1

The results of this screening-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 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 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 

expected 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 PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

PC Code: 270000

 DP Barcode: 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

Environmental Fate and Effects Division

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

Melanie Biscoe, Physical Scientist

Environmental Risk Branch III

Environmental Fate 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 ecological risk 

assessment for the Section 3 registration decision on the new broad-spectrum, systemic 

fungicide isofetamid (IKF-5411) (PC Code 270000). 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 single application rate is 0.572 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 expected 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-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 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 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 

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

There are a few notable uncertainties in the risk conclusions described above. Currently,

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

fathead minnow), therefore, there is uncertainty regarding the chronic freshwater fish 

endpoint. However, additional 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 

available 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 aquatic 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, 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 isofetamid

and the wet-harvested cranberry use. A definitive NOAEC would help address this 

uncertainty. 

The 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). The guidance 

document indicates that if exposure of bees to a pesticide is expected, a Tier I screeninglevel 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 risk 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 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 fullfield studies conducted with whole colonies. Below is the suite of honey bee toxicity and 

residues studies:

Tier I Data

 Acute oral toxicity to larval honey bees (Non-guideline, OECD TG 237)

 Chronic 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 terrestrial 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 FORMULATION ................................................................................. 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 Model ................................................................................... 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 Characterization .............................................................................. 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 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. .................................................................................................................. 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 Labels1. ...................... 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 wetharvested 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 Animals. ...................... 40

Table 12. Submitted Toxicity Data for Isofetamid and Aquatic Plants. .......................... 44

Table 13. Submitted Toxicity Data for Isofetamid and 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 Isofetamid 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-day 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 Proposed 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 (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. Both proposed end-use products have a single active 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 maximum 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 phenyl-oxo-ethyl thiophene amide and is a succinate dehydrogenase 

inhibitor (SDHI). Other fungicides that also target this site (complex II:succinatedehydro-genase) include, but are not limited to, carboxin, fluopyram, sedaxane, and 

boscalid. 

Two environmental 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 EPISuite v. 4.1; see APPENDIX E, Table E1 for structures). These 

two degradates, along with isofetamid, are considered in the Total Toxic Residues (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 

GPTC 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 (KFoc values are 274 to 603 mL/g-organic carbon) 

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

Major routes of degradation for isofetamid include photolytic degradation in water (halflife 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.

Isofetamid’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 KFoc values 110 - 355 mL/g-organic carbon, PPA EPISuite v.4.1 Koc 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 10-7torr and are therefore are not expected to 

volatilize under field conditions. 

Isofetamid and its degradates 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. Isofetamid 

and its degradates are less persistent in aerobic soil, with aerobic soil metabolism halflives ranging from 25 to 65 days. Results from terrestrial field dissipation studies suggest 

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

chemical 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 

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 effects (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 resulted 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, the most sensitive monocot in the seedling emergence study was 

ryegrass based on dry weight, with NOAEC and EC25 values of 83.7 and 576 lb ai/A, 

respectively. The most sensitive dicot was tomato, based on dry weight, with NOAEC 

and EC25 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 EC25 values of 1.07 

and 1.3 lb ai/A, respectively. The most sensitive dicot was determined to be soybean 

with NOAEC and EC25 values of 1.07 and 1.26 lb ai/A. The most sensitive aquatic plant 

tested was the marine diatom Skeletonema costatum with an EC50 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 terrestrial plants. Additionally, 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 RQ for estuarine/marine invertebrates is 0.466 

(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, the 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 

from 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 available 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 parent. However, given 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 fate 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 photolysis and metabolism studies conducted for isofetamid parent, 4HP and PPA 

did not consistently peak and decline by the end of each study (see APPENDIX E, Table 

E3). This introduces some uncertainty in the representative half-lives calculated for 

isofetamid TTR; 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 have 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 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). 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 isofetamid 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 profile of the chemical, 

additional data are not expected to alter risk conclusions.

The 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). The guidance 

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

low risk 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 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 fullfield 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-methyl-4-(1-methylethoxy)phenyl]-

2-oxoethyl] -3-methyl-2-thiophenecarboxamide) (PC Code: 270000). 

A. Stressor Source and Distribution

1. Source and Intensity

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

one manufacturing product and two end-use products) by the applicant ISK 

BIOSCIENCES CORPORATION (a subsidiary of ISHIHARA SANGYO KAISHA, 

LTD.). The isofetamid end-use products being proposed for registration in the United 

States are 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 labels, 

isofetamid is a broad-spectrum fungicide with preventative, systemic, and curative 

properties for foliar and soil-borne diseases. The turf product (Isofetamid Turf 

Fungicide) would be used to control dollar spot on turfgrasses. The Isofetamid 400SC 

product would be used to treat a variety of fungal diseases in almond, lettuce, grapes, 

low-growing berries, and rapeseed. The proposed application methods of isofetamid

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 enzyme 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, fluopyram, 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 does not have any usage information for 

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

berries, rapeseed, and turf.
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 

very 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 Effects in 

Screening-Level Risk Assessments.

Taxonomic Group Example(s) of Representative Species

Birds1Passerine

Mallard duck (Anas platyrhynchos), or

Bobwhite quail (Colinus virginianus)

Mammals Laboratory rat (Rattus norvegicus)

Terrestrial invertebrates Honey bee (Apis mellifera L.)

Freshwater fish2 Bluegill sunfish (Lepomis macrochirus)

Rainbow trout (Oncorhynchus mykiss)

Freshwater invertebrates Water flea (Daphnia magna)

Estuarine/marine fish Sheepshead minnow (Cyprinodon variegatus)

Estuarine/marine invertebrates Mysid (Americamysis bahia)

Eastern oyster (Crassostrea virginica)

Terrestrial plants3 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 species 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 to 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 aquatic 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 animals and plants (CFR 40 §158.630, 2009). 
15

D. Conceptual 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 and 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 presumes the following 

risk hypothesis for this screening level assessment:

Based on mode of action, the proposed use patterns, and the sensitivity of nontarget 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 through 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 plants. 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 aquatic 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.

Since volatility of isofetamid does not appear to be an issue, this assessment does not take 

into account atmospheric transport in estimating environmental concentrations. Exposure 

to terrestrial animals is based primarily on dietary consumption of foliar residues 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

This 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 toxicity 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 almond, 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 estimated environmental concentrations (EECs) are based on 

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

approach. Even though only the parent chemical is modeled in the terrestrial modeling, the 

terrestrial EECs are expected to account for the parent and all residues of concern, including 

4HP, PPA, and the metabolite, GPTC, because a default 35-day foliar half-life is used (due 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 concentration) 

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 fate 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 the 

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 deficiencies in the study that introduce uncertainty into our 

understanding of the mobility of 4HP. However, because the estimated KFs and KFocs suggest 

that 4HP is mobile to moderately mobile (KFocsrange from 110 to 355 mL/g-organic carbon), it 

is not expected 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 Koc values would 

range from 121 to 180 mL/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 study 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 the 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 used 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 at 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 chronic 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 EC50 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 PPA. 

Additionally there are uncertainties associated with estimating dietary exposures to birds and 

mammals from contaminated feed items with systemic pesticides since our current model (TREX) 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 environments, 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 concentrations 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 1.106) model and the Pesticide Flooded Application Model (PFAM 

version 0.70) was used to generate aquatic EECs. 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 exposures and 1-in-10-year EECs of isofetamid that may occur in 

surface water bodies adjacent to application sites receiving isofetamid through runoff and spray 

drift. SWCC simulates pesticide application, movement and transformation on an agricultural 

field and the resultant pesticide loadings to a receiving water body via runoff, erosion, and spray 

drift, 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 m3volume) with no outlet. The SWCC is used to estimate screening-level 

exposure 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 aquatic 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.

For 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 developed 

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, evaporation, 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 conditions 

(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 estimates exposure in the field effluent, which is eventually 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 (mass and volume) 

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

EECs using the varying volume pond model (FIFRA SAP 2004). This portion of the model is 

still under development and evaluation, so the derived estimates 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 

the 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 environmental assessment 

because the rapid metabolism could not be assumed for all taxa; therefore, they were assessed in 

the aquatic risk assessment using the total toxic residues approach. This approach was used to 

determine the environmental fate data parameters 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 for 

listed and non-listed animals in screening level assessments are the LD50, LC50 or EC50, 

depending on taxa (see Table 3). Endpoints for chronic measures of exposure for listed and nonlisted animals are the NOAEL or NOAEC. For non-listed plants, only acute exposures are 

assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants). For listed terrestrial plants 

the Agency uses the EC5 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 EC50 or LC50 (acute toxicity tests)

Chronic Lowest NOAEC (early life-stage or full life-cycle tests)

Terrestrial Animals

Birds

Acute/Sub-acute Lowest LD50 (single oral dose) and LC50 (subacute 

dietary)

Chronic Lowest NOAEC (21-week reproduction test)

Terrestrial Animals

Mammals

Acute Lowest LD50 (single oral dose test)

Chronic Lowest NOAEC (two-generation reproduction test)

Plants

Terrestrial non-listed (monocots 

and dicots)

Acute/Chronic Lowest EC25 (seedling emergence and vegetative vigor)

Plants

Terrestrial listed (monocots and 

dicots)

Acute/Chronic EC05 or NOAEC associated with the lowest EC25

(seedling emergence and vegetative vigor)

Plants

Aquatic non-listed (vascular and 

non-vascular)

Acute/Chronic Lowest EC50

Plants

Aquatic listed (vascular and 

algae)

Acute/Chronic EC05 or NOAEC associated with the lowest EC50

III. ANALYSIS

A. Use Characterization

The proposed isofetamid registration being assessed here is for almond, lettuce, grapes, lowgrowing berries (including wet-harvested cranberry), rapeseed, and turf (commercial and 

residential). Therefore, potential isofetamid use sites are found throughout much of the US. 

Isofetamid is applied as a foliar spray via ground or aerial equipment or via chemigation. There 

are two isofetamid end-use products being proposed for registration in the United States: 

Isofetamid 400SC Agricultural Fungicide (flowable suspension concentrate; 36.0% isofetamid; 

the product does not contain any other active ingredients); and Isofetamid Turf Fungicide 

(flowable suspension concentrate; 36.0% isofetamid; the product does not contain any other 

active ingredients). According to the proposed labels, 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 Information from the Proposed Isofetamid Labels1.

Crop

Maximum 

Individual

Application 

Rate

lb a.i./A

Number of

Applications/ 

year

Minimum

Application 

Interval 

(days)

Max Annual 

Application 

Rate in lb

a.i./A/year

Application 

Method Comments

Almond 0.442 4

2

7 with 14 

days between 

second and 

third 

applications

1.77

Ground

Aerial

Chemigation3

- 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 

application.

Lettuce 

(head and 

leaf)

0.320 2 14 0.64

Ground

Aerial

Chemigation3

- on direct 

seeded lettuce 

make first 

application 

after 

emergence, 

thinning or 

prior to onset 

of disease 

development; 

on transplanted 

lettuce make 

application 

immediately 

after 

transplanting 

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 

second and 

third 

applications

1.72

Ground

Aerial

Chemigation3

- 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 in lb

a.i./A/year

Application 

Method Comments

within 28 days 

of the second 

application.

Low 

growing 

berries 

(Crop 

Subgroup 

13-07G)5

0.400 3 applications 

of 0.4 lb 

a.i./acre and a 

fourth 

application of 

0.2 lb a.i./acre2

14 with 28 

days between 

second and 

third 

applications

1.4 Ground

Aerial

Chemigation3

- 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

Chemigation3

- Initiate 

applications at 

20 -40% 

flowering or 

prior to disease 

development. 

A second 

application 

may be made 

near the end of 

flowering.

- Do not make 

more than two 

sequential 

applications of 

isofetamid.

Turf70.567

8 applications 

are allowed at 

0.452 lb 

a.i./acre/applic

ation 

6 applications 

are allowed at 

0.567 lb 

a.i./acre/applic

ation in 

addition to 1 

application of

0.248 lb 

a.i./acre/applic

ation8

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 

isofetamid.

- 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

Includes 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, lingonberry, muntries, partridgeberry, 

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 commercial 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 single application rate of 0.248 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 to 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). Half-lives calculated for isofetamid parent in the aerobic soil metabolism studies 

ranged from 25 to 66 days, with comparable DT50s. Half-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 half-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, aerobic soil metabolism half-lives for isofetamid and its residues of concern range from 

25 to 65 days, with comparable DT50s. The aerobic aquatic metabolism half-lives range from 

173 to 361 days. There is some uncertainty with regard to the aerobic 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 APPENDIX E Table E3 footnotes. 

The soil photolysis half-lives for isofetamid and its degradates ranged from 230 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-lives 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. 

Isofetamid’s vapor pressure (4.4 ×10-11 Torr) and Henry’s Law Constant (1.2×10-5Pa-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 10-7torr and are 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 Kd values range from 6.59 to 19.43 

mL/g, while KF values range from 6.64 to 20.79 with 1/n values ranging from 0.873 to 0.991. Koc 

values range from 281 to 615 mL/g-organic carbon and KFoc values range from 274 to 603 mL/gorganic carbon. Results from this study are also summarized in APPENDIX 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 Koc’s and KFoc’s than for 

the Kd’s and KF’s indicating a correlation between isofetamid soil sorption and soil organic 

carbon content; however, a regression analysis of percent organic carbon versus KF for the five 

soils did not find this relationship to be statistically significant. Adsorption and desorption both 

decreased slightly with increasing concentration in the study. Based on its KFoc 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 KF values range from 3.9 (

1

/n = 0.93) to 

8.58 mL/g (1/n = 0.86) and the KFoc values range from 110 to 355 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 mobile 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 Koc values for PPA range from 121-180 mL/g-organic carbon, 

making it mobile to moderately mobile (FAO 2000). 

Based on their KFoc and Koc 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 waterbody’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 APPENDIX E, Table E4. Three studies were conducted on bare ground sites in 
27

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

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

made at each site. The single application rates in each study ranged between 500 and 800 g 

a.i./ha, which are comparable to the proposed application rate for isofetamid. 

Isofetamid parent dissipation half-lives calculated for the whole soil profile ranged from 38 to 47

days for four of the five studies. The half-life for the Aberdeen, Saskatchewan study was 247 

days, and this longer half-life was attributed to a prolonged winter. With the exception of the 

Saskatchewan study, DT50s in the terrestrial field 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 surface 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 ranged 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 field 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 was 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. Year-toyear accumulation of 4HP is not expected to occur, as no carryover of 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 

APPENDIX E, Table E1. A summary 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 parent, 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 and 

anaerobic 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 (Swiss 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 hydrolysis 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 metabolism, anaerobic soil metabolism, and 

anaerobic aquatic metabolism studies, reaching maxima of 2.0 %AR (moist soil, day 30), 4.4% 

AR (a United Kingdom 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 though 

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 ring 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 buffered 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 molecular 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 components 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-thiophenecarboxylic 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.

Unknowns 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 unknowns were less than 10% AR.
29

GPTC was observed in magnitude of residue studies for 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 any 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 summarized 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 

modeling 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. SWCC: Summary 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 

Scenarios5

FL Turf

PA Turf

CA Strawberry 

(RLF)

FL Strawberry1

OR Berries (OP)

CA 

Almond1

CA Grapes1

CA Fruit1

NY Grapes

CA Lettuce

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

0.448 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 

Footnote 3.

Application 

Efficiency 0.99 0.95 and0.99

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 

Guidance

Type of 

Application Foliar

See 

Footnote 2

Initial Date of 

Application5

(month/day)

FL Turf: 2/1

PA Turf: 4/1

CA Strawberry 

(RLF): 1/1

FL Strawberry: 

10/1

OR Berries (OP): 

4/1

CA 

Almond: 

1/16

CA Grapes: 

2/1

CA Fruit: 

1/16

NY Grapes: 

6/1

CA Lettuce: 

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 

second 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 Symbols 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 Rapeseed 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 exception 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 emergence.

5 With regard to SWCC scenario names, RLF is the acronym for Red-Legged Frog and OP is the acronym for Organophosphate.

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

toxic 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 KFoc

491 mL/goc

MRID 49011979

Mean of isofetamid KFoc's calculated for five 

soils2.

Hydrolysis Stable MRID 49011976

Aerobic Soil Metabolism Halflife (20°C) 66.62 days1MRIDs 49011981 and 49011982

The 90th percentile confidence bound on the 

mean of four soil half-lives. 

Anaerobic Soil Metabolism Halflife (20°C) Stable1 MRID 49011985

Aerobic Aquatic Metabolism 

Half-life (20°C) 556.30 days1

MRID 49011986

The 90th percentile confidence bound on the 

mean of two test system half-lives.

Anaerobic Aquatic Metabolism 

Half-life (20°C) Stable1 MRID 49011987

Aqueous Photolysis 

Half-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 water (20oC)

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 parent; although this KFoc was expected to result in lower EECs than the Kocs for

4HP and PPA reported in this assessment, a sensitivity analysis demonstrated that using the KFoc for isofetamid 

parent did not reduce EECs. Additionally, the KFoc for isofetamid parent is based on more reliable data than the 

reported Kocs for 4HP and PPA.

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

Input Parameter Value Comments Source

Water column half-life 

(d) at

20 °C

556.31

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 conditions. MRID 49011985

Unflooded half-life at 20 

°C (d) 66.621

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 halflife at

40° Latitude (d)

1.8

The longer half-life of the two halflives 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 (KOC) 

(L/kgOC)

180

For parent, the mean of isofetamid 

KFoc's calculated for five soils. For 

TTR, lowest Koc value for TTR in all 

submitted data and EpiSuite 4.1 

estimates using the Kow method2. 180 

L/kgOC 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 each 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 water 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 Estimated value (Estimated)

Max. aerial coverage 0.2 Value from OR berries PE scenario (Estimated)
33

Input Parameter Value Comments Source

Area of application (m2) 100,000

Parent: Represents 10x the area of the 

Index Reservoir

TTR: Represents 10 ha application 

area that drains to the Farm Pond

(Calculated)

Area of watershed (m2) 0

Parent: Area of the Index Reservoir 

watershed

TTR: No surrounding watershed 

considered

USEPA, 2010a

Watershed curve number 84 Value for fallow conditions in OR 

berries and other PE scenarios (Estimated)

Base flow (m3/sec) 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/kgOC was used for surface water modeling using the SWCC because a sensitivity analysis demonstrated that 

using the KFoc 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 nonflooded agricultural crops, the CA Strawberry (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 overall), LaCrosse, Wisconsin. For non-flooded agricultural crops, peak 1-in10 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 proposed uses of isofetamid 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 WetHarvested 

Cranberry

CAStrawberrynoplasticRLF_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

Boston, 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 Canola

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 uses is limited to foliar spray via ground

equipment, aerial equipment (except turf), and via chemigation (except turf). Therefore, for this 

terrestrial exposure assessment, we consider only foliar applications. 

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

isofetamid using the maximum annual application rates and the maximum proposed single

application rates for the plant analyses. Terrestrial exposure estimates for avian and mammalian 

risk assessments were derived using 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 terrestrial 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 contained in APPENDIX C. 
35

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).

USE DIETARY-BASED 

EECs 

KENAGA 

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 3rd 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 135

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 2nd

and 3rd 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-day application 

interval with 28 days between 2nd

and 3rd 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

Tall Grass 178.13

Broadleaf Plants 218.62

Fruits/Pods/Seeds 24.29

Arthropods 152.22

1 The ‘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 estimated using the TerrPlant (v1.2.2) screening model. 

TerrPlant estimates potential exposure from a single application using default assumptions for 

runoff (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). See APPENDIX D for more 

information.
36

Table 9. EECs on Plants Following Label-Specified Ground and Aerial Applications of 

Isofetamid Using the TerrPlant Model (lb a.i./A).

USE RATE

SPRAY 

DRIFT ONLY

(lb a.i./A)

TOTAL 

FOR DRY 

AREAS

(lb a.i./A)

TOTAL FOR 

SEMIAQUATIC 

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 0.003 0.006 0.035

Lettuce (aerial) 0.320 lb a.i./acre 0.016 0.019 0.048

Grapes (ground) 0.572 lb a.i./acre 0.006 0.011 0.063

Grapes (aerial) 0.572 lb a.i./acre 0.029 0.034 0.086

Low growing berries (ground) 0.400 lb a.i./acre 0.004 0.008 0.044

Low growing berries (aerial) 0.400 lb a.i./acre 0.020 0.024 0.060

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 effects (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 estuarine/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, 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, the most sensitive monocot in the seedling emergence study was ryegrass 

based on dry weight, with NOAEC and EC25 values of 83.675 and 576 lb a.i./A, respectively. 

The most sensitive dicot was tomato, based on dry weight, with NOAEC and EC25 values of 

2.615 and 10.3 lb a.i./A, respectively. In the vegetative vigor study, the most sensitive monocot 

was determined to be corn with NOAEC and EC25 values of 1.07 and 1.3 lb a.i./A, respectively. 

The most sensitive dicot was determined to be soybean with NOAEC and EC25 values of 1.07 

and 1.26 lb a.i./A.

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

EC50 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 Specific Assessment Endpoints for Animals and Plants Considered in this 

Assessment 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 LC50 = 2.27 mg a.i./L Mortality 49018402/Acceptable

Chronic

Pimephales promelas

Fathead minnow

NOAEC = 0.086 mg 

a.i./L Reduced growth 49018406/Acceptable

Freshwater 

Invertebrates

Acute

Daphnia magna

Waterflea EC50 = 4.7 mg a.i./L Mortality/ immobility 49011995/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

LC50 >2.8 mg a.i../L

None (no effects at 

the highest 

concentration tested)

49018404/

Acceptable

Chronic

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

Estuarine/Marine 

Invertebrates

Acute

Crassostrea virginica

Eastern oyster EC50 = 0.44 mg a.i./L Shell deposition 49011997/Acceptable

Americamysis bahia

Mysid LC50 =1.51 mg a.i./L Mortality 49011998/Acceptable

Chronic

Not Available

Aquatic Plants

Acute

Lemna gibba

Duckweed EC50 >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

EC50 = >4.1 mg a.i./L Reduction in yield 49018421/

Supplemental

Listed

Skeletonema 

costatum

Marine diatom

NOAEC = 4.1 mg 

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

Birds

Acute/Sub-Acute

Colinus virginianus

Northern bobwhite 

quail

LC50 = >5,180 mg

a.i./kg-diet;

LD50 = >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

LD50 >2,000 mg 

a.i./kg-bw No effects 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 

slightly delayed sex 

maturation in F1

females.

49011940/ 

Acceptable

Terrestrial 

Invertebrates

Acute

Apis mellifera

Honey Bee

LD50 =100 μg a.i./bee 

(contact)

LD50 > 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)

EC25 = 576 lb a.i./acre Reduced dry weight 49018415/

Acceptable

Dicot: sugarbeet

(Beta vulgaris); 

radish (Raphanus

sativus); lettuce 

(Lactuca sativa); flax 

(Linum 

usitatissimum); 

soybean (Glycine 

max); and tomato 

(Lycopersicon 

esculentum)

EC25 = 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/Acceptable

Dicot: sugarbeet

(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 

esculentum)

Non-listed (Vegetative vigor)

Monocot: corn (Zea 

mays); onion (Allium 

cepa); ryegrass 

(Lolium perenne), 

and wheat, (Triticum 

aestivum)

EC25 = 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)

EC25 = 1.3 lbs a.i./acre Reduced dry weight 49018416/Acce

ptable

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/Acceptable

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/Acceptable

1 N/A = not applicable

1. Aquatic Effects Characterization 

a. Aquatic Animals

Toxicity studies were submitted for four freshwater fish, i.e., rainbow trout (Oncorhynchus 

mykiss), bluegill sunfish (Lepomis macrochirus), common carp (Cyprinus carpio), and fathead 

minnow (Pimephales promelas); two freshwater invertebrates, 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/marine crustacean, i.e., mysid shrimp (Americamysis bahia), all 

exposed to technical grade isofetamid (see Table 11). Acute toxicity 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 

CLASSIFICATIONCOMMENTS

FRESHWATER FISH

Acute

Rainbow trout 

(Oncorhynchus 

mykiss)

96-hr LC50 2.27 

mg a.i./L TGAI (96.7% a.i.) 49018402 Acceptable

NOAEC = 0.528 based on 

mortality and sublethal 

effects; a probit slope could 

not be calculated

Bluegill sunfish 

(Lepomis 

macrochirus)

96-hr LC50 > 3.2

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

Common carp 

(Cyprinus 

carpio)

96-hr LC50 > 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 LC50 = 35

mg a.i./L 400SC (36.5% a.i.) 49018401 Supplemental (qualitative)

NOAEC < 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 Acceptable The LOAEC is based on 

reduced length.

ESTUARINE/MARINE FISH

Acute

Sheepshead 

minnow 

(Cyprinodon 

variegatus)

96-hr LC50 >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 EC50 =

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 

CLASSIFICATIONCOMMENTS

(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 LC50 = 

1.51 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 EC50 = 

0.44mg 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 submitted for the following freshwater fish species: 

Rainbow trout (Oncorhynchus mykiss), bluegill sunfish (Lepomis macrochirus), and common 

carp (Cyprinus carpio). The rainbow trout study, conducted with TGAI, resulted in a 96-hr LC50

of 2.27 mg a.i./L (mean-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. Sublethal 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 NOAEC 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 111).

In the acute bluegill sunfish study with isofetamid (TGAI), the 96-hr LC50 is > 3.2 mg a.i./L 

(mean-measured), the 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. Therefore, there were no 

compound-related effects on survival or sublethal effects 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 LC50 is >6.8 mg a.i./L (MRID 49011999). There was one mortality in 

the highest 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 LC50 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 included 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 concentration 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 NOAEC and LOAEC 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 negative 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 survival at any 

concentration tested. This is the only 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).

Based on the available data, an LC50 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 exposure, 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). The sheepshead minnow study resulted in a 96-hr 

LC50 value >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 currently 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 freshwater invertebrates and isofetamid are available for one species, i.e., 

waterfleas (Daphnia magna). The waterflea study with TGAI resulted in a 48-hr EC50 value of 

4.7 mg a.i./L (mean-measured), with a probit slope of 10.8 (MRID 49011995). Sublethal effects 

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-related 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, respectively), 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 reduced at 

the highest concentration tested (993 mg a.i./kg-sediment). The resulting EC50 for emergence 

was >993 mg a.i./kg-sediment. There were no effects to development rate or sex ratios in the 

treated groups. Therefore, the NOAEC was 483 mg a.i./kg-sediment, 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 EC50 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 invertebrates 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 bahia) and Eastern oyster (Crassostrea 

virginica). In the mysid study with isofetamid (TGAI), the 96-hr LC50 is 1.51 mg a.i./L (based 

on mean-measured values) (MRID 49011998). Percent mortality in the 0.31, 0.64, 1.2, 2.1, and 

4.1 mg a.i./L (mean-measured) test 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 EC50 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 (depending 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-tochronic ratio (ACR) could not be calculated because a definitive NOAEC value is not available 

for the freshwater invertebrate. 
44

b. Aquatic Plants

Acceptable or supplemental studies were submitted for a freshwater vascular plant [i.e., 

duckweed (Lemna gibba)], and three aquatic non-vascular plant species: a green algae 

(Pseudokirchneriella subcapitata formerly known as Selenastrum capricornutum), a freshwater 

diatom (Navicula pelliculosa), and a marine diatom (Skeletonema costatum) exposed to technical 

grade isofetamid (see Table 12). 

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

TAXON ENDPOINT FORMULATION MRID

STUDY 

CLASSIFICATIONCOMMENTS

AQUATIC VASCULAR PLANTS

Duckweed 

(Lemna gibba)

EC50 >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)

EC50 >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)

EC50 >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. Therefore, 

the results from 72-hrs are 

reported here.

Freshwater 

Diatom

(Navicula 

pelliculosa)

EC50 >4.8 mg 

a.i./L

NOAEC = 

0.412 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 EC50 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 EC50 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 EC50 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 effects at the highest treatment concentration 

tested (MRID 49018421). 
45

2. Terrestrial Effects Characterization

a. Terrestrial Animals

Birds

Based on the LD50 values for the northern bobwhite quail (Colinus virginianus) and canary 

(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 13). Isofetamid is no more than “slightly toxic” to avian species on a sub-acute 

dietary-exposure basis, with LC50 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 

CLASSIFICATIONCOMMENTS

Acute Oral

Bobwhite quail 

(Colinus 

virginianus)

14-day LD50

>2,000 mg 

a.i./kg-bw

TGAI (96.7% a.i.) 49018408 Acceptable

The NOAEL < 500 mg a.i./kgbw, based on reduced weight 

gain (in females); there were 

no treatment-related 

mortalities noted in the study.

Canary

(Serenus 

canaria)

14-day LD50

>2,000 mg 

a.i./kg-bw

TGAI (96.7% a.i.) 49018410 Acceptable

There were no treatmentrelated mortalities or sublethal 

effects noted in the study.

Sub-Acute Dietary

Bobwhite quail 

(Colinus 

virginianus)

8-day LC50 

>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 LC50 

>4930 mg 

a.i./kg-diet 

TGAI (96.7% a.i.) 49018412 Acceptable

There were no treatmentrelated 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 reductions 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 LD50 and LC50 endpoints are 

‘greater than’ values), therefore, these endpoints are not used to calculate RQ 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. In the acute oral study with bobwhite quail (MRID 

49018408) no 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 males 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 with bobwhite quail (MRID 49018411) bodyweight 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 treatment-related effects for feed consumption and no 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 mallard ducks 

(MRID 49018412).

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

> 2x the estimated environmental concentration (based on the highest application rate on the

proposed labels: 6.4 applications at 0.567 lb a.i./acre, 14-day application interval). The ‘2x’ 

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 LD50 or LC50 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 controls (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 eggshell thickness, the 

reproductive parameters of all treated groups 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 LD50 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 oralexposure 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 LD50 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 isofetamid in R. norvegicus. 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 maturation in F1 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 

highest 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 toxicity studies with young, adult honey bees

(Apis mellifera); one with TGAI and one with the formulated product, IKF-5411 400SC. The

TGAI study resulted in LD50 values of 100 μg a.i./bee (contact) and >30 μg a.i./bee (oral) 

(MRID 49018426). In the TGAI study the contact LD50 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 

wide confidence interval, the LD50 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 no 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 formulated product (400SC) resulted in LD50 values >100 μg a.i./bee 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 currently 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 LC50 value (based on mortality) was >1,000 mg 

a.i./kg-soil (MRID 49018422). The worms did show a reduction in body weight at the 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 formulated product 

(IKF-5411 400SC), the LD50 value was > 1,000 g a.i./ha (0.89 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 (400SC) there were no effects noted in the study resulting in an LD50

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 400SC, were tested on various 

monocots and dicots in Tier II seedling emergence and vegetative vigor studies (MRIDs

49018415 and 49018416, respectively). Both studies are classified as acceptable.

Seedling Emergence:

In the seedling emergence study, all 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 

and 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 14). 

Height in cabbage, cucumber, lettuce, oat, onion, and ryegrass were significantly reduced by up 

to 16, 13, 20, 8, 18, and 7%, respectively; however the 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 responses were not dose-dependent. There were dose-dependent reductions for 

cucumber, ryegrass and tomato 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 EC25 values of 

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

with NOAEC and EC25 values of 2.615 and 10.3 lb a.i./acre, respectively.
49

Vegetative Vigor:

In the vegetative vigor study, there were no significant reductions in survival for any species at 

any treatment level compared to the 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. 

EC25 values were generated for corn and soybean dry weight; although, these values ranged 

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 EC25 values of 1.07 and 1.3 lb a.i./acre, respectively. The most sensitive dicot was 

determined to be soybean with NOAEC and EC25 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 

CLASSIFICATIONCOMMENTS

Terrestrial 

plants 

(seedling 

emergence)

Monocot: ryegrass

EC25 = 576 lbs 

a.i./acre

NOEC = 83.7 lbs 

a.i./acre

Dicot: Tomato 

EC25 = 10.3 lbs 

a.i./acre

NOEC = 2.6 lbs 

a.i./acre

IKF-5411 400SC 49018415 Acceptable

The most sensitive 

endpoint was dry weight 

for both monocots and 

dicots

Terrestrial 

plants 

(vegetative 

vigor)

Monocot: corn 

EC25 = 1.3 lbs a.i./acre

NOEC = 1.1 lbs 

a.i./acre

Dicot: soybean 

EC25 = 1.3 lbs a.i./acre

NOEC = 1.1 lbs 

a.i./acre

IKF-5411 400SC 49018416 Acceptable

The most sensitive 

endpoint was dry weight 

for both monocots and 

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 chronic toxicity values. The resulting unitless RQs are compared to the 

Agency’s levels of concern (LOCs) (see Table 15), which are the Agency’s interpretive policy 

such that when LOCs are exceeded, the need for regulatory action may be considered. These 

criteria 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

Potential 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 > 0.05 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/marine 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 LC50/EC50 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 effects 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 EC50 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 0.003 (low-growing berries) to 0.09 (wet-harvested cranberries). The only 

chronic RQ exceedances for freshwater (and estuarine/marine) fish were for wet-harvested 

cranberry [the chronic RQs range from 0.07 (low-growing berries) to 2.29 (wet-harvested 

cranberries)]. None of the acute RQs for any of the proposed uses exceed an Agency LOC for 

freshwater invertebrates [RQs range from 0.001 (low-growing berries) to 0.044 (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 

invertebrates range from 0.01 (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 Table 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 RQ1

FW

Invertebrate 

RQ2

E/M 

Invertebrate 

RQ3, 4

Peak 21-

day

60-

day Acute Chronic Acute Acute

Turf

FLturfSTD 

Ground

13.2 12.1 11.

2

0.01 0.13 0.00 0.03

PAturfSTD 20.3 18.7 18 0.01 0.21 0.00 0.05

Lowgrowing 

Berries 

(Crop 

Subgrou

p 13-

07G) 

except 

WetHarvest

-ed 

Cranber

ry

CAStrawber

rynoplasticRL

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

WetHarvest

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 CAalmond_

WirrigSTD

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 

Aerial 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 freshwater 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 endpoint = 4.7 mg a.i./L (4,700 μg a.i./L)

3

For estuarine/marine invertebrates = 0.44 mg a.i./L (440 μg 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 exceed 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

NonListed 

Species

Listed 

Species

Turf

FLturfSTD 

Ground

13.2 <0.01 <0.003 <0.01

PAturfSTD 20.3 <0.01 <0.01 0.01

Low-growing 

Berries (Crop 

Subgroup 13-07G) 

except WetHarvested 

Cranberry

CAStrawberrynoplasticRLF_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 the endpoint = NOAEC = 4.9 mg a.i./L (4,900 μg a.i./L)

2

For non-vascular plants, the non-listed species endpoint = EC50 > 4.1 mg a.i./L (4,100 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 Terrestrial 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 nondefinitive (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 90th percentile Kenaga values (Table 18). The only RQs that exceed the Agency’s LOC 

for chronic risk are 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, which 

exceed the Agency LOC of 1. 

Table 18. Chronic Dietary-Based RQs for Birds and Isofetamid Using the T-REX Model (using the

default 35-day foliar half-life).

USE DIETARY ITEM 

DIETARYBASED 

CHRONIC RQ

Almond 

(4 applications of 0.442 lb 

a.i./acre; 7-day application 

interval with 14 days between the 

2

nd and 3rd 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

Fruits/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 2nd

and 3rd applications)

Short Grass 1.03

Tall Grass 0.47

Broadleaf Plants 0.58

Fruits/Pods/Seeds 0.06

Arthropods 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 2nd

and 3rd applications)

Short Grass 0.70

Tall Grass 0.32

Broadleaf Plants 0.40

Fruits/Pods/Seeds 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 7th 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 Agency’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 RQs 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 199) (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 diet (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 mammals (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 199). 

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-day application 

interval with 14 days between 

the 2nd and 3rd 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

Lettuce

(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 3rd 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 2nd and 3rd

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

Broadleaf 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 7th 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

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 Inhalation Risk (STIR) was 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) 

LD50 (oral) and LD50 (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) LD50 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 classified 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.

The 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). The 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 conservative that chemicals that 

pass the screen are considered to represent a relatively low risk 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 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 Data

 Acute oral toxicity to larval honey bees (Non-guideline, OECD TG 237)

 Chronic 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 Terrestrial and Semi-aquatic Plants

For monocots and dicots, all of the RQs calculated using TerrPlant are <0.1 for listed and nonlisted 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. Since 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 total 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 water 

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 assessment.

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. Additionally, they have the potential for 

direct adverse effects to listed and non-listed birds (and, thus, terrestrial-phase amphibians and 

reptiles) from chronic exposure. The proposed low-growing berry and grape uses have the 

potential to adversely impact listed estuarine/marine invertebrates (from acute exposure). 
58

Therefore, the risk hypothesis from the Problem Formulation [i.e., based on mode 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 through direct application, spray drift and/or 

runoff] is partially supported. Although direct adverse effects to aquatic freshwater 

invertebrates, aquatic plants and terrestrial plants from the proposed isofetamid uses 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, chronic fish RQs are also well below Agency 

LOCs. This indicates generally low risk to fish from proposed non-flooded crop uses of 

isofetamid. 

For aquatic 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. In 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 

invertebrates 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 90th percentile values from chemicalspecific empirical data to move off of the default value (which requires a minimum of three halflife values), this does 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 discussion 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 precluded. The dietary-based chronic RQs are 

not adjusted for body size, while the dose-based RQs are adjusted for body-size. Both the dosebased 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 LD50 or LC50

value (the LD50 and LC50 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 effects 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 currently 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: LD50 = 2,000 mg a.i./kg-bw; sub-acute: LC50 = 5,180 mg 

a.i./kg-diet). In this exercise all of the acute and sub-acute ratios calculated for all of the 

proposed uses using upper-bound Kenaga values are < 0.5. 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 foliar 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 RQ

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 3rd 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 2nd

and 3rd 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./acre and a 7th 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

Arthropods

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 LD50 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 assumption that the highest level 

tested is the endpoint value (i.e., acute: LD50 = 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 chronic dietary-based RQs for mammals exceed the Agency’s LOC of 1; the RQs

are < 1 for all uses and dietary categories. However, 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 

199) (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 proposed 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 except 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 exceed 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 

concentrations about half of the time. In summary, chronic RQs generally decreased when 

considering the 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-growing 

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 2nd and 3rd 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 3rd 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 2nd 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 0.02 0.02 0.01 0.01 0.01 0.01

Turf

(6 applications of 0.567 lb 

a.i./acre and a 7th 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 information 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

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 

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.

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. Review 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 

incidents 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 (Exposure Analysis Modeling System) 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 Protection 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 & Agriculture 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 and 

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 Environment. 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. 2004a. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic 

Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

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. United 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 2012b. NAFTA Guidance for Evaluating and Calculating Degradation Kinetics in 

Environmental Media. December 17, 2012. U.S. Environmental Protection Agency, Office of 

Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2012c. Standard Operating Procedure for Using the NAFTA Guidance to Calculate 

Representative Half-life Values 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 Risks 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 Brougher, 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 Technical: 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 IKF-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 

Common 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 prepared 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 International, 

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 Technical: 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(50)] 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: 272/147/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 Determine 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: Assessment 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.

49018415 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-5411 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 Toxicity 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 subcapitata): 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). Project 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 prepared 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 Leighton, 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 Spiked 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 

Huntingdon 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.

Environmental Fate and Transport Studies:

49018438 McDonald, J.; Wiedmann, J. (2013) 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.

49018441 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 Biosciences, 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 BioSciences 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 Fletcher, 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 Laboratories, 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-5411): 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 Laboratories, 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 Systems 

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: 2244/079/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 in 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 IKF5411 and 4HP in Sediment. Project 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 Pacific 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 

BioSciences 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. Unpublished 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.

Table 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/mole) 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 LD50 (mg/kg bw) 2000

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 2000

Enter Lowest Rat Inhalation LC50 (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

Maximum Vapor Concentration in Air at Saturation (mg/m3) 8.51E-07

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.07E-07

Adjusted Inhalation LD50 2.39E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 LD50 2.30E-03 Exposure not Likely Significant

RESULTS Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation (mg/m3) 8.51E-07

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.35E-07

Adjusted Inhalation LD50 2.55E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 LD50 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 non-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 Benthic 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+01 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+01 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

20 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) = 869.696658658743 

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 Transport 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) = 4.729380814254455E-004

***********************************************************************

Inputs:

 491.0 = oc partitioning coefficient

 556.3 = water column half Life

 20.00 = reference temp for water column degradation

 0.000 = benthic 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

 0.4400E-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 vol 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 sediment

 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: 12/19/2014 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 1.97E+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 benthic 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 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 ************************

******************************************************
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) 2000.00

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 Tall 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/Pods/

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 quotients

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

EEC 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 

NOAEL

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 2.03 108.98 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

Application Rate A 0.572 lb a.i./acre

Incorporation I 1 none

Runoff Fraction R 0.01 none

Drift Fraction D 0.05 none

Table 3. EECs for Isofetamid. Units in lb a.i./acre.

Description Equation EEC

Runoff to dry areas (A/I)*R 0.00572

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 derivation. 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 and/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 potential for risk to that plant group.
80

Appendix E Fate Data for Isofetamid Parent and Degradates and QSAR Analyses for 4HP and 

PPA.

Table E1. 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 = 317.40

PPA

(YN-6187)

2-[3-methyl-4-[2-methyl-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-methyl-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 E2. Isofetamid Parent: Select Physical-Chemical and Fate Properties.

Parameter Value and Units1Source and/or Comment

Water Solubility at 20oC 5.33 mg/L MRID 49011905

Vapor Pressure at 25oC

4.2×10-7 Pa

4.4 ×10-11 Torr

MRID 49011905

Non-volatile under field conditions

Henry’s Law constant 1.2×10-5Pa-m

3

/mol MRID 49011905

Log Dissociation 

Constant (pKa)

The pure active ingredient did not 

dissociate in pH 4 to 10 solutions. MRID 49011905

Octanol-water partition 

coefficient (Kow) log Kow = 2.5 MRID 49011905 Not likely to bioconcentrate. 

Soil Partition Coefficient 

KF (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: 14.63 mL/g

MRID 49011979

Acceptable

Soil Partition Coefficient 

KFoc (25°C)

US Loamy Sand: 602.6 mL/goc

US Loam: 591.9 mL/goc

UK Loam or Silt Loam: 534.9

mL/goc

UK Clay Loam: 274.3 mL/goc

Japanese Sandy Loam (Volcanic 

Ash): 449.6 mL/goc

Mean: 491 mL/goc

MRID 49011979

Acceptable

Terrestrial Field 

Dissipation DT50'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 Units1Source 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. Representative 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 photolysis were corrected for the moist dark control.
84

Table E3. 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)

Parent, 4HP, and 

PPA

(Kinetic 

Equation)

Abiotic Hydrolysis pH 4, 7, 9 at 50oC stable n/a 49011976

Supplemental

Aqueous Photolysis

Sterile Buffer

pH 7 ± 0.2

25±2oC

40°N sunlight

1.8 days

(SFO) n/a

49011977a

Natural Water Supplemental

pH 7.1

25±2oC

40°N sunlight

1.4 days

(SFO) n/a

Soil Photolysis

UK Silt Loam

pH 6.4

20±2oC

Dry Soil

293 days

(DFOP) 

Moist Soil¥

354 days

(SFO)

Dry Soil

296 days

(DFOP)

Moist Soil¥

230 days

(SFO)

49011978b

Supplemental

Aerobic Soil 

Metabolism†

ND Loamy Sand

pH 7.8

20±2°C

1.1% OC

46 days

(IORE)

57.5 days

(IORE)

49011981c

Supplemental

German Sandy 

Loam

pH 8.4

20±2°C

1.1% OC

24.5 days

(IORE)

24.9 days

(SFO)

49011982c

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)

Parent, 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)

49011985d

Supplemental

Aerobic Aquatic 

Metabolism

UK, Calwich Abbey 

Lake

pH 7.9

20±2°C

4.8% OC

173 days

(SFO)

361 days

(SFO)

49011986b

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)

49011987b

Supplemental ND, Golden Lake

pH 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 degradation 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 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. 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 comparable when using the same equation.

¥ Representative half-lives for moist soil photolysis were corrected for the moist dark control, which has a 

DT50 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 radiolabeled 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 it is unclear whether PPA 

concentrations are increasing or decreasing at study termination. 

Table E4. Summary of Terrestrial Field Dissipation Study Results For Isofetamid¤

MRID 

(Year)

Study Site, 

Crop, and 

Application 

Rate¥

% Carryover of 

Residues

Representative 

Half-Life*and 

DT50

DT90

Max 

Concentration in 

Soil (mg/kg-soil)

Max Depth 

detected

Parent 4HP

49011993

(2010)

Northwood, 

ND, USA

Bare ground 

- sandy loam

3 apps: 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)

DT50: 6.98 days

(IORE)

126 days

(IORE)

0.589

0-15 

cm

0.013 

0-15 cm

49018438

(2010)

Aberdeen, 

SK, Canada

Bare ground 

- clay loam

3 apps: 767, 

724 and 716 

g a.i./ha

46% - isofetamid, 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

49018441

(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)

Kerman, 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 on 

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. 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 Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-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

Aerobic 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

Aerobic 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 

same Reported 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 same

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 detected

a Only one sample was available for analysis at the end of this study; typically there are replicates.

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 DB 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 Profile

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

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 : Fish 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 41.855 *

Amides : Mysid (SW) 96-hr LC50 3.099

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

==========

Neutral Organic SAR : Fish 96-hr LC50 105.014 *

(Baseline 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 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 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)

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(OC(=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 LC50 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 96-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 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)

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 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: 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 Kow: 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 

Phenol Amines 

 Predicted

ECOSAR Class Organism Duration End Pt mg/L (ppm)

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

==========

Phenols : 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 ChV 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 below, 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 LogKow: 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 :

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Maximum 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:

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Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50)

Maximum LogKow: 6.4 (Green Algae EC50)

Maximum LogKow: 8.0 (ChV)