 23.

8 0.01 0.28 0.01 0.06

FLstrawberr y_WirrigST

D Aerial 19.3 17.6 16.

3 0.01 0.19 0.00 0.04

Ground 16.3 14.5 13.

1 0.01 0.15 0.00 0.04

ORberriesO

P Aerial 11.4 10.7 10 0.01 0.12 0.00 0.03

Ground 6.36 6.02 5.5

9 0.00 0.07 0.00 0.01

Wet

Harvest

ed

Cranber

ry LaCrosse,

WI 20% Aerial

coverage 205 200 197 0.09 2.29 0.04 0.47

Atlantic City, NJ 158 151 146 0.07 1.70 0.03 0.36

Boston, MA 167 160 153 0.07 1.78 0.04 0.38

Almond C A almond_

WirrigS TD Aerial 21.2 19.2 16.

8 0.01 0.20 0.00 0.05

Airblast 12.7 11.4 9.8

1 0.01 0.11 0.00 0.03

Grapes (Crop Subgrou p 13

- 07F) CAgrapes_

WirrigSTD Aerial 15.5 14.1 13.

3 0.01 0.15 0.00 0.04

Ground 9.62 8.67 8.2

7 0.00 0.10 0.00 0.02

CAfruit_Wir rigSTD Ae rial 16.7 15.6 14.

5 0.01 0.17 0.00 0.04

Ground 10.8 10.1 9.5

6 0.00 0.11 0.00 0.02

NYGrapesS

TD Aerial 26 24.6 23.

4 0.01 0.27 0.01 0.06

Ground 19.8 18.6 18.

1 0.01 0.21 0.00 0.05

Lettuce (head

and leaf) CA Lettuce

Aerial 14.5 13.1 11.

1 0.01 0.13 0.00 0.03

FL Cabbage 10.8 9.6 10.

8 0.00 0.13 0.00 0.02

Rapesee

d (Canola ) (Crop Subgrou p 20A) ND Canola

Aerial 10.9 10.1 9.5 0.00 0.11 0.00 0.02

ND Wheat 10.7 10.1 9.4 0.00 0.11 0.00 0.02

OR Wheat (OP) 9.4 9 8.6 0.00 0.10 0.00 0.02

### 53 1 For fre shwater fish, the acute endpoint = 2.27 mg a.i./L (2,270 μg a.i./L); the chronic endpoint = 0.086 mg a.i./L (86 ug a.i./L). The chronic endpoint is also used to assess chronic risk to estuarine/marine fish.

2 For freshwater invertebrates, the acute endpoin t = 4.7 mg a.i./L (4,700 μ g a.i./L)

3 For estuarine/marine invertebrates = 0.44 mg a.i./L (440 μ g a.i./L)

4 RQs of 0.05 that are not bolded are less than 0.05 but have been rounded up to the nearest hundredth for presentation purposes.

Bolded numbers excee d an Agency LOC

.



### Table 17

. RQs for Aquatic Plants and Isofetamid

.

Use Scenario or Weather File Application

Method Peak 1

-

in

- 10

Year

EECs (μg/L) Vascular

Plant RQs Nonvascular Plant

RQs

Listed Species Non

Listed Species List ed

Species

Turf FLturfSTD Ground 13.2 < 0.01 < 0.00 3 < 0.01

PAturfSTD 20.3 < 0.01 < 0.01 0.01

Low

- growing Berries (Crop Subgroup 13

- 07G) except Wet

Harvested Cranberry CAStrawberry

noplasticRLF_V2 Aerial 30.2 0.01 < 0.01 0.01

Ground 26.3 0.01 < 0.01 0.01

FLstrawberry_WirrigSTD Aerial 19.3 <0.01 <0.01 <0.01

Ground 16.3 <0.01 <0.004 <0.01

ORberriesOP Aerial 11.4 <0.01 <0.003 <0.01

Ground 6.36 <0.01 <0.002 <0.01

Wet

- Harvested Cranberry LaCrosse, WI 20% Aerial

coverage 205 0.04 < 0.05 0.05

Atlantic City, NJ 158 0.03 < 0.04 0.04

Boston, MA 167 0.03 < 0.04 0.04

Almond Caalmond_WirrigSTD Aerial 21.2 <0.01 <0.01 0.01

Airblast 12.7 <0.01 <0.003 <0.01

Grapes (Crop Subgroup 13

- 07F) CAgrapes_WirrigSTD Aerial 15.5 <0. 01 <0.004 <0.01

Ground 9.62 <0.01 <0.002 <0.01

CAfruit_WirrigSTD Aerial 16.7 <0.01 <0.004 <0.01

Ground 10.8 <0.01 <0.003 <0.01

NYGrapesSTD Aerial 26 0.01 < 0.01 0.01

Ground 19.8 <0.01 <0.01 <0.01

Lettuce (head and leaf) CA Lettuce Aerial 14.5 <0.01 <0.004 <0.01

FL Cabbage 10.8 <0.01 <0.003 <0.01

Rapeseed (Canola) (Crop Subgroup 20A) ND Canola

Aerial 10.9 <0.01 <0.003 <0.01

ND Wheat 10.7 <0.01 <0.003 <0.01

OR Wheat (OP) 9.4 <0.01 <0.002 <0.01

1 For listed vascular plants t he endpoint = NOAEC = 4.9 mg a.i./L (4,900 μg a.i./L )

2 For non

- vascular plants, the non

- listed species endpoint = EC 50 > 4.1 mg a.i./L ( 4,1 00 μg a.i./L); the listed species endpoint = NOAEC = 4.1 mg a.i./L ( 4,100 μg a.i./L)

### 54 2. Non

- target Terrestria l Animals

Birds

Isofetamid is classified as ‘practically nontoxic’ to birds on an acute and sub

- acute exposure basis. Since all of the endpoints from the acute and sub

- acute avian toxicity studies are non

definitive ( i.e ., they are ‘greater than’ values) , they will not be used to calculate RQs here

.

The dietary

- based RQs calculated for chronic exposure and birds range from 0.03 to 1. 41 using upper 90 th 

### percentile Kenaga values ( Table 18 ) . The only RQs that exceed the Agency’s LOC

for chronic risk are for birds that eat short grass (f or the proposed almond, grapes, and turf uses). The chronic RQs for birds that eat short grass and these uses range from 1. 03 to 1. 41 , which exceed the Agency LOC of 1.

Table 18

. Chronic Dietary

- B ased RQs for Birds and Isofetamid Using the T

- REX Model ( using the

default 35

- day foliar half

- life).

USE DIETARY ITEM DIETARY

BASED CHRONIC RQ

Almond (4 applications of 0.442 lb a.i./acre; 7

- day application interval with 14 days between the

2 nd and 3 rd applications) Short Grass 1.19

Tall Grass 0.55

Broadleaf Plants 0.67

Fruits/Pods/Seeds 0.07 Arthropods 0.47

Lettuce (2 applications of 0.320 lb a.i./acre; 14

- day application interval) Short Grass 0.49

Tall Grass 0.22

Broadleaf Plants 0.28

F ruits/Pods/Seeds 0.03 Arthropods 0.19
Grapes (3 applications of 0.572 lb a.i./acre; 7

- day application interval with 28 days between 2 nd

and 3 rd applications) Short Grass 1.03

Tall Grass 0.47

Broadleaf Plants 0.58

Fruits/Pods/Seeds 0.06 Arthropod s 0.40 Low growing berries ( 3 applications of 0.40 lb a.i./acre and 1 application of 0.20 lb

a.i./acre ; 14

- day application interval with 28 days between 2 nd

and 3 rd applications) Short Grass 0.70

Tall Grass 0.32

Broadleaf Plants 0.40

Fruits/Pods/See ds 0.04

Arthropods 0.28

Rapeseed (2 application of 0.312 lb a.i./acre; 14

- day application interval) Short Grass 0.48

Tall Grass 0.22

Broadleaf Plants 0.27

Fruits/Pods/Seeds 0.03 Arthropods 0.19

Turf (6 applications of 0.567 lb

a.i./acre and a 7 th application of

0.248 lb a.i./acre ; 14

- day interval between two sequential applications, 28 days between pairs of applications) Short Grass 1.41

Tall Grass 0.65

Broadleaf Plants 0.79

Fruits/Pods/Seeds 0.09

Arthropods
0.55 Bolded RQs exceed the A gency’s LOC of 1

### 55

Mammals

Isofetamid is classified as ‘practically nontoxic’ to mammals on an acute oral exposure basis. Since the endpoint from the toxicity study is non

- definitive ( i.e ., it is a ‘greater than’ value), it

will not be used to calculate R Qs here

.

The chronic dose

- based RQs for several of the proposed uses, dietary categories, and size classes

exceed the Agency’s LOC of 1 (see Table 19 9 ) (RQs range from 0.01 to 2.56 )

. None of the chronic RQs for mammals and the proposed lettuce or rapeseed uses exceed the Agency’s LOC. For the remaining proposed uses (almond, grapes, low

- growing berries, and turf), the RQs exceed the Agency’s LOC of 1 for the short

- grass d iet (all body sizes). The RQs for these uses also exceed the LOC for small mammals (15 g) that eat tall grass and broadleaf plants; and for turf, for small mam mals (15 g) that eat arthropods . There are also some exceedances for

medium

- sized mammals (35 g) that eat broadleaf plants, tall grass, and/or arthropods for some of the proposed uses (see Table 19 9 ).

None of the chronic dietary

- based RQs exceed the Agency’s LOC of 1; the RQS are < 1 for all uses and dietary categories

.

Table 19

. Chronic Dose

- Based RQs for Mammals and Isofetamid Using the T

- REX Model (the default

35

- day foliar half

- life was used in modeling).

USE DIETARY ITEM DOSE

- BASED CHRONIC RQs

15 g 35 g 1000 g

Almond (4 applications of 0.442 lb a.i./acre; 7

- da y application interval with 14 days between

the 2 nd and 3 rd applications) Short Grass 2.17 1.85 0.99

Tall Grass 1.00 0.85 0.46

Broadleaf Plants 1.22 1.04 0.56

Fruits/Pods/Seeds 0.14 0.12 0.06 Arthropods 0.85 0.73 0.39

Seeds 0.03 0.03 0.01

Lettuc e (2 applications of 0.320 lb a.i./acre; 14

- day application interval) Short Grass 0.89 0.76 0.41

Tall Grass 0.41 0.35 0.19

Broadleaf Plants 0.50 0.43 0.23

Fruits/Pods/Seeds 0.06 0.05 0.03 Arthropods 0.35 0.30 0.16

Seeds 0.01 0.01 0.01

Grapes (3 applications of 0.572 lb a.i./acre; 7

- day application interval with 28 days between

2 nd and 3 rd applications) Short Grass 1.88 1.60 0.86

Tall Grass 0.86 0.74 0.39

Broadleaf Plants 1.06 0.90 0.48

Fruits/Pods/Seeds 0.12 0.10 0.05 Arthropods 0.74 0.63 0.34

Seeds 0.03 0.02 0.01 Low growing berries ( 3 applications of 0.40 lb

a.i./acre and 1 application of

0.20 lb a.i./acre ; 14

- day application interval with 28 days between 2 nd and 3 rd
applications) Short Grass 1.28 1.09 0.59

Tall Grass 0.59 0.50 0.27

Broadleaf Plants 0.72 0.62 0.33

Fruits/Pods/Seeds 0.08 0.07 0.04 Arthropods 0.50 0.43 0.23

Seeds 0.02 0.02 0.01

### 56 USE DIETARY ITEM DOSE

- BASED CHRONIC RQs

15 g 35 g 1000 g

Rapeseed (2 application of 0.312 lb a.i./acre; 14

- day application interval) Short Grass 0.87 0.74 0.40

Tall Grass 0.40 0.34 0.18

B roadleaf Plants 0.49 0.42 0.22

Fruits/Pods/Seeds 0.05 0.05 0.02 Arthropods 0.34 0.29 0.16

Seeds 0.01 0.01 0.01

Turf (6 applications of 0.567 lb

a.i./acre and a 7 th application

of 0.248 lb a.i./acre ; 14

- day

interval between two sequential application s, 28 days between pairs of applications) Short Grass 2.56 2.19 1.17

Tall Grass 1.17 1.00 0.54

Broadleaf Plants 1.44 1.23 0.66

Fruits/Pods/Seeds 0.16 0.14 0.07 Arthropods 1.00 0.86 0.46

Seeds 0.04 0.03 0.02



### Inhalation

The Screening Tool for In halation Risk (STIR) w as used to determine if inhalation is a potentially significant route of concern for terrestrial animals.

STIR (v. 1.0) was used to calculate an upper bound estimate of exposure using isofetamid ’s vapor pressure and molecular weight for vapor phase exposure as well as the maximum application rate and method of application for spray drift. STIR incorporates results from several toxicity studies including acute oral and inhalation rat toxicity endpoints [rat ( R. Norvegicus )

LD 50 

### (oral) and LD 50 

### ( inhalation; 4

- hr exposure) of >2 ,000 mg a.i./kg

- bw (MRID 49011907) and

>4.28 mg a.i./L (MRID 49011909 ), respectively] as well as the most sensitive acute oral avian toxicity endpoint [bobwhite quail ( C. virginianus ) LD 50 

### of >2,000 mg a.i./kg

- bw (MRID

49018408 )]. Based on the results of the STIR model, inhalation exposure alone was determined not to be a potential pathway of concern for avian or mammalian species on an acute basis (see

APPENDIX A ).

Terrestrial Invertebrates

Isofetamid is classi fied as ‘practically nontoxic’ to non

- target terrestrial invertebrates on an acute exposure basis. Screening

- level risk assessments do not typically evaluate risks to terrestrial invertebrates; however, toxicity information for beneficial insects is used to develop precautionary label language where necessary. Based on the available data, precautionary label language for bees does not appear necessary.

T he Agency has issued guidance for assessing the potential risks of pesticides to bees and the

data ne eded to support such assessments (USEPA et al. , 2014). Th e guidance document indicates
that if exposure of bees to a pesticide is expected, a Tier I screening

- level risk assessment is

conducted . The Tier I assessment is intended to be sufficiently conserva tive that chemicals that pass the screen are considered to represent a relatively low ris k for potential adverse effects to
bees. Tier I toxicity data that are needed to complete screening

- level risk assessments include a

### 57

suite of laboratory

- based studies of individual bees and include the following tests: acute contact toxicity data to adult honey bees (honey bees serving as a surrogate for all bee species), acute and chronic oral toxicity to adult honey bees, and acute and chronic oral toxicity to honey b ee larvae. If risk concerns are identified in the screening

- level assessment, the assessment may be refined using data that further define exposure or through additional toxicity data from Tier II
semi

- field or Tier III full

- field studies conducted with wh ole colonies. Below is the suite of honey bee toxicity and residues studies:

Tier I D ata

 A cute oral toxicity to larval honey bees (Non

- guideline, OECD TG 237)

 C hronic oral toxicity to adult honey bees (Non

- guideline)

 Chronic oral toxicity to larval honey bees (Non

- guideline)

Tier II Data

 Field trial of residues in pollen and nectar (Non

- guideline)

 Semi

- field testing for pollinator (Non

- guideline, OECD Guidance 75)

Tier III Data

 Field testing for pollinators (Guideline 850.3040)

3. Non

- target Terrest rial and Semi

- aquatic Plants

For monocots and dicots, all of the RQs cal culated using TerrPlant are <0. 1 for listed and non

listed species (see APPENDIX D )

.

B. Risk Description

Based on the results of this assessment, isofetamid is characterized as moderately mobile. Although the parent compound is subject to both biotic and abiotic routes of degradation, its degradates 4HP and PPA are often less subject to degradation , particularly in anaerobic environments and in aerobic aquatic environments . Si nce the two degradates are similar in structure to the parent and there are no data to indicate whether they have similar toxicity, they are presumed to be as toxic and are considered in the aquatic exposure assessment of total toxic

residue . Based on tot al toxic residues, isofetamid is characterized as moderately persistent

. Given that the compound is both moderately persistent and moderately mobile, it may move into both surface and ground water. Although the compound is expected to move into surface w ater via runoff and spray drift, it not considered likely to bioaccumulate. Isofetamid is also not considered likely to volatilize. In addition to the environmental degradates, 4HP and PPA, the metabolite, GPTC, was also considered in the terrestrial ass essment.

The results of this screening

- level risk assessment indicate the proposed uses of isofetamid

, except the proposed lettuce and rapeseed uses

, have the potential for direct adverse effects to

listed and non

- listed mammals from chronic exposure. Ad ditionally, they have the potential for

direct adverse effects to listed and non

- listed birds (and, thus, terrestrial

- phase amphibians and reptiles) from chronic exposure

. T he proposed low

- growing berry and grape use s have the potential to adversely impact listed estuarine/marine invertebrates (from acute exposure).

### 58

Therefore, the risk hypothesis from the Problem Formulation [ i.e

. , b ased on mode of action, the proposed use patterns, and the sensitivity of non

- target aquatic and terrestrial species, the

pr oposed uses of isofetamid have the potential to reduce survival, reproduction, and/or growth in terrestrial and aquatic animals and plants through direct application, spray drift and/or runoff ] i s part ial ly supported. Although direct adverse effects to aq uatic freshwater invertebrates, aquatic plants and terrestrial plants from the proposed isofetamid use s are not expected, given the potential for effects on mammals and birds , indirect effects to other organisms are possible.

1. Risks to Aquatic Organisms

a. Animals

Based on the available data

, the acute fish RQs are well below Agency LOCs

. With the exception of the wet

- harvested cranberry use, c hronic fish RQs are also well below Agency

LOCs. This indicates generally low risk to fish fr om proposed non

- flooded crop uses of

isofetamid.

For aqua tic invertebrates, the acute RQs for non

- listed species are all below the Agency’s LOCs for freshwater and estuarine/marine species. For listed aquatic invertebrates, the only RQs that

exceed an Agency LOC are for estuarine/marine invertebrates and the proposed low

- growing berry (including wet

- harvested cranberry) and grape uses

. The only chronic exposure data currently available for isofetamid and an aquatic invertebrate are for the waterflea. I n the waterflea study there were effects (reduced length) at all treatment levels resulting in a NOAEC of <0.39 mg a.i./L (390 μg a.i./L)

. The effects at the 0.39 mg/L concentration were slight (the average lengths for the waterfleas in the control versus the waterfleas at the 0.39 mg/L

concentration were 4.92 mm and 4.85 mm, respectively ). Because the 0.39 mg a.i./L is only 2 times the highest 21

- day average for the uses modeled [wet

- harvested cranberry EEC of 200 μg a.i./L], there is uncertainty in this risk conclusion

. Overall, adverse effects to non

- listed aquatic

i nvertebrates are not considered likely from the proposed isofetamid uses based on the available toxicity data.

a. Plants

All of the RQs for aquatic vascular and non

- vascular plants are below Agency LOCs for risk to

non

- listed and listed species

. Therefore

, the likelihood of direct risk to non

- listed aquatic plants from the proposed isofetamid uses is considered low

.

2. Risks to Terrestrial Organisms

a. Animals

The chronic RQs for birds and mammals exceed the listed and non

- listed species LOC for most of the uses being proposed. These RQs are based on a 35

- day foliar half

- life. There are data available from a turf dissipation study that suggest that the foliar half

- life for isofetamid may be

shorter than 35

- days (average half

- lives in the turf were 13

- days and 16

- days; MRID 49018442).

### 59

Although, current EFED guidance requires using the 90 th 

### percentile values from chemical

specific empirical data to move off of the default value (which requires a minimum of three half

life values), this doe s introduce some uncertainty in the results for the chronic RQs. To explore the potential effects of a shorter foliar half

- life, RQs were re

- run using T

- REX to explore what the RQs would be if the half

- life was 16

- days instead of 35

- days , and further disc ussion is

included below

.

While RQs generally decreased (many of which are below the LOC), there are some uncertainties with the chronic RQs for mammals and birds, but at this time risk to these taxa from chronic exposure to isofetamid cannot be preclud ed. The dietary

- based chronic RQs are not adjusted for body size, while the dose

- based RQs are adjusted for body

- size. Both the dose

based and dietary

- based RQs can provide useful information about potential exposure to
terrestrial animals in the field, therefore, they are presented to help understand potential risk from dietary exposure.

Birds

None of the available acute or sub

- acute avian studies were able to determine an LD 50 

### or LC 50 

### value (the LD 50 

### and LC 50 

### values were all greater than the highest concentration tested). Frank sublethal effects ( e,g., reduced weight gain and reduced food consumption) were noted in the

available acute oral and sub

- acute dietary studies with bobwhite quails. There were no

treatment

- related mortalities or sublethal ef fects noted in the acute oral study with the canary or the sub

- acute dietary study with mallard ducks

.

In order to gain a better understanding of how the EECs for the maximum proposed isofetamid application rates relate to the acute toxicity data curren tly available for birds, T

- REX was used to calculate a ratio of the EEC/endpoint using the conservative assumption that the highest level tested is the endpoint value ( i.e ., acute: LD 50 

### = 2,000 mg a.i./kg

- bw; sub

- acute: LC 50 

### = 5,180 mg a.i./kg

- diet). In t his exercise all of the acute and sub

- acute ratios calculated for all of the proposed uses using upper

- bound Kenaga values are < 0.5

. Since the actual RQs based on definitive endpoints (if they were available) would be lower, adverse effects to birds from acute
or subacute exposure to isofetamid from the proposed uses are not expected.

The chronic RQs for birds exceed the listed and non

- listed species LOC for most of the uses being proposed (1.03

– 1.41)

. To explore the potential effects of a shorter fol iar half

- life, RQs

were re

- run using T

- REX to explore what the RQs would be if the foliar half

- life was 16

- days

instead of 35

- days. Using a 16

- day half

- life does reduce the avian chronic RQs to below the Agency’s LOC.

### 60

Table 20

. Chronic Dietary

- Based RQs for Birds and Isofetamid Using the T

- REX Model: Comparing the

35

- day and 16

- day foliar half

- life results.

USE DIETARY ITEM DIETARY

- BASED CHRONIC R Q

35

- day Foliar

Half

- Life 16

- day Foliar

Half

- Life

Almond (4 applications of 0 .442 lb a.i./acre; 7

- day application interval with 14 days between the

2 nd and 3 rd applications) Short Grass 1.19 0.94

Tall Grass 0.55 0.43

Broadleaf Plants 0.67 0.53

Fruits/Pods/Seeds 0.07 0.06

Arthropods 0.47 0.37

Grapes (3 applications of 0.572 lb a.i./acre; 7

- day application interval with 28 days between 2 nd

and 3 rd applications) Short Grass 1.03 0.86

Tall Grass 0.47 0.40

Broadleaf Plants 0.58 0.49

Fruits/Pods/Seeds 0.06 0.05

Arthropods 0.40 0.34

Turf (6 applications of 0.567 lb

a.i./a cre and a 7 th application of

0.248 lb a.i./acre ; 14

- day interval between two sequential applications, 28 days between pairs of applications) Short Grass 1.41 0.91

Tall Grass 0.65 0.41

Broadleaf Plants 0.79 0.51

Fruits/Pods/Seeds 0.09 0.06

Arthropod s 0.55 0.35



### Mammals

There were no mortalities or sublethal effects in the acute oral mammal study at the highest treatment level tested ( i.e ., the LD 50 

### endpoint is a ‘greater than’ value), therefore, this endpoint is not used to calculate RQ values.

In order to gain a better understanding of how the EECs for the maximum proposed isofetamid application rates relate to the toxicity data currently available for mammals, T

- REX was used to calculate a ratio of the EEC/endpoint using the conservative assump tion that the highest level tested is the endpoint value ( i.e ., acute: LD 50 

### = 2,000 mg a.i./kg

- bw). In this exercise all of the

acute and sub

- acute ratios calculated for all of the proposed uses using upper

- bound Kenaga values are ≤ 0.10. Since the actual RQs based on a definitive endpoint (if it was available) would be lower, adverse effects to mammals from acute exposure to isofetamid from the proposed uses are not expected

.

### 61

None of the c hronic dietary

- based RQs for mammals excee d the Agency’s LOC of 1; the RQs are < 1 for all uses and dietary categories. However, t he chronic dose

- based RQs for several of the proposed uses, dietary categories, and size classes exceed the Agency’s LOC of 1 (see Table

19 9 ) (RQs range from 0.01 to 2.56 ). None of the chronic RQs for the proposed lettuce or rapeseed uses exceed the Agency’s LOC. For the remaining proposed uses (almond, grapes,

low

- growing berries, and turf), the RQs exceed the Agency’s LOC of 1 for the short

- grass diet ( 15 g and 35 g body sizes). The RQs for the almond, grapes, and turf uses also exceed the LOC for small mammals (15 g) that eat broadleaf plants, and the RQs for almond and turf exceed the LOC for small mammals (15 g) that eat tall grass. For turf, the RQ exceeded the LOC for small mammals (15 g) that eat arthropods. There are also some exceedances for medium

- sized mammals (35 g) that eat broadleaf plants and tall grass for some of the p roposed uses

.

To explore the potential effects of a shorter foliar half

- life, using a 16

- day half

- life does reduce the avian chronic RQs to below the Agency’s LOC, however, the chronic RQs for mammals still exceed the Agency’s LOC for all of the uses ex cept the proposed berry use when using upper bound Kenaga values. EFED additionally explored how the risk picture would look if mean Kenaga values, instead of Upper bound values are used. When mean values are used, none of the avian or mammalian RQs exce ed the Agency’s LOC. When using mean values, however, caution should be used because there is a possibility for the residues to be higher than estimated

concentr ations about half of the time. In summary, chronic RQs generally decreased when considering th e 16

- day half

- life value and mean (versus upper bound) Kenaga values

, but potential risks to mammals (for a variety of size classes and dietary categories) cannot be precluded from chronic exposure to isofetamid from the proposed almond, grapes, low

- growin g berries, and turf uses.

### 62

Table 21

. Chronic Dose

- Based RQs for Mammals and Isofetamid Using the T

- REX Model: Comparing

the 35

- day and 16

- day foliar half

- life results

.

USE DIETARY ITEM DOSE

- BASED CHRONIC RQs

35

- Day Foliar

Half

- Life DOSE

- BASED CHRONIC RQs

16

- Day Foliar

Half

- Life

15 g 35 g 1000 g 15 g 35 g 1000 g

Almond (4 applications of 0.442 lb a.i./acre; 7

- day application interval with 14 days between

the 2 nd and 3 rd applications) Short Grass 2.17 1.85 0.99 1.71 1.46 0 .78

Tall Grass 1.00 0.85 0.46 0.78 0.67 0.36

Broadleaf Plants 1.22 1.04 0.56 0.96 0.82 0.44

Fruits/Pods/Seeds 0.14 0.12 0.06 0.11 0.09 0.05

Arthropods 0.85 0.73 0.39 0.67 0.57 0.31

Seeds 0.03 0.03 0.01 0.02 0.02 0.01

Grapes (3 applications of 0. 572 lb a.i./acre; 7

- day application interval with 28 days between

2 nd and 3 rd applications) Short Grass 1.88 1.60 0.86 1.57 1.34 0.72

Tall Grass 0.86 0.74 0.39 0.72 0.62 0.33

Broadleaf Plants 1.06 0.90 0.48 0.89 0.76 0.41

Fruits/Pods/Seeds 0.12 0.10 0.05 0.10 0.08 0.05

Arthropods 0.74 0.63 0.34 0.62 0.53 0.28

Seeds 0.03 0.02 0.01 0.02 0.02 0.01

Low growing berries ( 3 applications of 0.40 lb

a.i./acre and 1 application of

0.20 lb a.i./acre ; 14

- day application interval with 28 days between 2 nd and 3 rd
applications) Short Grass 1.28 1.09 0.59 0.98 0.84 0.45

Tall Grass 0.59 0.50 0.27 0.45 0.38 0.21

Broadleaf Plants 0.72 0.62 0.33 0.55 0.47 0.25

Fruits/Pods/Seeds 0.08 0.07 0.04 0.06 0.05 0.03

Arthropods 0.50 0.43 0.23 0.38 0.33 0.18

Seeds 0.0 2 0.02 0.01 0.01 0.01 0.01

Turf (6 applications of 0.567 lb

a.i./acre and a 7 th application

of 0.248 lb a.i./acre ; 14

- day

interval between two sequential applications, 28 days between pairs of applications) Short Grass 2.56 2.19 1.17 1.65 1.41 0.75

Tall Grass 1.17 1.00 0.54 0.76 0.64 0.35

Broadleaf Plants 1.44 1.23 0.66 0.93 0.79 0.42

Fruits/Pods/Seeds 0.16 0.14 0.07 0.10 0.09 0.05

Arthropods 1.00 0.86 0.46 0.65 0.55 0.30

Seeds 0.04 0.03 0.02 0.02 0.02 0.01



### Terrestrial Invertebrates

Toxicity i nformation for beneficial insects in screening

- level risk assessments is used to develop precautionary label language where necessary. Based on the available data, precautionary label language for bees is not necessary for the proposed isofetamid uses

.

### 63

T ier I toxicity data that are needed to complete screening

- level risk assessments include a suite of laboratory

- based studies of individual bees and include the following tests: chronic oral toxicity to adult honey bees, and acute and chronic oral toxicity to honey bee larvae. If risk concerns are identified in the screening

- level assessment, the assessment may be refined using data that further define exposure or through additional toxicity data from Tier II semi

- field or

Tier III full

- field studies conduct ed with whole colonies.

b. Plants

None of the RQs for terrestrial plants exceed the Agency’s LOCs for listed or non

- listed plant species. Therefore, risks to terrestrial plants are not expected from the proposed uses of

isofetamid.

3. Revi ew of Incident Data

Reviews of the Ecological Incident Information System (EIIS, version 2.1) and the Avian Incident Monitoring System (AIMS) 1 

### were conducted on April 28, 2014 . There are no reported

incidents for isofetamid in the EIIS or AIMS databases. In addition to the incidents recorded in EIIS and AIMS, additional pesticide incidents are reported to the Agency in aggregated incident reports. Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ ( W

- B), ‘minor plant’ (P

- B), and ‘other non

- target’ (ONT) incidents. ‘Other

non

- target’ incidents include reports of adverse effects to insects and other terrestrial

invertebrates. As of April 28, 2014 , there have been no aggregate isofetamid ecological

in cidents reported to the Agency. Because this is a new chemical that has not been registered for use in the United States, the existence of ecological incident reports would be unlikely

.

1 http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm

### 64

V. REFERENCES

Burns, L. A. 2002. EXAMS ( Ex posure A nalysis M ode ling S ystem) Version 2.98.04.06. Environmental Research Laboratory. U. S. Environmental Protection Agency. Athens, GA.

Carsel et al. 1997. PRZM (Pesticide Root Zone Model) Version 3.12.2 Environmental Research Laboratory. U. S. Environmental Protect ion Agency. Athens, GA.

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 & Agr iculture Organization of the United Nations (FAO). http://www.fao.org/docrep/003/x2570e/x2570e00.htm

FIFRA SAP. 2004. Refined (Level II) Terrestrial and Aquatic Models for Probabilistic an d Ecological Assessment of Pesticides. March 30

- April2, 2004. http://www.epa.gov/scipoly/sap/meetings/2004/033004 mtg.htm

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of the

EPA food

- chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants.

Environ. Tox. Chem. 13:1383

- 1391.

Hoerger, F. and E. E. Kenaga. 1972. Pesticide Residues on Plants: Correlation of Representative Data as a Basis for Estimation of their Magnitude in the Enviro nment. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ., Stuttgart, West Germany, pp. 9

- 28.

Luo, Y. 2011. Report 263: Review and Evaluation of Pesticide Modeling Approaches in Rice Paddies. California Department of Pesticide Regulation, Environmental Monitoring Branch. June 29, 2011. http://www.cdpr.ca.gov/docs/emon!surfwtr/protocols/study263protocol.pdf

USEPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and Development, Washington, D.C. EPA/630/R

- 95/002F. April 1998. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

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

USEPA. 2004b. Exposure Analysis Modeling System (EXAMS): User Manual and System

Documentation. EPA/600/R

- 00/81

- 023. May 2004. Ecosystems Research Division. United States Environmental Protection Agency.

USEPA. 2006. User’s Guide TerrPlant version 1.2.2 . December 2006. Unite d States Environmental Protection Agency. Environmental Fate and Effects Division. Office of Pesticide Programs.

### 65

USEPA 2009a. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides. Version 2.1 October 22, 2009. http://www.epa.gov/oppefed1/models/water/input_guidance2_28_02.htm . U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2009b. DRAFT Guidance for Modeling Pesticides Total Toxic Residues (TTR) May 20, 2009. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2009c. Guidance on the Development, Evaluation, and Application of Environmental

Models. EPA/100/K

- 09/003 March 2009. US Environmental Protection Agency, Washington,

DC.

USEPA 2012a. Guidance for Residues of Concern in Ecological Risk Assessment. December 20, 2012. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2012 b . NAFTA Guidance for Evaluating and Calculating Degradation Kinetics in

Environmental Media. Dece mber 17, 2012. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2012 c . Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half

- life Valu es and Characterizing Pesticide Degradation. November 30, 2012. U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA, PMRA, and CDPR, 2014. Guidance for Assessing Pesticide Ri sks to Bees. Office of Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramento, CA. June 23, 2014.

### 66

Submitted Studies :

Ecotoxicity Studies :

MRID Citation Reference

49011995 Anai, M. (2010) A 48

- Hour Acute Immobilization Study of IKF

- 5411 Technical

with Daphnia magna. Project Number: 95077/OCR. Unpublished study prepared by Chemicals Evaluation and Research Institute. 38p.

49011997 Bro ugher, D. (2012) IKF

- 5411 Technical: A 96

- Hour Shell Deposition Test

with the Eastern Oyster (Crassostrea virginica). Project Number: 272A/121/OCR. Unpublished study prepared by Wildlife International, Ltd. 50p.

49011998 Brougher, D. (2012) IKF

- 5411 Techn ical: A 96

- Hour Flow

- through Acute

Toxicity Test with the Saltwater Mysid (Americamysis bahia). Project Number: 272A/119B/OCR. Unpublished study prepared by Wildlife International, Ltd. 49p.

49011999 Matsura, T. (2010) A 96

- Hour Acute Toxicity Study of IK F

- 5411 Technical

with Common Carp (Includes Amendment to Report). Project Number: 95078/OCR. Unpublished study prepared by Chemicals Evaluation and Research Institute. 46p.

49018401 Anai, M. (2011) A 96

- Hour Acute Toxicity Study of IKF

- 5411 400SC in

Commo n Carp: Final Report. Project Number: 95082, 662/09/E/5082/OCR. Unpublished study prepared by Chemicals Evaluation and Research Institute. 45p.

49018402 Burlingham, J. (2012) IKF

- 5411 Technical: Acute Toxicity to Rainbow Trout.

Project Number: JSM0134/OCR . Unpublished study prepared by Huntingdon Life Sciences, Ltd. 45p.

49018403 Brougher, D. (2012) IKF

- 5411 Technical: A 96

- Hour Flow

- through Acute

Toxicity Test with the Bluegill (Lepomis macrochirus). Project Number: 272A/123/OCR. Unpublished study prepar ed by Wildlife International, Ltd. 46p.

49018404 Brougher, D. (2012) IKF

- 5411 Technical: A 96

- Hour Flow

- through Acute

Toxicity Test with the Sheepshead Minnow (Cyprinodon variegatus). Project Number: 272A/120/OCR. Unpublished study prepared by Wildlife In ternational, Ltd. 46p.

49018405 Anai, M. (2011) Daphnia magna Reproduction Study of IKF

- 5411 Technical.

Project Number: 95079/OCR. Unpublished study prepared by Chemicals Evaluation and Research Institute. 58p.

49018406 Schneider, S. (2011) IKF

- 5411 Tech nical: An Early Life

- Stage Toxicity Test

with the Fathead Minnow (Pimephales promelas). Project Number: 272A/118/OCR. Unpublished study prepared by Wildlife International, Ltd.

### 67 80p.

49018408 Rodgers, M. (2011) IKF

- 5411 Technical: Acute Oral Toxicity [LD(5 0)] to the

Bobwhite Quail. Project Number: JSM0080/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 36p.

49018410 Hubbard, P. (2012) IKF

- 5411 Technical: An Acute Oral Toxicity Study with the

Canary (Serinus canaria). Project Number: 27 2/147/OCR. Unpublished study prepared by Wildlife International, Ltd. 50p.

49018411 Rodgers, M. (2011) IKF

- 5411 Technical: Dietary Toxicity (LC(50)) to the

Bobwhite Quail. Project Number: JSM0079/OCR. Unpublished study prepared by Huntingdon Life Sciences , Ltd. 35p.

49018412 Rodgers, M. (2011) IKF

- 5411 Technical: Dietary Toxicity (LC(50)) to the

Mallard Duck. Project Number: JSM0082/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 27p.

49018413 Dias, N. (2012) IKF

- 5411: Assessment to Det ermine the Effects on

Reproduction in the Bobwhite Quail: (Includes Report Amendment

- Pages 9 and 20 Replaced). Project Number: JSM0081/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 288p.

49018414 Dias, N. (2012) IKF

- 5411 Technical: A ssessment to Determine the Effects on

Reproduction in the Mallard Duck. Project Number: JSM0084/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 199p.

49018425 Taylor, K. (2012) IKF

- 5411 400SC: Acute Toxicity to Honey Bees. Project

Number : JSM0216/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 41p.

49018426 Taylor, K. (2010) IKF

- 5411 Technical: Acute Toxicity to Honey Bees. Project

Number: JSM0094/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 42p.

4 9018415 Taylor, K. (2012) KF

- 5411 400SC: Terrestrial (Non

- target) Plant Growth Test

Seedling Emergence: Amended Final Report. Project Number: JSM0207/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 160p.

49018416 Taylor, K. (2012) IKF

- 54 11 400SC: Terrestrial (Non

- target) Plant Growth Test

Vegetative Vigour: Final Report. Project Number: JSM0206/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 158p.

49018417 Porch, J. (2012) IKF

- 5411 Technical: A 7

- Day Static

- Renewal Toxi city Test

with Duckweed (Lemna gibba G3). Project Number: 272/A/114/OCR. Unpublished study prepared by Wildlife International, Ltd. 69p.

49018419 Porch, J. (2012) IKF

- 5411 Technical: A 96

- Hour Toxicity Test with the

Freshwater Alga (Pseudokirchneriella su bcapitata): Amended Final Report. Project Number: 272A/115/OCR. Unpublished study prepared by Wildlife International, Ltd. 71p.

### 68

49018420 Porch, J. (2012) IKF

- 5411 Technical: A 96

- Hour Toxicity Test with the

Freshwater Diatom (Navicula pelliculosa). Projec t Number: 272A/113/OCR. Unpublished study prepared by Wildlife International, Ltd. 71p.

49018421 Porch, J. (2012) IKF

- 5411 Technical: A 96

- Hour Toxicity Test with the Marine

Diatom (Skeletonema costatum). Project Number: 272A/116/OCR. Unpublished study pr epared by Wildlife International Ltd. 71p.

49011907 Moore, E. (2010) IKF

- 5411 Technical: Acute Oral Toxicity to the Rat (Acute

Toxic Class Method). Project Number: JSM0141/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 29p.

49011909 Le ighton, V. (2010) IKF

- 5411 TGAI: Acute 4 Hour (Nose Only) Inhalation

Study in the Rat. Project Number: 8224246/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 36p.

49011940 Takahashi, K. (2013) IKF

- 5411 Technical: Reproduction Toxicity Study in

Rats: (Second Revised Final Report). Project Number: IET/10/0023/OCR. Unpublished study prepared by Institute of Environmental Toxicology. 493p.

49018407 Last, G. (2012) [Carbon 14]

- IKF

- 5411: Sediment

- Water Chironomus riparius

Toxicity Test Using Spik ed Sediment. Project Number: 8245961/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 68p.

49018422 Rodgers, M. (2011) IKF

- 5411 Technical: Acute Toxicity (LC(50)) to the

Earthworm. Project Number: JSM0085/OCR. Unpublished study prepared by

Hu ntingdon Life Sciences, Ltd. 24p.

49018423 Taylor, K. (2010) IKF

- 5411 400 SC: Acute Toxicity to Typhlodromus pyri in

the Laboratory. Project Number: JSM0095/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 37p.

49018424 Taylor, K. (2010) IKF

- 5411 400SC Acute Toxicity to Aphidius rhopalosiphi in

the Laboratory. Project Number: JSM0096/OCR. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 37p.

E nvironmental Fate and Transport Studies:

49018438 McDonald, J.; Wiedmann, J. (201 3) Terrestrial Field Dissipation of IKF

- 5411

Applied to Bareground in Aberdeen, SK, Canada

- 2010. Project Number: IB/2010/JLW/005/OCR, 100349. Unpublished study prepared by ISK BioSciences Corporation and Golden Pacific Laboratories, LLC (GPL). 406p.

490 18441 McDonald, J.; Wiedmann, J. (2013) Field Soil Dissipation for IKF

- 5411 400SC

Applied to Turf in Proctor, AR

- USA 2011. Project Number: IB/2011/JLW/010/01/01/OCR, RICERCA/027501. Unpublished study prepared by ISK BioSciences Corporation and Ricerca Bi osciences, LLC. 342p.

49018442 McDonald, J. ; Wiedmann, J. (2013) Field Soil Dissipation for IKF

- 5411 400SC

### 69 Applied to Turf in Goldsboro, NC

- USA 2011. Project Number: IB/2011/JLW/008/01/01/OCR, RICERCA/027502. Unpublished study prepared by

ISK BioScienc es Corporation and Ricerca Biosciences, LLC. 362p.

49018445 Wiedmann, J. (2013) Summary of the Environmental Fate of IKF

- 5411 (Isofetamid).

Project Number: IB/2013/MG/005/01/OCR. Unpublished study prepared by ISK BioSciences Corporation. 16p.

49011976 Fl etcher, T. (2010) [Carbon 14]IKF

- 5411: Hydrolytic Stability. Project Number:

2244/073/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 43p.

49011977 Graham, R. (2012) [Carbon 14]IKF

- 5411: Photodegradation and Quantum Yield in

Sterile, Aqueous Solution. Project Number: 2244/074/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 182p.

49011978 Lewis, C. (2010) [Carbon 14]IKF

- 5411: Photodegradation on Soil Surface. Project

Number: 2244/075/OCR. Unpublished study prepared by Covance La boratories, Ltd. 113p.

49011979 Fletcher, T. (2010) [Carbon 14]IKF

- 5411: Adsorption/Desorption in Five Soils.

Project Number: 2244/078/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 87p.

49011980 Lewis, C. (2012) 4HP (Metabolite of IKF

- 541 1): Adsorption/Desorption in Five

Soils. Project Number: 8204073/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 136p.

49011981 Lewis, C. (2010) [Carbon 14]IKF

- 5411: Aerobic Soil Metabolism and Degradation:

Final Report. Project Number: 2244 /068/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 85p.

49011982 Lewis, C. (2010) [Carbon 14]IKF

- 5411: The Rate of Degradation in Three Soils

Under Aerobic Conditions. Project Number: 2244/084/OCR. Unpublished study prepared by Covance Lab oratories, Ltd. 78p.

49011983 Lewis, C. (2010) [Carbon 14]IKF

- 5411: The Rate of Degradation in One Soil at 10

(Degrees Celsius) Under Aerobic Conditions. Project Number: 8204074/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 59p.

49011985 Fletcher, T. (2010) [Carbon 14]IKF

- 5411: Anaerobic Soil Metabolism and

Degradation. Project Number: 2244/076/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 77p.

49011986 Hurst, I. (2012) [Carbon 14]IKF

- 5411: Degradation in Water

- sediment Sy stems

Under Aerobic Conditions. Project Number: 2244/072/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 99p.

49011987 Hurst, L. (2011) [Carbon 14]IKF

- 5411: Degradation in Water

- Sediment Systems

Under Anaerobic Conditions. Project Number: 22 44/079/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 116p.

49011988 Schoenan, E. (2010) Independent Laboratory Validation of Ishihara Sangyo Kaisha

(ISK) Residue Analytical Method for the Determination of IKF

- 5411 and its

### 70 Metabolites 4HP i n Soil: (Document Number: F

- 559). Project Number: IB/2010/JLW/008/01/00/OCR, 100341. Unpublished study prepared by Golden Pacific Laboratories, LLC (GPL). 117p.

49011989 Furuo, R. (2010) Validation of the Residue Analytical Method for the Determination

of IKF

- 5411 and its Metabolite 4HP in Soil. Project Number: F/559/OCR. Unpublished study prepared by Ishihara Sangyo Kaisha, Ltd. 58p.

49011990 Furuo, R. (2012) Validation of an Analytical Method for the Determination of IKF

5411 and 4HP in Sediment. Projec t Number: F/561/OCR. Unpublished study prepared by Ishihara Sangyo Kaisha, Ltd. 39p.

49011991 Boatwright, M. (2012) Freezer Storage Stability of IKF

- 5411 in Soil. Project

Number: IB/2010/JLW/011/01/00/OCR, 100354. Unpublished study prepared by

Golden Paci fic Laboratories, LLC (GPL). 126p.

49011992 McDonald, J.; Wiedmann, J. (2012) Terrestrial Field Dissipation of IKF

- 5411

Applied to Bareground in Kerman, CA

- USA 2010. Project Number: IB/2010/JLW/003/01/01/OCR, 100347. Unpublished study prepared by ISK

Bi oSciences Corp. and Golden Pacific Laboratories, LLC (GPL). 333p.

49011993 McDonald, J.; Wiedmann, J. (2012) Terrestrial Field Dissipation of IKF

- 5411

Applied to Bareground in Northwood, ND

- USA 2010. Project Number: IB/2010/JLW/004/01/01, 100348/OCR. Un published study prepared by Golden Pacific Laboratories, LLC (GPL). 334p.

49011994 Richardson, M. (2012) IKF

- 5411 and its Metabolites 3

- MTCAM, IBA and PPA:

Validation of an Analytical Method for the Determination of Residues in Surface and Drinking Water. Project Number: 8261479/OCR. Unpublished study prepared by Covance Laboratories, Ltd. 120p.

### 71

Appendix A

. Sample Screening Tool for Inhalation Risk (STIR v. 1.0) Inputs and Outputs for the Proposed Uses of Isofetamid

.



### Ta ble 1. Inputs

APPLICATION AND CHEMICAL INFORMATION

Enter Chemical Name Isofetamid

Enter Chemical Use Grapes
Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) air
Enter Chemical Molecular Weight (g/mo le) 359.5
Enter Chemical Vapor Pressure (mmHg) 4.4E

- 11
Enter Application Rate (lb a.i./acre) 0.572

TOXICITY PROPERTIES

Bird

Enter Lowest Bird Oral LD 50 (mg/kg bw) 2000
Enter Mineau Scaling Factor 1.15
Enter Tested Bird Weight (kg) 0.17 8

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 2 000

Enter Lowest Rat Inhalation LC 50 (mg/L) 4. 25
Duration of Rat Inhalation Study (hrs) 4
Enter Rat Weight (kg) 0.35



### Table 2. Outputs

RESULTS Avian (0.020 kg ) CONCLUSIONS

Maximu m Vapor Concentration in Air at Saturation (mg/m 3 ) 8.51E

- 07

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.07E

- 07
Adjusted Inhalation LD 50 2.39E+01
Ratio of Vapor Dose to Adjusted Inhalation LD 50 4.48E

- 09 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 5.49E

- 02
Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.30E

- 03 Exposure not Likely Significant

RESULTS Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 8.51 E

- 07

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 1.35E

- 07
Adjusted Inhalation LD 50 2.55E+02

Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.28E

- 10 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 6.91E

- 02
Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.71E

- 04 Exposure not Likely Significant

### 72

Appendix B

. Isofetamid Total Toxic Residues Aquatic Modeling Results

SWCC Output Data for highest Peak EECs for n on

- flooded agricultural crops

Variable Volume Water Model, SWCC Compatible Version

*******************************************

Performed on: 7/28/2014 at 10:31

Peak 1

- in

- 10 = 68.9 ppb

Chronic 1

- in

- 10 = 32.0 ppb Simulation Avg = 22.1 ppb

4

- day avg 1

- in

- 10 = 67.2 ppb

21

- day avg 1

- in

- 10 = 62.3 ppb

60

- day avg 1

- in

- 10 = 53.7 ppb

90

- day avg 1

- in

- 10 = 49.1 ppb

Benthic Pore Water Peak 1

- in

- 10 = 41.5 ppb

Benthic Pore Water 21

- day avg 1

- in

- 10 = 41.4 ppb

Benthic Conversion Factor = 20.0

- Pore water (ug/L) to (total mass, ug)/(dry sed mass,kg)

Benthic Mass Fraction in Pore Water = 0.185E

- 01

YEAR Peak 4

- day 21

- day 60

- day 90

- day Yearly Avg Bent hic Pk Benthic 21

- day

1 3.10E+01 3.01E+01 2.80E+01 2.44E+01 2.23E+01 1.37E+01 1.67E+01 1.67E+01

2 4.15E+01 4.08E+01 3.86E+01 3.36E+01 3.11E+01 2.08E+01 2.63E+01 2.62E+01

3 7.01E+01 6.84E+01 6.30E+01 5.39E+0 1 4.92E+01 3.12E+01 3.96E+01 3.96E+01

4 4.95E+01 4.85E+01 4.69E+01 4.15E+01 3.85E+01 2.57E+01 3.38E+01 3.37E+01

5 3.44E+01 3.38E+01 3.29E+01 2.99E+01 2.82E+01 1.95E+01 2.57E+01 2.57E+01

6 4.39E+01 4.29E+ 01 4.05E+01 3.55E+01 3.27E+01 2.16E+01 2.78E+01 2.77E+01

7 8.22E+01 8.02E+01 7.39E+01 6.48E+01 5.94E+01 3.75E+01 4.72E+01 4.71E+01

8 7.02E+01 6.87E+01 6.34E+01 5.58E+01 5.15E+01 3.44E+01 4.47E+01 4.46E+01

9 5.79E+01 5.70E+01 5.57E+01 5.15E+01 4.82E+01 3.21E+01 4.17E+01 4.16E+01

10 4.97E+01 4.88E+01 4.68E+01 4.30E+01 4.03E+01 2.70E+01 3.54E+01 3.54E+01

11 2.89E+01 2.84E+01 2.71E+01 2.52E+01 2.44E+01 1.73E+01 2.29E+01 2.28E+01

12 2.50E+01 2.46E+01 2.38E+01 2.15E+01 2.02E+01 1.38E+01 1.82E+01 1.82E+01

13 4.39E+01 4.32E+01 4.15E+01 3.89E+01 3.62E+01 2.35E+01 2.95E+01 2.95E+01

14 3.01E+01 2.96E+01 2.82E+01 2.67E+01 2.55E+01 1.78E+01 2.32E+01 2.32E+01

15 4.95E+01 4.88E+01 4.60E+01 3.95E+01 3.61E+01 2.34E+01 2.97E+01 2.97E+01

16 2.73E+01 2.69E+01 2.56E+01 2.40E+01 2.34E+01 1.68E+01 2.19E+01 2.19E+01

17 2.72E+01 2.67E+0 1 2.53E+01 2.36E+01 2.28E+01 1.59E+01 2.02E+01 2.02E+01

18 4.58E+01 4.48E+01 4.18E+01 3.78E+01 3.56E+01 2.37E+01 2.98E+01 2.98E+01

19 4.81E+01 4.71E+01 4.50E+01 4.18E+01 3.99E+01 2.70E+01 3.44E+01 3.44E+01

2 0 4.06E+01 4.01E+01 3.84E+01 3.65E+01 3.50E+01 2.40E+01 3.10E+01 3.10E+01

21 5.34E+01 5.21E+01 4.84E+01 4.24E+01 3.91E+01 2.55E+01 3.29E+01 3.29E+01

22 4.50E+01 4.42E+01 4.15E+01 3.92E+01 3.78E+01 2.60E+01 3.32E+01 3.32E+01

23 5.52E+01 5.40E+01 5.24E+01 4.71E+01 4.35E+01 2.83E+01 3.65E+01 3.64E+01

24 2.79E+01 2.74E+01 2.63E+01 2.48E+01 2.36E+01 1.65E+01 2.27E+01 2.27E+01

25 3.47E+01 3.40E+01 3.13E+01 2.73E+01 2.53E+01 1.72E+01 2.21E+01 2.21E+01

26 3.53E+01 3.49E+01 3.36E+01 3.06E+01 2.84E+01 1.92E+01 2.47E+01 2.46E+01

27 3.46E+01 3.40E+01 3.17E+01 2.83E+01 2.67E+01 1.85E+01 2.39E+01 2.38E+01

28 3.18E+01 3.12E+01 2.98E+01 2.69E+01 2.50E+01 1.67E+01 2.18E+01 2.18E+01

29 2.41E+01 2.37E+01 2.26E+01 2.10E+01 1.99E+01 1.37E+01 1.79E+01 1.78E+01

30 2.45E+01 2.41E+01 2.31E+01 2.20E+01 2.09E+01 1.41E+01 1.81E+01 1.81E+01

*** ***********************************************************************************

************** Effective compartment halflives averaged over simulation duration:

### 73

zero washout 0 water col metab halflife (days) = 869.696 658658743 zero hydrolysis 0 photolysis halflife (days) = 174.600147059045 volatile halflife (days) = 50380428.0741190 total water col halflife (days) = 145.407632582224

zero burial 0

zero benthic metab 0 zero benthic hydrolysis 0 zero benthic total degradation 0

***********************************************************************

Fractional Contribution of Tra nsport Processes to Waterbody & Total Mass (kg):

Due to Runoff = 0.6008 13.97

Due to Erosion = 0.0000 0.7879E

- 03

Due to Drift = 0.3991 9.281

********************************************************* ************** Flow in/out Characteristics of Waterbody: Average Daily Runoff Into Waterbody (m3/s) = 4.729380814254334E

- 004 Baseflow Into Waterbody (m3/s) = 0.000000000000000E+000 Average Daily Flow Out of Waterbody (m3/s) = 4.729380 814254455E

- 004

*********************************************************************** Inputs: 491.0 = oc partitioning coefficient

556.3 = water column half Life 20.00 = reference temp for water column degradation

0.000 = bent hic Half Life 20.00 = Reference temp for benthic degradation 2.000 = Q ten value 1.800 = photolysis half life 40.00 = reference latitude for photolysis study 0.000 = hydrolysis half life

359.5 = molecular wt

0.44 00E

- 10 = vapor pressure 5.330 = solubility

0.1000E+06 = field area 0.1000E+05 = water body area 2.000 = initial depth 2.000 = maximum depth 2 1=vvwm, 2=usepa pond, 3 = usepa reservoir, 4 = const vol no flow, 5 = const vo l w/flow F T = burial, else no burial

0.1000E

- 07 = mass transfer coefficient

0.5000 = PRBEN

0.5000E

- 01 = benthic compartment depth 0.5000 = benthic porosity 1.350 = benthic bulk density

0.4000E

- 01 = OC frcation in benthic sedi ment 5.000 = DOC in benthic compartment

0.6000E

- 02 = benthic biomass

1.190 = DFAC

30.00 = SS

0.5000E

- 02 = chlorophyll

0.4000E

- 01 = OC frcation in water column SS

5.000 = DOC in water column

### 74

0.4000 = biomass in water column

FRACTION AREA CROPPED = 1.00000000000000



### PFAM Output Data for highest Peak EECs for flooded agricultural crops (wet

- harvested cranberry)

Variable Volume Water Model, Version 0.0

*******************************************

Performed on: 1 2/19/2014 at 14:19 Standard Pond, Area = 10000 m2, Depth = 2 m

Chemical # 1

Peak 1

- in

- 10 = 2.05E+02 ppb

Chronic 1

- in

- 10 = 1.84E+02 ppb

4

- day avg 1

- in

- 10 = 2.03E+02 ppb

21

- day avg 1

- in

- 10 = 2.00E+02 ppb

60

- day avg 1

- in

- 10 = 1.97E+02 ppb

90

- day avg 1

- in

- 10 = 1.97E+02 ppb

YEAR Peak 4

- day 21

- day 60

- day 90

- day Yearly Avg

1 9.92E+01 9.88E+01 9.73E+01 9.56E+01 9.37E+01 6.97E+01

2 1.50E+02 1.48E+02 1.46E+02 1.41E+02 1.37E+ 02 1.24E+02

3 1.53E+02 1.52E+02 1.48E+02 1.46E+02 1.45E+02 1.35E+02

4 1.61E+02 1.61E+02 1.59E+02 1.56E+02 1.53E+02 1.38E+02

5 2.18E+02 2.17E+02 2.13E+02 2.07E+02 2.03E+02 1.84E+02

6 1.74E+02 1.74E+02 1.72E+02 1.75E+02 1.83E+02 1.60E+02

7 1.61E+02 1.59E+02 1.56E+02 1.57E+02 1.61E+02 1.38E+02

8 1.86E+02 1.86E+02 1.85E+02 1.84E+02 1.83E+02 1.69E+02

9 1.89E+02 1.87E+02 1.81E+02 1.79E+02 1.78E+02 1.71E+02

10 1.97E+02 1.97E+02 1.96E+02 1.94E+02 1.92E+02 1.78E+02

11 2.02E+02 1.99E+02 1.96E+02 1.93E+02 1.91E+02 1.83E+02

12 2.22E+02 2.21E+02 2.19E+02 2.15E+02 2.13E+02 2.01E+02

13 2.05E+02 2.03E+02 2.00E+02 1.97 E+02 2.00E+02 1.86E+02

14 2.00E+02 2.00E+02 2.00E+02 1.97E+02 1.95E+02 1.82E+02

15 1.84E+02 1.82E+02 1.79E+02 1.89E+02 1.92E+02 1.61E+02

16 1.50E+02 1.49E+02 1.46E+02 1.52E+02 1.57E+02 1.29E+02

17 1.79E+02 1.78E+02 1.78E+02 1.76E+02 1.75E+02 1.60E+02

18 1.94E+02 1.92E+02 1.86E+02 1.81E+02 1.79E+02 1.70E+02

19 2.05E+02 2.03E+02 1.98E+02 1.87E+02 1.84E+02 1.69E+02

20 1.93E+02 1.91E+02 1.90E+02 1.86E+02 1.83E+02 1.62E+02

21 1.90E+02 1.88E+02 1.85E+02 1.81E+02 1.81E+02 1.69E+02

22 1.80E+02 1.79E+02 1.78E+02 1.75E+02 1.72E+02 1.62E+02

23 1.70E+02 1.69E+02 1.68E+02 1.66E+02 1.64E+02 1.57E+02

24 1.81E+02 1.81E+02 1. 80E+02 1.77E+02 1.74E+02 1.57E+02

25 1.81E+02 1.79E+02 1.74E+02 1.67E+02 1.63E+02 1.46E+02

26 1.91E+02 1.88E+02 1.85E+02 1.79E+02 1.78E+02 1.63E+02

27 1.78E+02 1.76E+02 1.72E+02 1.67E+02 1.64E+02 1.52E+02

28 1.41E+02 1.40E+02 1.39E+02 1.41E+02 1.47E+02 1.29E+02

29 1.52E+02 1.52E+02 1.49E+02 1.47E+02 1.45E+02 1.34E+02

30 1.81E+02 1.78E+02 1.72E+02 1.66E+02 1.63E+02 1.46E+02

***************************************** ****************************** Effective compartment halflives averaged over simulation duration:

### 75

zero washout water col metab halflife (days) = 974.4096 hydrolysis halflife (days) = 100039.6 photolysis halflife (days) = 258.8398 volatile halflife (days) = 9.0573864E+07 total water col halflife (days) = 204.0957

zero burial benthic metab halflife (days) = 175159.0 benthic hydrolysis halflife (days) = 2043979.

total bent hic halflife (days) = 161333.5

***********************************************************************

**************** Inputs *******************

Chemical # 1

556.300000000000 Water Column System Halflife(except photo & hydrolysis = 100000.000000000 Benthic Compartment Halflife (except hydrolysis) = 1.80000000000000 Photolysis Halflife = 100000.000000000 Hydrolysis Halflife = 359.480000000000 Molecular Wieght =

4.400000000000000E

- 011 Vapor Pressure = 5.33000000000000 Solubility =

180.000000000000 Koc = 20.0000000000000 Aerobic Reference Temper =

20.0000000000000 Anaerobic Reference Temper =

40.0000000000000 Reference Latitude = 54872.4000000000 Enthalpy of Henry = 25.0000000000000 Henry Reference Temperature

****************** End of Run ************************

************* *****************************************

*********************************************************************** **************** Inputs *******************

Chemical # 1

556.300000000000 Water Column System Halflife(except phot o & hydrolysis = 100000.000000000 Benthic Compartment Halflife (except hydrolysis) = 1.80000000000000 Photolysis Halflife = 100000.000000000 Hydrolysis Halflife = 359.480000000000 Molecular Wieght =

4.400000000000000E

- 011 Vapor Pressure = 5.33000000000000 Solubility =

180.000000000000 Koc = 20.0000000000000 Aerobic Reference Temper =

20.0000000000000 Anaerob ic Reference Temper =

40.0000000000000 Reference Latitude = 54872.4000000000 Enthalpy of Henry = 25.0000000000000 Henry Reference Temperature

****************** End of Run ************************

*********** *******************************************

### 76

Appendix C

. Sample T

- REX Inputs and Outputs for the Proposed Uses of Isofetamid

.



### INPUTS:

Chemical Name: Isofetamid

Use Grapes

Application Rate 0 .572 lbs a.i./acre

Half

- life 35 days

Application Interval 7 days

Maximum # Apps./Year 3

Length of Simulation 1 year

Endpoints

Avian Bobwhite quail LD50 (mg/kg

- bw) 2000.00

Bobwhite quail LC50 (mg/kg

- diet) 5180 .00

Bobwhite quail NOAEC (mg/kg

- diet ) 276

Mammals LD50 (mg/kg

- bw) 2 000.00
NOAEL (mg/kg

- bw) 65.8

NOAEC (mg/kg

- diet) 1000

Dietary

- based EECs (ppm) Kenaga

Values

Short Grass 360.8

Tall Grass 165.4
Broadleaf plants/sm Insects 203
Fruits/pods/seeds/lg insects 22.6
Arthropods 141.3

### 77

OUTPUTS: Summary of Risk Quotient Calculations Based on Upper Bound Kenaga EECs.

Table 1. Upper Bound Kenaga, Acute Avian Dose

- Based Risk Quotients

Size

Class (grams) Adjusted

LD50 EECs and RQs

Short Grass Tal l Grass Broadleaf Plants/

Small Insects Fruits/Pods/

Seeds/ Large Insects Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

20 1440.86 410.95 0.29 188.35 0.13 231.16 0.16 25.68 0.02 160.95 0.11

100 1834.29 234.34 0.13 107.41 0.06 131.82 0.07 14.65 0.01 91. 78 0.05

1000 2591.00 104.92 0.04 48.09 0.02 59.02 0.02 6.56 0.00 41.09 0.02

Table 2. Upper Bound Kenaga, Subacute Avian Dietary Based Risk Quotients.

LC50 EECs and RQs

Short Grass Tall Grass Broadleaf

Plants/

Small Insects Fruits/P ods/

Seeds/ Large Insects

EEC RQ EEC RQ EEC RQ EEC RQ

5180 360.83 0.07 165.38 0.03 202.97 0.04 22.55 0.00 Size class not used for dietary risk quotients

Table 3. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients

.

NOAEC (ppm) EECs and RQs

Short Grass Tall Grass Broadleaf

Plants/

Small Insects Fruits/Pods/

Seeds/ Large Insects

EEC RQ EEC RQ EEC RQ EEC RQ

276 360.83 1.31 165.38 0.60 202.97 0.74 22.55 0.08

Size class not used for dietary risk qu otients

Table 4. Upper Bound Kenaga, Acute Mammalian Dose

- Based Risk Quotients.

Size

Class (grams) Adjusted

LD50 EECs and RQs

Short Grass Tall Grass Broadleaf Plants/

Small Insects Fruits/Pods/

Seeds/ Large Insects Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15 4395.66 344.02 0.08 157.68 0.04 193.51 0.04 21.50 0.00 134.742 0.0307

35 3556.56 237.77 0.07 108.98 0.03 133.74 0.04 14.86 0.00 93.1247 0.0262

1000 1538.32 55.13 0.04 25.27 0.02 31.01 0.02 3.45 0.00 21.5913 0.014

### 78

Table 5. Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients.

NOAEC (ppm) EECs and RQs

Short Grass Tall Grass Broadleaf

Plants/

Small Insects Fruits/Pods/

Seeds/ Large Insects

E EC RQ EEC RQ EEC RQ EEC RQ

1000 360.83 0.36 165.38 0.17 202.97 0.20 22.55 0.02
Size class not used for dietary risk quotients

Table 6. Upper Bound Kenaga, Chronic Mammalian Dose

- Based Risk Quotients

Size

Class (grams) Adjusted

N OAEL EECs and RQs

Short Grass Tall Grass Broadleaf Plants/

Small Insects Fruits/Pods/

Seeds/ Large Insects Granivore

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

15 144.62 344.02 2.38 157.68 1.09 193.51 1.34 21.50 0.15 134.74 0.93

35 117.01 237.77 2.03 108.9 8 0.93 133.74 1.14 14.86 0.13 93.12 0.80

1000 50.61 55.13 1.09 25.27 0.50 31.01 0.61 3.45 0.07 21.59 0.43

### 79

Appendix D

. SAMPLE TerrPlant Inputs and Outputs for the Proposed Isofetamid Uses.



### Table 1. Chemical Identity.

Chemical Name Isofetamid

PC code 270000

Use Grapes
Application Method Aerial
Application Form Liquid
Solubility in Water (ppm) 5



### Table 2. Input parameters used to derive EECs.

Input Parameter Symbol Value Units
Ap plication Rate A 0. 572 lb a.i./acre
Incorporation I 1 none
Runoff Fraction R 0.0 1 none

Drift Fraction D 0.0 5 none



### Table 3. EECs for Isofetamid . Units in lb a.i./acre.

Description Equation EEC
Runoff to dry areas (A/I)*R 0.0057 2

Runoff to semi

- aquatic areas (A/I)*R*10 0.0572
Spray drift A*D 0.0286
Total for dry areas ((A/I)*R)+(A*D) 0.03432

Total for semi

- aquatic areas ((A/I)*R*10)+(A*D) 0.0858



### Table 4. Plant survival and growth data used for RQ derivat ion. Units are in lb a.i./acre.

Seedling Emergence Vegetative Vigor

Plant type EC25 NOAEC EC25 NOAEC

Monocot 576 83.7 1.3 1.1

Dicot 10.3 2.6 1.3 1.1



### Table 5. RQ values for plants in dry and semi

- aquatic areas exposed to through runoff a nd/or spray drift.*

Plant Type Listed Status Dry Semi

- Aquatic Spray Drift

Monocot non
- listed <0.1 <0.1 <0.1

Monocot listed <0.1 <0.1 <0.1

Dicot non
- listed <0.1 <0.1 <0.1

Dicot listed <0.1 <0.1 <0.1

*If RQ > 1.0, the LOC is exceeded, resulting in po tential for risk to that plant group.

### 80

Appendix E Fate D ata for Isofetamid Parent and Degradates and QSAR Analyses for 4HP and

PPA

.

Table E 1

. Chemical Identification Information for Isofetamid and Isofetamid Degradates

and Metabolites

.

Common

Name and Registrant

Code Name Chemical Name and Smiles Code Structure

Isofetamid ( IKF

- 5411) N

- [1,1

- dimethyl

- 2

- [2

- methyl

- 4

- (1

-

methylethoxy)phenyl]

- 2

- oxoethyl]

- 3

- methyl

- 2

- thiophenecarboxamide

C(C)(C)(C(=O)c1c(C)cc(OC(C)C)cc1)NC(=O)C

1= C(C)C=CS1

Molecular Weight = 359.48

4HP (YN

- 5394) N

- [1,1

- dimethyl

- 2

- (4

- hydroxy

- 2

- methylphenyl)

-

2

- oxoethyl]

- 3

- methyl

- 2

- thiophenecarboxamide

C(C)(C)(C(=O)c1c(C)cc(O)cc1)NC(=O)C1=C(C)

C=CS1

Molecular Weight = 317.4 0

PPA (YN

- 6187) 2

- [3

- methyl

- 4

- [2

- m ethyl

- 2

- (3

- methylthiophene

- 2

-

carboxamido)propanoyl]phenoxy]propanoic acid

C(C)(C)(C(=O)c1c(C)cc(OC(=O)O)cc1)NC(=O) C1=C(C)C=CS1

Molecular Weight = 389.46

IBA (HM

- 939) 2

- methyl

- 4

- (2

- propyloxy)benzoic acid

C(=O)(O)c1c(C)cc(OC(=O)O)cc1

3

- MTCAM 3

- m ethyl

- 2

- thiophenecarboxamide

C(N)(=O)C1=C(C)C=CS1

### 81

Common

Name and Registrant

Code Name Chemical Name and Smiles Code Structure

3

- MTCA 3

- methyl

- 2

- thiophenecarboxylic acid

C(=O)(O)C1=C(C)C=CS1

GPTC N

- [l ,1

– dimethyl

- 2

- (4

- β

- D

- glucopyranosyloxy

- 2

- methylphenyl)

- 2

- oxoethyl]

- 3

- methyl

- 2

- thiophenecarboxamide

C(C)(C)(C(=O)c1c(C)cc(OC2C(O)C(O)C(O)C(C O)O2)cc1)NC(=O)C1=C(C)C=CS1

### 82

Table E 2

. Isofetamid Parent: Select Physical

- Chemical and Fate Propertie s.

Parameter Value and Units 1 Source and/or Comment

Water Solubility at 20 o C 5.33 mg/L MRID 49011905

Vapor Pressure at 25 o C 4.2×10 - 7 Pa

4.4 ×10

- 11 Torr MRID 49011905

Non

- volatile under field conditions

Henry’s Law constant 1.2×10 - 5 Pa

- m 3 /mol MRID 4901 1905

Log Dissociation Constant (pK

a ) The pure active ingredient did not dissociate in pH 4 to 10 solutions. MRID 49011905

Octanol

- water partition coefficient (K

ow ) log K

ow = 2.5 MRID 49011905 Not likely to bioconcentrate.

Soil Partition Coefficient

K F (25°C) US Loamy Sand: 6.64 mL/g ( 1 /

n = 0.873)

US Loam: 17.17 mL/g ( 1 /

n = 0.921)

UK Loam or Silt Loam: 20.79

mL/g ( 1 /

n = 0.991)

UK Clay Loam: 13.68 mL/g ( 1 /

n = 0.924)

Japanese Sandy Loam (Volcanic Ash): 14.86 mL/g ( 1 /

n = 0.933)

Mean: 14.6 3 mL/g MR ID 49011979 Acceptable

Soil Partition Coefficient

K F oc (25°C) US Loamy Sand: 602.6 mL/g

oc

US Loam: 591.9 mL/g

oc

UK Loam or Silt Loam: 534.9

mL/g

oc

UK Clay Loam: 274.3 mL/g

oc

Japanese Sandy Loam (Volcanic Ash): 449.6 mL/g

oc

Mean: 491 mL/g

oc MRID 490 11979 Acceptable

Terrestrial Field Dissipation DT 50 's ND, USA: 6.98 days (IORE) SK, Canada: 217 days (SFO) AR, USA: 35 days (SFO) CA, USA: 46.5 days (SFO) NC, USA: 29 days (SFO) MRIDs 49011993, 49018438, 49018441, 49011992, and 49018442

Supplemental

SFO= single first order; DFOP=double first order in parallel; IORE=indeterminate order (IORE)

### 83

Parameter Value and Units 1 Source and/or Comment

1 Representative half

- lives are estimated SFO half

- lives (for EFED modeling inputs) from a degradation curve that does not necessarily follow the SFO equation. Repr esentative half

- life values were calculated using nonlinear regression and SFO, DFOP, or IORE equations. The equations can be found in the document, Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative

Half

- life Values and Characterizing Pesticide Degradation ( US EPA 2012). Representative half

- life values calculated in this table do not include unextracted residues, as exhaustive extraction methods were

used in the studies.

2 Representative half

- lives for moist soil pho tolysis were corrected for the moist dark control.

### 84

Table E 3. Representative Half

- Lives for Isofetamid Parent and Total Toxic Residues ( Isofetamid, 4HP, and PPA )

.

Study System Details Representative Half

- Life*

MRID Parent Only

(Kinetic Equation) Pa rent, 4HP , and

PPA

(Kinetic Equation)

Abiotic Hydrolysis pH 4, 7, 9 at 50 o C stable n/a 49011976 Supplemental

Aqueous Photolysis Sterile Buffer pH 7 ± 0.2

25±2 o C 40°N sunlight 1.8 days (SFO) n/a

49011977 a Supplemental Natural Water pH 7.1

25±2 o C

40°N sunlight 1.4 days (SFO) n/a

Soil Photolysis UK Silt Loam pH 6.4

20±2 o C Dry Soil

293 days (DFOP)

Moist Soil

¥
354 days (SFO) Dry Soil

296 days (DFOP)

Moist Soil

¥
230 days (SFO) 49011978 b

Supplemental

Aerobic Soil

Metabolism † ND Loamy Sand pH 7.8

20±2°C

1.1% OC 46 days

(IORE) 57.5 days

(IORE) 49011981 c

Supplemental

German Sandy

Loam pH 8.4

20±2°C

1.1% OC 24.5 days

(IORE) 24.9 days

(SFO)

49011982 c

Supplemental UK Silt Loam pH 7.5

20±2°C

2.2% OC 50.6 days

(DFOP) 65.3 days

(DFOP)

UK Sand pH 8.3

20±2° C

0.8% OC 66.2 days

(IORE) 59.2 days

(SFO)

### 85 Study System Details Representative Half

- Life*

MRID Parent Only

(Kinetic Equation) Pa rent, 4HP , and

PPA

(Kinetic Equation)

Anaerobic Soil

Metabolism ND Sand pH 7.1

20±2°C

1.1% OC 572 days

(SFO) 700 days

(SFO) 49011985 d

Supplemental

Aerobic Aquatic

Metabolism UK, Calwich Abbey

Lake pH 7.9

20±2°C

4.8% OC 173 days

(SFO) 361 days

( SFO )

49011986 b

Supplemental UK, Swiss Lake pH 6.4

20±2°C

0.8% OC 108 days

( SFO ) 173 days

( SFO )

Anaerobic Aquatic

Metabolism ND, Goose River pH 7.8

20±2°C

3.1% OC Stable

( 1,307 days,

SFO ) Stable

( 1,385 days, SFO )

49011987 b

Supplemental ND, Golden Lake

p H 8.2

20±2°C

1.0% OC Stable

(1,944 days, SFO) Stable

(2,715 days, SFO)

OC=organic carbon SFO=single first order; DFOP=double first order in parallel; IORE=indeterminate order (IORE)

* Representative half

- lives are estimated SFO half

- lives from a degra dation curve that does not necessarily follow the SFO equation. Representative half

- life values were calculated using nonlinear regression and SFO, DFOP, or IORE degradation kinetics equations. The equations can be found in the document, Standard Operati ng Procedure for Using the NAFTA Guidance to Calculate Representative Half

- life Values and Characterizing Pesticide Degradation ( US EPA

. 2012 )

. Representative hal f

- life v alue s calculated in this table do not include unextracted residues , as exhaustive extraction methods were used in

the studies

. Note that one aerobic soil metabolism half

- life calculated for total toxic residues is longer than

those calculated for the parent compound, and thus not comparable to the half

- life calculated for the parent compound. This is an artifact of selecting amongst multiple degradation kinetics equations. In general,

half

- lives for the parent and total toxic residues were compar able when using the same equation.

¥ Representative half

- lives for moist soil photolysis were corrected for the moist dark control, which has a

DT 50 of 312 days (IORE) and a stable representative half

- life (285,000 days, IORE).
† Representative half

- lives for the ND Loamy Sand (MRID 49011981 ) include both benzene and thiophene radiolabeled compounds. The half

- life for the benzene ring only is 47.9 days (IORE) and the half

- life for the thiophene ring only is 44.1 days (IORE). Only the benzene ring was rad iolabeled for tests conducted on the three other soils (MRID 49011982).

a 4HP and PPA formation was not observed in the aqueous photolysis study.

b A formation and decline pattern was not observed for all degradates included in the representative half

- life

calculation

.

### 86 c Degradates included in the representative half

- life calculation peak and decline within the duration of the study period. For the UK Silt Loam in MRID 49011982 , there is some uncertainty as the decline was only observed on the last sample date.

d PPA is included in the representative half

- life calculation, although i t is unclear whether PPA concentrations are increasing or decreasing at study termination.



### Table E4 . Summary of Terrestrial Field Dissipation Study Results For Isofetamid ¤

M RID (Year) Study Site,

Crop, and Application

Rate ¥ % Carryover of

Residues Representative

Half

- Life * and

DT 50 DT 9 0 Max

Concentration in Soil (mg/kg

- soil) Max Depth

detected

Parent 4HP

49011993 (2010) Northwood,

ND, USA Bare ground

- sandy loam

3 a pps: 752,

755 and 745 g a.i./ha 9.3%

- isofetamid,

0%

- 4HP at 359 days after last application Representative

Half

- Life: 37.9 days (IORE)

DT 50 : 6.98 days (IORE) 126 days

(IORE) 0.589

0

- 15

cm 0.013

0

- 15 cm

49018438 (2010) Aberdeen,

SK, Canada Bare groun d

- clay loam 3 apps: 767,

724 and 716 g a.i./ha 46%

- iso fetamid, 0%

- 4HP at 301 days after last application

8.7%

- isofetamid,

0%

- 4HP at study termination, 709 days after last application 247 days

(SFO) 822 days

(SFO) 0.543

0

- 15

cm 0.025

0

- 15 cm

49 018441 (2011) Proctor, AR,

USA

Bermuda Turfgrass grown on silt

loam 8 apps: 509 g

a.i./ha 28.6%

- isofetamid

(0

- 8 cm),

0%

- 4HP (0

- 8 cm) at 120 days after last application 79.8 days

(SFO) 265 days

(SFO) 0.0789

8

- 15

cm 0.0104

0

- 8 cm

49011992 (2010) Kerm an, CA,

USA

Bare ground

- loamy sand

soil 3 apps: 746,

731 and 749 g a.i./ha 3% isofetamid (0

- 15

cm) at 365 days after last application 39 days (SFO) 130 days

(SFO) 0.515

15

- 30

cm No

Detections

49018442 (2011) Goldsboro,

NC, USA

Fescue Turfgrass

grown o n sandy loam 8 apps: 509 g

a.i./ha 37%

- isofetamid (0

- 8

cm),

38%

- 4 HP (0

- 8 cm) at 119 days after last application 39.4 days

(SFO) 131 days

(SFO) 0.112

15

- 30

cm 0.015

8

- 15 cm

### 87

¤ Turf Dissipation Studies also analyze thatch for degradates 4HP and GPTC . Thatch results are not reported in this table. ¥ Formulation applied in each study is a suspension concentrate

* Representative half

- lives are estimated SFO half

- lives from a degradation curve that does not necessarily follow the SFO equation. Represen tative half

- life values were calculated using nonlinear regression and SFO, DFOP, or IORE degradation kinetics equations. The equations can be found in the document, Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Hal f

- life Values and Characterizing Pesticide Degradation ( US EPA

. 2012 )

.



### Table E5

. Summary of maximum amount of transformation products observed in

fate studies.

Compound Maximum % of Applied Radioactivity Associated with Degradate (Day of Peak)

Maximum Amount Detected at Final Sampling Interval in Corresponding Study, Radiolabel, and for Hydrolysis, pH (Day of Study Termination) Hydrolysis Soil Photolysis

Ae robic Soil Anaerobic Soil b Aqueous Photolysis Aerobic Aquatic Anaerobic Aquatic Observed in Field Dissipation

Isofetamid 93.3 (0) 98.7 (0) 100.3 (0) 69.9 (30) 97.0 (0) 97.0 (0) 107.8 (7)

Yes 95.2 (5) 72.6

(30) 24.0

(120) 60.9

(150) ND (30) 52.0

(100) 82 .7

(365)

4HP 3.7 (21) 10.4 (30) 10.3

(150) 7.6

(100) 2.5 (365)

Yes 2.7 (30) 6.0

(120) same same same

PPA 2.0 (30) 4.4 (30) 2.0 (150) 11.8 (100) 3.3 (365)

N/A same ND

(120) same same same

IBA 6.2 (30) ND (all) 0.4 (150) 80.8 (10) 7.5 (59) 1.0 (59)

same ND

(120) same 73.9

(30) 0.5

(100) 0.3 (365)

3

- MTCAM 5.5 (14) 0.5 (14) 0.9 (30) 0.7 (0) 0.9 (0)

5.0 (30) ND

(120) ND

(150) ND

(100) ND

(365)

3

- MCTA 2.0 (21) 2.4 (59) 0.6 (120) 1.5 (59) 0.7 (7)

1.0 (30) 0. 5

(120) 0.5 (150) 0.9 (100) ND

(365)

Polar Compound 66.8 (20)

64.3 (30)

UnkAnS01 1.3 (60)

0.4 (150)

UnkAE02 4.0 (92, 120)

same

UnkSP01 2.6 (30)

### 88

Compound Maximum % of Applied Radioactivity Associated with Degradate (Day of Peak)

Maximum Amount Detected at Final Sampling Interval in Corresponding Study, Radiolabel, and for Hydrolysis, pH (Day of Study Termination) Hydrolysis Soil Photolysis

Ae robic Soil Anaerobic Soil b Aqueous Photolysis Aerobic Aquatic Anaerobic Aquatic Observed in Field Dissipation

same

Largest

Unknown 2.0 (30) 6.0 (92) Not Reported 8.0 (10) Not Reported same 2.9

(120) 4.7 (30)

Total Other

Unknowns 0.5 (0) 7.0 (30) 12.0 (92) 6.3 (150) 13.1 (2) 20.2 (100) 5.8 (365)

ND (5) same 11.4

(120) same 11.9

(30) same s ame

Unextracted

Residues 10.5 (30) 55.4

(92) a 14.8

(120) 9.7

(100) 11.6

(365)

same 53.6

(120) a 14.7

(150) same same

ND=not dete cted

a Only one sample was available for analysis at the end of this study; typically there are replicate s.
b In this study, the test system was aerobic from days 0

- 30 and flooded on day 30.

### 89

ECOSAR Version 1.11 Results Page

Parent:

SMILES : C(C)(C)(C(=O)c2c(C)cc(OC(C)C)cc2)NC(=O)c1c(C)ccs1

CHEM : IKF

- 5411

CAS Num:

ChemID1:

MOL FOR: C20 H25 N1 O3 S1

MOL WT : 359.49 Log Kow: 5.582 (EPISuite Kowwin v1.68 Estimate) Log Kow: 2.500 (User Entered) Log Kow: (PhysProp DB exp value

- for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp D B exp value for Wat Sol estimate) Wat Sol: 39.78 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: 5.33 (mg/L, User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Prof ile

-------------------------------------- Log Kow: 2.500 (User Entered) Wat Sol: 5.33 (mg/L, User Entered)

-------------------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Thiophenes

Amides

Predicted

ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

========== Thiophenes : Fish 96

- hr LC50 27.583 * Thiophenes : Daphnid 48

- hr LC50 18.476 * Thiophenes : Green Algae 96

- hr EC50 33.400 * Thiophenes : Fi sh ChV 2.180 ! Thiophenes : Daphnid ChV 1.874 ! Thiophenes : Green Algae ChV 26.369 *

Amides : Fish 96

- hr LC50 47.146 * Amides : Daphnid 48

- hr LC50 41.229 * Amides : Green Algae 96

- hr EC50 1.652

Amides : Fish ChV 0.109 Amides : Daphnid ChV 3.217

### 90

Amides : Green Algae ChV 1.916 Amides : Fish (SW) 96

- hr LC50 4 1.855 * Amides : Mysid (SW) 96

- hr LC50 3.099

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

========== Neutral Organic SAR : Fish 96

- hr LC50 105.014 * (Basel ine Toxicity) : Daphnid 48

- hr LC50 62.445 *

: Green Algae 96

- hr EC50 56.299 *

: Fish ChV 10.839 * : Daphnid ChV 6.925 * : Green Algae ChV 16.340 *

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- chronic ratios p er methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effects at saturation are expected for those endpoints.

Thiophenes:

---------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Amides :

------- Maximum LogKow: >8.5 (LC50)

Maxim um LogKow: >8.0 (EC50,ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

### 91

PPA:

SMILES : C(C)(C)(C(=O)c2c(C)cc(O C(=O)O)cc2)NC(=O)c1c(C)ccs1

CHEM : PPA

CAS Num:

ChemID1:

MOL FOR: C18 H19 N1 O5 S1

MOL WT : 361.42 Log Kow: 3.903 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value

- for comparison only ) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate) Wat Sol: 2.453 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 3.903 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 2.453 (mg/L, EPISuite WSKowwin v1.43 Estimate)

---------- ---------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Thiophenes

Amides

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

========== Thiophenes : Fish 96

- hr LC50 3.049 * Thiophenes : Daphnid 48

- hr L C50 2.286 Thiophenes : Green Algae 96

- hr EC50 2.945 * Thiophenes : Fish ChV 0.211 ! Thiophenes : Daphnid ChV 0 .236 ! Thiophenes : Green Algae ChV 3.342 *

Amides : Fish 96

- hr LC50 4.703 * Amides : Daphnid 48

- hr LC50 2.155

Amides : Green Algae 96

- hr EC50 0.223

Amides : Fish ChV 0.025 Amides : Daphnid ChV 0.425

Amides : Green Algae ChV 0.467 Amides : Fish (SW) 96

- hr LC50 4.235 * Amides : Mysid (SW) 96

- hr LC50 0.488

### 92

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

========== Neutral Organic SAR : Fish 96

- hr LC50 5.800 * (Baseline Toxicity) : Daphnid 48

- hr LC50 3.926 *

: Green Algae 9 6

- hr EC50 6.048 *

: Fish ChV 0.698 : Daphnid ChV 0.624 : Green Algae ChV 2.342

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- chronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effects at saturation are expected for those endpoints.

Thiophenes:

---------- Maximum Lo gKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50 ; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

### 93

4HP:

SMILES : C(C)(C)(C(=O)c2c(C)cc(O)cc2)NC(=O)c1c(C)ccs1

CHEM : 4HP

CAS Num:

ChemID1:

MOL FOR: C17 H19 N1 O3 S1

MOL WT : 317.41 Log Kow: 4.112 (EPISuite Koww in v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value

- for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate)

Wat Sol: 11.35 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Ko w: 4.112 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 11.35 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Phenols Thiophenes

Amides

Ph enol Amines

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

========== Ph enols : Fish 96

- hr LC50 1.367 Phenols : Daphnid 48

- hr LC50 1.054 Phenols : Green Algae 96

- hr EC50 3.950

Phenols : Fish ChV 0.188 Phenols : Daphnid ChV 0.200

Phenols : Green Algae ChV 1.807

Phenols : Fish (SW) 96

- hr LC50 0.417

Phenols : Earthworm 14

- day LC50 40.351 * Phenols : Lemna gibba 7

- day EC50 0.578

Thiophenes : Fish 96

- hr LC50 1.927 Thiophenes : Daphnid 48

- hr LC50 1.469 Thiophenes : Green Algae 96

- hr EC50 1.799 Thiophenes : Fish Ch V 0.131 !

### 94

Thiophenes : Daphnid ChV 0.152 ! Thiophenes : Green Algae ChV 2.155

Amides : Fish 96

- hr LC50 2.926 Amides : Daphnid 48

- hr LC50 1.217 Amides : Green Algae 96

- hr EC50 0.145

Amides : Fish ChV 0.018

Amides : Daphnid ChV 0.275

Amides : Green Algae ChV 0.332 Amides : Fish (SW) 96

- hr LC50 2.641

Amides : Mysid (SW) 96

- hr LC50 0.325

Phenol Amines : Fish 96

- hr LC50 1.553 Phenol Amines : Daphnid 48

- hr LC50 0.593 Phenol Amines : Green Algae 96

- hr EC50 0.426

Phenol Amines : Fish ChV 0.035 !

Phenol Amines : Daphnid ChV 0.036

Phenol Amines : Green Algae ChV 0.166

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

========== Neutral Organic SAR : Fish 96

- hr LC50 3.304 (Baseline Toxicity) : Daphnid 48

- hr LC50 2.280

: Green Algae 96

- hr EC50 3.805

: Fish ChV 0.407 : Daphnid ChV 0.383 : Green Algae ChV 1.538

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- chronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented be low, then no effects at saturation are expected for those endpoints.

Phenols:

------- Maximum LogKow: 7.0 (Fish 96

- hr LC50, Daphnid LC50) Maximum LogKow: 6.4 (Earthworm, Lemna)

### 95

Maximum LogKow: 7.0 (Green Algae EC50 Maximum LogKow: 8.0 (ChV) Maximum LogKo w: 5.0 (Fish (SW) 96

- hr LC50, Mysid)

Thiophenes:

---------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Amides :

------- Maximum LogKow: >8.5 (LC50) Maximum LogKow: >8.0 (EC50,ChV)

Phenol Amines :

-------------- Ma ximum LogKow: 5.0 (Fish 96

- hr LC50) Maximum LogKow: 7.0 (Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50 Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50 ) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)