2 

Functioning as the first stage of the risk assessment process for Registration Review, this 

problem formulation provides an overview of what is currently known about the environmental 

fate and ecological effects associated with cymoxanil and its degradates. It also describes the 

preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing risk to 

non-target species in support of the registration review of cymoxanil. This document also 

recommends studies that should be included in a generic data call-in (DCI) to address 

uncertainties surrounding the environmental fate and potential ecological effects of cymoxanil. 
3 

 

 

Problem Formulation for the Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support of the 

Registration Review of Cymoxanil 

1-[(EZ)-2-Cyano-2-methoxyiminoacetyl]-3-ethylurea 

CAS Registry Number: 57966-95-7 

PC Code: 129106 

Prepared by:

Cheryl Sutton, Ph. D., Environmental Scientist 

Elizabeth Bosecker, Biologist

Scott Glaberman, Ph.D., Biologist

U.S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Thomas Steeger, Ph.D, Senior Science Advisor

Jim Carleton, Ph.D, Senior Fate Scientist

Marietta Echeverria, Branch Chief, ERB IV 

March 7, 2012 

N

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4 

Table of Contents 

1. Purpose ....................................................................................................................................... 5

2. Problem Formulation ................................................................................................................. 5

2.1. Nature of Regulatory Action ............................................................................................... 5

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

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

2.2.2. Drinking Water Exposure Assessments ....................................................................... 8

3. Stressor Source and Distribution ............................................................................................... 9

3.1. Mechanism of Action .......................................................................................................... 9

3.2. Overview of Pesticide Use and Usage ................................................................................ 9

3.3. Environmental Fate and Transport.................................................................................... 12

3.4. Degradates of Concern ...................................................................................................... 14

3.5. Water Quality .................................................................................................................... 16

4. Receptors.................................................................................................................................. 17

4.1. Effects to Aquatic Organisms ........................................................................................... 17

4.2. Effects to Terrestrial Organisms ....................................................................................... 20

4.3. Incident Databases Review ............................................................................................... 22

4.4. Ecosystems Potentially at Risk ......................................................................................... 22

5. Assessment Endpoints ............................................................................................................. 23

6. Conceptual Model .................................................................................................................... 23

6.1. Risk Hypothesis ................................................................................................................ 24

6.2. Conceptual Diagram ......................................................................................................... 24

7. Analysis Plan ........................................................................................................................... 26

7.1. Stressors of Concern ......................................................................................................... 27

7.2. Measures of Exposure ....................................................................................................... 31

7.3. Measures of Effect ............................................................................................................ 33

7.4. Integration of Exposure and Effects ................................................................................. 34

7.5. Deterministic and Probabilistic Assessment Methods ...................................................... 36

7.6. Endangered Species Assessments ..................................................................................... 36

7.7. Drinking Water Assessment ............................................................................................. 37

7.8. Endocrine Disruptor Screening Program .......................................................................... 37

7.9. Preliminary Identification of Data Gaps ........................................................................... 38

7.9.1. Environmental Fate .................................................................................................... 38

7.9.2. Effects Data ................................................................................................................ 41

8. References ................................................................................................................................ 45

APPENDIX A: Registered Uses and Application Rates for Cymoxanil Based on Information 

from OPP/BEAD1. ........................................................................................................................ 57

APPENDIX B1: Names and Structures of Major Environmental Degradates of Cymoxanil. .... 60

APPENDIX B2: Environmental Fate Studies Details .................................................................. 65

APPENDIX C: Ecotox Open Literature Studies for Cymoxanil. ................................................ 67

APPENDIX D: Submitted Ecological Effects Toxicity Data for Cymoxanil ............................. 70

APPENDIX E: Output from ECOSAR for Cymoxanil and its Major Degradates ....................... 84

APPENDIX F: Screening Imbibition Program (SIP) v.1.0 and Screening Tool for Inhalation 

Risk (STIR) v.1.0 Description, Assumptions, Inputs and Outputs ............................................. 103

APPENDIX G. Data Call-In Justification Tables for Ecological Effects Studies ...................... 107
5 

1. Purpose 

The purpose of this problem formulation is to provide an understanding of what is known about 

the environmental fate and ecological effects of cymoxanil, considering its currently registered 

uses. Cymoxanil is a urea compound that was initially developed for control of late blight 

(Phytophthora infestans) on potatoes throughout the U.S. and has been registered since the late 

1970s for use throughout the world to control the fungal diseases late blight and downy mildew 

in a variety of crops. The initial registration in the United States occurred in1998. There are no 

residential uses for cymoxanil nor are there formulations of the pesticide classified as “restricted 

use.” This document provides a plan for analyzing data relevant to cymoxanil and for 

conducting environmental fate, ecological risk, endangered species, and drinking water exposure 

assessments for its registered uses. Additionally, this problem formulation identifies data gaps, 

uncertainties, and potential assumptions used to address those uncertainties relative to 

characterizing the potential ecological risk associated with the registered uses of cymoxanil on 

agricultural crops. 

2. Problem Formulation 

2.1. Nature of Regulatory Action 

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), all pesticides distributed 

or sold in the United States generally must be registered by the Environmental Protection 

Agency (Agency). In determining whether a pesticide can be registered in the U.S., the Agency 

evaluates the safety of the chemical to non-target species based on a wide range of 

environmental and health effects studies. In 1996, FIFRA was amended by the Food Quality 

Protection Act (FQPA), and the Agency was mandated to implement a new program for the 

periodic review of pesticides, i.e., Registration Review1

. The Registration Review program is 

intended to ensure that, as the ability to assess risk evolves and as policies and practices change, 

all registered pesticides continue to meet the statutory standard of no unreasonable adverse 

effects to human health and the environment. Changes in science, public policy, and pesticide 

use practices will occur over time. Through the new Registration Review program, the Agency 

periodically reevaluates pesticides to make sure that as change occurs, products in the 

marketplace can be used safely. 

As part of the implementation of the Registration Review program pursuant to Section 3(g) of 

the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the Agency is beginning its 

evaluation of cymoxanil to determine whether it continues to meet the FIFRA standard for 

registration. This problem formulation for the environmental fate, ecological risk, Federallylisted threatened and endangered species (hereafter referred to as “listed”), and drinking water 

assessment chapter in support of the registration review of cymoxanil will be posted in the initial 

docket which will open the public phase of the review process. 

 

1 http://www.epa.gov/oppsrrd1/registration_review/
6 

2.2. Previous Assessments 

EFED has assessed multiple uses of cymoxanil for Section 3, IR-4, and Section 18 registrations. 

The registrant, E. I. du Pont de Nemours and Company, was previously granted registration of 

cymoxanil on potatoes with the October 23, 1997 Section 3 New Chemical Environmental Risk 

Assessment (DP Barcode D233366). Additional uses (including fruiting vegetables, head 

lettuce, and cucurbits) were added and the application rate on potatoes was increased with the 

January 29, 2003 updated drinking water and ecological risk assessment (DP Barcode D261193); 

grapes (east of the Rocky Mountains) and hops with the September 20, 2006 Inter-Region 4 (IR4) tolerance petition (DP Barcode D323681); caneberries with the September 22, 2006 IR-4 

tolerance petition (DP Barcode D332755) and the September 21, 2006 drinking water assessment 

(DP Barcode D331978); and leafy greens, bulb vegetables, caneberries, cilantro leaves, onions, 

spinach and leaf lettuce with the May 6, 2008 IR-4 tolerance petition (DP barcode D348437) and

the May 13, 2008 revised drinking water assessment (DP Barcode D347651). 

Multiple Section 18 Emergency Exemption petitions under FIFRA Section 18 were reviewed for 

cymoxanil, mainly on potatoes, hops and tomatoes. Curzate M-8 (8% ai) and Manex C-8, the 

end-use products associated with most of these requests, are no longer registered. 

The major findings from the Section 3 and IR-4 assessments are summarized below. Following 

review of the previous risk assessments, conclusions were noted; however, modifications to the 

previous risk conclusions are possible. These changes (e.g., evaluating drinking water exposure 

to birds and mammals) are due to an evolution of Agency policy since cymoxanil was first 

registered. While non-target terrestrial and aquatic plants were previously assessed, an 

assessment of listed species in these taxa was not performed. Further, environmental fate and 

ecological toxicity data are re-evaluated as part of the Registration Review process and certain 

studies that previously met guideline standards or registration requirements may no longer meet 

current guideline standards. 

2.2.1. Previous Ecological Risk Assessments 

Cymoxanil was first registered in 1997 by E. I. du Pont de Nemours and Company. According 

to the initial assessment (D233366; USEPA, 1997), risks to non-target terrestrial plants2

, acute or 

chronic risks to non-target insects, or chronic risks from granular/bait formulations to 

mammalian or avian species were not assessed by EFED at that time. In contrast, the Agency’s 

acute and chronic risk Levels of Concern (LOCs)3

 for non-granular products were not exceeded 

for the maximum broadcast application rate of 0.12 lb a.i./A for birds or mammals. Risk to nontarget aquatic plants were considered low following the assessed use pattern, and no aquatic 

acute or chronic risk LOCs were exceeded at the maximum application rate of 0.12 lbs a.i./A 

(0.84 lbs. a.i./year). No risk to listed or non-listed species was identified at the time of the 

 

2

 Non-target plants were not assessed because data have not been submitted for cymoxanil 

3

 LOC's are criteria used to indicate potential risk to nontarget organisms and the need for a regulatory decision. The 

criteria indicate that a chemical, when used as directed, has the potential to cause undesirable effects on nontarget 

organisms. In order to determine if an LOC has been exceeded, a risk quotient must be derived and compared to the 

LOC. A risk quotient is calculated by dividing an appropriate exposure estimate by an appropriate toxicity test effect 

level. Please see Section 7.4 for further description of the LOC approach. 
7 

assessment. The formulated product Curzate® M8, which is no longer registered, contained 64% 

mancozeb [known to be toxic to fish, highly toxic to freshwater invertebrates (daphnid EC50 = 

1.0 mg/L), and very highly toxic to estuarine invertebrates (mysid LC50 = 0.011 mg/L)], and it 

was not known if the combination of cymoxanil and mancozeb was more toxic than either 

chemical was separately. 

The IR-4 Tolerance Petition for Cymoxanil (Curzate® 60 DF; 60% ai) use on hops completed in 

August of 2001 (D271572) was assessed at an application rate that was less than previous 

Section 3 (D233366) use on potatoes, so no new risk assessment was conducted. However, the 

assessment recommended that the label language used in the previous assessment remain in 

effect due to the uncertainty pertaining to the ecological effects of cymoxanil when used in 

combination with protectant fungicides (mancozeb, chlorthalonil, triphenyltin hydroxide, or 

metiram). 

The Section 3 new use that was assessed in January of 2003 (D261193) increased the application 

rate on potatoes to 0.1875 lbs a.i./acre (maximum 6 applications per year) and added the uses of 

fruiting vegetables, head lettuce, and cucurbits at the same application rate. In the screeninglevel assessment, EFED determined that the newly proposed cymoxanil application rates resulted 

in exceedences of the chronic risk LOC for freshwater fish, avian species, and wild mammals. 

The reported chronic risk quotients (RQs) for fish, birds, and wild mammals were 2.6, 2.1, and 

2.1, respectively. Acute risks were expected to be substantially lower than OPP’s LOC. The 

calculated risks were found to be higher than those submitted in previous risk assessments 

primarily because of differences in model versions used and model inputs. GENEEC 2 was 

used, which contains improved estimates of spray drift that account for the likelihood that 

cymoxanil was applied using nozzles with a fine droplet size distribution. 

The IR-4 Tolerance Petition for cymoxanil (Tanos®; 25% cynmoxanil, 25% famoxadone) use on 

grapes and hops completed in September of 2006 (D323681) had higher single application rates 

(0.25 lbs ai/acre with a maximum of 10 applications per year for grapes and 6 applications per 

year for hops, with respective annual rates of 2.5 lb a.i./A/yr and 1.5 lbs a.i./A/yr) than those 

evaluated in the previous Section 3 registration for the use of cymoxanil on potatoes (D233366) 

and for the initial IR-4 tolerance petition for use of cymoxanil (Curzate® 60 DF) on hops 

(D271572). Based on the environmental fate and ecological effects data contained in the original 

Section 3 and on estimates of terrestrial and aquatic exposure generated using the higher 

application rates, neither acute nor chronic risk LOCs were exceeded for aquatic animals. 

Additionally, acute risk quotients for birds and mammals were also below LOCs. However, 

based on a default foliar dissipation half-life of 35 days for cymoxanil on avian and mammalian 

forage items, the chronic risk LOC was exceeded for terrestrial animals, but the default foliar 

dissipation value was considered conservative given that cymoxanil degrades relatively quickly 

by hydrolysis and by aqueous photolysis under ideal conditions. In addition, uncertainty 

regarding the potential risks to non-target organisms from the formulated product Tanos® was 

identified because of the increased toxicity associated with cymoxanil’s co-formulated product, 

famoxodone. No aquatic animal LOCs were exceeded for listed or non-listed species. No 

aquatic plant toxicity data were submitted, so risks to aquatic plants could not be determined. No 

acute risk LOCs were exceeded for listed birds or mammals; however the chronic risk LOC was 

exceeded for birds and mammals when a 35-day foliar dissipation half-life was used. 
8 

The IR-4 Tolerance Petition for cymoxanil (Tanos®) use on caneberries in September 2006 

(D332755) included lower application rates than those evaluated in the previous new use of 

cymoxanil on grapes and hops (D323681). The assessed rate was the maximum application rate 

for caneberries: 0.19 lbs a.i./acre with a maximum of 6 applications at 7-day intervals, with a 

maximum annual rate of 1.1 lbs a.i./acre. Based on environmental fate and ecological effects 

data contained in the original Section 3 and on the estimates of terrestrial and aquatic exposure 

generated using the proposed lower application rate of cymoxanil, neither acute nor chronic 

LOCs were exceeded for aquatic animals. Again, uncertainty was identified in this assessment 

because of lack of data on foliar dissipation rates. If the default foliar dissipation rate of 35 days 

was used for terrestrial assessments, the chronic risk LOC was exceeded for both birds and 

mammals, but the default foliar dissipation value was considered conservative given the limited 

persistence of cymoxanil in the environment. 

Finally, an IR-4 Tolerance Petition for use of cymoxanil (Tanos®) on leafy greens, bulb 

vegetables, and caneberries was assessed in May of 2008 (D348437). The proposed single 

application rates were less than those evaluated in the previous new use of cymoxanil on grapes 

and hops (D323681). The maximum application rates assessed were: 0.16 lbs a.i./A with a 

maximum of 8 applications (5-day interval) for bulb vegetables per season, with a maximum 

annual rate of 1.3 lbs a.i./A. For spinach, which can have up to 2 seasons per year, the maximum 

annual application rate was assessed at 2.6 lbs a.i./A/year. The acute and chronic LOCs were not 

exceeded for aquatic animals or plants. In addition, if the default foliar dissipation half-life of 35 

days is used for the terrestrial risk assessment, the chronic risk LOCs are exceeded for birds and 

both acute and chronic LOCs are exceeded for mammals. Again, the default foliar dissipation 

value was considered conservative given the limited persistence of cymoxanil in the 

environment. 

2.2.2. Drinking Water Exposure Assessments 

The initial “water resources assessment” for cymoxanil was conducted by EFED in 10/1997 for 

the Section 3 new use registration on potatoes (D233366). The end-use product (Curzate M-8, 

no longer registered; 8% ai) also contained the fungicide mancozeb (64% a.i.). The assessment 

was essentially qualitative, and concluded that cymoxanil is not likely to persist in (most) surface 

waters, although it “may be more persistent in deeper and/or unclear waters with low 

microbiological populations, long hydrologic residence times and acidic pH.” The assessment 

also stated that the compound “is expected to be degraded rapidly in the environment,” and 

although it was “mobile in four soils tested, EFED believes that the chemical does not pose a 

threat to ground water quality.” 

A Tier 1 Drinking Water Assessment (DWA) was conducted for the IR-4 registration for the use 

of cymoxanil on caneberries (9/21/2006). The DWA was performed using the FQPA Index 

Reservoir Screening Tool (FIRST; version 1.0) for surface water and the Screening 

Concentration in Ground Water (SciGRow; version 2.3) model for groundwater. The proposed 

application rate was less than the rates evaluated in the previous new use of cymoxanil grapes 

and hops (DP D323681), so Estimated Drinking Water Concentrations (EDWCs) reported in the 

assessment were based on the use on grapes. 
9 

Most recently, a revised Tier 1 DWA was conducted for the use of cymoxanil on leafy greens, 

bulb vegetables, caneberries, cilantro leaves, onions, spinach and leaf lettuce (D347651; 

5/13/08). The EDWCs determined in that assessment for spinach (0.0018 ppb for groundwater 

and 9.3 ppb and 0.05 ppb for acute and chronic surface water, respectively) were higher than 

previously reported values and currently represent the maximum EDWCs that have been 

recommended for use in the Health Effects Division’s (HED) human dietary risk assessment. 

3. Stressor Source and Distribution 

3.1. Mechanism of Action 

Cymoxanil is a locally systemic fungicide that penetrates plant tissue rapidly after application. 

The systemic characteristic is intended to provide anti-fungal activity post-infection. Cymoxanil 

is in the chemical group cyanoacetamideoxime, which is listed as a Group 27 fungicide by the 

Fungicide Resistance Action Committee (FRAC)4

. It is the only fungicide in its FRAC chemical 

group. The fungicidal activity of cymoxanil is due to the inhibition of a number of cellular 

processes which are critical to the growth and development of fungal pathogens, including 

nucleic acid, protein and lipid biosynthesis, respiration and membrane permeability. In general, 

cymoxanil is active on fungi that belong to the order Peronosporales and is mainly used to 

control late blight and other Phytophthora diseases, and downy mildews (USEPA, 2011b). 

3.2. Overview of Pesticide Use and Usage 

Cymoxanil is a urea compound that was initially developed for control of late blight 

(Phytophthora infestans) on potatoes throughout the U.S. and has been registered since the late 

1970s for use throughout the world, and since 1998 in the U.S., to control the fungal diseases late 

blight and downy mildew in a variety of crops (USEPA, 2011b). 

Cymoxanil is formulated as dry flowable and dust. One end-use product, Curzate® 60 DF, is used 

as a tank-mix with a protectant fungicide, such as a copper product. Another cymoxanil 

containing product is Tanos®, which includes 25% cymoxanil and 25% femoxadone. The third 

registered product is Evolve®, which is a potato seed-piece treatment containing 1 % cymoxanil, 

2.5% thiophanate-methyl, and 6% mancozeb. Cymoxanil may be applied as a seed treatment to 

potato seed pieces and also to peas (as seeds for export only). Seed treatments may be made 

using slurry or mist seed treatment equipment. Foliar applications may be made using ground, 

aerial, and chemigation equipment (USEPA, 2011b). 

Cymoxanil is registered for use on potatoes, tomatoes, peppers, cucurbits, leafy vegetables 

(except Brassica group 4), bulb vegetables (bulb onion and green onion subgroup), grapes grown 

east of the Rocky mountains, caneberries (except in California), and hops (except in California). 

There are also FIFRA Section 24c Special Local Need (SLN) registrations for use on the 

following crops: spinach, cabbage, Swiss chard, and table beets when they are grown for seed. In 

 

4

 FRAC is characterized as a specialist technical gropu of CropLife International 

http://www.frac.info/frac/index.htm 
10 

addition, there is a SLN registration for use for commercial seed treatment for peas intended for 

export. 

Maximum label rates for registered cymoxanil uses are presented in Table 3.1. Rates are based 

on labels for the end-use products DuPontTM Tanos® fungicide (dry flowable; 25% a.i.; coformulated with famoxadone at 25%; Reg. No. 352-604); DuPontTM Curzate® 60 DF fungicide 

(60% a.i.; Reg. No. 352-592); and EVOLVE® Potato Seed-Piece Treatment Fungicide (1% a.i.; 

co-formulated with mancozeb, thiophanate-methyl, and ethylene bis-dithiocarbamate ion; Reg. 

No. 264-973). 

Table 3.1. Summary of Cymoxanil Application Rates from Current Labels. 

Use 

Max. Single 

Applic.Rate 

(lbs a.i./A) 

Max. No. 

Applic./Crop 

Cycle 

Max. 

Applic. 

Rate/Crop 

Cycle 

(lbs 

a.i./A/cc) 

Max. No. 

Applic./Yr Max. Annual 

Applic. Rate 

(lbs a.i./A/yr) 

Min. Applic. 

Interval 

(days) 

Bulb 

Vegetables 0.156 NS1 1.3 NS NS 5 

Caneberries 0.156 NS 1.1 NS 1.1 5 

Cucurbits 0.1875 NS NS NS 1.1 5 

Grapes 0.125 9 1.1 NS NS 10 

Hops 0.125 6 0.75 NS 0.75 6 

Leafy 

Vegetables 0.156 NS 0.75 NS NS 5 

Lettuce (Head 

and Leafy) 0.1875 NS NS NS 1.1 5 

Spinach 0.1875 NS NS NS 1.1 5 

Peppers 0.156 NS 1.1 NS 1.1 5 

Potatoes 0.125 6 0.75 NS 1.1 5 

Tomatoes 0.1875 NS NS NS 1.1 5 

Potato/Seed 

Treatment 

0.0375 lb a.i./ 

lb seed NS NS NS NS NS 

1

NS = Not specified on the label. 

Based on information for the years 2001 – 2008 from the USDA-NASS (United States 

Department of Agriculture's National Agricultural Statistics Service) and from private pesticide 

market research, the September 2011 Screening Level Usage Analysis (SLUA; Table 3.2) 

generated by OPP’s Biologic and Economic Analysis Division (BEAD) states that the main 

crops on which cymoxanil is used include potatoes, cucumbers, tomatoes, other vegetables, 

grapes and melons (USEPA, 2011a). Usage data for hops are not available. Use data collected 

by the California Department of Pesticide Regulation (CADPR; Table 3.3) for the years 2007 – 

2009 indicate that the main usages of cymoxanil in California are for head lettuce, potatoes and 

tomatoes (USEPA, 2011a). 

For the years 2008-2010, the main crops in terms of total pounds of active ingredient applied 

were potatoes (49%), cucumbers (22%), tomatoes (8%), pumpkins (5%), and peppers (5%) 

(USEPA, 2011a). These crops were also the top in terms of the total acres treated. Over the 

broader timeframe of 1998-2010 timeframe, usage on potatoes was highest in 1998 and 2000 and 

has generally leveled off (Figure 3.1). Usage overall has increased since the addition of several 
11 

new crops in 2004. For the most recent years of 2008-2010, cymoxanil usage in agriculture 

(excluding seed treatments) averaged approximately 50,000 pounds for 400,000 treated acres 

(USEPA, 2011a). Seed treatments were excluded throughout this use analysis because usage data 

are only available for potatoes for 2009-2010. However, as a general estimate, seed treatments 

on potatoes accounted for less than 3% of the total acre treatments to potatoes in 2009 and 2010. 

 

Table 3.2. Screening Level Estimates of Agricultural Uses of Cymoxanil for 2003-2010 

(BEAD, 9/13/2011) 

Percent Crop Treated 

Crop Lbs. A.I. Avg. Max. 

Caneberries 1,000 10 15 

Cantaloupes <500 <2.5 <2.5 

Cucumbers 9,000 25 45 

Grapes, wine <500 <2.5 <2.5 

Lettuce 2,000 5 10 

Onions 1,000 5 15 

Peppers 2,000 10 15 

Potatoes 20,000 10 20 

Pumpkins 2,000 10 20 

Spinach <500 <2.5 <2.5 

Squash 1,000 10 25 

Tomatoes 4,000 5 10 

Watermelons <500 <2.5 5 

Table 3.3. CADPR Cymoxanil Use Information for 2007 – 2009. 

Commodity 2007 Pounds Applied 2008 Pounds Applied 2009 Pounds Applied 

Celery, General 1 

Lettuce, Head (All Or Unspec) 1197 1743 1709 

Lettuce, Leaf (All Or Unspec) 28 

N-Grnhs Grwn Trnsplnt/Prpgtv 

Mtrl 39 9 25 

N-Outdr Grwn Trnsplnt/Prpgtv 

Mtrl 9 2 

Peppers (Fruiting Vegetable), 

(Bell,Chili, Etc.) 16 15 5 

Potato (White, Irish, Red, 

Russet) 308 1074 256 

Spinach 7 

Squash (All Or Unspec) 1 1 

Tomato 171 898 206 

Tomatoes, For 

Processing/Canning 60 276 93 

Watermelons 1 

Grand Total 1803 4015 2332 
12 

The states with the highest agricultural usage in terms of pounds AI applied are Michigan (19%), 

Washington (13%), Florida (11%), California (10%), Wisconsin (6%), and Idaho (5%) (USEPA, 

2011a). These states were also the ones with the highest usage in terms of the total acres treated. 

3.3. Environmental Fate and Transport 

Cymoxanil is a relatively nonvolatile, highly water soluble compound that is not expected to 

significantly persist in the aquatic environment when neutral and alkaline conditions are 

prevalent. Its persistence in acidic aquatic environments is uncertain. It hydrolyzes quickly in 

alkaline and neutral media, and photodegrades quickly in aqueous media under optimal 

conditions. Its persistence in soil is not well defined due to limited data, although hydrolysis will 

also play a role in higher pH soils. It is susceptible to aerobic biodegradation in soil, with 

mineralization to CO2, although additional data are needed to fully understand the fate of the 

parent and its numerous transformation products in aerobic soil. While most of the major 

hydrolytic and photolytic degradates were not observed in large amounts in the aerobic soil 

metabolism studies, only IN-KQ960 (see Appendix B1) and oxamic acid were detected in the 

aerobic soil metabolism studies, but not in the hydrolysis or aqueous photolysis studies. 

However, all soil metabolism degradates may not have been identified, as the extraction method 

used in these studies was questionable given the large amount of nonextractced residues present 

in the soil samples from as early as day 1. While submitted data indicate that cymoxanil will 

degrade in water/sediment (aquatic) systems, particularly at high pHs, the data are uncertain due 

to high levels of nonextracted residues throughout these studies as well. Also, the observed 

degradation was likely due to hydrolysis based on the high pHs of the study systems, which 

tended toward neutral or alkaline levels. Thus, it remains unclear how the compound will 

behave in more acidic environments where hydrolysis will not be a major route of dissipation. 

With organic carbon (oc) partitioning coefficients (Koc; in mL/g oc) of 22-138 in four soils, 

cymoxanil has been shown to be mobile to highly mobile in soil based on the Food and 

Agriculture Organization (FAO) classification scheme. Although a batch equilibrium study on 

the degradates was classified as not acceptable because only one concentration was studied, the 

results indicated that the cymoxanil degradates IN-W3595, In-R3273 and In-KQ960 are all 

highly mobile in soil. The single point measurements of Koc ranged from 0 to 50 mL/g oc. The 

degradate IN-U3204 was unstable in the test system. 

Based on the measured vapor pressure (1.1x10-6 Torr) and the estimated Henry’s Law Constant 

(3.3 x 10-10 atm-m3/mol), cymoxanil is not expected to significantly volatilize from water or soil. 

While no fish bioconcentration data are available, the ocatanol-water partition coefficient (Kow) 

values (3.9, 4.7) indicate that the compound is not likely to be bioconcentrated in fish tissue. 

Additional details on the fate of cymoxanil and its degradates are presented in Appendix B2.

Table 3.4 summarizes the general physical, chemical, and fate and transport properties of 

cymoxanil. 
13 

Table 3.4. General Chemical Properties and Environmental Fate Properties of Cymoxanil, 

(E)-2-cyano-N-[ethylamino)carbonyl]-2-(methoxyimino)acetamide. 

Parameter Value Reference 

(MRIDs/ 

Classification) 

Comments 

Selected Physical/Chemical Parameters

Molecular mass 198.2 g/mol Product chemistry 

Section 3 New Chemical 

Risk Assessment 

(D233366). 

Vapor pressure (20°C) 1.1 x 10-6 Torr Product chemistry 

Section 3 New Chemical 

Risk Assessment 

(D233366). 

Water solubility (20°C) 780 mg/L (pH 7) 

890 mg/L (pH 5) Product chemistry 

Section 3 New Chemical 

Risk Assessment 

(D233366). 

Henry’s law constant (20°C, pH 7) 3.3 x 10-10 atm-m3

/mol Estimated1 

Octanol-water partition coefficient (Kow) 

(20°C) 

3.9 in pH 5 buffer, 

4.7 in pH 7 buffer Product chemistry 

Section 3 New Chemical 

Risk Assessment 

(D233366). 

Hydrolysis (t 1⁄2; days; @ 25°C) 

Stable @ pH 5 

1.4 @ pH 7 

0.022 @ pH 9 

44180738 

(Acceptable) 

Aqueous Photolysis (t 1⁄2; days ) 3.6 

44180739 & 

44180740 

(Acceptable) 

In pH 5 buffer. Half-life 

was corrected for 

continuous irradiation, so 

differs from that reported in 

past assessments. 

Soil Photolysis (t 1⁄2; days ) 74 

44180741 

(Supplemental) 

Half-life was corrected for 

natural sunlight, so differs 

from that reported in past 

assessments. Not a 

significant fate pathway. 

Aerobic Soil Metabolism 

(t 1⁄2; days ) No data 

44180742 

(Supplemental) 

44180743 & 

45357101 (Not 

Acceptable) 

AMR 1988-91 

(Supplemental) 

No useable half-life data 

available. Submitted studies 

are classified not acceptable 

or supplemental, and halflives will not be used in risk 

assessments. Data are from 

foreign and/or volcanic ash 

soils and are of 

questionable validity (thus, 

not upgradeable) due to 

analytical method/residue 

extraction issues. 

Anaerobic Soil Metabolism No data No data have been 

submitted. 
14 

Parameter Value Reference 

(MRIDs/ 

Classification) 

Comments 

Anaerobic Aquatic Metabolism No data 

44180744 (Not 

Acceptable) 

AMR 2446-92 

(Supplemental) 

No usable data available. 

Supplemental data are not 

representative of typical use 

conditions. 

Aerobic Aquatic Metabolism No data 44180741 (Not 

Acceptable) 

Submitted data are 

classified not acceptable. 

Mobility

Soil Adsorption Coefficient Kd (mL/g) 0.3 (sandy loam, 1.3% 

om) 

2.9 (clay loam, 4.5% om)

1.4 (silt loam, 1% om) 

0.8 (silt loam, 1.3% om) 

44180745 

(Acceptable) Parent compound 

44180746 

(Not Acceptable) 

Deficient since only single 

concentration studied. For 

degradates W3595, R3273, 

KQ960 & JX915, all Kf‘s 

were ≤1.5 and Koc’s were 0-

50. 

AMR 2724-93 

(Acceptable) 

Leaching column study. 

Organic Carbon Partitioning Coefficient 

Koc (mL/g oc) 

22 (sandy loam, 1.3% om)

64 (clay loam, 4.5% om) 

138 (silt loam, 1% om) 

57 (silt loam, 1.3% om) 

44180745 

(Acceptable) 

Koc model is valid for this 

pesticide. FAO mobility 

classes are mobile (3 soils) 

to moderately mobile (1 

soil). 

Field Dissipation

Terrestrial Field Dissipation (t 1⁄2; days ) 

(top 15 cm of soil) 

0.9 (Silt loam; pH 6.5; 

MD site) 

8.7 (Loam; pH 7.8; CA 

site) 

44180747 

(Acceptable) 

Parent not detected below 

15 cm. Degradates not 

monitored. 

45294105 

45294105 

44946410 

(All 

Supplemental) 

Studies were on 

famoxadone plus cymoxanil 

mixture. Cymoxanil was 

not monitored. 

Bioaccumulation in Fish 

Fish Bioaccumulation (BCF) No data Data not needed based on 

low Kow values. 

1

Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) 

3.4. Degradates of Concern 

Major degradates are compounds that form at greater than 10% of the applied in at least one fate 

study, or are known to be toxicologically significant. The degradates reported in the abiotic 
15 

laboratory fate studies (presented in Table 3.5), which are potentially degradates of concern, 

include 1-ethyldihydro-6-imino-2,3,5(3H)pyrimidinetrione-5-(O-methyloxime) (IN-U3204); 

{[(ethylamino) carbonyl]} ethylamino)carbonyl]amino}oxoacetic acid (IN-KP533); 

cyano(methoxyimino)acetic acid (IN-U3595); 3-ethyl-4-(methoxyamino)-2,5-dioxo-4-

imidazolidinecarbonitriile (IN-JX915); ethylimidazolidinetrione-5-(O-methyloxime) (INR3273); 1-ethyldihydro-6-imino-2,4,5{3H}-pyrimidinetrione-5-(O-methyloxime) (IN-U3204); 

ethylimidiazolidinetrione (IN-T4226); and oxalic acid. All of the degradates listed above are 

hydrolysis products and/or photodegradates in soil and/or water (Appendix B2 for additional 

details). 

In the aerobic soil metabolism studies, the compounds 3-ethyl-4-(methoxyamino)-2,5-dioxo-4-

imidazolidinecarboxamide (IN-KQ960), IN-W3595, CO2, and IN-U3204 were present as major 

degradates in one or more soils (including foreign and volcanic ash soils); while IN-18474

(oxamic acid), IN-R3273, IN-KP533, and IN-JX915 were present as minor degradates in all 

soils in which they were detected. Of these, only IN-KQ960 and oxamic acid were not detected 

in the hydrolysis and/or photolysis studies. However, as noted earlier, there remains a data gap 

for aerobic soil metabolism data and it is uncertain whether all residues were adequately 

characterized in the submitted studies, as well as whether the soils used in the studies are 

representative of intended use sites. There are no anaerobic soil metabolism data, and the 

submitted data for aerobic aquatic metabolism are not acceptable. In the one supplemental 

anaerobic aquatic metabolism study, degradates were likely due to hydrolysis and were not 

identified. None of the degradates were monitored in the terrestrial field dissipation study. 

In a batch equilibrium study, the degradates IN-W3595, IN-R3273 and IN-KQ960 were all 

shown to be highly mobile in soil, and in an aged soil column leaching study, the degradates 

oxamic acid (IN-18474) and IN-KP533 were detected in the leachate. 

Degradates from the submitted environmental fate studies and their maximum detections are 

briefly summarized in Table 3.5 below, while Appendix B1 lists the major degradates, chemical 

structures, and chemical names. 

Based on the available information the main degradates of concern with respect to exposure 

include IN-3204, IN-KP533, IN-R3273, IN-JX915, and IN-U3595. In addition, IN-KQ960 is of 

concern due to its toxicity. Potential exposure to IN-KQ960 is uncertain due to aerobic soil 

metabolism data gaps. 

Table 3.5. Summary of cymoxanil degradates from the environmental fate studies. 

Study/Data Source Metabolites Maximum Detection(s) 

Soil Photolysis 

(44180741) 

IN-JX915 

 CO2

11% (day 7) 

14% 

Hydrolysis 

(44180738) 

IN-U3204 

IN-KP533 

IN-U3595 

53% (day 2, pH 7), 61% (0.2 days, 

pH 9) 

57% (day 30, pH 7), 32% (day 10, 

pH 9) 

39% (day 3, pH 9) 
16 

Oxalic acid and oxamic acid (IN18474) <10% each (pH 9) 

Aquatic Photolysis 

(44180739 & 

44180740) 

IN-JX915 

IN-R3273 

IN-KP533 

IN-18474 (oxamic acid) 

IN-U3204 

IN-T4226 

52% (day 4) 

35% (day 15; end of study) 

8% (day 15) 

2.1% 

≤1% 

6.7% (day 15) 

Aerobic Soil Metabolism1

(44180742, AMR 1988-91) 

Volcanic Ash Soil (AMR 1988-91)

IN-KQ960 

IN-W3595 

CO2

IN-18474 (oxamic acid) 

IN-U3204 

IN-R3273 

4 Foreign Soils Including 1 Volcanic 

Ash Soil (44180742)

IN-KQ960 

IN-W3595 

CO2

IN-18474 (oxamic acid) 

IN-U3204 

IN-R3273 

IN-KP533 

IN-JX915 

Volcanic Ash Soil (AMR 1988-91)

18.5% (day 7) 

9.0-11.1% (day 1) 

26.4-30.8% (day 365) 

Value not reported. 

22.6-26.8% (8 hours) 

5.9-6.3% (8 hours) 

4 Foreign Soils Including 1 Volcanic 

Ash Soil (44180742)

5% (d 9) 

8% (d 2), 18% (d 7) 

Values not reported. 

5% (d 5), 5% (d 15), 5% (d 30), 8% 

(d 3) 

22.5% (4 hr), 61% (8 hr), 5% (d 5), 

8% (d 0) 

2% 

2% (d 2) 

<2%, 8% (d 0) 1

Data are from studies classified as supplemental for multiple reasons including the use of only foreign soils and/or volcanic ash soils, which have 

not been shown to be representative of intended use areas in the U.S. There remains a data gap for this study type, and these studies are not 

upgradeable due to questionable validity resulting from extraction method deficiencies. Information on degradates is included here only to 

indicate which degradates may potentially form in soil. 

 

3.5. Water Quality 

Cymoxanil is not identified as a cause of impairment for any water bodies under section 303(d) 

of the Clean Water Act5. In addition, no Total Maximum Daily Loads (TMDL) have been 

developed for this pesticide6

 and there are no aquatic life criteria for it7. More information on 

impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/. 

The Agency invites submission of water quality data for this pesticide. To the extent possible, 

data should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process (see: 

 

5

 based on information provided at 

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

9/13/2011 

6

 based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES, accessed 9/13/2011 7

 based on information provided at http://www.epa.gov/waterscience/criteria/aqlife/index.html, accessed 9/13/2011 
17 

http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf), in order to ensure 

they can be used quantitatively or qualitatively in pesticide risk assessments. 

No surface water monitoring data were available for cymoxanil. Neither the USGS’s National 

Water Quality Assessment (NAWQA) program nor the California Department of Pesticide 

Regulation monitoring programs included cymoxanil as an analyte. 

Cymoxanil is not listed on the Title 3 California Code of Regulation’s “Ground Water Protection 

List” (3CCR section 6800(b) http://www.cdpr.ca.gov/docs/legbills/calcode/040101.htm#a6800

4. Receptors 

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

assessment for cymoxanil relies on a surrogate species approach. Toxicological data generated 

from surrogate test species, which are intended to be representative of broad taxonomic groups, 

are used to extrapolate the potential effects on a variety of species (receptors) included under 

these taxonomic groupings. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature are used to evaluate the potential direct and indirect effects of 

cymoxanil to aquatic and terrestrial receptors. This includes toxicity of the technical grade 

active ingredient, degradates, and when available, formulated products (e.g., “Six-Pack” studies). 

The open literature studies are identified through EPA’s ECOTOXicology (ECOTOX; USEPA 

20118

) database, which employs a literature search engine for locating chemical toxicity data for 

aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data may also 

provide insight into the direct and indirect effects of cymoxanil on biotic communities from loss 

of species that are sensitive to the chemical and from changes in structure and functional 

characteristics of the affected communities. An ECOTOX run conducted in August 2011 for 

cymoxanil found that sixteen aquatic studies and six terrestrial studies are available; however, 

these studies have not been formally reviewed as part of this Problem Formulation. References 

to all ECOTOX studies are presented in Appendix C. Data from these studies and data from an 

up-dated ECOTOX run for cymoxanil will be evaluated for possible quantitative and/or 

qualitative inclusion in the risk assessment in support of Registration Review. 

A summary of the most sensitive data representing non-target organisms exposed to cymoxanil 

in aquatic and terrestrial habitats is provided in Sections 4.1 and 4.2. A summary of ecological 

incidents associated with cymoxanil and a description of ecosystems potentially at risk are 

provided in Section 4.3. 

4.1. Effects to Aquatic Organisms 

Based on the available data, cymoxanil is categorized as slightly toxic to freshwater fish (LC50 = 

29,000 μg a.i./L) and estuarine/marine fish (LC50 > 47,500 μg a.i./L) on an acute exposure basis 

(Table 4.1). It is considered slightly toxic to both freshwater invertebrates (LC50 = 28,000 μg 

 

8

 USEPA. 2011. ECOTOX Database. http://cfpub.epa.gov/ecotox/ 
18 

a.i./L) and estuarine/marine invertebrates (LC50 > 44,400 μg a.i./L) on an acute basis. 

Additionally, chronic data on aquatic organisms for freshwater and estuarine/marine fish and 

freshwater invertebrates are also available. The most sensitive endpoint for chronic freshwater 

fish was based on total length (NOAEC = 0.98 μg a.i./L; MRID 443446-10), while the most 

sensitive endpoint for chronic estuarine/marine fish was based on survival at test termination 

(NOAEC = 94.2 μg a.i./L; MRID 441807-26). The most sensitive endpoint for chronic 

freshwater invertebrates was based on survival at test termination (NOAEC = 67 μg a.i./L; 

MRID 441807-24). The most sensitive species for each taxa from submitted aquatic animal 

toxicity studies are presented in Table 4.1. A summary of all submitted ecotoxicity data for 

cymoxanil and one degradate is provided in Appendix D. 

Degradates toxicity data for cymoxanil are only available for the degradate 3-ethyl-4-

(methoxyamino)-2,5-dioxo-4-imidazolidinecarboxamide (IN-KQ960) based on a study in the 

freshwater invertebrate Daphnia magna (Table 4.1). The data indicate that this degradate is 

approximately 35 times more toxic to freshwater invertebrates than the parent compound with a 

48-hr EC50 of 800 μg a.i./L (MRID 456892-01) versus 28,000 μg a.i./L (MRID 441807-19) for 

the parent. The parent and degradate are of similar molecular weight so the toxicity values are 

able to be directly compared without needing to correct for molecular weight. 

Toxicity and risk from cymoxanil degradates is an area of uncertainty for aquatic organisms. As 

discussed in the environmental fate section, several degradates may form via hydrolysis, 

photolysis, and metabolism, yet there are little to no toxicity data available for them. There is an 

exposure concern for several of these degradates (IN-3204, IN-KP533, IN-R3273, IN-JX915, 

and IN-U3595) due to their mobility and magnitude of formation, as noted in Section 3.4. 

Potential exposure to IN-KQ960 is uncertain due to aerobic soil metabolism data gaps. 

A formulation containing 6.58% cymoxanil and 26.5% elemental copper was also tested under 

acute exposure conditions with D. magna (MRID 465038-03; Table 4.1). When the 

concentration of cymoxanil in the formulation is corrected for percentage a.i., the 48-hour EC50

(2.8 μg ai/L) is 4 orders of magnitude lower than when cymonil is tested under similar conditions 

as technical active ingredient alone (28,000 μg ai/L). 

Table 4.1. Summary of the Most Sensitive Species by Taxon from Submitted Aquatic 

Animal Toxicity Studies for Cymoxanil. 

TAXON SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID STUDY CLASSIFICATION 

Freshwater 

Fish (Acute) 

Bluegill Sunfish 

(Lepomis 

macrochirus) 

96-hr LC50 

29,000 μg a.i./L 

Cymoxanil 

(97.8%) 441807-18 Acceptable 

Estuarine/ 

Marine Fish 

(Acute) 

Sheepshead 

Minnow 

(Cyprinodon 

variegatus) 

96-hr LC50 

>47,500 μg 

a.i./L 

Cymoxanil 

(97.8%) 441807-20 Acceptable 

Estuarine/ 

Marine 

Invertebrates 

(Acute) 

Mysid Shrimp 

(Americamysis 

bahia) 

96-hr LC50 

>44,400 μg 

a.i./L 

Cymoxanil 

(97.8%) 441807-22 Acceptable 

Freshwater 

Fish 

Rainbow Trout 

(Oncorhynchus 

NOAEL: 0.98 

μg a.i./L 

Cymoxanil 

(97.3%) 443646-10 Acceptable 
19 

(Chronic) mykill) LOAEL: 2.4 μg 

a.i./L 

Most Sensitive 

Endpoint (Total 

Length) 

Freshwater 

Invertebrates 

(Acute) 

Waterflea 

(Daphnia 

magna) 

48-hr EC50: 

28,000 μg a.i./L 

Cymoxanil 

(97.8%) 441807-19 Acceptable 

Freshwater 

Invertebrates 

(Acute) 

Waterflea 

(Daphnia 

magna) 

48-hr EC50: 2.8 

μg a.i./L 

DPX-HYZ80 31 

WG 

Cymoxanil 

(6.58%) 

Metallic Copper 

(26.5%) 

465038-03 Supplemental 

Freshwater 

Invertebrates 

(Acute) 

Waterflea 

(Daphnia 

magna) 

48-hr EC50 = 

800 μg a.i./L 

NOAEC = 560 

μg a.i./L 

Cymoxanil 

Degradate 

3-ethyl-4-

(methoxyamino)-

2,5-dioxo-4-

imidazolidinecarbo

xamide (INKQ960) (94.6%) 

456892-01 Acceptable 

Freshwater 

Invertebrates 

(Chronic) 

Waterflea 

(Daphnia 

magna) 

NOEC: 67 μg 

a.i./L 

LOEC: 150 μg 

a.i./L 

Most Sensitive 

Endpoint 

(Survival) 

Cymoxanil 

(97.8%) 441807-24 Acceptable 

Estuarine/ 

Marine Fish 

(Chronic) 

Sheepshead 

Minnow 

(Cyprinodon 

variegatus) 

NOEC: 94.2 μg 

a.i./L 

LOEC: 178 μg 

a.i./L 

Most Sensitive 

Endpoint 

(Survival) 

Cymoxanil 

(97.8%) 441807-26 Acceptable 

Estuarine/ 

Marine 

Invertebrates 

(Chronic) 

Mysid Shrimp 

(Americamysis 

bahia) 

NOEC: 1.700 

μg a.i./L 

LOEC: 3,770 

μg a.i./L 

Most Sensitive 

Endpoint 

(Number of 

young/female, 

male and 

female length, 

and female dry 

weight) 

Cymoxanil 

(97.8%) 441807-27 Acceptable 

 

For non-vascular aquatic plants, several toxicity studies were submitted for the cymoxanil 

technical active ingredient: Pseudokirchneriella subcapitata (green algae; MRIDs 441807-30, 

441807-33); Navicula pelliculosa (freshwater diatom; MRID 441807-32); Skeletonema costatum 

(marine diatom; 441807-31); Anabaena flos-aquae (cyanobacteria; MRID441807-29). The most 

sensitive endpoint from among these studies is an EC50 of 202 μg a.i./L based on average cell 
20 

density in N. pelliculosa (Table 4.2; see Appendix D for full list of studies and endpoints); this 

endpoint value will be used in risk assessment to quantify risk to non-vascular plants. A 

duckweed study was also submitted to represent vascular aquatic plants; the maximum 

application rate tested (793.8 μg a.i./L) resulted in no reduction in frond number over the 14-day 

test period. 

Table 4.2. Summary of the Most Sensitive Endpoints from Submitted Aquatic Plant 

Toxicity Studies for Cymoxanil. 

TAXON ENDPOINT CHEMICAL/ 

FORMULATION MRID STUDY CLASSIFICATION

Aquatic Nonvascular Plants 

Freshwater Diatom 

(Navicula 

pelliculosa) 

120-hr EC50 = 202 μg 

a.i./L 

NOAEC = 63.3 μg 

a.i./L 

(Based on algal cell 

density) 

DPX-T3217-113 

(Cymoxanil; 97.3%) 441807-32 Acceptable 

Aquatic Vascular Plants 

Duckweed 

(L. gibba) 

14-day EC50 > 793.8 

μg a.i./L 

NOAEC = 793.8 μg 

a.i./L 

(Based on frond 

growth) 

DPX-T3217-113 

(Cymoxanil; 97.3%) 441807-28 Acceptable 

4.2. Effects to Terrestrial Organisms 

Table 4.3 summarizes the most sensitive terrestrial animal toxicity endpoints for cymoxanil 

based on an evaluation of submitted studies. Cymoxanil technical is categorized as practically 

nontoxic to birds on both an acute oral (LD50 > 2250 mg ai/kg-bw; MRID 441807-11) and 

subacute dietary (LC50 > 5620 mg ai/kg-diet; MRID 441807-13) exposure basis. Treatmentrelated mortalities were observed in acute oral studies. Cymoxanil is slightly toxic to mammals 

on an acute oral exposure basis (LD50 > 960 mg/kg-bw; MRID 436165-12) 

Chronic toxicity studies of mallard duck (Anas platyrhynchos; MRID 441807-15) and laboratory 

rat (Rattus norvegicus) (MRID 436165-20) are included in the summary table below. The 

endpoint for the chronic bird study was based on significant reductions in egg production (eggs 

laid, eggs set, and viable embryos), while the endpoint for the chronic mammal study was based 

upon decreased F1 pup viability on postnatal days 0-4 and on significant F1 pup viability on 

postnatal days 0-4 and on a significant reduction in F2b pup weight. 

Cymoxanil technical is practically nontoxic to young adult honeybees on an acute contact 

exposure basis (LD50 > 25 μg a.i./bee; MRID 441807-35) and exhibits low toxicity to honeybees 

on an acute oral exposure basis (LD50 > 1,000 mg a.i./bee; MRID 441807-36). 

Passerine bird toxicity data as well as terrestrial plant toxicity studies for vegetative vigor or 

seedling emergence are not available for cymoxanil. 
21 

Table 4.3. Summary of the Most Sensitive Endpoints from Submitted Terrestrial Toxicity 

Studies for Cymoxanil Technical. 

TAXON ENDPOINT CHEMICAL/ 

FORMULATION MRID STUDY CLASSIFICATION 

BIRDS

Acute Oral 

Mallard Duck 

(Anas 

platyrhynchos) 

14-day LD50 > 2250 

mg a.i./kg-bw Cymoxanil (97.8%) 441807-11 Acceptable 

Sub-Acute Dietary

Bobwhite quail 

(Colinus 

virginianus) 

8-day LC50 > 5620 

mg a.i./kg-diet Cymoxanil (97.8%) 441807-13 Acceptable 

Chronic

Mallard Duck 

(Anas 

platyrhynchos) 

NOAEC:100 mg 

a.i./kg diet 

LOAEC: 300 mg 

a.i./kg diet 

(Based on significant 

reductions in egg 

production) 

Cymoxanil (97.8%) 441807-15 Acceptable 

MAMMALS 

Acute 

Laboratory Rat 

(Rattus norvegicus) 

LD50 > 960 mg/kgbw Cymoxanil (97.8%) 436165-12 Acceptable 

Chronic 

Laboratory Rat 

(Rattus norvegicus) 

NOAEL: 6.5 mg 

a.i./kg-bw 

LOEAL:32.1 mg 

a.i./kg-bw 

(Based on reduction 

in mean bodyweight, 

overall body weight 

gain, and food 

consumption in 

parental (F0) males; 

reduced mean 

bodyweight during 

gestation and 

lactation of F1

females; decreased 

mean F1 pup 

viability; reduced F2

pup weight) 

Cymoxanil (97.8%) 436165-20 Acceptable 

TERRESTRIAL INVERTEBRATES 

Honey Bee 

(contact) (Apis 

melifera) 

LD50 > 25 μg a.i./bee Cymoxanil (97.8%) 441807-35 Acceptable 

Honey Bee (oral)

(Apis melifera)

LC50 > 1000 mg 

a.i./bee Cymoxanil (97.8%) 441807-36 Acceptable 

Earthworm 

(Eisenia fetida) 

14-day LC50 = 2109 

mg a.i./ kg dw soil Cymoxanil (96.0%) 442007-02 Supplemental 
22 

TAXON ENDPOINT CHEMICAL/ 

FORMULATION MRID STUDY CLASSIFICATION 

Predatory Mite 

(Typhlodromus 

pyri) 

7-days: No statistical 

difference seen at 9 g 

a.i./ha for growth or 

reproduction; 

however, statistical 

difference were seen 

at 120 g a.i./acre 

Cymoxanil (60%) 454754-01 Supplemental 

4.3. Incident Databases Review 

Preliminary reviews of the Ecological Incident Information System (EIIS, version 2.1) and the 

Avian Incident Monitoring System (AIMS)9 were conducted on August 27, 2011. No incidents 

associated with cymoxanil use have been reported in EIIS. In addition, no incidents involving 

birds were reported in the AIMS database for cymoxanil. 

In addition to the major incidents recorded in EIIS, additional incidents may be reported to the 

Agency in aggregated incident reports. Pesticide registrants report certain types of incidents to 

the Agency as aggregate counts of incidents occurring per product per quarter. Ecological 

incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (WB), ‘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. However, for 

cymoxanil, as of August 27, 2011, no aggregated incidents have been reported. 

Actual incidents associated with the use of cymoxanil may be higher than what is reported to the 

Agency. Incidents may go unreported since effects may not be immediately apparent and/or 

readily attributed to the use of a chemical. As such, the absence of incident reports cannot be 

construed as the absence of incidents. 

4.4. Ecosystems Potentially at Risk 

The ecosystems at risk are often extensive in scope; therefore, it may not be possible to identify 

specific ecosystems during the development of a nation-wide ecological risk assessment. 

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

field and immediately adjacent areas that may receive drift or runoff. Areas adjacent to the 

treated field could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or 

grasslands, woodlands, wetlands and riparian habitats, and other uncultivated areas. 

Aquatic ecosystems potentially at risk include water bodies adjacent to or downstream from, the 

treated field and could include impounded bodies such as ponds, lakes and reservoirs, or flowing 

waterways such as streams or rivers. For uses in coastal areas, aquatic habitat also includes 

marine ecosystems, including estuaries. 

 

9

 http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm 
23 

5. Assessment Endpoints 

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

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

(USEPA, 1998). For cymoxanil, the ecological entities may include the following: birds, 

mammals, terrestrial-phase amphibians, reptiles, freshwater fish and invertebrates, aquatic-phase 

amphibians, estuarine/marine fish and invertebrates, terrestrial plants, terrestrial invertebrates, 

and aquatic plants. The attributes for each of these entities include growth, reproduction, and 

survival. 

6. Conceptual Model 

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically 

significant concentrations. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure. 

The conceptual model for cymoxanil provides a written description and visual representation of 

the predicted relationships between cymoxanil, potential routes of exposure, and the predicted 

effects for the assessment endpoint. A conceptual model consists of two major components: risk 

hypothesis and a conceptual diagram (USEPA, 1998). 

Based on the submitted environmental fate data, cymoxanil is a highly water soluble compound 

that is not expected to volatilize. It will degrade quickly in neutral and alkaline media, but may 

be persistent in acidic environments (water and soil), although the chemical photodegrades 

quickly in aqueous media under optimal (i.e. clear) conditions. Cymoxanil has been shown to be 

mobile to highly mobile in soil (FAO classification scheme), and its degradates IN-W3595, INR3273 and IN-KQ960 are all expected to be highly mobile in soil based on limited available 

data. Based on its very low Kow value, cymoxanil is not expected to bioaccumulate in aquatic or 

terrestrial food chains. 

Based on submitted ecological effect data, cymoxanil is characterized as slightly toxic to fish 

[and aquatic-phase amphibians for which fish serve as surrogates] and aquatic invertebrates on 

an acute exposure basis. Chronic exposure resulted in effects on growth and survival. The 

compound is characterized as slightly toxic to mammals on an acute oral exposure basis but is 

practically non-toxic to birds [and terrestrial-phase amphibians and reptiles for which birds serve 

as surrogates] on both an acute oral and subacute dietary exposure basis. Chronic exposure 

resulted in decreased survival in mammals and in reductions in egg production in birds. The 

compound is practically nontoxic to honey bees on both an acute contact and oral exposure basis. 

Although there are no toxicity data currently available for terrestrial plants, aquatic plant toxicity 

data indicate that nonvascular plants are several orders of magnitude more sensitive to cymoxanil 

than vascular plants. Available toxicity data also indicate that several formulations of cymoxanil 

and the degradate IN-KQ960 are considerably more toxic to nontarget organisms than the 

technical grade active ingredient. 
24 

Previous ecological risk assessments for cymoxanil highlighted possible risk to birds, mammals, 

and aquatic organisms due to cymoxanil use. As such, listed species in all taxa may potentially 

be affected indirectly due to alterations in their habitat and effects on primary productivity. It 

was previously determined that all other taxa were not at direct risk from cymoxanil use. 

However, this determination was based on an incomplete dataset. Risks to passerine bird species 

and terrestrial plants are uncertain. 

6.1. Risk Hypothesis 

A risk hypothesis describes the predicted relationship among the stressor, exposure, and 

assessment endpoint response along with the rationale for their selection. Because data are 

incomplete with which to assess effects to all taxa, the following ecological risk hypothesis is 

being employed for this ecological risk assessment: 

Given the uses of cymoxanil as a fungicide, and its environmental fate properties, there is 

potential exposure from cymoxanil, its potential degradates of concern (i.e., IN-3204, INKP533, IN-R3273, IN-JX915, IN-U3595, and IN-KQ960), and formulated products to 

non-target terrestrial and/or aquatic organisms. When used in accordance with the 

label, cymoxanil, its degradates, and formulated products may result in potential adverse 

effects upon the survival, growth, and reproduction of non-target terrestrial and/or 

aquatic organisms. 

6.2. Conceptual Diagram 

The environmental fate properties of cymoxanil indicate that runoff, spray drift and direct spray 

represent potential transport mechanisms to aquatic and terrestrial habitats where non-target 

organisms may be either directly or indirectly exposed. These transport mechanisms (i.e., 

sources) are depicted in the conceptual diagrams below (Figures 6.1 and 6.2) along with the 

receptors of concern and the potential attribute changes in the receptors due to exposures of 

cymoxanil. While not captured in Figure 6.2, exposure of terrestrial vertebrates from drinking 

water containing cymoxanil and degradates of concern is also a route of exposure that will be 

assessed. 
25 

Figure 6.1. Conceptual Model for Cymoxanil and Degradate Effects on Aquatic 

Organisms. Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood of 

Contributing to Ecological Risk. 

Stressor

Source

Receptors

Attribute

Change

Cloransulam-methyl and Degradates of Concern applied to use site

Spray drift

Aquatic animals

Invertebrates 

Vertebrates

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in nonvascular 

and vascular plants

Reduction in prey

Modification of PCEs

related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to 

habitat

Surface water/

Sediment

Runoff

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Uptake/gills 

or integument

Ingestion Ingestion

Atmospheric 

transport

Wet/dry deposition

Soil Leaching to

Groundwater

Uptake/gills 

or integument

Aquatic Plants

Non-vascular

Vascular

Uptake/cell, 

roots, leaves Riparian plants

terrestrial 

exposure 

pathways see 

Figure 6.2

Cymoxanil and Degradates of Concern applied to the use site 
26 

Figure 6.2. Conceptual Model for Cymoxanil and Degradate Effects on Terrestrial 

Organisms. Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood of 

Contributing to Ecological Risk. 

7. Analysis Plan 

In order to address the risk hypothesis, the potential for adverse effects on the environment will 

be estimated. The use, environmental fate, and ecological effects of cymoxanil will be 

characterized and integrated to assess the risks. Risk quotients (RQ) will be derived for 

cymoxanil by dividing estimated environmental concentrations (EEC) by the most sensitive 

endpoint from the relevant, available toxicity data for cymoxanil. 

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket. 

Stressor

Source

Attribute

Change

Cloransulam-methyl and Degradates of Concern applied to use site

Direct

application Spray drift

Terrestrial 

vertebrates

Terrestrial 

inverts

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey and food

Modification of PCEs

related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

to habitat

Terrestrial plants

grasses/forbs, fruit, seeds 

(trees, shrubs)

Runoff

Terrestrial 

Vertebrates 

Exposure Media 

& Receptors Soil

Ingestion

Ingestion

Ingestion

Dermal uptake/Ingestion

Atmospheric 

transport

Root uptake/contact

Wet/dry deposition

Ingestion

Leaching to

Groundwater Irrigation 

water

Cymoxanil and Degradates of Concern applied to the use site 
27 

7.1. Stressors of Concern 

The stressors or residues of concern in this assessment will include cymoxanil and any 

degradates for which there are both toxicological and exposure concerns. Based on the available 

information (presented in Table 3.5), the main degradates of concern with respect to exposure 

include IN-3204, IN-KP533, IN-R3273, IN-JX915, and IN-U3595. There is toxicological 

concern for IN-KQ960, but exposure is uncertain due to aerobic soil metabolism data gaps. All 

of the major degradates of cymoxanil were run through EPA’s ASTER (Assessment Tools for 

the Evaluation of Risk)10 Program to check for a specific mode of action; however, ASTER put 

all of the major degradates into a non-polar narcosis class and predicted less toxicity than the 

parent compound. The nonpolar narcosis QSAR is invoked only if the structural characteristics 

of a chemical do not suggest a more specific mode of action or if there is insufficient information 

in the ASTER training database for the specific chemical group under examination (i.e., a lack of 

mechanistic information on specific functional moieties). Given that such a non-specific mode of 

action was used to estimate toxicity of degradates in ASTER, it is not appropriate to use these 

results alone to assess the potential toxicity of cymoxanil degradates. 

Empirical toxicity data are only available for one cymoxanil degradate, IN-KQ960, in the form 

of an acute freshwater invertebrate toxicity study (MRID 456892-01) with Daphnia magna. 

Based on this study IN-KQ960 is 35 times more toxic than cymoxanil technical (MRID 443646-

10) to D. magna on an acute exposure basis. In addition, IN-KQ960 was determined to be more 

mobile than the parent compound. Based on this information, IN-KQ960 will be considered a 

stressor of concern at the time the risk assessment is carried out. Modeled exposure estimates 

resulting from cymoxanil use will reflect the predicted environmental fate of cymoxanil and INKQ960. 

Since empirical toxicity data are only available for the degradate IN-KQ960, the relevance of 

other major cymoxanil degradates for risk assessment was considered by estimating toxicity 

endpoints using EPA’s Ecological Structure Activity Relationships (ECOSAR) Program11. 

ECOSAR uses structure-activity relationships (SARs) to predict the aquatic toxicity of untested 

chemicals based on their structural similarity to chemicals for which aquatic studies are 

available. The toxicity data used to build the SARs are collected from publicly available 

experimental studies and confidential submissions provided to the U.S. EPA New Chemicals 

Program. Although ECOSAR is maintained as a stand-alone program, the ECOSAR QSARs are 

also included in the EPA EPISuite program and the web-based PBT Profiler tool. The SARs in 

ECOSAR express correlations between a compound's physicochemical properties and its toxicity 

within specific chemical classes. Table 7.1 shows all of the chemical classes into which the 

major degradates fit (see cymoxanil and degradate structures in Appendix B). Bolded values 

indicate that the ECOSAR-estimated toxicity endpoint was lower (more sensitive) than that 

measured for the parent. These toxicity estimates are only used to prioritize which degradates 

are likely a risk concern and how they should be handled in the risk assessment. The estimated 

values may over- or underestimate actual toxicity of the compounds. Appendix E provides the 

output from ECOSAR. In Table 7.1, similarly structured degradates are grouped together. 

 

10 http://www.epa.gov/med/Prods_Pubs/aster.htm 

11 http://www.epa.gov/oppt/newchems/tools/21ecosar.htm 
28 

The degradate IN-KP533 is similarly structured to the parent and has similar ECOSAR results; 

thus, toxicity of this degradate will be assumed to be equivalent to the parent across aquatic 

organisms unless additional data toxicity data becomes available. 

For the degradate IN-W3595, acute toxicity endpoints estimated by ECOSAR were much lower 

(more sensitive) than what was measured for the parent. Because there are also exposure 

concerns for this degradate, additional acute toxicity data for IN-W3595 is recommended for one 

freshwater fish (preferably bluegill sunfish [Lepomis macrochirus]; 850.1075), one invertebrate 

(Daphnia; 850.1010), and one nonvascular plant species (preferably green algae 

(Pseudokirchneriella subcapitata); 850.5400) to provide a basic foundation for comparing 

toxicity of parent and degradate 

The degradates IN-U3204, IN-R3273, IN-JX915, IN-KQ960, and IN-T4226 all form in 

appreciable amounts and have exposure concerns. Moreover, these degradates all have similar 

molecular structures and produce similar toxicity estimates in ECOSAR. Empirical toxicity data 

is only available for IN-KQ960, which showed that the degradate is 35 times more toxic than the 

parent in freshwater invertebrates. It is worth noting that ECOSAR did not flag IN-KQ960’s 

toxicity to daphnids; thus, there is uncertainty in the use of ECOSAR for these chemicals.12 

ECOSAR results predict that toxicity of this entire group of degradates is higher relative to the 

parent for green algae, which may be associated with their carbonyl urea structure. Submission 

of additional effects data for IN-KQ960 would help determine if this particular degradate is more 

toxic than the parent to other aquatic organisms, given the available empirical data. In addition, 

data on IN-KQ960 could also represent potential toxicity of the entire degradate group to aquatic 

organisms so that experimental data on each degradate is not necessary for evaluating risk. Since 

data on IN-KQ960 is already available for freshwater invertebrates, two additional acute studies 

on freshwater fish (preferably bluegill sunfish (Lepomis macrochirus); 850.1075) and algae 

(preferably the freshwater diatom Navicula pelliculosa; 850.5400) would provide a basic 

foundation for comparing toxicity of parent and degradates. 

Oxalic acid is considered to have negligible toxicity when compared to the parent compound. 

Table 7.1. Comparison of Measured Toxicity Endpoints for Cymoxanil with Estimated 

Aquatic Toxicity Endpoints for Major Degradates of Cymoxanil (Estimated Using 

ECOSAR v.1) and Resulting Structure-Activity Relationships (SARs).* 

Compound 

(compounds class 

used by ECOSAR) 

Estimated Toxicity Endpoint (mg/L) 

96-hr FW fish 

EC50/LC50

48-hr 

Daphnid 

LC50

96-hr EC50

Green Algae 

Fish Chronic 

Value 

Daphnid 

Chronic 

Value 

Cymoxanil Parent 

(measured) 

29 28 4.1 0.01 0.07 

Cymoxanil (Ecosar) 

Aliphatic Amines 

284 29.0 32.5 26.5 2.1 

Cymoxanil (Ecosar) 

Carbonyl Ureas 

134 144 0.02 1.0 3.4 

Cymoxanil (Ecosar) 2537 1043 960 215 88.3 

 

12 More information about the uncertainties associated with ECOSAR can be found in the following documents: 

http://www.epa.gov/oppt/newchems/tools/ecosarusersguide.pdf

http://www.epa.gov/oppt/newchems/tools/ecosartechfinal.pdf
29 

Compound 

(compounds class 

used by ECOSAR) 

Estimated Toxicity Endpoint (mg/L) 

96-hr FW fish 

EC50/LC50

48-hr 

Daphnid 

LC50

96-hr EC50

Green Algae 

Fish Chronic 

Value 

Daphnid 

Chronic 

Value 

Neutral Organic 

SAR 

IN-U3204 (Ecosar) 

Aliphatic Amines 

433 42.8 51.1 44.5 2.9 

IN-U3204 (Ecosar) 

Carbonyl Ureas 

191 274 0.015 1.4 5.1 

IN-U3204 (Ecosar) 

Neutral Organic 

SAR 

4517 1762 1619 371 143 

IN-KP533 (Ecosar) 

Carbonyl Ureas 

1333 10592 0.012 9.7 51.5 

IN-KP533 (Ecosar) 

Neutral Organic 

SAR 

1.17e+005 33302 30308 8024 2063 

IN-W3595 (Ecosar) 

Aliphatic Amines 

0.79 0.12 0.06 0.02 0.01 

IN-W3595 (Ecosar) 

Neutral Organic 

SAR 

0.96 0.78 0.74 0.12 0.12 

IN-R3273 (Ecosar) 

Aliphatic Amines 

29 3.5 2.9 1.7 0.29 

IN-R3273 (Ecosar) 

Carbonyl Ureas 

19.1 4.9 0.013 0.14 0.36 

IN-R3273 (Ecosar) 

Neutral Organic 

SAR 

121 65 60 11.9 6.9 

IN-JX915 (Ecosar) 

Aliphatic Amines 

1364 123 176 184 7.8 

IN-JX915 (Ecosar) 

Carbonyl Ureas 

506 1575 0.015 3.7 16 

IN-JX915 (Ecosar) 

Neutral Organic 

SAR 

21692 7326 6703 1639 526 

IN-KQ960 (Ecosar) 

Aliphatic Amines 

10172 794 1513 2148 43.3 

IN-KQ960 (Ecosar) 

Carbonyl Ureas 

2824 32099 0.016 20.5 118 

IN-KQ960 (Ecosar) 

Amides 

25732 1.51e+005 369 5.08 769.6 

IN-KQ960 (Ecosar) 

Neutral Organic 

SAR 

3.28e+005 86912 78939 21543 5092 

IN-T4226 (Ecosar) 

Carbonyl Ureas 

184 334 0.011 1.3 5.2 

IN-T4226 (Ecosar) 

Neutral Organic 

SAR 

5219 1948 1788 418 152 
30 

Compound 

(compounds class 

used by ECOSAR) 

Estimated Toxicity Endpoint (mg/L) 

96-hr FW fish 

EC50/LC50

48-hr 

Daphnid 

LC50

96-hr EC50

Green Algae 

Fish Chronic 

Value 

Daphnid 

Chronic 

Value 

Oxalic Acid 

(Ecosar) Neutral 

Organics 

1.68e+005 67877 39659 10918 2519 

*Bolded values indicate that the ECOSAR-estimated toxicity endpoint was much lower (more sensitive) than that 

measured for the parent. 

For degradates assumed to have similar toxicity to aquatic organisms relative to the parent due to 

structural similarities (e.g., IN-KP533), a total toxic residue (TTR) approach will be used by 

summing the residues observed in fate studies and then estimating degradation rates based on the 

total summed residues. The TTR degradation rates will then be used to estimate exposure in 

place of degradation rates for the parent alone. The modeled EECs for TTR will then be 

compared to toxicity endpoints for the parent. 

For degradates that are potentially more highly toxic to aquatic organisms relative to the parent, 

available toxicity data will be compared to EECs for the particular degradate and will be used to 

derive degradate-specific RQ values that can be compared to agency LOCs. If toxicity data does 

not exist for a particular degradate or group of structurally similar degradates, ECOSAR 

predictive toxicity data, as well as other available toxicity information from the open-literature, 

will be used to characterize uncertainties and pinpoint critical knowledge gaps. Toxicity studies 

that would help reduce degradate uncertainties in risk assessment are described in the preceding 

paragraphs, in Tables 7.5 and 7.6, and in Appendix G. 

The Agency does not routinely include an evaluation of mixtures of active ingredients in its 

ecological risk assessments. This applies to mixtures of multiple active ingredients in product 

formulations as well as those in the applicator’s tank. In the case of the product formulations of 

active ingredients (that is, a registered product containing more than one active ingredient), each 

active ingredient is subject to an individual risk assessment for regulatory decision regarding the 

active ingredient on a particular use site. If effects data are available for a formulated product 

containing more than one active ingredient, the data may be used qualitatively or quantitatively 

in accordance with the Agency’s Overview Document and the Services’ Evaluation 

Memorandum (USEPA, 2004; USFWS/NMFS, 2004). Available toxicity data for environmental 

mixtures of cymoxanil with other pesticides will be presented as part of the ecological risk 

assessment. It is expected that the toxic effect of cymoxanil, in combination with other 

pesticides used in the environment, is likely to be a function of many factors including but not 

necessarily limited to: (1) the exposed species, (2) the co-contaminants in the mixture, (3) the 

ratio of cymoxanil and co-contaminant concentrations, (4) differences in the pattern and duration 

of exposure among contaminants, and (5) the differential effects of other physical/chemical 

characteristics of the receiving waters (e.g. organic matter present in sediment and suspended 

water). Quantitatively predicting the combined effects of all these variables on mixture toxicity 

to any given taxa with confidence is beyond the capabilities of the available data and current 

methodologies; however some data does exist on mixtures of cymoxanil with other chemicals 

indicating the possibility of increased toxicity of the co-formulation relative to cymoxanil alone. 

Specifically, LC50 values for a co-formulation of cymoxanil (6.58%) with copper hydroxide 

(26.5%) in freshwater crustaceans (D. magna), fish (O. mykiss), and algae (P. subcapitata) are 
31 

2.78, 10.3, and 9.4 μg cymoxanil a.i./L (values corrected for percent a.i. in formulation), 

respectively, while endpoint values for the same groups exposed to cymoxanil technical are 

28,000, 61,000, and 4,110 μg a.i./L, indicating several orders of magnitude difference in all cases 

(see Table 1 in Appendix E for further study information). However, in order to demonstrate 

synergism between these active ingredients, the co-formulation must also increase toxicity of 

copper hydroxide. At the time of this problem formulation, sufficient toxicity data on copper 

hydroxide is not readily available in the EFED database to make this comparison. However, 

sufficient open-literature data (e.g. via EPA’s ECOTOX database) may exist and will be 

collected and examined at the time of the registration review risk assessment in order to evaluate 

potential synergistic effects with cymoxanil. Also, a qualitative discussion of implications of the 

available pesticide mixture effects data on the confidence of risk assessment conclusions will be 

addressed as part of the uncertainty analysis. 

7.2. Measures of Exposure 

In order to estimate risks of cymoxanil exposures in aquatic and terrestrial environments, all 

exposure modeling and resulting risk conclusions will be made based on maximum application 

rates for the currently registered uses as discussed in Section 3.2. Measures of exposure are 

based on aquatic and terrestrial models that estimate environmental concentrations of cymoxanil 

using the maximum labeled application rate and application methods that have the greatest 

potential for off-site transport of the chemical. The models used to generate aquatic estimated 

environmental concentrations (EEC) are the Pesticide Root Zone Model (PRZM) coupled with 

the EXposure Analysis Model System (EXAMS). As discussed in the preceding section, the 

EECs will be based on the parent compound plus any other degradates that are determined to be 

of toxicological concern based on information available at the time of the assessment. 

Environmental inputs for the TTR in aquatic systems will be calculated using the total residue 

approach. 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. 

PRZM (v3.12.2, May 2005) and EXAMS (v2.98.4.6, April 2005) are screening simulation 

models coupled with the graphical user interface, PE (v5.0, November 2006) to generate daily 

exposures and 1-in-10-year EECs of cymoxanil (and residues of concern) that may occur in 

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

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

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

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

The standard 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 m3

 volume) with no outlet. The composite model PRZM/EXAMS is used to 

estimate screening-level exposure of aquatic organisms to cymoxanil. 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. 
32 

Exposure estimates for terrestrial animals assumed to be in the target area or in an area exposed 

to spray drift are derived using the T-REX model (version 1.4.1, 10/08/2008). This model 

incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is based on a 

large set of actual field residue data. The upper limit values from the nomograph represent the 

95th percentile of residue values from actual field measurements (Hoerger and Kenaga 1972). 

The Fletcher et al. (1994) modifications to the Kenaga nomograph are based on measured field 

residues from 249 published research papers, including information on 118 species of plants, 121 

pesticides, and 17 chemical classes. For input into T-REX, the default foliar dissipation half-life 

of 35 days will be used due to insufficient foliar dissipation rate data on cymoxanil. The initial 

Section 3 assessment (DP Barcode D233366) relied on a foliar dissipation half-life of 2 days 

based on the upper 90th percentile aerobic soil metabolism half-life. However, without 

magnitude of residue data with which to estimate foliar dissipation half-lives, the current 

approach is to utilize a default half-life of 35 days. Since cymoxanil appears to be susceptible to 

both biotic and abiotic degradation (aqueous photolysis t1⁄2=3.6 days; hydrolysis at pH 7 t1⁄2=1.4 

days), the use of the 35-day default value is likely conservative. Therefore, estimated 

environmental concentrations on terrestrial forage items will be calculated based both on the 35-

day default foliar dissipation half-life and assuming a half-life roughly an order of magnitude 

lower. If terrestrial plant toxicity data are available, EECs for terrestrial plants inhabiting dry 

and wetland areas are derived using TerrPlant (version 1.2.2, 12/26/2006). This model uses 

estimates of pesticides in runoff and in spray drift to calculate EECs. EECs are based upon 

solubility, application rate and minimum incorporation depth. If terrestrial plant data is not 

available at the time of the registration review risk assessment, risks of concern will be assumed 

for this group. 

The AgDRIFT spray drift model (v2.01; May, 2001) is used to assess exposures of organisms to 

cymoxanil deposited on terrestrial habitats by spray drift. 

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

upper-bound estimate of exposure of birds and mammals to cymoxanil through drinking water 

using the compounds solubility value, the most sensitive acute and chronic avian toxicity 

endpoints (i.e., bobwhite quail LD50 >2250 mg a.i./kg-bw; NOAEC 300 mg a.i./kg-diet) and the 

most sensitive acute and chronic mammalian toxicity endpoints (i.e., laboratory rat LD50 >960 

mg a.i./kg-bw and NOAEL = 100 mg a.i./kg-bw, respectively). Appendix F provides a 

description of the model and assumptions in deriving an upper-bound exposure estimate. 

Cymoxanil’s reported solubility in water at 20°C is 780 mg/L at pH 7 (and 890 mg/L at pH 5). 

Drinking water exposure alone was determined to be a potential concern for mammals on a 

chronic exposure basis (see Appendix F for model results). Although this model flags acute 

exposure to birds and mammals as a potential concern based on potential estimated 

environmental concentrations in drinking water at pH 8.5 and above, toxicity data demonstrate 

that acute/subacute effects from cymoxanil exposure are not likely a concern for birds or 

mammals given that the compound is characterized as practically nontoxic to birds on both an 

acute oral and subacute dietary exposure basis and the compound is only slightly toxic to 

mammals on an acute oral exposure basis. This exposure pathway though will be explored 

further with the development of SIP v.2.0 in the Ecological Risk Assessment for cymoxanil. 

Detailed information about the SIP v.1.0, as well as the tool, can be found on the EPA’s website 

at http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial. 
33 

The Screening Tool for Inhalation Risk (STIR v. 1.0, Released November 23, 2010) was used to 

assess the potential for risk to bird and mammals from inhalation exposure. Appendix F also 

provides a description of this model and assumptions in deriving exposure estimates. The 

exposure pathways that are assessed by this tool include both droplet inhalation and vapor phase 

inhalation. Allometric equations that relate inhalation rate to body weight are used to derive an 

estimated inhalation dose of either droplets or vapor for a 0.020 kg bird and a 0.015 kg mammal 

(Mineau et al. 1996; Sample and Arenal 1999; USEPA 1993). 

Results from acute inhalation toxicity studies for mammals from the "six-pack" that are routinely 

submitted to the Registration Division of the Office of Pesticide Programs can be directly 

compared with the estimated inhalation doses from vapor and droplets. In most cases however, 

avian inhalation data are lacking. STIR uses the avian oral toxicity data together with both the 

mammalian oral and inhalation toxicity data to derive an estimate of avian inhalation toxicity. 

Based on the findings of the 2004 Science Advisory Panel (USEPA, 2004), an adjustment factor 

is applied to these data to adjust the estimate of avian inhalation toxicity for differences in 

diffusion efficiency across the avian lung membrane compared to the mammalian lung 

membrane. 

STIR relies on the application rate, application method, defined droplet spectra (if applicable), 

molecular weight, vapor pressure and the temperature associated with the vapor pressure of a 

specific chemical to obtain an estimate of the droplet and vapor concentration in the air. These 

concentrations are compared with an estimated inhalation LD50 of a specific chemical as a ratio 

that is then compared with a threshold of 0.1. If the ratio of the exposure to the toxicity exceeds 

0.1, then the screening tool indicates that a reviewer is to "Proceed to Refinements", at which 

point the reviewer can request specific studies that will help to address uncertainty related to 

inhalation risk. The user's guide contains information for the specific studies that may be 

requested. However, if the screening tool indicates "Exposure not Likely Significant", then the 

reviewer can assume that the inhalation pathway is not expected to be a significant source of 

risk. 

The results of STIR for cymoxanil indicated “Exposure not Likely Significant;” thus, no 

additional studies will be requested to address uncertainties related to inhalation risk to birds (see 

Appendix F for model results). 

7.3. Measures of Effect 

 

Ecological effects data are used as measures of direct and indirect effects to biological receptors. 

As discussed previously, data are obtained from registrant-submitted studies or from literature 

studies identified by ECOTOX (USEPA, 2007b). The ECOTOX database provides more 

ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a source for 

locating single chemical toxicity data and potential chemical mixture toxicity data for aquatic 

life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the USEPA, 

Office of Research and Development, and the National Health and Environmental Effects 

Research Laboratory's Mid-Continent Ecology Division. 
34 

Also as discussed previously, information on the potential effects of cymoxanil on non-target 

animals is also collected from the Ecological Incident Information System (EIIS; USEPA, 

2007a). The EIIS is a database containing adverse effect (typically mortality) reports on nontarget organisms where such effects have been associated with the use of pesticides. 

Incidents reported in the aggregate incident reports and the Avian Incident Monitoring System 

(AIMS) will also be searched again. AIMS is a database administered by the American Bird 

Conservancy with partial funding from EPA). It contains publicly available data on reported 

avian incidents involving pesticides 

(http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm). 

Where available, sub-lethal effects observed in both registrant-submitted and open literature 

studies will be evaluated qualitatively. Such effects may include behavioral changes (e.g., 

lethargy and changes in coloration). Quantitative assessments of risks, though, are limited to 

those endpoints that can be directly linked to the Agency’s assessment endpoints of impaired 

survival, growth and reproduction. 

The assessment of risk for direct effects to non-target organisms makes the assumption that 

toxicity of cymoxanil to birds is similar to toxicity to terrestrial-phase amphibians and reptiles. 

The same assumption is made for fish and aquatic-phase amphibians. 

The acute measures of effect used for animals in this assessment are the LD50, LC50 and EC50. 

LD stands for "Lethal Dose", and LD50 is the amount of a material, given all at once, that is 

estimated to cause the death of 50% of the test organisms. LC stands for “Lethal Concentration” 

and LC50 is the concentration of a chemical that is estimated to kill 50% of the test organisms. 

EC stands for “Effective Concentration” and the EC50 is the concentration of a chemical that is 

estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic 

measures of exposure for listed and non-listed animals are the NOAEL/NOAEC and NOEC. 

NOAEL stands for “No Observed-Adverse-Effect-Level” and refers to the highest tested dose of 

a substance that has been reported to have no harmful (adverse) effects on test organisms. The 

NOAEC (i.e., “No-Observed-Adverse-Effect-Concentration”) is the highest test concentration at 

which none of the observed effects were statistically different from the control. The NOEC is 

the No-Observed-Effects-Concentration. For non-listed plants, only acute exposures are 

assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants); for listed plants either the 

NOAEC or EC05 is used. 

7.4. Integration of Exposure and Effects 

Risk characterization is the integration of exposure and ecological effect characterizations to 

determine the potential ecological risk from the use of cymoxanil and the likelihood of direct and 

indirect effects to non-target organisms in aquatic and terrestrial habitats. The exposure and 

effects data are integrated in order to evaluate potential adverse ecological effects on non-target 

species. For the assessment of cymoxanil risks, the risk quotient (RQ) method is used to 

compare estimated exposure and measured toxicity values. Acute and chronic EECs are divided 

by acute and chronic toxicity values. The resulting RQs are then compared to the Agency’s 

Levels of Concern (LOC) (USEPA, 2004) (Table 7.2). These criteria are used to indicate when 
35 

cymoxanil’s use, as directed on the labels, has the potential to cause adverse direct or indirect 

effects to non-target organisms. In addition, incident data from EIIS, aggregate incident reports, 

and AIMS will be considered as part of the risk characterization. 

Table 7.2. Agency risk quotient (RQ) metrics and levels of concern (LOC) for Federallylisted (listed) threatened/endangered and non-listed species per risk class.

Risk Class Risk Description RQ LOC 

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from 

acute exposures Peak EEC/LC501

 0.5 

Acute Restricted 

Use 

Potential for effects to animals from acute 

exposures 

Risks may be mitigated through restricted use 

classification 

Peak EEC/LC501

 0.1 

Acute Listed 

Species 

Listed species may be potentially affected by 

acute exposures Peak EEC/LC501

 0.05 

Chronic Potential for effects to non-listed and listed 

animals from chronic exposures 

60-day EEC/NOEC (fish) 

1 21-day EEC/NOEC 

(invertebrates) 

Terrestrial Animals (mammals and birds) 

Acute Potential for effects to non-listed animals from 

acute exposures 

EEC2

/LC50 (Dietary) 

0.5 

EEC/LD50 (Dose) 

Acute Restricted 

Use 

Potential for effects to animals from acute 

exposures 

Risks may be mitigated through restricted use 

classification 

EEC2

/LC50 (Dietary) 

0.2 

EEC/LD50 (Dose) 

Acute Listed 

Species 

Listed species may be potentially affected by 

acute exposures 

EEC 2

/LC50 (Dietary) 

0.1 

EEC/LD50 (Dose) 

Chronic Potential for effects to non-listed and listed 

animals from chronic exposures EEC 2

/NOAEC 1 

Plants 

Non-Listed Potential for effects to non-target, non-listed 

plants from exposures EEC/ EC25

1 

Listed Plant Potential for effects to non-target, listed plants 

from exposures 

EEC/ NOEC 

1 

EEC/ EC05
36 

7.5. Deterministic and Probabilistic Assessment Methods 

The quantitative assessment of risk will primarily depend upon the deterministic point estimatebased approach described in the risk assessment. Depending on the risk manager’s need for 

additional information regarding risk, an effort will be made to further qualitatively describe risk 

using probabilistic tools that the Agency has developed. These tools have been reviewed by 

FIFRA Scientific Advisory Panels (http://www.epa.gov/scipoly/sap/index.htm) and have been 

deemed as appropriate means of refining assessments where deterministic approaches have 

identified risks. 

7.6. Endangered Species Assessments 

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the 

Agency will evaluate risks to Federally-listed threatened and/or endangered (listed) species from 

registered uses of cymoxanil. This assessment will be conducted in accordance with the 

Overview Document (USEPA, 2004), provisions of the ESA, and the Services’ Endangered 

Species Consultation Handbook (USFWS/NMFS, 1998). 

The action area is used to identify all listed (threatened and endangered) species and designated 

critical habitat that could be affected by the Federal action. The Federal action is the 

authorization or registration of pesticide use or uses as described on the label(s) of pesticide 

products containing a particular active ingredient. The action area is defined by the Endangered 

Species Act as, “all areas to be affected directly or indirectly by the Federal action and not 

merely the immediate are involved in the action” (50 CFR §402.2). Based on an analysis of the 

Federal action, the action area is defined by the actual and potential use of the pesticide. 

In the case of nationwide ecological risk assessment conducted for cymoxanil under Registration 

Review, the action area will encompass the entire United States and its territories. The purpose 

of defining the action area as the entire United States and its territories is to ensure that the initial 

area of consideration encompasses all areas where cymoxanil may be used now and in the future, 

including the potential for off-site transport via spray drift and downstream dilution. 

Additionally, the concept of a nationwide action area takes into account the potential for direct 

and indirect effects and any potential modification to critical habitat based on ecological effect 

measures associated with reduction in survival, growth, and reproduction, as well as the full suite 

of sublethal effects available in the effects literature. It is important to note that the nationwide 

action area does not imply that direct and/or indirect effects and critical habitat modification are 

expected to or are likely to occur over the full extent of the action area, but rather to identify all 

listed species and critical habitat that may potentially be affected by the action. The Agency will 

use more rigorous analysis including consideration of available land cover data, toxicity data, 

and exposure information to determine areas where individual listed species and designated 

critical habitat may be affected or modified via endpoints associated with reduced survival, 

growth, or reproduction. 
37 

7.7. Drinking Water Assessment 

A drinking water assessment (DWA) will be conducted to support future human health dietary 

risk assessments of cymoxanil. The drinking water assessment will incorporate model estimates 

of cymoxanil residues of concern plus any degradates of toxicological concern in surface water 

and groundwater. Potential degradates of concern include IN-KP533, which was a maximum 

average of 57.0% of the applied at the end of the hydrolysis study period at pH 7, and was a 

maximum average of 31.6% of the applied at day 10, after which it declined slowly to an average 

of 27.6% of the applied at day 30 at pH 9. Another potential degradate of concern is IN-U3595, 

which was present at significant concentrations only at pH 9 in the hydrolysis study, in which it 

was a maximum average of 39.0% of the applied at day 3 and declined very slowly thereafter. 

Two aquatic photolysis degradates that may be of potential concern include IN-JX915, which 

was a maximum of 52% of the applied at day 4 and decreased slowly to 25% by 15 days, and INR3273, which was a maximum of 35.4% of the applied at the end of the 15 day irradiation 

period. 

Past DWAs have been limited to the parent compound only and were conducted at the Tier I 

screening level. The final determination of the residues of concern for the DWA for Registration 

Review will be made through consultation with the Health Effects Division (HED) and through 

any proceedings of the ROCKS (Residues of Concern Knowledge Subcommittee). 

Concentrations of cymoxanil and any identified residues of concern in surface water will be 

estimated using PRZM/EXAMS (see description in Section 7.2). Groundwater exposure 

estimates for cymoxanil and its residues of concern will be estimated using the Screening 

Concentration in Ground Water (SCI-GROW) model (v.2.3, July 2003) followed by a higher-tier 

model if necessary. The drinking water assessment will also include a summary of available 

surface and groundwater monitoring data. 

 

7.8. Endocrine Disruptor Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its registration decision, EPA reviews these data and selects the 

most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), cymoxanil is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 
38 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Cymoxanil is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for cymoxanil. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

7.9. Preliminary Identification of Data Gaps 

 7.9.1. Environmental Fate 

The environmental fate database for cymoxanil is partially complete, with a few significant 

exceptions. For all of the soil and/or sediment laboratory degradation studies, the extraction 

method was questionable given the high levels of nonextractables present from early sampling 

intervals onward in the studies. While two of the submitted aerobic soil metabolism studies are 

classified supplemental, none of the studies were conducted using domestic (U.S.) soils, and data 

were not presented showing that the soils used were representative of intended use sites in the 

U.S. Additionally, some soils were volcanic ash soils that are not representative of intended use 

areas. Aerobic soil metabolism data are needed for at least three soils obtained from intended 

use areas in the United States. While studies conducted using foreign soils are allowable if the 

soils are shown to be representative of intended use sites in the U.S., the submitted studies 

remain of questionable use due to multiple problems such as inadequate extraction methods, high 

nonextractables from early on in the studies, and high inter-replicate data variability. Thus, the 

submitted aerobic soil metabolism studies are not upgradeable. Anaerobic soil metabolism data 

have not been submitted. Both anaerobic and aerobic aquatic metabolism data are still needed, 

as the submitted studies are either not acceptable or were conducted using a system not 

representative of intended use conditions. For both aquatic metabolism studies, it is necessary 

that data be submitted for at least two aquatic sediment systems, one of which is at an acidic pH. 

The mobility study on the degradates IN-W3595, IN-R3273 and IN-KQ960 is classified 

supplemental because only a single concentration was studied. However, additional mobility 

data on these compounds are not needed at this time, as the compounds were all determined to be 

very mobile and a new study would not likely provide additional useful information. Mobility 

data on the degradates IN-KP533 and IN-JX915 are not needed, as these degradates are either 

not detected or present as minor degradates early on in the soil metabolism studies, or will be 
39 

mainly associated with degradation in water. Similarly, while the photodegradation on soil study 

is classified supplemental, an additional study is not needed because the submitted study 

demonstrates that this will not be a significant environmental fate pathway. 

While the terrestrial field dissipation study provided information on the parent compound, 

degradates were not monitored because in an aerobic soil metabolism study that was previously 

classified “acceptable,” CO2 was the only major degradate. However, that metabolism study has 

since been classified “not acceptable” due to multiple deficiencies including some associated 

with residue characterization. An additional terrestrial field dissipation study is not 

recommended because it is unlikely to provide new useful information on cymoxanil. 

Table 7.3 identifies studies by the master record identification (MRID) number that offer data 

for each guideline requirement, as well as study classifications and whether or not further data 

are needed in order to support risk assessment (i.e., whether there is a data gap). 

Table 7.3. Environmental Fate Data Requirements for Cymoxanil Uses, Status, and Data 

Gaps. 

OPPTS 

Guideline 

Data 

Requirement 

Submitted 

Studies 

(MRID) 

Classification Data Gap? Comment 

835.1230 

Adsorption/ 

desorption and 

leaching 

44180745 Acceptable 

No

Batch equilibrium study on parent. 

44180746 Not Acceptable 

Multiple degradates shown to be very 

mobile, so additional data are not 

needed. 

No MRID Acceptable AMR 2724-93 Soil column leaching 

study. 

835.2120 Hydrolysis 

44180738 Acceptable 

No 

−

No MRID Supplemental 

Lab. Proj. ID AMR-2018-91. 

Inadequate analytical method for 

separating degradates. 

835.2240 Aqueous 

photolysis 

44180739 

44180740 Acceptable No −

835.2410 Soil photolysis 44180741 Supplemental No 

Dark control results show a 

discrepancy with results of aerobic soil 

metabolism, but soil photodegradation 

is not a significant fate pathway for this 

chemical, so new data are not 

necessary. 

835.4100 Aerobic soil 

metabolism 

44180742 Supplemental 

Yes 

All foreign soils including Japanese 

volcanic ash; method deficiencies; 

incomplete data reported. Data will not 

be used in risk assessments. 

44180743 

45357101 Not Acceptable 

 Only one soil studied. High 

nonextractables by day 2. Extraction 

method inadequate. High inter-replicate 

variability. Study was downgraded 

from “acceptable.” 
40 

OPPTS 

Guideline 

Data 

Requirement 

Submitted 

Studies 

(MRID) 

Classification Data Gap? Comment 

No MRID Supplemental 

Initial and supplement reports AMR 

1988-91. Data obtained from a volcanic 

ash soil not representative of intended 

use sites. Data will not be used in risk 

assessments. 

835.4200 Anaerobic soil 

metabolism None Not Applicable No 

No data have been submitted. The 

study is not recommended unless useful 

data on the anaerobic aquatic 

metabolism of cymoxanil are not 

submitted. 

835.4300 Aerobic aquatic 

metabolism 44180741 Not Acceptable Yes 

Inadequate extraction of residues. No 

data for an acidic pH system or sterile 

control, so degradation in both systems 

studied was only due to hydrolysis. 

Sediments had very little organic 

carbon (0.1 and 0.8%) so not likely 

representative of sediments near 

intended use sites. Data are needed for 

at least two aquatic sediment systems, 

one of which is at an acidic pH. 

835.4400 Anaerobic aquatic 

metabolism 

44180744 Not Acceptable 

Yes 

Inadequate material balances; high 

nonextracted residues; conducted at pH 

with rapid hydrolysis. Data are needed 

for at least two aquatic sediment 

systems, one of which is at an acidic 

pH. Study was downgraded from 

“acceptable.” 

No MRID Supplemental 

AMR 2446-92. Conditions not 

definitively aerobic or anaerobic 

throughout. Conducted at pH 9, so 

rapid hydrolysis and system not 

representative of intended use sites. 

Degradates not identified. Data will not 

be used in risk assessment. 

835.6100 

Terrestrial field 

dissipation 

44180747 Acceptable 

No 

 

−

45294105 

45294105 

44946410 

Supplemental 

All three studies were on famoxadone 

plus cymoxanil mixture. Cymoxanil 

was not monitored in any of them. 

Analytical 

method with 

ILV– soil 

44180749 

44180752 Acceptable No −

Analytical 

method with ILVwater 

44180750 

44180751 Acceptable No −

Analytical 

method with ILV 

- sediment 

None Not Applicable No −

850.1730 Fish 

bioconcentration No Data Not Applicable No Based on very low Kow (4.7 @pH7), 

not likely to bioconcentrate in fish. 
41 

7.9.2. Effects Data 

Although many submissions have been made to provide information on the effects of cymoxanil 

technical to aquatic and terrestrial organisms, data gaps remain (Tables 7.4-7.6). The following 

studies are recommended to address ecological effects data gaps and uncertainties. Data call-in 

justification tables for non-guideline and degrade studies are provided in Appendix G. 

Avian Acute Oral Toxicity (1 study) 

Acute avian oral toxicity data were submitted for exposures of bobwhite quail and mallard duck 

to cymoxanil; however, data are not available for passerines, which are now required under the 

new 40 CFR Part 158 (Oct. 26, 2007) data requirements for conventional pesticides. Therefore, 

an acute oral toxicity study (850.2100) with a passeriform species is recommended. 

Honeybee Larval Toxicity Study (1 study) 

Although cymoxanil is practically non-toxic to honeybees on an acute contact and oral exposure 

basis, these studies are conducted with young adult honeybees and do not provide information on 

the potential toxicity of cymoxanil to developing brood (larvae and pupae). In addition, since 

cymoxanil is a systemic fungicide, it may be transferred to pollen and nectar and subsequently 

brought back to hive where larvae and pupae may be exposed. Honeybee brood studies are not 

currently a data requirement in the U.S., however, there is uncertainty regarding the potential 

effects of cymoxanil on honeybee brood. Therefore, a non-guideline honeybee larval toxicity 

study is recommended as a special study. 

Terrestrial Plant Studies (2 studies) 

Terrestrial plant toxicity studies are required for registration of pesticides with outdoor uses 

(CFR Part 158). Tier II vegetative vigor (OSCPP 850.4100) and Tier II seedling emergence 

(OCSPP 850.4150) studies are required on a TEP to investigate the effects of the pesticide enduse product on the growth and survival of terrestrial plants if a tested terrestrial species exhibits a 

25% or greater detrimental effect in the Tier 1 study. The studies should be conducted on the 

same species as Tier 1. In the absence of these data, risk to terrestrial plants will be assumed. 

Degradate Studies (5 studies) 

Several ecological effects studies on cymoxanil degradates IN-KQ960 and IN-W3595 are 

recommended to better assess the potential risk of cymoxanil exposure to non-target organisms. 

The studies listed below should be submitted to increase certainty in the risk estimation: 

• Freshwater Fish-Acute Toxicity (850.1075) with IN-KQ960 and IN-W3595 

• Freshwater Invertebrates-Acute Toxicity (850.1010) with IN-W3595 

• Aquatic Plant Growth Algal Toxicity (850.5400) with IN-KQ960, and IN-W3595 

(preferably with freshwater diatom, Navicula pelliculosa, since it is the most sensitive 

species tested with the parent compound) 
42 

EFED recommends requesting data on the degradate IN-KQ960 because of an acceptable acute 

freshwater aquatic invertebrate study (850.1010) showing that this degradate is 35 times more 

toxic to Daphnia magna than the parent compound (MRID 45689201). IN-KQ960 has a similar 

chemical structure to the other major degradates: IN-R3273, IN-JX915, IN-T4226 and 

IN-U3204. Thus, studies carried out on IN-KQ960 could be used to interpret risk from the other 

three similarly structured major degradates listed above. Without these data, uncertainty as to the 

toxicity of these degradates will be highlighted as a critical uncertainty in the risk assessment. 

All of the acute toxicity endpoints for IN-W3595 predicted in ECOSAR are much lower (more 

toxic) than measured values for the parent; therefore additional data is recommended on this 

degradate as well. Without additional data, toxicity of this degradate will be reported as a critical 

uncertainty in the risk assessment. 

Table 7.4. Available Ecological Effects Data for Terrestrial Animals Exposed to Cymoxanil 

and Remaining Data Gaps.

Guideline Description MRID/ 

Accession Classification Data Gap? Comments 

850.2100 Avian acute oral 

toxicity 

441807-10 Acceptable Yes* *Avian acute oral toxicity data 

are not available for 

passerines, which are required 

under the new 40 CFR Part 

158. 

**EPA’s process related to 

terrestrial invertebrates and 

pollinators is changing, and 

honeybee acute oral data 

(already submitted for 

cymoxanil (MRID 44180736) 

will soon be used to support 

screening-level assessment. 

*** Recommended since 

cymoxanil is a systemic 

fungicide and may be 

transferred to pollen and 

nectar and subsequently 

brought back to hive 

441807-11 Acceptable 

850.2200 Avian sub-acute 

dietary toxicity 

441807-12 Acceptable No 

441807-13 Acceptable 

850.2300 Avian reproduction 441807-15 Acceptable No 

441807-14 Acceptable No 

850.3020 Honeybee acute 

contact toxicity 441807-35 Acceptable No** 

850.3030 Honeybee Toxicity of 

Residues on Foliage 463504-03 Acceptable No 

Nonguideline Honeybee Larval 

Toxicity None Not 

Applicable Yes*** 
43 

Table 7.5. Available Ecological Effects Data for Aquatic Animals Exposed to Cymoxanil 

and Remaining Data Gaps. 

Guideline Description MRID/ 

Accession Classification Data Gap? Comments 

850.1075 

Freshwater fish – 

Acute toxicity with 

TGAI 

441807-17 Acceptable 

No 

* Freshwater acute 

invertebrate study (MRID 

456892-01) showed degradate 

IN-KQ960 to be 35 times 

more toxic than the TGAI. 

Without additional data, risk 

to aquatic organisms will be 

assumed for IN-KQ960 and 

similarly structured 

degradates. ECOSAR results 

reported IN-W3595 to be 

much more toxic than the 

parent; if no additional data is 

available, uncertainty in the 

toxicity of this degradate will 

be reported in the risk 

assessment 

** Data is already available on 

IN-KQ960, but not on INW3595; thus, data on INW3595 is recommended. 

441807-18 Acceptable 

Freshwater fish – 

Acute toxicity with 

TEP 

465038-02 Supplemental No 

Freshwater fish – 

Acute toxicity with 

degradate IN-KQ960 

and IN-W3595 

None None available Yes* 

850.1010 

Freshwater 

invertebrates – 

Acute toxicity 

441807-19 Acceptable No 

Freshwater 

invertebrates – 

Acute toxicity with 

TEP 

465038-03 Supplemental No 

Freshwater 

invertebrates – 

Acute toxicity with 

degradate INW3595** 

456892-01 Acceptable Yes* 

850.1075 

Estuarine/Marine fishAcute toxicity with 

TGAI 

441807-20 Acceptable No 

850.1025/ 

850.1035 

Estuarine/Marine 

Organisms – 

Acute toxicity with 

TGAI 

441807-21 Acceptable 

No 

441807-22 Acceptable 

850.1300 

Freshwater 

invertebrate – 

 life cycle test 

441807-24 Acceptable No 

850.1350 

Estuarine/marine 

invertebrates – 

life cycle test 

441807-27 Acceptable No

850.1400 

Freshwater fish – 

early life stage test 443646-10 Acceptable No 

Saltwater fish – 

early life stage test 441807-26 Acceptable No 
44 

Table 7.6. Available Ecological Effects Data for Plants Exposed to Cymoxanil and 

Remaining Data Gaps.

Guideline Description MRID Classification Data 

Gap? Comments 

850.4100 

Terrestrial Plant 

toxicity: Tier I 

seedling emergence 

with TEP 

None None available Yes 

850.4225 

Terrestrial Plant 

toxicity: Tier II 

seedling emergence 

with TEP or TGAI 

None None available Yes 

Conduct Tier 1 study first. 

Tier 2 required if a tested 

terrestrial species exhibits a 

25% or greater detrimental 

effect in the Tier 1 study. 

Study should be conducted on 

the same species as Tier 1. 

850.4150 

Terrestrial Plant 

toxicity: Tier I 

vegetative vigor with 

TEP 

None None available Yes 

850.4250 

Terrestrial Plant 

toxicity: Tier II 

vegetative vigor with 

TEP or TGAI 

None None available Yes 

Conduct Tier 1 study first. 

Tier 2 required if a tested 

terrestrial species exhibits a 

25% or greater detrimental 

effect in the Tier 1 study. 

Study should be conducted on 

the same species as Tier 1. 

850.5400 

Aquatic Plant Growth: 

algae with TGAI 

441807-30 Acceptable 

No 441807-32 Acceptable 

441807-31 Acceptable 

441807-29 Acceptable 

Aquatic Plant Growth: 

algae with TEP 46503801 Supplemental No 

Contamination of copper 

hydroxide was seen in the 

controls of this study; thus, 

interpretation of results should 

be analyzed with caution 

Aquatic Plant Growth: 

algae with degradate 

IN-KQ960 and INW3595 

None None available Yes

Freshwater acute invertebrate 

study (MRID 456892-01) 

showed degradate IN-KQ960 

to be 35 times more toxic than 

the TGAI and ECOSAR 

results reported IN-W3595 to 

be much more toxic than the 

parent; thus, without the data, 

the degradates will be 

assumed to be 35 times more 

toxic than the parent to all 

aquatic organisms. 

850.4400 

Aquatic Plant Growth: 

vascular plants with 

TGAI 

44180728 Acceptable No 
45 

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EPA food-chain (Kenaga) nomogram, an instrument for estimating pesticide residues on 

plants. Environ. Tox. Chem. 13:1383-1391. 

Herbicide Resistance Action Committee (HRAC). 2009. Classification of Herbicides According 

to Mode of Action. Accessed on August 20, 2010. Online at 

http://www.hracglobal.com/Publications/ClassificationofHerbicideModeofAction/tabid/2

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Hoerger, F. and E. E. Kenaga. 1972. Pesticide Residues on Plants: Correlation of 

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Toxicology, and Technology, Georg Thieme Publ., Stuttgart, West Germany, pp. 9-28. 

Mineau, P., B.T. Collins, and A. Baril. 1996. On the use of scaling factors to improve 

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Sample, B.E. and C.A. Arenal. 1999. Allometric Models for Interspecies Extrapolation of 

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USDA. 1997. Usual Planting and Harvesting Dates for U.S. Field Crops. National Agricultural 

Statistics Service. United States Department of Agriculture. Accessed August 9, 2010. 

Online at: http://usda.mannlib.cornell.edu/usda/nass/planting/uph97.pdf 

USEPA. 1997. EFED Section 3 Registration for Cymoxanil PC Code No. 129106; Case No. 

 061132. DP Barcode: D233366. U.S. Environmental Protection Agency, Office of 

 Pesticide Programs. October 23,1997. 

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. 2001. IR-4 Tolerance Petition for Cymoxanil (Curzate 60 DF) use on Hops. PC Code 

 No. 129106; Case No. 061132. DP Barcode: D271572. U.S. Environmental Protection 

 Agency, Office of Pesticide Programs. October 13, 2001. 

USEPA. 2003. EFED Amended Registration for Cymoxanil PC Code No. 129106; Case No. 

 061132. DP Barcode: D261193. U.S. Environmental Protection Agency, Office of 

 Pesticide Programs. January 29, 2003. 
46 

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

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

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

USEPA. 2003. EFED Amended Registration for Cymoxanil PC Code No. 129106; Case No. 

 061132. DP Barcode: D261193. U.S. Environmental Protection Agency, Office of 

 Pesticide Programs. January 29, 2003. 

USEPA. 2006. EFED IR-4 Tolerance Petition for Cymoxanil (Tanos®) Use on Grapes and 

 Hops. PC Code No. 129106; Case No. 061132. DP Barcode: D261193. U.S. 

 Environmental Protection Agency, Office of Pesticide Programs. September 20, 2006. 

USEPA. 2006. EFED IR-4 Tolerance Petition for Cymoxanil (Tanos®) Use on Caneberries. 

. PC Code No. 129106; Case No. 061132. DP Barcode: D261193. U.S. Environmental 

 Protection Agency, Office of Pesticide Programs. September 20, 2006. 

USEPA. 2007a. Ecological Incident Information System. 

http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

USEPA. 2007b. ECOTOXicology Database. Office of Research and Development National 

Health and Environmental Effects Research Laboratory’s (NHEERL’s) Mid-Continent 

Ecology Division (MED). http://cfpub.epa.gov/ecotox/. 

USEPA. 2008. IR-4 Tolerance Petition for the use of cymoxanil (Tanos®) on leafy greens, bulb 

vegetables, caneberries, cilantro leaves, onions, spinach and leaf lettuce. May 6, 2008. 

USEPA. 2008. Revised Drinking Water Assessment for the Proposed New Use of cymoxanil 

(Tanos®) on leafy greens, bulb vegetables, caneberries, cilantro leaves, onions, spinach 

and leaf lettuce. May 13, 2008. 

USEPA. 2011a. Cymoxanil (129106): Screening Level Usage Analysis. U.S. Environmental 

Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Biological 

and Economic Analysis Division. Sept. 13, 2011. 

USEPA. 2011b. BEAD Chemical Profile for Registration Review: Cymoxanil (129106). U.S. 

Environmental Protection Agency, Office of Prevention, Pesticides and Toxic 

Substances, Biological and Economic Analysis Division. Sept. 21, 2011. 

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. 

Endangered Species Consultation Handbook: Procedures for Conducting Consultation 

and Conference Activities Under Section 7 of the Endangered Species Act. Final Draft. 

March 1998. 

USFWS/NMFS/NOAA.2004. 50 CFR Part 402. Joint Counterpart Endangered Species Act 

Section 7 Consultation Regulations; Final Rule. Federal Register Volume 69. Number 

20.Pages 47731-47762. August 5, 2004. 
47 

U.S. Geological Survey (USGS). 2011. Pesticide Use Maps. U.S. Geological Survey, National 

Water-Quality Assessment (NAWQA) Program, Pesticide National Synthesis Program. 

Accessed on September 2011. Online at: 

http://water.usgs.gov/nawqa/pnsp/usage/maps/compound_listing.php?year=02
48 

SUBMITTED ENVIRONMENTAL FATE STUDIES:

MRID 44180738 Lawler, S. (1996) Hydrolysis of Cymoxanil (DPX-T3217) in Buffer Solutions 

of pH 5, 7, and 9: Lab Project Number: AMR 3677-95. Unpublished study prepared by DuPont 

Agricultural Products. 77 p. 

No MRID Horne, P. (1992) HYDROLYSIS DF-[2-14C]DPX-T3217. Submitted, Sponsored 

and Performed by E.I. DuPont de Nemours and Company, DuPont Agricultural Products, 

Wilmington, DE under Laboratory Project ID AMR-2018-91, Study Completed on 19 August 

1992, Received by EPA in 1995. 

MRID 44180738 Proposed Hydrolytic Degradation Pathway. 

MRID 46348602 Willems, I.; Slangen, P.; Hoitink, M. (2003) Aqueous Hydrolysis of 

Cymoxanil. Project Number: 308734. Unpublished study prepared by Notox V.O.F. 177 p. 

MRID 44180739 Anderson, J.; Horne, P.; Lawler, S.; et al. (1993) Photodegradation of (2-

(carbon 14))DPX-T3217 (Cymoxanil) in Pond Water and Sterile Buffer pH 5: Lab Project 

Number: AMR 1990-91. Unpublished study prepared by DuPont Agricultural Products. 63 p. 

MRID 44180740 Anderson, J.; Lawler, S.; Swain, R. (1993) Quantum Yield Determination of 

DPX-T3217 (Cymoxanil) and LC/MS Confirmation of Unknown Degradates in Sterile Buffer 

pH 5: Supplement No. 1 to “Photodegradation of (2-(carbon 14))DPX-T3217 (Cymoxanil) in 

Pond Water and Sterile Buffer pH 5”: Lab Project Number: AMR 1990-91. Unpublished study 

prepared by DuPont Agricultural Products. 42 p. 

MRID 45465101 Contract draft available. Trabue, S.; Lydick, T. (2001) Degradation of 

Cymoxanil in Two Water/Sediment Systems: Lab Project Number: 2695. Unpublished study 

prepared by DuPont Agricultural Products. 97 p. 

MRID 44180741 Berg, D. (1996) Photodegradation of Radiolabeled Cymoxanil on Soil Under 

Simulated Sunlight: Lab Project Number: AMR 3582-95. Unpublished study prepared by 

DuPont Agricultural Products. 51 p. 

44180742 Boucher, C. (1994) Degradation Rate of (carbon 14)Cymoxanil on Four Soils: Lab 

Project Number: AMR 2869-93. Unpublished study prepared by DuPont Agricultural Products. 

57 p. 

44180743 Boucher, C. (1996) Aerobic Metabolism of (carbon 14)-Cymoxanil: Lab Project 

Number: AMR 3438-95. Unpublished study prepared by DuPont Agricultural Products. 48 p. 

45357101 Anderson, J. (2001) Aerobic Soil Metabolism of (carbon 14)-Cymoxanil: Revision 

No. 1: Lab Project Number: AMR 3438-95: 3438-95. Unpublished study prepared by DuPont 

Agricultural Products. 42 p. 
49 

No MRID Boucher, Caroline, R. (1993) Aerobic Soil Metabolism of [2-14C]DPX-T3217 

(Cymoxanil). Performed and Submitted by E.I. du Pont Nemours and Company, DuPont 

Agricultural Products, Wilmington, DE. Supplement Report Number AMR 1988-91. 

No MRID Knoch, E. (1993) Degradation and Metabolism of Cymoxanil (DPX-T3217) in 

Water/Sediment Systems. Unpublished Study Conducted by RCC Unmweltchemie & Co., K.G. 

RoBdorf, Germany and Submitted by Dupont. Protocol AMR 2446-92. 

44180744 Hausmann, S. (1996) Anaerobic Aquatic Metabolism of Cymoxanil: Lab Project 

Number: AMR 3407-95. Unpublished study prepared by DuPont Agricultural Products. 75 p. 

No MRID Knoch, E. (1993) Degradation and Metabolism of Cymoxanil (DPX-T3217) in 

Water/Sediment Systems. Unpublished Study Conducted by RCC Unmweltchemie & Co., K.G. 

RoBdorf, Germany and Submitted by Dupont. Protocol AMR 2446-92. 

44180745 Horne, P. (1992) Batch Equilibrium (Adsorption/Desorption) Studies of (carbon 

14)DPX-T3217: Lab Project Number: AMR 2112-91. Unpublished study prepared by DuPont 

Agricultural Products. 34 p. 

44180746 Hausmann, S.; Adams, G. (1996) Soil Batch Equilibrium Study of Cymoxanil 

Degradates: Lab Project Number: AMR 3722-95. Unpublished study prepared by DuPont 

Agricultural Products. 97 p. 

No MRID Lawler, S.M. (1993) Soil Column Leaching Study of 14C-Cymoxanil. Study 

Performed and Submitted by E.I. du Pont de Nemours and Company, Wilmington, Delaware. Du 

Pont Report No. AMR 2724-93. 

44180747 McClory, J.; Jones, W. (1996) Field Soil Dissipation of Cymoxanil Following 

Application of Curzate M-8 Fungicide: Lab Project Number: AMR 3401-95: AMR 3595-95. 

Unpublished study prepared by DuPont Agricultural Products. 106 p. 

44946410 McClory, J.; Holt, J. (1999) Field Soil Dissipation of Famoxadone and Cymoxanil 

Following Application of DPX-KP481 Fungicide, USA: Lab Project Number: ML97-0705DUP: 

AMR 4329-97. Unpublished study prepared by DuPont Agricultural Products and Morse 

Laboratories, Inc. 214 p. 

45294105 McClory, J. (2000) Field Soil Dissipation of Famoxadone and Cymoxanil Following 

Application of DPX-KP481 50WG Fungicide, WG, USA, 1999: Lab Project Number: 2342: 

ML99-0780-DUP. Unpublished study prepared by E.I. du Pont de Nemours and Company and 

Morse Laboratories. 221 p. 

45294106 McClory, J. (2000) Field Soil Dissipation of Famoxadone and Cymoxanil Following 

Application of DPX-KP481 50WG Fungicide, WG, USA, 1999: Lab Project Number: AMR 

4329-97: ML97-0705-DUP. Unpublished study prepared by E.I. du Pont de Nemours and 

Company and Morse Laboratories. 205 p. 
50 

44180749 McClory, J.; Jones, W.; DeLuke, P. (1996) Analytical Method for the Determination 

of Residues of Cymoxanil in Soil Using Liquid Chromatography: Lab Project Number: AMR 

3595-96. Unpublished study prepared by DuPont Agricultural Products. 39 p. 

44180750 Nathan, E.; Hill, S. (1995) Analytical Method for the Determination of Cymoxanil in 

Water Using Liquid Chromatography: Lab Project Number: AMR 3430-95. Unpublished study 

prepared by DuPont Agricultural Products. 62 p. 

44180751 Nathan, E. (1996) Independent Laboratory Validation of the Analytical Method for 

the Determination of Residues of Cymoxanil in Water Using Liquid Chromatography: Lab 

Project Number: AMR 3683-95: ML96-0585-DUP. Unpublished study prepared by Morse Labs, 

Inc. 144 p. 

44180752 Lochhaas, C. (1996) Independent Laboratory Validation of an Analytical Method for 

the Determination of Cymoxanil Residues in Soil by High-Pressure Liquid Chromatography: 

Lab Project Number: AMR 4119-96: 43550: AMR 3595-95. Unpublished study prepared by 

ABC Labs, Inc. 53 p. 

45317701 Hertl, J. (2001) Cymoxanil (DPX-T3217) Technical: Activated Sludge, Respiration 

Inhibition Test: Final Report: Lab Project Number: 8951171: 4483. Unpublished study prepared 

by Institut fur Biologische Analytik und Consulting IBACON GmbH. 26 p. 

 
51 

SUBMITTED ECOLOGICAL EFFECTS STUDIES:

44180716 Baer, K. (1992) Static, Acute, 96-Hour LC50 of DPX-T3217-113 

(Cymoxanil) to Common Carp, Cyprinus carpio: Lab Project Number: 

HLR 734-92: 9581-023: 734-92. Unpublished study prepared by 

DuPont's Haskell Lab for Toxicology and Industrial Medicine. 32 p. 

44180717 Baer, K. (1993) Static, Acute, 96-Hour LC50 of DPX-T3217-113 

(Cymoxanil) to Rainbow Trout, Oncorhynchus mykiss: Lab Project 

Number: HLR 735-92: 4581-936: 735-92. Unpublished study prepared 

by DuPont's Haskell Lab for Toxicology and Industrial Medicine. 28 p. 

44180718 Baer, K. (1993) Static, Acute, 96-Hour LC50 of DPX-T3217-113 

(Cymoxanil) to Bluegill Sunfish, Lepomis macrochirus: Lab Project 

Number: HLR 934-92: 4581-936: 834-92. Unpublished study prepared 

by DuPont's Haskell Lab for Toxicology and Industrial Medicine. 29 p. 

44180719 Baer, K. (1993) Static, Acute, 48-Hour EC50 of DPX-T3217-113 

(Cymoxanil) to Daphnia magna: Lab Project Number: HLR 736-92: 

4581-936: 736-92. Unpublished study prepared by DuPont's Haskell 

Lab for Toxicology and Industrial Medicine. 30 p. 

45689201 Samel, A. (2002) IN-KQ960: Static, Acute, 48-Hour EC(50) to 

Daphnia magna: Lab Project Number: 13219: 9559: DUPONT-9559. 

Unpublished study prepared by E.I. du Pont de Nemours and 

Company. 36 p. 

46503803 Hoke, R. (2005) Metallic Copper (as Copper Hydroxide)/Cymoxanil 

(DPX-HYZ80) 31 WG (4.2:1): Acute Toxicity to Daphnia magna. 

Project Number: DUPONT/14373, 15203. Unpublished study prepared 

by Dupont Haskell Laboratory and E.I. du Pont de Nemours and 

Company. 46 p. 

43987601 Bowman, Jane and John Bucksath (1995) Acute Flow-Through 

Toxicity of S-1668 to Daphnia magna. ABC Laboratories, Inc., 

Columbia, MO. Sumitomo Chemical Company, Ltd., Osaka 541, 

Japan 

 44180720 Boeri, R.; Kowalski, P.; Ward, T. (1996) Acute Toxicity of DPXT3217-113 (Cymoxanil) to the Sheepshead Minnow, Cyprinodon 

variegatus: (Final Report): Lab Project Number: HLO 634-96: 10372-

001: 808-DU. Unpublished study prepared by T. R. Wilbury Labs, Inc. 

41 p. 

44180721 Boeri, R.; Kowalski, P.; Ward, T. (1996) Acute Flow-Through 

Mollusc Shell Deposition Test with DPX-T3217-113 (Cymoxanil): 

(Final Report): Lab Project Number: HLO 633-96: 10372-001: 810-

DU. Unpublished study prepared by T. R. Wilbury Labs, Inc. 38 p. 
52 

44180722 Boeri, R.; Kowalski, P.; Ward, T. (1996) Acute Toxicity of DPXT3217-113 (Cymoxanil) to the Mysid, Mysidopsis bahia: (Final 

Report): Lab Project Number: HLO 632-96: 10372-001: 809-DU. 

Unpublished study prepared by T. R. Wilbury Labs, Inc. 38 p. 

44180723 

Kreamer, G. (1996) DPX-T3217-113 (Cymoxanil): Early-Life Stage 

Toxicity to Rainbow Trout, Oncorhynchus mykiss: Lab Project Number: 

HLR 411-96: 10495: 411-96. Unpublished study prepared by DuPont's 

Haskell Lab for Toxicology and Industrial Medicine. 469 p. 

44180724 Baer, K. (1993) Chronic Toxicity of DPX-T3217-113 (Cymoxanil) to 

Daphnia magna: 24-Hour Renewal: Revised Report: Lab Project 

Number: HLR 354-93: 4581-936: 354-93. Unpublished study prepared 

by DuPont's Haskell Lab for Toxicology and Industrial Medicine. 493 p. 

44180725 Baer, K. (1992) Flow-Through, 21-Day Toxicity of DPX-T3217-113 

(Cymoxanil) to Rainbow Trout, Oncorhynchus mykiss: Lab Project 

Number: HLR 545-92: 9581-023: 545-92. Unpublished study prepared 

by DuPont's Haskell Lab for Toxicology and Industrial Medicine. 65 p. 

44180726 Boeri, R.; Kowalski, P.; Ward, T. (1996) Early Life Stage Toxicity of 

DPX-T3217-113 (Cymoxanil) to the Sheepshead Minnow, Cyprinodon 

variegatus: (Final Report): Lab Project Number: HLO 913-96: 10372-

002: 812-DU. Unpublished study prepared by T. R. Wilbury Labs, Inc. 

816 p. 

44180727 Boeri, R.; Kowalski, P.; Ward, T. (1996) Chronic Toxicity of DPXT3217-113 (Cymoxanil) to the Mysid, Mysidopsis bahia: (Final Report): 

Lab Project Number: HLO 914-96: 10372-002: 811-DU. Unpublished 

study prepared by T. R. Wilbury Labs, Inc. 742 p. 

44364610 Boeri, R.; Magazu, J.; Ward, T. (1997) DPX-T3217-113 (Cymoxanil): 

Early Life-Stage Toxicity to Rainbow Trout, Oncorhynchus mykiss: 

(Final Report): Lab Project Number: 1013-96: 11104: 1204-DU. 

Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 540 p. 

44180728 Leva, S.; Sloman, T. (1996) Cymoxanil: Influence on Growth and 

Reproduction of Lemna gibba G3: Lab Project Number: AMR 3775-96: 

MR 10615. Unpublished study prepared by DuPont Stine-Haskell 

Research Center. 39 p. 

44180729 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Anabaena flosaquae: Lab Project Number: 19-06-2: AMR 4109-96. Unpublished study 

prepared by Carolina Ecotox, Inc. 74 p. 

44180730 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Selenastrum 

capricornutum: Lab Project Number: 19-06-1: AMR 4110-96. 

Unpublished study prepared by Carolina Ecotox, Inc. 61 p. 
53 

44180731 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Skeletonema 

costatum: Lab Project Number: 19-06-4: AMR 4111-96. Unpublished 

study prepared by Carolina Ecotox, Inc. 61 p. 

44180732 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Navicula 

peliculosa: Lab Project Number: 19-06-3: AMR 4112-96. Unpublished 

study prepared by Carolina Ecotox, Inc. 72 p. 

44180733 Douglas, M.; Handley, J. (1988) The Algistatic Activity of Cymoxanil 

Technical: (Final Report): Lab Project Number: DPT 171(Q)/88601. 

Unpublished study prepared by Huntingdon Research Centre Ltd. 20 p. 

45039001 Hoke, R.; Sloman, T. (2000) Cymoxanil Aquatic Degradate Mixture 

Including RF1: Influence on Growth and Growth Rate of the BlueGreen Alga, Anabaena flos-aquae: Lab Project Number: 12453: 324: 

DUPONT-3529. Unpublished study prepared by E.I. Du Pont de 

Nemours and Company. 56 p. 

44180729 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Anabaena 

flos-aquae: Lab Project Number: 19-06-2: AMR 4109-96. 

Unpublished study prepared by Carolina Ecotox, Inc. 74 p. 

44180732 Hughes, J.; Williams, T.; Conder, L. (1996) DPX-T3217-113 

(Cymoxanil): Influence on Growth and Reproduction of Navicula 

peliculosa: Lab Project Number: 19-06-3: AMR 4112-96. Unpublished 

study prepared by Carolina Ecotox, Inc. 72 p. 

45039001 Hoke, R.; Sloman, T. (2000) Cymoxanil Aquatic Degradate Mixture 

Including RF1: Influence on Growth and Growth Rate of the BlueGreen Alga, Anabaena flos-aquae: Lab Project Number: 12453: 324: 

DUPONT-3529. Unpublished study prepared by E.I. Du Pont de 

Nemours and Company. 56 p. 

46503801 Sloman, T. (2005) Metallic Copper (as Copper Hydroxide)/Cymoxanil 

(DPX-HYZ80) 31 WG (4.2:1): Influence on Growth and Growth Rate 

of Green Alga Pseudokirchneriella subcapitata: Trade Secret. Project 

Number: DUPONT/14371, 15203. Unpublished study prepared by 

Dupont Haskell Laboratory and E.I. du Pont de Nemours and 

Company. 49 p. 

44180735 Hoxter, K.; Bernard, W.; Smith, G. (1993) H #19,062-02: An Acute 

Contact Toxicity Study with the Honey Bee: Final Report: Lab Project 

Number: 112-275: HLO 100-93: 100-93. Unpublished study prepared 

by Wildlife International Ltd. 17 p. 

44180736 Hoxter, K.; Bernard, W.; Smith, G. (1993) H #19,062-02: A Dietary 

LC50 Toxicity Study with the Honey Bee: Final Report: Lab Project 
54 

Number: 112-274: HLO 99-93: 99-93. Unpublished study prepared by 

Wildlife International Ltd. 16 p. 

46477601 Bocksch, S. (2004) Metallic Copper (as Copper 

Hydroxide)/Cymoxanil (DPX-HYZ80) 31WG (4.2:1): Acute Oral and 

Contact Toxicity to the Honeybee, Apis Mellifera L.: Final Report. 

Project Number: DUPONT/14369, 20041156/01/BLEU, 15203. 

Unpublished study prepared by Arbeitsgemeinschaft GAB 

Biotechnologie. 32 p. 

46350402 Candolfi, M.P. (1996) DPX-KX007-5: Laboratory Acute Oral and 

Contact Toxicity Test with the Honeybee (Apis mellifera), Based on 

the EPPO Guideline 170 (1992) and FIFRA Gudieline 141-1. 

Laboratory: Springborn Laboratories (Euroupe) AG, Health and 

Environmental Sciences, Seestrasse 21, 9326 Horn, Switzerland, Du 

Pont Agricultural Products, Experimental Station, BLDG. E402-5236, 

Wilmington, Delaware 18990-0402. 

46350403 A.B. Sindermann, J.R. Porch and H.O. Krueger (2004) 

Cymoxanil/Famoxadone (DPX-KP481) 50 WG (1:): A Foliage 

Residue Toxicity Study with the Honey Bee. Laboratory: Wildlife 

International, Ltd. 8598 Commerce Drive, Easton, Maryland 21601. 

E.I. Dupont de Nemours and Company, Wilmington, Delaware 19898. 

44946327 Kuhner, C. (1997) DPX-KP481, a Water Dispersible Granular (WG) 

Formulation Containing DPX-JE874 (254 g ai/kg) and Cymoxanil 

(266 g ai/kg): Acute Toxicity to the Staphylinid Beetle, Aleochara 

bilineata Gyll. (Coleoptera, Staphylinidae) in the Laboratory: Final 

Report: Lab Project Number: AMR 4235-96: 96259/01-NLAB. 

Unpublished study prepared by GAB Biotechnologie GmbH and IFU 

Umweltanalytik GmbH. 22 p. DPX-KP481 = Famoxadone + 

Cymoxonil 

44946328 Kuhner, C. (1997) DPX-KP481, a Water Dispersible Granular (WG) 

Formulation Containing DPX-JE874 (254 g ai/kg) and Cymoxanil 

(266 g ai/kg): Acute Toxicity to the Green Lacewing, Chrysoperla 

carnea steph. (Neuroptera, Chrysopidae) in the Laboratory: Final 

Report: Lab Project Number: AMR4234-96: 96259/01-NLCC. 

Unpublished study prepared by GAB Biotechnologie GmbH IFU 

Umweltanalytik GmbH. 25 p. 

44946329 Kuhner, C. (1997) DPX-KP481, a Water Dispersible Granular (WG) 

Formulation Containing DPX-JE874 (254 g ai/kg) and Cymoxanil 

(266 g ai/kg): Acute Toxicity to the Hoverfly, Episyrphus balteatus 

DEG. (Diptera; Syrphidae) in the Laboratory: Final Report: Lab 

Project Number: AMR4232-96: 96259/01-NLEB. Unpublished study 

prepared by GAB Biotechnologie GmbH IFU Umweltanalytik 

GmbH. 30 p. 
55 

44946330 Kuhner, C. (1997) DPX-KP481, a Water Dispersible Granular (WG) 

Formulation Containing DPX-JE874 (254 g ai/kg) and Cymoxanil 

(266 g ai/kg): Acute Toxicity to the Ground Beetle, Poecilus cupreus 

L. (Coleoptera, Carabidae) in the Laboratory: Final Report: Lab 

Project Number: AMR4233-96: 96259/01-NLPC. Unpublished study 

prepared by GAB Biotechnologie GmbH IFU Umweltanalytik 

GbmH. 29 p. 

44946331 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX-KP481) 50 

WG (25%:25%). An Extended Laboratory Study to Evaluate the 

Effects on the Green Lacewing, Chrysoperla carnea: Lab Project 

Number: DP-97-8: AMR4540-97. Unpublished study prepared by 

Agrochemical Evaluation Unit School of Biological Sciences 

University of Southampton. 24 p. 

44946332 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX-KP481) 50 

WG (25%:25%): an Extended Laboratory Study to Evaluate the 

Effects on the Hoverfly, Episyrphus balteatus: Lab Project Number: 

DP-97-9: AMR4541-97. Unpublished study prepared by 

Agrochemical Evaluation Unit School of Biological Sciences 

University of Southampton. 32 p. 

44946333 Beech, P.; Mead-Briggs, M. (1998) Cymoxanil/Famoxadone (DPXKP481) 50 WG (25%:25%). An Extended Laboratory Study to 

Evaluate the Effects on the Ground Beetle, Poecilus cupreus: Lab 

Project Number: DP-97-10: AMR4539-97. Unpublished study 

prepared by Agrochemical Evaluation Unit School of Biological 

Sciences University of Southampton. 22 p. 

44946334 Thompson, B. (1999) Cymoxanil/Famoxadone (DPX-KP481) 50 

WG (25%:25%). A Semi-field Study to Evaluate the Effects on 

Aphid Parasitoids (Hymenoptera, Aphidiinae) in a Potato Crop: Lab 

Project Number: DP-97-3: AMR4542-97. Unpublished study 

prepared by Agrochemical Evaluation Unit School of Biological 

Sciences University of Southampton. 35 p. 

45475401 Gossmann, A. (2001) Cymoxanil (DPX-T3217) 60%WG: A 

Laboratory Test to Study the Effects on the Predatory Mite 

Typhlodromus pyri (Acari, Phytoseiidae): Lab Project Number: 

1731: 4932063. Unpublished study prepared by Institut fur 

Biologische Analytik und Consulting IBACON GmbH. 41 p. 

 46430401 Warmers, C. (2004) Metallic Copper (as Copper 

Hydroxide)/Cymoxanil (DPX-HYZ80) 31WG (4.2:1): A Multiple 

Rate Test to Study the Effects on the Predatory Mite 

Typhlodromus pyri (Acari, Phytoseiidae): Final Report. Project 

Number: 20041156/01/NLTP, DUPONT/14360, 15203. 

Unpublished study prepared by GAB Biotechnologie Gmbh. 34 p. 
56 

44200702 Armstrong, K.; Caley, C.; Hall, B.; et al. (1991) Cymoxanil (Tech.) 

Determination of Acute Toxicity (LC50) Earthworms: Lab Project 

Number: 8548: 381499: IRI 8548. Unpublished study prepared by 

Inveresk Research International. 33 p. 

44967203 Caley, C.; Knight, B.; Boyle, J. (1994) DPX-JE874-221: 

Determination of Acute Toxicity (LC50) in Earthworms: Lab 

Project Number: 10206: 383475: IRI 383475. Unpublished study 

prepared by Inveresk Research International. 33 p. 

46464301 Muther-Paul, J. (2005) Metallic Copper (As Copper 

Hydroxide)/Cymoxanil (DPX-HYZ80) 31WG (4.2:1): Sublethal 

Toxicity to the Earthworm Eisenia fetida in Artificial Soil: Final 

Report. Project Number: 20041156/01/NREF, DUPONT/14375, 

15203. Unpublished study prepared by GAB Biotechnologie 

Gmbh. 31 p. 

46785301 Luhrs, U. (2006) Metallic Copper (As Copper 

Oxychloride)/Cymoxanil (DPX-KK807) 44WG (9.5:1): Effects on 

Reproduction and Soil Growth of the Earthworm, Eisenia fetida, in 

Artificial Soil: Final Report. Project Number: DUPONT/17203, 

15950, 1502. Unpublished study prepared by Institut fuer 

Biologische Analytik und Consulting IBACON. 42 p. 
57 

APPENDIX A: Registered Uses and Application Rates for Cymoxanil Based on 

Information from OPP/BEAD1

. 

Use 

Max 

Single 

Applic. 

Rate (lb 

ai/A) 

Max No. 

Applic./

Crop 

Cycle 

Max. Applic. 

Rate/Crop Cycle 

Max. No. 

Applic./Yr 

Max. 

Applic. 

Rate/Yr (lb 

ai/A/yr) 

Min. 

Applic. 

Interval 

Amaranth, 

Chinese 0.1563 NS 0.75 NS NS 5 d 

Beets 

(Unspecified) 00.12 NS NS 5/yr NS 5 d 

Blackberry 0.1563 NS 1.1 NS NS 5 d 

Cabbage 0.12 NS NS 5/yr NS 5 d 

Caneberries 0.1563 NS 1.1 NS NS 5 d 

Cardoon 0.1563 NS 0.75 NS NS 5 d 

Celery 0.1563 NS 0.75 NS NS 5 d 

Celtuce 0.1563 NS 0.75 NS NS 5 d 

Chard, Swiss 0.1563 NS 0.75 NS NS 5 d 

Chervil 0.1563 NS 0.75 NS NS 5 d 

Chive 0.1563 NS 1.3 NS NS 5 d 

Chrysanthemu

m, Garland 0.1563 NS 0.75 NS NS 5 d 

Corn Salad 0.1563 NS 0.75 NS NS 5 d 

Cress, Garden 0.1563 NS 0.75 NS NS 5 d 

Cress, Upland 0.1563 NS 0.75 NS NS 5 d 

Cucumber 0.1563 NS 0.5 NS 1.1 5 d 

Cucurbit 

Vegetables 0.1875 NS NS NS 1.1 5 d 

Dandelion 0.1563 NS 0.75 NS NS 5 d 

Dock (Sorrel) 0.1563 NS 0.75 NS NS 5 d 

Endive 

(Escarole) 0.1563 NS 0.75 NS NS 5 d 

Fennel 0.1563 NS 0.75 NS NS 5 d 

Garlic 0.1563 NS 1.3 NS NS 5 d 

Grapes 0.125 9 1.1 NS NS 10 d 
58 

Hops 0.125 6 0.75 NS .75 10 d || 6 d 

Leafy Greens 0.1563 NS 0.75 NS NS 5 d 

Leafy 

Vegetables 0.1563 NS 0.75 NS NS 5 d 

Leek 0.1563 NS 1.3 NS NS 5 d 

Lettuce, Head 0.1875 NS NS NS 1.1 5 d 

Lettuce, Leaf 

(Black Seeded 

Simpson, 

Salad Bowl, 

Etc.) 0.1875 NS NS NS 1.1 5 d 

Loganberry 0.1563 NS 1.1 NS NS 5 d 

Melons, 

Cantaloupe 0.1563 NS 0.5 NS 1.1 5 d 

Melons, 

Honeydew 0.1563 NS 0.5 NS 1.1 5 d 

Melons, Musk 0.1563 NS 0.5 NS 1.1 5 d 

Melons, Water 0.1563 NS 0.5 NS 1.1 5 d 

Onion 0.1563 NS 1.3 NS NS 5 d 

Onions 

(Green) 0.1563 NS 1.3 NS NS 5 d 

Orach 

(Mountain 

Spinach) 0.1563 NS 0.75 NS NS 5 d 

Parsley 0.1563 NS 0.75 NS NS 5 d 

Peas 

(Unspecified) 

0.0199 lb / 

lb seed NS NS NS NS 

Pepper 0.1563 NS 1.1 NS 1.1 5 d 

Pimento 0.1563 NS 1.1 NS 1.1 5 d 

Potato, 

White/Irish 

0.0075 lb / 

lb seed NS NS NS NS 

Potato, 

White/Irish 

0.0375 lb / 

lb seed NS NS NS NS 5 d 

Potato, 

White/Irish 0.125 6 0.75 NS 1.1 5 d 

Pumpkin 0.1563 NS 0.5 NS 1.1 5 d 

Purslane, 

Garden 0.1563 NS 0.75 NS NS 5 d 

Purslane, 

Winter 0.1563 NS 0.75 NS NS 5 d 

Radicchio 0.1563 NS 0.75 NS NS 5 d 
59 

Raspberry 

(Black, Red) 0.1563 NS 1.1 NS NS 5 d 

Rhubarb 0.1563 NS 0.75 NS NS 5 d 

Roquette 

(Arrugula) 0.1563 NS 0.75 NS NS 5 d 

Shallot 0.1563 NS 1.3 NS NS 5 d 

Spinach 0.1875 NS NS NS 1.1 5 d 

Spinach, New 

Zealand 0.1563 NS 1.3 NS NS 5 d 

Squash 

(Summer) 0.1563 NS 0.5 NS 1.1 5 d 

Squash 

(Winter) 

(Hubbard) 0.1563 NS 0.5 NS 1.1 5 d 

Tomato 0.1875 NS NS NS 1.1 5 d 

Vegetables 

(Unspecified) 0.1563 NS 1.3 NS NS 5 d 

Chrysanthemu

m 0.1563 NS 0.75 NS NS 5 d 

Peas 

(Unspecified) 

0.02 lb / lb 

seed NS NS 1/yr NS 1

Information extracted from table: PRD Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review Work 

Planning; USEPA/OPP/BEAD 2/16/2011). 

 
60 

APPENDIX B1: Names and Structures of Major Environmental Degradates of Cymoxanil. 

Cymoxanil 

[DPX-T3217] 

IUPAC Name: 1-[(EZ)-2-Cyano-2-methoxyiminoacetyl]-3-ethylurea. 

1-(2-Cyano-2-methoxyiminoacetyl)-3-ethylurea. 

CAS Name: 2-Cyano-N-[(ethylamino)carbonyl]-2-(methoxyimino)acetamide. 

CAS Number: 57966-95-7. 

SMILES String: O=C(NCC)NC(=O)C(=NOC)C#N (EPI Suite, v3.12 SMILES). 

 

 “E” configuration 

IN-U3204 

IUPAC Name: 6-Imino-1-methyl-5-methylenedihydropyrimidine-2,4(1H,3H)-dione 

(ISIS/Draw with ACD/Name add-in). 

CAS Name: 1-Ethyldihydro-6-imino-2,4,5(3H)-pyrimidinetrione 5-(O-methyloxime). 

CAS Number: 71342-66-0. 

 

 

IN-W3595 

IUPAC Name: (2E)-Cyano(methoxyimino)acetic acid (ISIS/Draw with ACD/Name addin). 

CAS Name: Cyano(methoxyimino)acetic acid. 

CAS Number: 78325-17-4. 

N

H

H3C

O

N

H

O

N

O

CN

CH3

N

NH

O

NOCH3

HN O

CH2CH3
61 

 

 “E” configuration

IN-R3274 

IUPAC Name: (2E)-Cyano(hydroximino)acetic acid (ISIS/Draw with ACD/Name add-in). 

CAS Name: Cyano(hydroxyimino)acetic acid. 

CAS Number: 78325-18-5; 38157-71-0 (E isomer); 95679-11-1 (Z isomer). 

 

 “E” configuration

IN-R3273 

IUPAC Name: 1-Methyl-5-methyleneimidazolidine-2,4-dione (ISIS/Draw with 

ACD/Name add-in). 

CAS Name: Ethylimidazolidinetrione 5-(O-methyloxime). 

CAS Number: 71342-67-1. 

 

 

HO

O

N

O

CN

CH3

HO

O

N

OH

CN

N

NH

O

NOCH3

C2H5 O
62 

IN-KP533 

IUPAC Name: {[(Ethylamino)carbonyl]amino}(oxo)acetic acid (ISIS/Draw with 

ACD/Name add-in). 

CAS Name: [[(Ethylamino)carbonyl]amino]oxoacetic acid. 

CAS Number: 105919-00-4. 

 

 

IN-JX915 

IUPAC Name: 3,4-Dimethyl-2,5-dioxoimidazolidine-4-carbonitrile (ISIS/Draw with 

ACD/Name add-in). 

CAS Name: 3-Ethyl-4(methoxyamino)-2,5-dioxo-4-imidazolidinecarbonitrile. 

CAS Number: Not reported. 

 

 

IN-KQ960 

IUPAC Name: 3,4-Dimethyl-2,5-dioxoimidazolidine-4-carboxamide (ISIS/Draw with 

ACD/Name add-in). 

CAS Name: 3-Ethyl-4-(methoxyamino)-2,5-dioxo-4-imidazolidinecarboxamide. 

CAS Number: Not reported. 

 

N

H

H3C

O

N

H

O

O

OH

HN N

O

O NHOCH3

C2H5

CN

HN N

O

O NHOCH3

C2H5

CONH2
63 

 

IN-T4226 

IUPAC Name: 1-Methylimidazolidine-2,4,5-trione (ISIS/Draw with ACD/Name add-in). 

CAS Name: Ethylimidazolidinetrione. 

CAS Number: 57012-86-9. 

 

 

IN-18474 

(Oxamic acid) 

IUPAC Name: Amino(oxo)acetic acid (ISIS/Draw with ACD/Name add-in). 

CAS Name: Aminooxoacetic acid. 

CAS Number: 471-47-6. 

 

 

Oxalic acid 

IUPAC Name: Oxalic acid (ISIS/Draw with ACD/Name add-in). 

CAS Name: Ethanodioic acid. 

CAS Number: 144-62-7. 

 

HN N

O

O

C2H5

O

HO

O

O

NH2

HO

O

O

OH
64 

 

Carbon Dioxide 

IUPAC Name: Carbon dioxide. 

CAS Name: Carbon dioxide. 

CAS Number: 124-38-9. 

 

 

IN-Q8761 

IUPAC Name: Not reported. 

CAS Name: 2-Cyano-N-[(ethylaminocarbonyl]-2-methoxyimino)acetamide. 

CAS Number: Not reported. 

 

 

O C O

N

H

H3C

O

N

H

O

N

CN

-OCH3
65 

APPENDIX B2: Environmental Fate Studies Details 

Abiotic Degradation 

Hydrolysis is a significant fate pathway in some environments. Cymoxanil hydrolyzes with a pH 

dependent pattern, as it is relatively stable at pH 5, but hydrolyzes rapidly in neutral and alkaline 

media (t1/2 of 1.4 days at pH 7, 0.022 days at pH 9; MRID 441807-38). The major hydrolytic 

degradates observed are: IN-U3204, IN-KP-533 (which appears to persist), and IN-U3595. 

Cymoxanil also photodegrades quickly in water (t1/2 of 3.6 days at pH 5). The major 

photoproducts are IN-JX915 and IN-R3273. Cymoxanil photodegrades slowly on soil, with a 

half-life of 74 days. 

Metabolism in Soil and Aquatic Environments 

In soils aged for 30 days under aerobic soil metabolism conditions for a leaching column study 

(AMR 2724-93), approximately 40-42% of the applied cymoxanil was recovered as 12CO2. 

However, while cymoxanil clearly does degrade in aerobic soil, including through mineralization 

to CO2, it is uncertain how quickly this will occur in soils at intended use sites in the U.S., or 

what transformation products may be produced and possibly persist, due to a lack of acceptable 

data. Submitted aerobic soil metabolism studies are classified as not acceptable (44180743 & 

45357101) or supplemental (44180742; AMR 1988-91), and half-lives from such will not be 

used in risk assessments. All of the submitted data are from foreign and/or volcanic ash soils and 

the studies had multiple problems such as inadequate extraction methods, high nonextractables 

from early on in the studies, and high inter-replicate data variability. There are no anaerobic soil 

metabolism data available. 

The submitted anaerobic aquatic metabolism studies do not provide usable data. One submitted 

study (MRID 44180744) is classified as not acceptable due to numerous deficiencies, while the 

other study (AMR 2446-92) is classified as supplemental, but was conducted at an alkaline pH 

(9) at which the observed degradation was likely due to hydrolysis and is not considered 

representative of intended use conditions. Similarly, in the single submitted aerobic aquatic 

metabolism study (MRID 44180741), extraction of residues was inadequate, there were no data 

for an acidic pH system, and degradation in both systems studied was only due to hydrolysis. 

Additionally, the sediments had very little organic carbon (0.1 and 0.8%), so are not likely 

representative of sediments near intended use sites. 

New studies are needed to adequately understand the role of metabolism in the degradation of 

cymoxanil in aerobic soils. To understand the fate of cymoxanil in anaerobic aquatic 

environments, new data are needed for at least two anaerobic aquatic sediment systems, one of 

which is at an acidic pH. Data are also needed for at least two aerobic aquatic sediment systems, 

one of which is at an acidic pH. 

 

Degradates detected in the submitted aerobic soil metabolism studies included IN-KQ960, INW3595, CO2, IN-U3204, IN-18474 (oxamic acid), IN-R3273, IN-KP533, and IN-JX915. The 

first four of these were present as major degradates in one or more soils, while the latter four 

were present as minor degradates in all soils in which they were detected. Of these, only IN-
66 

KQ960 and oxamic acid were not detected in the hydrolysis or aqueous photolysis studies. 

Degradates detected in the aquatic metabolism studies were likely due only to hydrolysis. 

However, it is uncertain whether all residues were adequately characterized in the submitted soil 

and aquatic metabolism studies, as well as whether the soils/sediments and conditions (e.g., pH) 

used in the studies are representative of intended use sites. 

In a terrestrial field dissipation study (MRID 44180747) conducted at two sites, the parent 

dissipated with half-lives of 0.9 days (silt loam; pH 6.5; MD site) and 8.7 days (loam; pH 7.8; 

CA site). Degradates were not monitored in the study. 

Transport and Soil Mobility 

Cymoxanil is not expected to significantly volatilize from soil or water based on its vapor 

pressure (1.1x10-6 Torr) and estimated Henry’s Law Constant (3.3 x 10-10 atm-m3

/mol). 

In four soils, cymoxanil has been shown to be mobile to highly mobile in soil based on the FAO 

classification scheme and organic carbon partitioning coefficients (Koc; in mL/g oc) of 22-138 

(MRID 44180745). Based on a batch equilibrium study, the degradates W3595, R3273 and 

KQ960 are highly mobile in soil, with single point measurements of Koc ranging from 0 to 50. 

While the study was classified "not acceptable“ because only one concentration was studied, the 

results did indicate that the cymoxanil degradates are all highly mobile (44180746). The 

degradate U3204 was unstable in the test system. In an unaged leaching column study (no 

MRID; AMR 2724-93), parent cymoxanil, oxamic acid (IN-18474) and IN-KP533 were all 

detected in leachate. In the aged leaching column from that study, oxamic acid was the only 

degradate detected in the leachate. The leaching of degradates was not determined in the field, 

as degradates were not monitored in the single acceptable terrestrial field dissipation study 

(MRID 44180747). Parent cymoxanil was not detected in field studies below the 0-15 cm soil 

depth at any of the sampling intervals. 

Cymoxanil is not expected to bioconcentrate/bioaccumulate in aquatic organisms based on the 

low measured Kow’s of 3.9 (pH 5) and 4.7 (pH 7). Bioconcentration in fish data have not been 

submitted. 
67 

APPENDIX C: Ecotox Open Literature Studies for Cymoxanil. 

Ecotox Aquatic Literature Cited 

Office of Pesticide Programs. 2000. Anabaena flosaquae. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Navicula pelliculosa. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Pseudokirchneriella subcapitata. Pesticide Ecotoxicity 

Database (Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects 

Division, U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Pseudokirchneriella subcapitata. Pesticide Ecotoxicity 

Database (Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects 

Division, U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Skeletonema costatum. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Daphnia magna. Pesticide Ecotoxicity Database (Formerly: 

Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, U.S.EPA, 

Washington, D.C. 

Office of Pesticide Programs. 2000. Americamysis bahia. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Cyprinodon variegates. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Cyprinus carpio. Pesticide Ecotoxicity Database (Formerly: 

Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, U.S.EPA, 

Washington, D.C. 

Office of Pesticide Programs. 2000. Lepomis macrochirus. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 
68 

Office of Pesticide Programs. 2000. Oncorhynchus mykiss. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Oncorhynchus mykiss. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Lemna gibba. Pesticide Ecotoxicity Database (Formerly: 

Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, U.S.EPA, 

Washington, D.C. 

Office of Pesticide Programs. 2000. Crassostrea virginica. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Svobodova, Z., and M. Pecena. 1988. Cyprinus carpio. Changes in the Red and White Blood 

Picture of Carp After Acute Exposure to Toxic Substances. Pr. Vyzk. Ustav Ryb. Hydrobiol. 

Vodnany17: 116-128 

Svobodova, Z., and M. Pecena. 1988. Cyprinus carpio. Changes in the Red and White Blood 

Picture of Carp After Acute Exposure to Toxic Substances. Pr. Vyzk. Ustav Ryb. Hydrobiol. 

Vodnany17: 116-128 

Ecotox Terrestrial Literature Cited 

Office of Pesticide Programs. 2000. Anas platyrhynchos. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Colinus virginianus. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Colinus virginianus. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Anas platyrhynchos. Pesticide Ecotoxicity Database 

(Formerly: Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, 

U.S.EPA, Washington, D.C. 

Office of Pesticide Programs. 2000. Apis mellifera. Pesticide Ecotoxicity Database (Formerly: 

Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, U.S.EPA, 

Washington, D.C. 
69 

Office of Pesticide Programs. 2000. Apis mellifera. Pesticide Ecotoxicity Database (Formerly: 

Environmental Effects Database (EEDB)). Environmental Fate and Effects Division, U.S.EPA, 

Washington, D.C. 
70 

APPENDIX D: Submitted Ecological Effects Toxicity Data for Cymoxanil 

Data from acceptable acute 96-hour freshwater fish studies were submitted for rainbow trout, 

Oncorhynchus mykiss, (MRID 441807-17) and bluegill sunfish, Lepomis macrochirus (MRID 

441807-18). For rainbow trout, sublethal effects included dark coloration (MRID 441807-17); 

the resulting LC50 value was 61 mg a.i./L with concentrations of 19, 32, 54, 90, and 150 mg 

a.i./L tested. The bluegill sunfish Lepomis macrochirus (most sensitive freshwater fish species 

tested) exhibited sublethal effects, including lethargy erratic swimming, irregulator respiration, 

and dark coloration; the LC50 value was >29 mg a.i./L with concentrations measure of 19, 32, 54, 

90, and 150 mg a.i./L tested. Two additional freshwater fish studies were submitted for 

cymoxanil technical. The first was a supplemental acute 96-hour study carried out on the 

common carp (Cyprinus carpio) (MRID 441807-16). The resulting LC50 value was 91 mg a.i./L 

when exposed at concentrations of 19, 32, 54, 90, and 150 mg a.i./L tested. Sublethal effects 

included fish surfacing and loss of equilibrium. The second freshwater fish study submitted on 

cymoxanil technical was a supplemental 21-day study carried out on rainbow trout (MRID 

441807-25). Mortality was seen at the lowest treatment level (0.22 mg a.i./L) when exposed to 

concentrations of 0.26, 0.64, 1.6, 4.0, and 10 mg a.i/L; however, the reviewer of the study did not 

believe that this was treatment related. Mortality was also seen at the three highest treatment 

levels. In addition, sublethal effects were seen at the three highest treatment levels. These 

effects included, gasping, lying on the bottom, erratic swimming, and partial loss of equilibrium. 

The 21-day LC50 was determined to be 1.5 mg a.i./L. 

In addition to the freshwater fish studies submitted on cymoxanil technical, there were also a 

number of formulated product studies submitted. One supplemental study with rainbow trout was 

submitted on the formulated product DPX-HYZ80 31 G (26.5% metallic copper and 6.58% 

cymoxanil; MRID 46503802). The 96-hour LC50 was 10 μg ai/L. Sub-lethal effects observed 

during the study included erratic swimming, lethargy, partial loss of equilibrium, and rapid 

respiration. Based on the absense of mortality or sub-lethal effectsthe NOAEC and LOAEC 

were 2.97 and 6.37 μg cymoxanil /L, respectively. Nevertheless, this study is confounded by the 

high levels of copper detected in the controls. Based on the results of this study and the toxicity 

value for cymoxanil, the formulated product is classified as very highly toxic to freshwater fish 

on an acute exposure basis. A supplemental non-guideline study was submitted on the 

formulated product DPX-KP481-25 50 WG (26.6% cymoxanil and 25.4% famoxadone) using 

juvenile rainbow trout (MRID 461448-01). The 96-hour LC50 for the formulated product was 9.3 

μg ai/L (a.i. is cymoxanil), which categorizes the formulated product as very-highly toxic to 

juvenile rainbow trout on an acute exposure basis. Sub-lethal effects included lethargy, dark 

coloration, and fish at the surface. No signs of toxicity were observed in either control group, or 

in the 8 or 14 μg/L test groups during the study. In addition, two 96-hour static acute sediment 

toxicitystudies of cymoxanil co-formulated with famoxadone were submitted for the rainbow 

trout. Both studies were classified as supplemental. One study was carried out on DPX-KP481-

25 which contained 25.63% cymoxanil and 25.06% famoxadone (MRID 449463-03). All test 

groups experienced >50% mortality; thus, an LC50 could not be reliably calculated. The other 

study was carried out on the formulated product DPX-KX007-5, which contained 30.84% 

cymoxanil and 23.04% famoxadone (MRID 449463-02). The 96-hour LC50 was determined to 

be >30 μg ai/L, with no mortalities observed at any of the treatment concentrations tested. 

 
71 

Data are available for one estuarine/marine fish, the sheepshead minnow, Cyprinodon variegatus

(MRID 441807-20), resulting in a visually determined 96-hr LC50 >47.5 mg a.i./L and a NOEC 

of 11.3 mg a.i./L with concentrations measured at 6.6, 11.3, 18.8, 29.0, and 47.5 mg a.i./L. 

Mortality and sublethal effects, including lethargy and surfacing, were observed at 

concentrations ≥18.8 mg a.i./L. 

One acceptable chronic freshwater fish study on the rainbow trout (Oncorhynchus mykiss) 

(MRID 443646-10) was submitted for cymoxanil technical. The NOEC was found to be 0.98 μg 

a.i./L and the LOEC was 2.4 μg a.i./L, with the most sensitive endpoint being reductions in total 

length. In addition, another chronic study was submitted on the rainbow trout (MRID 441807-

23); however, this study was classified as supplemental because the NOEC could not be 

determined due to adverse effects detected at all of the treatment concentrations; effects at ≥0.11 

mg a.i./L included erratic swimming, loss of equilibrium, rapid respiration, lethargy, reductions 

in growthcompared to controls, and partial loss of equilibrium The LOEC was 0.031 mg a.i./L, 

which was the lowest concentration tested. 

An acceptable chronic estuarine/marine fish study on the sheepshead minnow (Cyprinodon 

variegatus) (MRID 441807-26) was submitted. The NOEC was detemined to be 0.0942 mg 

a.i./L and the LOEC was 0.178 mg a.i./L based on reduced survival. Some of the fish observed 

at the two highest test concentrations exhibited behavioral effects including lethargy, erratic 

swimming, and loss of equilibrium. 

One acceptable toxicity study was submitted on freshwater aquatic invertebrates for cymoxanil 

technical. The study was an acute toxicity study to the waterflea, Daphnia magna, (MRID 

441807-19). The 48-hour EC50 was 28 mg a.i./L, which classifies cymoxanil as slightly toxic to 

freshwater invertebrates on an acute exposure basis. A supplemental study was also submitted 

on the waterflea for the formulated product DPX-HYZ80 31 WG (6.58% cymoxanil and 26.5% 

copper hydroxide; MRID 465038-03) in which the 48-hour EC50 was found to be 2.78 μg a.i./L 

classifying the formulated product as very highly toxic to freshwater invertebrates on an acute 

exposure basis. The fact that this endpoint is four orders of magnitude lower than for the parent 

may reveal that when cymoxanil is formulated with other compounds it increases in toxicity. In 

addition, mortality or sublethal effects from cymoxanil exposure were reported for the mysid 

shrimp (Americamysis bahia formerly Mysidopsis bahia); the 96-hr LC50 was >44.4 mg a.i./L 

(MRID 441807-22). This endpoint classifies cymoxanil as no more than slightly toxic to 

estuarine/marine invertebrates on an acute exposure basis. A study was also carried out on the 

Eastern oyster (Crassostrea virginica) (MRID 441807-21); the 96-hr EC50 for Eastern oyster was 

>46.9 mg a.i./L tested. Mean shell deposition was decreased 35% compared to the negative 

control at the highest concentration tested, and no additional adverse effects were noted;he 96-hr 

NOAEC was 28.2 mg a.i./L based on mean shell deposition. 

An acute study of waterfleas (Daphnia magna) was submitted on the degradate IN-KQ960 

(MRID 456892-01). The 48-hour EC50 was calculated at 0.8 mg a.i./L, which classifies INKQ960 as very highly toxic to freshwater invertebrates on an acute exposure basis. Sub-lethal 

effects observed in surviving daphnia from all treatment levels including lethargy and pale 

coloration. 
72 

Two acceptable chronic studies for freshwater aquatic invertebrates have been submitted for 

cymoxanil technical (97.8%). One was done on the waterflea (Daphnia magna) (MRID 441807-

24), and resulted in a NOEC of 0.067 mg a.i./L and a LOEC of 0.15 mg a.i./L based on the 

survival endpoint. The other study was done on the mysid shrimp (Mysidopsis bahia) (MRID 

441807-27) in which a NOEC of 1.70 mg a.i./L and a LOEC of 3.77 mg a.i./L was determined 

based on reduction in growth and reproduction. No chronic estuarine/marine chronic studies 

have been submitted. 

A supplemental acute oral study on the bobwhite quail was submitted on the formulated product 

DPX-KX007-5 (30.4% cymoxanil; 22.7% famoxadone) resulting in an LD50 of >684 mg a.i./L. 

This categorizes the formulated product, DPX-KX007-5 as slightly toxic to birds on an acute 

exposure basis. Clinical signs of toxicity were seen in two males from the second to highest 

treatment level and one male and two females from the highest concentration measured 

beginning on day 2 and day 1, respectively. Effects included ruffled appearance, lethargy, 

reduced reaction to sound and movement, wing droop, loss of coordination, lower limb 

weakness, prostrate posture, loss of righting reflex, and/or coma. 

An acceptable acute oral toxicity study on the laboratory rat was conducted for the registration of 

cymoxanil. In one study conducted on cymoxanil (96.5-97.8%) (MRID 436165-12), rats were 

given a single oral dose of cymoxanil technical and were observed for 14 days. Sublethal effects 

in both sexes included lethargy and low posture, but clinical signs were resolved within one day 

of exposure. The combined oral 14-day LD50 was determined to be 960 mg/kg-bw. 

In a two-generation reproduction study (MRID 436165-20) rats were exposed to cymoxanil 

through their diet. Based on increased pup deaths, the NOAEL and LOAEL for 

developmental/offspring systemic toxicity are 100 mg/kg-diet/day and 500 mg/kg-diet/day, 

respectively. The equivalent NOAEC for parental systemic toxicity is 6.5 mg/kg-bw/day. . 

Cymoxanil technical is classified as practically non-toxic to young adult honey bees (Apis 

mellifera) based on the one acute contact toxicity study (MRID 441807-35). The resulting 48-

hour LD50 and NOAEL based on immobile/lethargic bees are >25 μg a.i./bee and 25 μg a.i./bee, 

respectively. In addition, an acceptable acute oral toxicity study was carried out on cymoxanil 

technical that also classified the chemical as practically non-toxic to young adult honeybees 

(MRID 441807-36). The resulting LC50 and NOAEC based on immobile/lethargic bees are 

>1000 mg a.i./bee and 1000 mg a.i./bee, respectively. 

A supplemental acute contact and acute oral study on the honeybee was submitted on the 

formulated product DPX-HYZ80 31 WG (6.58% cymoxanil and 25.5% copper hydroxide) 

(MRID 464776-01). This study resulted in an acute oral 72-hour LC50 of 0.79 μg a.i./bee and 

72-hour NOEL of 0.21 μg a.i./bee and an acute contact 72-hour LD50 of 4.5 μg a.i./bee and 72-

hour NOAEL of 0.82 μg a.i./bee. Thus, the formulated product DPX-HYZ80 31 WG is 

classified as very highly toxic to honeybees on an acute oral exposure basis and is moderately 

toxic to honeybees on an acute contact exposure basis. 

An acceptable acute contact and supplemental acute oral honeybee study was submitted on the 

formulated product DPX-KX007-5 (30.4% cymoxanil and 22.7% famoxadone) (MRID 463504-
73 

02). Both the acute oral and the acute contact LD50 was estimated at 61.4 μg a.i./bee, and as a 

result DPX-KX007-5 is classified as practically non-toxic to honeybees on an acute contact 

exposure basis. 

An acceptable toxicity of residues on foliage test was submitted for the formulated product 

cymoxanil/famoxadone (DPX-KP481) 50 WG (1:1) (MRID 463504-03). The study indicated 

that the RT25 for cymoxanil technical was <1 hour when applied at a rate of 0.1875 lbs DPXKP481/acre. No sub-lethal effects were noted during the 24-hour exposure period. 

A supplemental 14-day earthworm (Eisenia fetida) study was carried out on cymoxanil technical 

(MRID 442007-02). The LC50 was 2109 mg a.i./kg dw soil and the NOAEC was 125 mg a.i./kg 

dw soil; however, more than 10% mortality was noted in the control group, so results must be 

interpreted with caution. 

A 28-day study of the formulated product DPX-HYZ80 31 WG (26.5% metallic copper and 

6.58% cymoxanil) was conducted using E. fetida (MRID 464643-01). The 28-day LC50 was 

determined to be >65.8 mg a.i./kg dw soil and the NOAEC was 149 mg a.i./kg dw soil. 

A 7-day toxicity study of the predatory mite (Typhlodromus pyri) using cymoxanil technical 

(60%) (MRID 454754-01) found that under the conditions tested, predatory mite mortality (mean 

39%) after 7 days was statistically different (p<0.05) than the controls (mean = 17%) following 

treatment at a rate equivalent to 120 g a.i./ha. 

No toxicity data have been submitted for terrestrial plants. Although the cxymoxanil is used on a 

broad range of terrestrial plants and there are no incidents reported involving terrestrial plants, 

the Agency cannot be certain without additional data that terrestrial plants are not affected by 

cymoxanil. 

TABLE 1. Ecological Effects Data for Terrestrial and Aquatic Animals 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

BIRDS 

Birds (Acute) 

Bobwhite quail

(Colinus 

virginianus) 

14-day LD50

>2250 mg 

a.i./kg-bw 

Cymoxanil (97.8%) 441807-10 Acceptable 

Mallard Duck

(Anas 

platyrhynchos)

14-day LD50

>2250 mg 

a.i./kg-bw 

Cymoxanil (97.8%) 441807-11 Acceptable 

Bobwhite quail

(Colinus 

virginianus)

14-day LD50

>684 mg 

a.i./kg-bw 

DPX-KX007-5 

Cymoxanil (30.4%) 

Famoxadone 

(22.7%) 

449463-18 Supplemental 

Birds (Acute/Sub-Acute)

Mallard Duck

(Anas 

platyrhynchos) 

8-day LC50

>5620 mg 

a.i./kg-diet 

Cymoxanil (97.8%) 441807-12 Acceptable 
74 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

Bobwhite quail 

(Colinus 

virginianus) 

8-day LC50

>5620 mg 

a.i./kg-diet 

Cymoxanil (97.8%) 441807-13 Acceptable 

Birds (Chronic) 

Mallard Duck 

(Anas 

platyrhynchos)

NOAEC: 100 

mg a.i./kg diet 

LOAEC: 300 

mg a.i./kg diet 

Cymoxanil (97.8%) 441807-15 Acceptable 

Endpoints 

based on eggs 

laid, eggs set, 

viable embryos, 

live 3-week 

embryos, 

normal 

hatchlings, 14-

day old 

survivors, and 

hatchling 

weight 

Bobwhite quail 

(Colinus 

virginianus)

NOAEC: 300 

mg a.i./kg diet 

LOAEC: 1200 

mg a.i./kg diet 

Cymoxanil (97.8%) 441807-14 Acceptable 

Live 3-week 

embryos, 

normal 

hatchlings, 14-

day survivors, 

live 3-week 

embryos of 

eggs set, normal 

hatchlings of 

eggs laid, 

normal 

hatchlings of 

eggs set, and 

14-day 

survivors of 

eggs set 

MAMMALS 

Mammals (Acute) 

Laboratory Rat

(Rattus 

norvegicus) 

LD50 > 960 mg 

a.i./kg-bw Cymoxanil (97.8%) 436165-12 Acceptable 
75 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

Mammals (Chronic) 

Laboratory Rat 

(Rattus 

norvegicus) 

NOAEL: 100 

mg a.i./kg-bw 

LOEAL:500 

mg a.i./kg-bw 

Cymoxanil 436165-20 Acceptable 

Based on 

reduction in 

mean 

bodyweight, 

overall body 

weight gain, 

and food 

consumption in 

parental (F0) 

males; reduced 

mean 

bodyweight 

during gestation 

and lactation of 

F1 females; 

decreased

TERRESTRIAL INVERTEBRATES 

Honey Bee

(oral) (Apis 

melifera) 

LC50 > 1000 mg 

a.i./bee Cymoxanil (97.8%) 441807-36 Acceptable 

Honey Bee

(contact) (Apis 

melifera)

LD50 >25 μg 

a.i./bee Cymoxanil (97.8%) 441807-35 Acceptable 

Honey Bee

(Apis melifera) 

(Toxicity of 

Residues on 

Foliage Test) 

RT25: <1 hour 

(@0.1875 lbs 

DPX-Kp481/A 

with a spray 

volume of 20 

gal/A) 

Cymoxanil/ 

Famoxadone 

50WG (1:1) 

Cymoxanil (25%) 

Famoxadone 

(25%) 

463504-03 Acceptable 

Honey Bee 

(Apis melifera) 

(acute oral/ 

acute contact) 

Acute oral: 

LD50 > 61.4 μg 

cymoxanil/bee 

Acute contact: 

LD50 > 61.4 μg 

cymoxanil/bee 

DPX-KX007-5 

Cymoxanil (30.4%) 

Famoxadone 

(22.7%) 

463504-02 

Acute Oral: 

Supplemental 

Acute Contact: 

Acceptable 

Honey Bee 

(Apis melifera) 

(acute 

oral/acute 

contact) 

Acute oral: 

LC50 = 0.7896 

μg 

cymoxanil/bee 

NOAEL = 

0.2118 μg 

cymoxanil/bee 

Acute contact: 

LD50 = 4.474 

μg 

cymoxanil/bee 

NOAEL = 

0.8225 μg 

cymoxanil/bee 

DPX-HYZ80 31 

WG 

Cymoxanil (6.58%) 

Copper Hydroxide 

(25.5%) 

464776-01 

Acute Oral: 

Supplemental 

Acute Contact: 

Supplemental 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement
76 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

Earthworm 

(Eisenia fetida) 

14-day LC50: 

2109 mg a.i./L 

Cymoxanil 

(>96.0%) 442007-02 Supplemental >10% mortality in the controls 

Earthworm 

(Eisenia fetida) 

28-day LC50: 

>65.8 mg 

a.i./kg dw soil 

NOAEC: 149 

mg a.i./kg dw 

soil 

DPX-HYZ80 31 

WG 

Metallic Copper 

(26.5%) 

Cymoxanil (6.58%) 

464643-01 Supplemental 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement

Predatory Mite 

(Typhlodromus 

pyri) 

7-days: No 

statistical 

difference seen 

at 9 g a.i./ha for 

growth or 

reproduction; 

however, 

statistical 

difference were 

seen at 120 g 

a.i./acre 

Cymoxanil (60%) 454754-01 Supplemental 

FRESHWATER FISH 

Freshwater Fish (Acute) 

Common Carp 

(Cyprinus 

carpio) 

96-hr LC50: 91 

mg a.i./L Cymoxanil (97.8%) 441807-16 Supplemental 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

96-hr LC50: 61 

mg a.i./L Cymoxanil (97.8%) 441807-17 Acceptable 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

96-hr LC50: 

10.3 μg a.i./L 

DPX-HYZ80 31 

WG 

Metallic Copper 

(26.5%) 

Cymoxanil (6.58%) 

465038-02 Supplemental 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

21-day LC50: 

1.5 mg a.i./L Cymoxanil (97.8%) 441807-25 Supplemental 

Bluegill Sunfish 

(Lepomis 

macrochirus) 

96-hr LC50: 29 

mg a.i./L Cymoxanil (97.8%) 441807-18 Acceptable 

Rainbow Trout 

(Oncorhynchus 

mykiss)

96-hr LC50: 9.3 

μg a.i./L 

DPX-KP481-25 50 

WG Famoxadone 

DPX-JE874 

(25.4%); DPXT3217 Cymoxanil 

(26.6%) 

461448-01 Acceptable 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement 

Freshwater Fish (Chronic) 
77 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

NOEC: Not 

Determined 

LOEC: 0.031 

mg a.i./L 

Cymoxanil (97.3%) 441807-23 Supplemental 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

NOEL: 0.98 μg 

a.i./L 

LOEL: 2.4 μg 

a.i./L 

Cymoxanil (97.3%) 443646-10 Acceptable Based on total 

length 

ESTUARINE/MARINE FISH 

Estuarine/Marine Fish (Acute) 

Sheepshead 

Minnow 

(Cyprinodon 

variegatus) 

96-hr LC50 > 

47.5 mg a.i./L Cymoxanil (97.8%) 441807-20 Acceptable 

Estuarine/Marine Fish (Chronic)

Sheepshead 

Minnow 

(Cyprinodon 

variegatus) 

NOEC: 0.0942 

mg a.i./L Cymoxanil (97.8%) 441807-26 Acceptable 

Based on 

survival at test 

termination 

 

FRESHWATER INVERTEBRATES 

Freshwater Invertebrates (Acute) 

Waterflea 

(Daphnia 

magna) 

48-hr EC50: 28 

mg a.i./L Cymoxanil (97.8%) 441807-19 Acceptable 

Waterflea 

(Daphnia 

magna)

48-hr EC50: 

2.78 μg a.i./L 

DPX-HYZ80 31 

WG 

Cymoxanil (6.58%) 

Copper Hydroxide 

(26.5%) 

465038-03 Supplemental 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement

Freshwater Invertebrates (Chronic) 

Waterflea 

(Daphnia 

magna)

NOEC: 0.067 

mg a.i./L 

LOEC: 0.15 mg 

a.i./L 

Cymoxanil (97.8%) 441807-24 Acceptable Based on 

survival 

ESTUARINE/MARINE INVERTEBRATES 

Estuarine/Marine Invertebrate (Acute) 

Eastern Oyster

(Crassostrea 

virginica) 

96-hr EC50 > 

46.9 mg a.i./L Cymoxanil (97.8%) 441807-21 Acceptable 

Mysid Shrimp

(Americamysis 

bahia)

96-hr LC50 > 

44.4 mg a.i./L Cymoxanil (97.8%) 441807-22 Acceptable 
78 

SPECIES ENDPOINT CHEMICAL/ 

FORMULATION MRID 

STUDY 

CLASSIFICATION COMMENTS 

Estuarine/Marine Invertebrate (Chronic) 

Mysid 

(Mysidopsis 

bahia) 

NOEC: 1.70 mg 

a.i./L 

LOEC: 3.77 mg 

a.i./L 

Cymoxanil (97.8%) 441807-27 Acceptable 

Based on 

number of 

young/female, 

male and 

female length, 

and female dry 

weight. 

An acceptable Tier I toxicity study on the green alga, Psuedokirchneriella subcapitata (formerly 

Selenastrum capricornatum; MRID 441807-30) was submitted for cymoxanil technical using 

DPX-T3217-113 Cymoxanil yielding an 120-hr IC50>1,050 μg a.i/L the maximum growth 

inhibition was 23.3%. In addition, an acceptable Tier 1 toxicity study on the saltwater diatom 

(Skeletonema costatum) (MRID 441807-31) was submitted for cymoxanil technical again 

resulted in an IC50>920 μg a.i./L; the maximum inhibition was 1.50%. 

An acceptable Tier II toxicity study was submitted for cymoxanil technical on the cyanobacteria 

(Anabaena flos-aquae) (MRID 441807-29) with a 120-hour EC50 of 230 μg a.i./L and a NOAEC 

of 65 μg a.i./L. In addition, an acceptable Tier II study with the freshwater diatom (Navicula 

pelliculosa) (MRID 441807-32) was submitted with a 120-hour EC50 of 200 μg a.i./L and a 

NOAEC of 63 μg a.i./L (most sensitive endpoint for non-vascular aquatic plants). 

A Tier II study of cymoxanil technical (MRID 441807-33) was conducted with P. subcapitata. 

The study is classified as supplemental. The 120-hour EC50 was 4,110 μg a.i./L and the NOAEC 

was 62.5 μg a.i./L. 

Another Tier II study (MRID 465038-01) that was carried out on P. subcapitata was submitted 

on the formulated product DPX-HYZ80 31 WG (6.58% cymoxanil and 26.5% metallic copper as 

copper hydroxide). The 120-hr IC50 (9.4 μg ai/L) and NOAEC (5.13 μg a.i./L) are based on 

plant biomass. This study was confounded by copper in the controls; however, it is uncertain 

whether the contamination affected the power of the study to detect treatment effects. 

A Tier 1 study on cymoxanil was conducted on the aquatic vascular plant duckweed, Lemna

gibba, with the technical grade active ingredient (MRID 441807-28). The study was classified 

as acceptable and resulted in an IC50>794 μg a.i./L. 

TABLE 2. Ecological Effects Data for Plants 

SPECIES ENDPOINT 

CHEMICAL/ 

FORMULATION 

(percent a.i.) 

MRID 

STUDY 

CLASSIFICATION COMMENTS 

Aquatic Nonvascular Plants 
79 

Green Alga 

(Psuedokirchneriella 

subcapitata, 

reported as 

Selenastrum 

capricornutum

Printz) 

120 hr-23.3% 

growth 

inhibition at 

1050 μg a.i./L 

(Tier 1) 

Cymoxanil 

(97.3%) 44180730 Acceptable 

Green Alga 

(Psuedokirchneriella 

subcapitata) 

72 hr-Cell 

Density: 

EC05: 5.2 μg 

a.i./L 

EC50: 9.5 μg 

a.i./L 

NOAEC: 5.13 

μg a.i./L 

Biomass: 

EC05: <5.13 μg 

a.i./L 

EC50: 9.4 μg 

a.i./L 

NOAEC: 5.13 

μg a.i./L 

Growth Rate: 

EC05: 6.9 μg 

a.i./L 

EC50: 16 μg 

a.i./L 

NOAEC: 7.88 

μg a.i./L 

DPX-HYZ80 31 

WG 

Cymoxanil 

(6.58%) 

Metallic Copper 

(26.5%) 

46503801 Supplemental 

Study carried 

out on 

Formulated 

Product, not AI, 

so does not 

fulfill guideline 

requirement 

Freshwater Diatom 

(Navicula 

pelliculosa) 

120-hr EC50 = 

202 μg a.i./L 

NOAEC = 63.3 

μg a.i./L 

Cymoxanil 

(97.3%) 44180732 Acceptable 

Saltwater Diatom 

(Skeletonema 

costatum) 

120 hr-1.50% 

growth 

inhibition at 

916 μg a.i./L 

(Tier 1) 

Cymoxanil 

(97.3%) 44180731 Acceptable 

Cyanobacteria 

(Anabaena flosaquae) 

120-hr EC50 = 

231 μg a.i./L 

NOAEC = 65.2 

μg a.i./L 

Cymoxanil 

(97.3%) 44180729 Acceptable 

Green Alga 

(Psuedokirchneriella 

subcapitata, 

reported as 

Selenastrum 

capricornutum

Printz) 

120-hr EC50 = 

4.11 mg a.i./L 

NOAEC = 

0.625 mg a.i./L 

Cymoxanil (95%) 44180733 Supplemental 
80 

Aquatic Vascular Plants 

Duckweed 

(L. gibba) (Tier 1) 

14 day- 0% 

frond growth 

inhibition when 

compared to 

the control 

Cymoxanil 

(97.27%) 44180728 Acceptable 

Cymoxanil Ecological Effects Data for Terrestrial Plants

None Available 

TABLE 3. Degradate Ecological Effects Data 

SPECIES ENDPOINT 

CHEMICAL/ 

FORMULATI

ON (percent 

a.i.) 

MRID 

STUDY 

CLASSIFICATION COMMENTS 

Freshwater Invertebrates (Acute)

Waterflea 

(Daphnia 

magna)

48-hr EC50: 0.8 

mg a.i./L 

IN-KQ960 

Cymoxanil 

(94.6%) 

45689201 Acceptable 

Carried out on 

the Degradate 

IN-KQ960 

A supplemental non-guideline extended laboratory two month study on the predatory mite 

(Typhlodromus pyri) was also carried out for the formulated products DPX-KP007 (8.3% 

famoxadone and 12% cymoxanil) and DPX-KX007 WG (22.7% famoxadone and 30.4% 

cymoxanil) (MRID 449672-02). Juvenile mortality in treated groups was similar or higher than 

that seen in control groups; however, the majority of mites in the treated groups developed much 

slower than in the control group. Despite relatively low mortality in the first week, the total 

effect in all treatments was high. The effect on reproduction was caused by both failure to 

develop to the adult stage and by poor reproductive performance in surviving females. 

Two supplemental/non-guideline studies were carried out on the formulated product DPXKP481-25 (cymoxanil 26.6% and famoxadone 25.4%) on the ground beetle (Poecilus cupreus). 

The first, 15-day acute study, (MRID 449463-30) was carried out to determine the effect of the 

formulated product under worst case laboratory conditions. The second, 3 month extended 

laboratory study (MRID 449463-33), was carried out to determine the effects on Poecilus 

cupreus when exposed on field grown potatoes. Both studies were carried out at an application 

rate that included 0.175 cymoxanil/ha. Both studies found no significant reduction in survival or 

feeding capacity when compared to the control survival and feeding rates. 

In addition, two other supplemental/non-guideline studies were carried out on the formulated 

product DPX-KP481-25 (cymoxanil 26.6% and famoxadone 25.4%) on the hoverfly 

(Ephisyrphus balteatus). The first, an acute toxicity study (MRID 449463-29) lasted 6 weeks, 

and the second, an extended laboratory study (MRID 449463-32) lasted 4 months. Both tested at 

an application rate that included 0.175 cymoxanil/ha. The first study found no significant 

reductions in survival; however, there was a significant reduction (33.5%) in reproduction rate 

(percent fertile eggs/female) when compared to the control. The second study found no 

significant reduction in survival when compared to control survival after the 3rd or 6th

application. However, there was a reduction in fecundity rates (eggs/female/day and in egg 

viability), compared to the control, after the 3rd and 6th applications (10 day intervals for 

applications). 
81 

A supplemental/non-guideline 8-week acute study was also carried out on the formulated product 

DPX-KP481-25 (25.4% famoxadone and 26.6% cymoxanil) for the green lacewing, 

(Chrysoperla carnea). Tested at an application rate that included 0.175 cymoxanil/ha, there was 

no significant reduction in survival or reproduction when compared to control survival or 

reproduction. 

Finally, a supplemental/non-guideline 4.5 month semi-field study looking at the toxicity of DPXKP481-25 to aphid parasitoids (Aphidius colmani) was submitted. The purpose of the study was 

to determine the effects of DPX-KP481-25 on aphid parasitoids when exposed to fresh residues 

in a potato crop. The crop was treated on nine 10-day intervals, and statistical analysis was 

attempted by the reviewer for analysis. However, during the study, treatment applications and 

methods were altered because of the spread of potato blight. Thus, it was determined by the 

reviewer that the results of the study were inconclusive, and the effect of DPX-KP481-25 to 

aphid parasitoids (Aphidius colmani) could not be determined. 

TABLE 4. Non-Guideline Ecological Effects Data 

Non-Guideline Studies Co-formulated with Famoxadone 

SPECIES ENDPOINT 

CHEMICAL/ 

FORMULATION 

(percent active 

ingredient) 

MRID STUDY 

CLASSIFICATION 

Ground Beetle 

(Poecilus cuperus) 

At an application 

rate of 0.16 lbs 

ai/acre or 0.175 

kg ai/acre, no 

significant 

reduction in 

survival or 

feeding rates 

when compared 

to control 

survival and 

feeding rates 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(26.6%) 

Famoxadone 

(25.4%) 

44946330 Supplemental 

Ground Beetle 

(Poecilus cuperus) 

At an application 

rate of 0.16 lbs 

ai/acre or 0.175 

kg ai/acre, no 

significant 

reduction in 

survival or 

feeding capacity 

when compared 

to control after 

the 1st, 4th, 6th, or 

9th application. 

(10 day interval 

for applications) 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(26.6%) 

Famoxadone 

(25.4%) 

44946333 Supplemental 
82 

Green Lacewing 

(Chrysoperla 

carnea) 

At an application 

rate of 0.16 lbs 

ai/acre or 0.175 

kg ai/acre, no 

significant 

reduction in 

survival or 

reproduction 

when compared 

to control 

survival and 

reproduction 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(26.6%) 

Famoxadone 

(25.4%) 

44946328 Supplemental 

Hoverfly 

(Episyrphus 

balteatus) 

At an application 

rate of 0.16 lbs 

ai/acre or 0.175 

kg ai/acre, no 

significant 

reduction in 

survival; 

however, 

significant 

reduction 

(33.5%) in 

reproduction rate 

(percent fertile 

eggs/female) 

when compared 

to control existed 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(26.6%) 

Famoxadone 

(25.4%) 

44946329 Supplemental 

Hoverfly 

(Episyrphus 

balteatus) 

At an application 

rate of 0.16 lbs 

ai/acre or 0.175 

kg ai/acre, no 

significant 

reduction in 

survival when 

compared to 

control survival 

after the 3rd and 

6th application. 

However, there 

was a reduction 

in fecundity 

rates, 

(eggs/female/day/ 

and in the egg 

viability), 

compared to the 

control after the 

3X and 6X 

application (10 

day interval for 

applications). 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(25.50%) 

Famoxadone 

(25.24%) 

449463-32 Supplemental 
83 

Predatory Mite 

(Typhlordomus 

pyri) 

Juvenile 

mortality in 

treated groups 

was similar or 

higher than in the 

control group. 

The majority of 

mites in the 

treatment group 

developed much 

slower than the 

control group. 

Low mortality in 

the first week, 

but total effect on 

all treatments 

was high. Effect 

on reproduction 

was seen in both 

failure to develop 

to adult stage and 

poor 

reproduction 

performance of 

surviving 

females. 

DPX-KX007 SC 

(TEP) (12% 

cymoxanil; 8.3% 

famoxadone) 

DPX-KX007 WG 

(TEP) (30.4% 

cymoxanil; 22.7% 

famoxadone) 

44967202 Supplemental 

Aphid Parasitoid 

(Aphidius colmani) 

Inconclusive 

Results 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(25.50%) 

Famoxadone 

(25.24%) 

44946334 Supplemental 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

96-hour Static 

Acute Tox in 

Presence of 

Sediment. 

All test groups 

experienced 

>50% mortality; 

thus, no LC50 

could be reliably 

calculated 

DPX-KP481-25 

(TEP) 

Cymoxanil 

(25.63%) 

Famoxadone 

(25.08%) 

44946303 Supplemental 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

96-hour Static 

Acute Tox in 

Presence of 

Sediment: 96-hr 

LC50 > 30 μg 

a.i./L 

NOEL: 30 μg 

a.i./L 

DPX-KX007-5 

(TEP) 

Cymoxanil 

(30.84%) 

Famoxadone 

(23.04%) 

44946302 Supplemental 
84 

APPENDIX E: Output from ECOSAR for Cymoxanil and its Major Degradates 

ECOSAR Version 1.10 Results Page 

Parent Cymoxanil 

SMILES : O=C(NCC)NC(=O)C(=NOC)C(#N) 

CHEM : Acetamide, 2-cyano-N- (ethylamino)carbonyl -2-(methoxyimino)- 

CAS Num: 057966-95-7 

ChemID1: 

MOL FOR: C7 H10 N4 O3 

MOL WT : 198.18 

Log Kow: 4.244 (EPISuite Kowwin v1.68 Estimate) 

Log Kow: 0.672 (User Entered) 

Log Kow: 0.59 (PhysProp DB exp value - for comparison only) 

Melt Pt: (User Entered for Wat Sol estimate) 

Melt Pt: 160.50 (deg C, PhysProp DB exp value for Wat Sol est) 

Wat Sol: 2993 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: 780 (mg/L, User Entered) 

Wat Sol: 890 (mg/L, PhysProp DB exp value) 

 

 

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

Values used to Generate ECOSAR Profile 

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

Log Kow: 0.672 (User Entered) 

Wat Sol: 780 (mg/L, User Entered) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 Measured 

CAS No Organism Duration End Pt mg/L (ppm) Ecosar Class Reference 

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

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

057966-95-7 Daphnid ChV 0.1 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB 

057966-95-7 Daphnid 48-hr LC50 0.8 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB 

057966-95-7 Fish ChV 0.0015 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB 

057966-95-7 Fish 96-hr LC50 29 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB; LC50>SH2 

057966-95-7 Fish 96-hr LC50 61 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB; LC50>SH2 
85 

057966-95-7 Fish (SW) ChV 0.12 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB 

057966-95-7 Mysid ChV 2.5 Carbonyl Urea OPP Pesticide 

Ecotoxicity DB 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

Carbonyl Ureas 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 283.832 

Aliphatic Amines : Daphnid 48-hr LC50 28.993 

Aliphatic Amines : Green Algae 96-hr EC50 32.469 

Aliphatic Amines : Fish ChV 26.457 

Aliphatic Amines : Daphnid ChV 2.050 

Aliphatic Amines : Green Algae ChV 9.643 

Carbonyl Ureas : Fish 96-hr LC50 133.595 

Carbonyl Ureas : Daphnid 48-hr LC50 144.144 

Carbonyl Ureas : Green Algae 96-hr EC50 0.015 

Carbonyl Ureas : Fish ChV 0.961 

Carbonyl Ureas : Daphnid ChV 3.379 

Carbonyl Ureas : Green Algae ChV 0.004 

Carbonyl Ureas : Fish (SW) 96-hr LC50 116.724 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 496.004 

Carbonyl Ureas : Fish (SW) ChV 3.503 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 2537.129 * 

(Baseline Toxicity) : Daphnid 48-hr LC50 1043.315 * 

 : Green Algae 96-hr EC50 960.274 * 

 : Fish ChV 214.599 

 : Daphnid ChV 88.346 

 : Green Algae ChV 113.951 

 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. 

 
86 

 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae ChV) 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

IN-U3204 

SMILES : O=C1(C(C(N(C(=O)(N1))CC)=N)=NOC) 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C7 H10 N4 O3 

MOL WT : 198.18 

Log Kow: 0.393 (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: 2.063E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: (User Entered) 

Wat Sol: (PhysProp DB exp value) 

 

 

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

Values used to Generate ECOSAR Profile 

-------------------------------------- 
87 

Log Kow: 0.393 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 2.063E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

Carbonyl Ureas 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 432.812 

Aliphatic Amines : Daphnid 48-hr LC50 42.801 

Aliphatic Amines : Green Algae 96-hr EC50 51.107 

Aliphatic Amines : Fish ChV 44.535 

Aliphatic Amines : Daphnid ChV 2.932 

Aliphatic Amines : Green Algae ChV 14.828 

Carbonyl Ureas : Fish 96-hr LC50 191.132 

Carbonyl Ureas : Daphnid 48-hr LC50 274.088 

Carbonyl Ureas : Green Algae 96-hr EC50 0.015 

Carbonyl Ureas : Fish ChV 1.376 

Carbonyl Ureas : Daphnid ChV 5.135 

Carbonyl Ureas : Green Algae ChV 0.004 

Carbonyl Ureas : Fish (SW) 96-hr LC50 166.983 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 1177.595 

Carbonyl Ureas : Fish (SW) ChV 4.547 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 4516.715 

(Baseline Toxicity) : Daphnid 48-hr LC50 1761.627 

 : Green Algae 96-hr EC50 1618.813 

 : Fish ChV 370.609 

 : Daphnid ChV 142.678 

 : Green Algae ChV 167.829 
88 

 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. 

 

 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae ChV) 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

IN-W3595 

ECOSAR Version 1.10 Results Page 

 

SMILES : C(C(=O)(O))(=NOC)C(#N) 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C4 H4 N2 O3 

MOL WT : 128.09 

Log Kow: 4.270 (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: 52.43 (mg/L, EPISuite WSKowwin v1.43 Estimate) 
89 

Wat Sol: (User Entered) 

Wat Sol: (PhysProp DB exp value) 

 

 

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

Values used to Generate ECOSAR Profile 

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

Log Kow: 4.270 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 52.43 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 0.794 

Aliphatic Amines : Daphnid 48-hr LC50 0.123 

Aliphatic Amines : Green Algae 96-hr EC50 0.060 

Aliphatic Amines : Fish ChV 0.021 

Aliphatic Amines : Daphnid ChV 0.013 

Aliphatic Amines : Green Algae ChV 0.024 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 0.963 

(Baseline Toxicity) : Daphnid 48-hr LC50 0.784 

 : Green Algae 96-hr EC50 0.736 

 : Fish ChV 0.121 

 : Daphnid ChV 0.118 

 : Green Algae ChV 0.499 

 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. 
90 

 

 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae 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) 

IN-R3273 

ECOSAR Version 1.10 Results Page 

 

SMILES : O=C1(C(N(C(=O)(N1))CC)=NOC) 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C6 H9 N3 O3 

MOL WT : 171.16 

Log Kow: 2.072 (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: 1033 (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: 2.072 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 1033 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 
91 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

Carbonyl Ureas 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 29.493 

Aliphatic Amines : Daphnid 48-hr LC50 3.545 

Aliphatic Amines : Green Algae 96-hr EC50 2.877 

Aliphatic Amines : Fish ChV 1.674 

Aliphatic Amines : Daphnid ChV 0.294 

Aliphatic Amines : Green Algae ChV 0.961 

Carbonyl Ureas : Fish 96-hr LC50 19.118 

Carbonyl Ureas : Daphnid 48-hr LC50 4.947 

Carbonyl Ureas : Green Algae 96-hr EC50 0.013 

Carbonyl Ureas : Fish ChV 0.137 

Carbonyl Ureas : Daphnid ChV 0.357 

Carbonyl Ureas : Green Algae ChV 0.003 

Carbonyl Ureas : Fish (SW) 96-hr LC50 16.709 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 5.586 

Carbonyl Ureas : Fish (SW) ChV 0.817 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 121.202 

(Baseline Toxicity) : Daphnid 48-hr LC50 65.002 

 : Green Algae 96-hr EC50 60.312 

 : Fish ChV 11.940 

 : Daphnid ChV 6.882 

 : Green Algae ChV 14.096 

 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) 
92 

 are reported. 

 

 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae ChV) 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

IN-KP533 

ECOSAR Version 1.10 Results Page 

 

SMILES : C(N(C(=O)(N(C(=O)(C(=O)O)))))C 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C5 H8 N2 O4 

MOL WT : 160.13 

Log Kow: -1.285 (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: 4.192E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: (User Entered) 

Wat Sol: (PhysProp DB exp value) 

 
93 

 

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

Values used to Generate ECOSAR Profile 

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

Log Kow: -1.285 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 4.192E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Carbonyl Ureas 

 Predicted 

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

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

========== 

Carbonyl Ureas : Fish 96-hr LC50 1333.035 

Carbonyl Ureas : Daphnid 48-hr LC50 10591.899 

Carbonyl Ureas : Green Algae 96-hr EC50 0.012 

Carbonyl Ureas : Fish ChV 9.653 

Carbonyl Ureas : Daphnid ChV 51.480 

Carbonyl Ureas : Green Algae ChV 0.003 

Carbonyl Ureas : Fish (SW) 96-hr LC50 1164.161 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 1.73e+005 * 

Carbonyl Ureas : Fish (SW) ChV 17.666 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 1.17e+005 * 

(Baseline Toxicity) : Daphnid 48-hr LC50 33302.348 

 : Green Algae 96-hr EC50 30308.281 

 : Fish ChV 8024.026 

 : Daphnid ChV 2063.463 

 : Green Algae ChV 1393.932 

 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. 

 
94 

 

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

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. 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

IN-JX915 

ECOSAR Version 1.10 Results Page 

 

SMILES : O=C1N(C(C(=O)N1)(C(#N))NOC)CC 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C7 H10 N4 O3 

MOL WT : 198.18 

Log Kow: -0.366 (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: 2441 (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: -0.366 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 2441 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 
95 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

Carbonyl Ureas 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 1364.051 

Aliphatic Amines : Daphnid 48-hr LC50 123.499 

Aliphatic Amines : Green Algae 96-hr EC50 175.589 

Aliphatic Amines : Fish ChV 183.659 

Aliphatic Amines : Daphnid ChV 7.764 

Aliphatic Amines : Green Algae ChV 47.806 

Carbonyl Ureas : Fish 96-hr LC50 506.427 

Carbonyl Ureas : Daphnid 48-hr LC50 1574.787 

Carbonyl Ureas : Green Algae 96-hr EC50 0.015 

Carbonyl Ureas : Fish ChV 3.656 

Carbonyl Ureas : Daphnid ChV 16.031 

Carbonyl Ureas : Green Algae ChV 0.004 

Carbonyl Ureas : Fish (SW) 96-hr LC50 442.364 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 12377.822 * 

Carbonyl Ureas : Fish (SW) ChV 9.248 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 21692.068 * 

(Baseline Toxicity) : Daphnid 48-hr LC50 7326.005 * 

 : Green Algae 96-hr EC50 6702.749 * 

 : Fish ChV 1638.714 

 : Daphnid ChV 525.683 

 : Green Algae ChV 481.223 

 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. 

 

 
96 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae ChV) 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

IN-KQ960 

ECOSAR Version 1.10 Results Page 

 

SMILES : O=C1(N(C(C(=O)(N1))(C(=O)N)NOC)CC) 

CHEM : 

CAS Num: 

ChemID1: IN-KQ960 

MOL FOR: C7 H12 N4 O4 

MOL WT : 216.20 

Log Kow: -1.636 (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: 4.409E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: (User Entered) 

Wat Sol: (PhysProp DB exp value) 

 

 

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

Values used to Generate ECOSAR Profile 
97 

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

Log Kow: -1.636 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 4.409E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Aliphatic Amines 

Amides 

Carbonyl Ureas 

 Predicted 

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

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

========== 

Aliphatic Amines : Fish 96-hr LC50 10171.875 

Aliphatic Amines : Daphnid 48-hr LC50 794.452 

Aliphatic Amines : Green Algae 96-hr EC50 1512.983 

Aliphatic Amines : Fish ChV 2148.461 

Aliphatic Amines : Daphnid ChV 43.264 

Aliphatic Amines : Green Algae ChV 370.316 

Amides : Fish 96-hr LC50 25731.789 

Amides : Daphnid 48-hr LC50 1.51e+005 * 

Amides : Green Algae 96-hr EC50 369.274 

Amides : Fish ChV 5.078 

Amides : Daphnid ChV 769.602 

Amides : Green Algae ChV 74.813 

Amides : Fish (SW) 96-hr LC50 21906.361 

Amides : Mysid (SW) 96-hr LC50 439.944 

Carbonyl Ureas : Fish 96-hr LC50 2824.336 

Carbonyl Ureas : Daphnid 48-hr LC50 32099.426 

Carbonyl Ureas : Green Algae 96-hr EC50 0.016 

Carbonyl Ureas : Fish ChV 20.477 

Carbonyl Ureas : Daphnid ChV 117.670 

Carbonyl Ureas : Green Algae ChV 0.004 

Carbonyl Ureas : Fish (SW) 96-hr LC50 2466.339 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 6.94e+005 * 
98 

Carbonyl Ureas : Fish (SW) ChV 33.119 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 3.28e+005 * 

(Baseline Toxicity) : Daphnid 48-hr LC50 86912.406 * 

 : Green Algae 96-hr EC50 78938.883 * 

 : Fish ChV 21543.480 

 : Daphnid ChV 5091.974 

 : Green Algae ChV 3063.213 

 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. 

 

 

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

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. 

 

Aliphatic Amines: 

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

Maximum LogKow: 6.0 (Fish, Mysid LC50) 

Maximum LogKow: 5.0 (Daphnid LC50) 

Maximum LogKow: 7.0 (Green Algae EC50) 

Maximum LogKow: 8.0 (Fish, Daphnid ChV) 

Maximum LogKow: 7.0 (Green Algae ChV) 

 

Amides : 

------- 

Maximum LogKow: >8.5 (LC50) 

Maximum LogKow: >8.0 (EC50,ChV) 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 
99 

Maximum LogKow: 8.0 (ChV) 

IN-T4226 

ECOSAR Version 1.10 Results Page 

 

SMILES : O=C1(C(=O)(N(C(=O)(N1))CC)) 

CHEM : 

CAS Num: 

ChemID1: 

MOL FOR: C5 H6 N2 O3 

MOL WT : 142.12 

Log Kow: 0.162 (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: 5.961E+004 (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: 0.162 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 5.961E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Carbonyl Ureas 

 Predicted 

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

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

========== 

Carbonyl Ureas : Fish 96-hr LC50 184.319 

Carbonyl Ureas : Daphnid 48-hr LC50 334.446 

Carbonyl Ureas : Green Algae 96-hr EC50 0.011 

Carbonyl Ureas : Fish ChV 1.328 
100 

Carbonyl Ureas : Daphnid ChV 5.205 

Carbonyl Ureas : Green Algae ChV 0.003 

Carbonyl Ureas : Fish (SW) 96-hr LC50 161.022 

Carbonyl Ureas : Mysid (SW) 96-hr LC50 1726.573 

Carbonyl Ureas : Fish (SW) ChV 4.046 

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

========== 

Neutral Organic SAR : Fish 96-hr LC50 5219.018 

(Baseline Toxicity) : Daphnid 48-hr LC50 1948.366 

 : Green Algae 96-hr EC50 1788.037 

 : Fish ChV 417.609 

 : Daphnid ChV 152.098 

 : Green Algae ChV 165.779 

 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. 

 

 

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

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. 

 

Carbonyl Ureas : 

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

Maximum LogKow: 5.0 (LC50) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

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

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Oxalic Acid 

ECOSAR Version 1.10 Results Page 

 

SMILES : O=C(O)C(=O)O 

CHEM : Ethanedioic acid 

CAS Num: 000144-62-7 

ChemID1: 
101 

MOL FOR: C2 H2 O4 

MOL WT : 90.04 

Log Kow: -1.737 (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: 189.50 (deg C, PhysProp DB exp value for Wat Sol est, 189.5 dec) 

Wat Sol: 1E+006 (mg/L, EPISuite WSKowwin v1.43 Estimate) 

Wat Sol: (User Entered) 

Wat Sol: 1350 (mg/L, PhysProp DB exp value) 

 

 

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

Values used to Generate ECOSAR Profile 

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

Log Kow: -1.737 (EPISuite Kowwin v1.68 Estimate) 

Wat Sol: 1350 (mg/L, PhysProp DB exp value) 

 

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

Available Measured Data from ECOSAR Training Set 

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

 No Data Available 

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

ECOSAR v1.1 Class-specific Estimations 

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

Neutral Organics 

 Predicted 

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

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

========== 

Neutral Organics : Fish 96-hr LC50 1.68e+005 * 

Neutral Organics : Fish 14-day LC50 1.47e+005 * 

Neutral Organics : Daphnid 48-hr LC50 67876.813 * 

Neutral Organics : Green Algae 96-hr EC50 39658.563 * 

Neutral Organics : Fish ChV 10917.655 * 

Neutral Organics : Daphnid ChV 2519.062 * 

Neutral Organics : Green Algae ChV 1466.058 * 

Neutral Organics : Fish (SW) 96-hr LC50 2.07e+005 * 

Neutral Organics : Mysid 96-hr LC50 1.93e+006 * 

Neutral Organics : Fish (SW) ChV 2289.450 * 

Neutral Organics : Mysid (SW) ChV 5.05e+005 * 

Neutral Organics : Earthworm 14-day LC50 382.024 
102 

 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. 

 

 

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

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. 

 

Neutral Organics: 

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

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

Maximum LogKow: 6.0 (Fish 14-day LC50; Earthworm LC50) 

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

 
103 

APPENDIX F: Screening Imbibition Program (SIP) v.1.0 and Screening Tool for 

Inhalation Risk (STIR) v.1.0 Description, Assumptions, Inputs and Outputs 

SIP v.1.0 

SIP v.1.0 provides an upper bound estimate of exposure of birds and mammals to pesticides through 

drinking water alone. This model is intended for use in problem formulation to determine whether or not 

drinking water exposure alone is a potential pathway of concern. This does not aggregate drinking water 

exposure with other exposure routes (i.e., diet, inhalation, dermal). 

Assumptions:

 

SIP employs the following conservative assumptions to derive upper bound exposure 

estimates: 

1) The chemical concentration in drinking water is at the solubility limit in water (at 25oC). 

2) The assessed animals obtain 100% of their daily water needs through drinking water. 

3) The daily water need is equivalent to the daily water flux rate as calculated by Nagy and 

Peterson (1988). 

4) The body weight of the assessed bird is equivalent to the smallest generic bird modeled in 

T-REX (i.e., 20 g). This assumption results in the highest ratio of exposure to toxicity for the 3 

assessed avian body weights of T-REX (i.e., 20, 100, 1000 g). 

5) The body weight of the assessed mammal is equivalent to the largest generic mammal 

modeled in T-REX (i.e., 1000 g). This results in the highest ratio of exposure to toxicity for the 3 

assessed mammalian body weights of T-REX (i.e., 15, 35, 1000 g). 

 Table 1. Inputs 

 

 Parameter Value 

 Chemical name Cymoxanil 

 

Solubility (in water at 25oC; 

mg/L) 890 

 

 Mammalian LD50 (mg/kg-bw) 960 

 Mammalian test species laboratory rat 

 

Body weight (g) of "other" 

mammalian species 

 

 Mammalian NOAEL (mg/kg-bw) 100 

 Mammalian test species laboratory rat 

 

Body weight (g) of "other" 

mammalian species 

 

 Avian LD50 (mg/kg-bw) 2250 

 Avian test species mallard duck 

 

Body weight (g) of "other" avian 

species 

 Mineau scaling factor 1.15 

 

 Mallard NOAEC (mg/kg-diet) 100 
104 

 

Bobwhite quail NOAEC (mg/kgdiet) 300 

 

NOAEC (mg/kg-diet) for other 

bird species 

 

Body weight (g) of other avian 

species 

 

NOAEC (mg/kg-diet) for 2nd 

other bird species 

 

 

 Table 2. Mammalian Results 

 Parameter Acute Chronic 

 

Upper bound exposure (mg/kgbw) 153.0800 153.0800 

 

Adjusted toxicity value (mg/kgbw) 738.3941 76.9161 

 Ratio of exposure to toxicity 0.2073 1.9902 

 

Conclusion* 

Exposure through 

drinking water alone is 

a potential concern for 

mammals 

Exposure through drinking 

water alone is a potential 

concern for mammals 

 

 Table 3. Avian Results 

 Parameter Acute Chronic 

 

Upper bound exposure (mg/kgbw) 720.9000 720.9000 

 

Adjusted toxicity value (mg/kgbw) 1168.2572 4.9613 

 

Ratio of exposure to acute 

toxicity 0.6171 145.3059 

 

Conclusion* 

Exposure through 

drinking water alone is 

a potential concern for 

birds 

Exposure through drinking 

water alone is a potential 

concern for birds 

 

*Conclusion is for drinking water exposure alone. This does not combine all routes of 

exposure. Therefore, when aggregated with other routes (i.e., diet, inhalation, dermal), 

pesticide exposure through drinking water may contribute to a total exposure that has 

potential for effects to non-target animals. 

STIR v.1.0 

Inhalation is a potentially important route of exposure to pesticides for mammalian and avian wildlife 

(Driver et al. 1991; USEPA 2004a). STIR is a screening tool that can be used at the Problem Formulation 

phase to assess the potential for risk to bird and mammals from inhalation exposure. The exposure 

pathways that are assessed by this tool include both droplet inhalation and vapor phase inhalation. 

Allometric equations that relate inhalation rate to body weight are used to derive an estimated inhalation 
105 

dose of either droplets or vapor for a 0.020 kg bird and a 0.015 kg mammal (Mineau et al. 1996; Sample 

and Arenal 1999; USEPA 1993). 

Assumptions

* The saturated air concentration is the theoretical maximum pure product air concentration at 25oC and 1 

atm of pressure. 

* The height of the direct spray column is 3.3 m for aerial applications and 1 m for ground applications. 

* The duration of vapor inhalation is assumed to be 1 hour and the duration of direct spray inhalation is 

assumed to be 1.5 minutes for aerial and 3 seconds for ground applications. 

* The fraction of direct spray that can be inhaled is assumed to be 90%, unless a droplet spectra is 

specified on the label. 

* This model accounts for the difference in both avian and mammalian field active inhalation rate 

compared to the resting rate by multiplying the resting inhalation rate by 3 according to USEPA, 1993. 

* Both of the mammalian and avian inhalation LD50's are adjusted for body weight using allometric 

equations based on work by Mineau et al. 1996. The avian allometric equation uses the Mineau scaling 

factor to modify the equation based on chemical specific data. If chemical-specific data are available the 

user can specify the avian scaling factor (see Mineau, et al.,1996). Otherwise, enter the EFED default 

value of 1.15. STIR will not run unless a Mineau scaling factor is entered. However, 1 can be entered if 

the assessor believes that body weight does not influence the toxicity of the chemical being assessed. 

* The inhalation of droplets and the inhalation of vapor phase pesticide are accounted for in this model as 

two separate routes of exposure. The corresponding dose estimations should not be combined to obtain 

a composite exposure value. 

Table 1. EFED Screening Tool for Inhalation for Cymoxanil 

Input 

Application and Chemical Information 

Enter Chemical Name Cymoxanil 

Enter Chemical Use Fungicide 

Is the Application a Spray? (enter y or n) y 

If Spray What Type (enter ground or air) ground 

Enter Chemical Molecular Weight (g/mole) 198.18 

Enter Chemical Vapor Pressure (mmHg) 1.10E-05 

Enter Application Rate (lb a.i./acre) 0.1875 

 

Toxicity Properties 

Bird 

Enter Lowest Bird Oral LD50 (mg/kg bw) 2250 

Enter Mineau Scaling Factor 1.15 

Enter Tested Bird Weight (kg) 0.178 

Mammal 

Enter Lowest Rat Oral LD50 (mg/kg bw) 960 

Enter Lowest Rat Inhalation LC50 (mg/L) 5.06 

Duration of Rat Inhalation Study (hrs) 4 

Enter Rat Weight (kg) 0.35 

 

Output 
106 

Results Avian (0.020 kg ) 

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.17E-01 

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.47E-02 

Adjusted Inhalation LD50 6.61E+01 

Ratio of Vapor Dose to Adjusted Inhalation LD50 2.23E-04 Exposure not Likely Significant 

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 1.98E-02 

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 3.00E-04 Exposure not Likely Significant 

 

Results Mammalian (0.015 kg ) 

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.17E-01 

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.85E-02 

Adjusted Inhalation LD50 3.01E+02 

Ratio of Vapor Dose to Adjusted Inhalation LD50 6.15E-05 Exposure not Likely Significant 

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.49E-02 

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 8.27E-05 Exposure not Likely Significant 

 
107 

APPENDIX G. Data Call-In Justification Tables for Ecological Effects Studies 

Study Title: Pollinator Larval Toxicity Study 

Guideline Number: Non-guideline 

Test Substance: Cymoxanil 

Rationale for Requiring the Data 

Although cymoxanil is practically non-toxic to young adult honeybees on an acute contact 

exposure basis, these studies do not provide information on the potential toxicity of cymoxanil to 

developing honeybee brood (larvae and pupae). Since cymoxanil is a systemic pesticide, there is 

the potential for pollen and nectar to be contaminated with the product and subsequently brought 

back to the hive where larvae may be exposed. Therefore, a non-guideline honeybee larval toxicity 

study is recommended. The registrant should submit a proposed protocol for review and approval 

by EFED prior to initiation of the study.

Practical Utility of the Data 

How will the data be used? 

Data will be used to assess risk to non-target listed and non-listed terrestrial invertebrate species. 

This study would allow the Agency to refine the screening-level hazard assessment for beneficial 

terrestrial invertebrates. The effects data will be used to determine the potential for adverse effects 

on beneficial terrestrial invertebrates through direct effects on larval bees. 

How could the data impact the Agency’s future decision-making? 

EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action 

it authorizes or takes “...is not likely to jeopardize the continued existence of any endangered or 

threatened species or result in the destruction or adverse modification of critical habitat” and “to 

use the best scientific data available” in carrying out this obligation. The data EPA intends to call 

in are necessary to inform the determination required by ESA as to whether continued registration 

of a pesticide is or is not likely to jeopardize the species or its critical habitat. The lack of these 

data will limit the flexibility that the Agency and registrants have in coming into compliance with 

ESA and could result in use restrictions that are unnecessarily severe. 

Study Title: Freshwater Fish Acute Toxicity Test 

Guideline Number: 850.1075 

Test Substance: Degradates IN-KQ960 and IN-W3595 

Rationale for Requiring the Data 

Acute freshwater fish toxicity data are being recommended for two degradates of cymoxanil: 

IN-KQ960 and IN-W3595. 

For cymoxanil degradate IN-KQ960, a freshwater aquatic invertebrate study (850.1010) showed 

that this degradate is 35 times more toxic to Daphnia magna than the parent compound, indicating 

that this degradate is potentially more toxic to other aquatic organisms as well. Additional data 

are recommended to reduce uncertainty in the potential effects of IN-KQ960 on fish. Moreover, 

IN-KQ960 has a similar chemical structure to several other major degradates: IN-R3273, INJX915, IN-T4226, and IN-U3204. Thus, studies carried out on IN-KQ960 could be used to 

interpret potential risk from the other three similarly structured major degradates listed above. 
108 

For cymoxanil degradate IN-W3595, all acute toxicity endpoints predicted by ECOSAR are much 

lower (more toxic) than measured for the parent; therefore additional data are recommended on 

this degradate for freshwater fish. 

Practical Utility of the Data 

How will the data be used? 

These data will be used to assess risk to non-target listed and non-listed freshwater fish species for 

the major cymoxanil degradates IN-KQ960, IN-R3273, IN-JX915, IN-T4226, IN-U3204, and INW3595. Since few data are available on the toxicity of these degradates to particular aquatic taxa, 

information on acute effects of these degradates to freshwater fish would help reduce uncertainty 

as to the effects of cymoxanil degradates on aquatic organisms in general and determine whether 

further testing with other species is warranted. 

How could the data impact the Agency’s future decision-making? 

Submission of additional data on cymoxanil degrade toxicity may eliminate the need of having to 

presume risk of degradates to aquatic organisms in the ecological risk assessment. 

Study Title: Freshwater Invertebrate (Daphnia) Acute Toxicity Test 

Guideline Number: 850.1010 

Test Substance: Degradate IN-W3595 

Rationale for Requiring the Data 

Acute toxicity endpoints predicted by ECOSAR for cymoxanil degradate IN-W3595 are much 

lower (more toxic) than measured for the parent; therefore additional data is recommended on this 

degradate for freshwater invertebrates. 

Practical Utility of the Data 

How will the data be used? 

These data will be used to assess potential risks to non-target listed and non-listed freshwater 

invertebrate species for cymoxanil degradate IN-W3595. Since no data are available on the 

toxicity of this degradate to aquatic taxa, information on acute effects of IN-W3595 to Daphnia 

would help determine if they are of potential ecological concern to aquatic organisms in general 

and perhaps warrant further testing with other species. 

How could the data impact the Agency’s future decision-making? 

Submission of additional data on IN-W3595 toxicity may eliminate the need of having to presume 

risk of this degradate to aquatic organisms in the ecological risk assessment. 

Study Title: Nonvascular Aquatic Plant Toxicity Test (preferably with freshwater diatom, 

Navicula pelliculosa) 

Guideline Number: 850.5400 

Test Substance: Degradates IN-KQ960 and IN-W3595 

Rationale for Requiring the Data 

Nonvascular aquatic plant toxicity data (preferably with N. pelliculosa) are being recommended 

for two degradates of cymoxanil: IN-KQ960 and IN-W3595. 

For cymoxanil degradate IN-KQ960, a freshwater aquatic invertebrate study (850.1010) showed 

that this degradate is 35 times more toxic to D. magna than the parent compound, indicating that 

this degradate is potentially more toxic to other aquatic organisms as well. Additional data are 
109 

recommended to reduce uncertainty in effects of IN-KQ960 to aquatic plants. Moreover, 

IN-KQ960 has a similar chemical structure to several other major degradates: IN-R3273, 

IN-JX915, IN-T4226, and IN-U3204. Thus, studies carried out on IN-KQ960 could be used to 

interpret potential risk from the other three similarly structured major degradates listed above. 

For IN-W3595, all acute toxicity endpoints predicted by ECOSAR are much lower (more toxic) 

than measured for the parent; therefore additional data are recommended on this degradate for 

nonvascular aquatic plants. 

N. pelliculosa is the recommended test species because it is the most sensitive to the parent 

compound. 

Practical Utility of the Data 

How will the data be used? 

These data will be used to assess potential risks to non-target listed and non-listed aquatic plants 

for degradates IN-KQ960, IN-R3273, IN-JX915, IN-T4226, IN-U3204, and IN-W3595. Since few 

data are available on the toxicity of these degradates to particular groups of aquatic organisms, 

information on acute effects of these degradates to at least one aquatic plant species could help 

determine if they are of potential ecological concern to aquatic organisms in general and perhaps 

warrant further testing with other species. Therefore, these data would reduce uncertainty as to the 

effects of cymoxanil degradates on aquatic organisms in general. 

How could the data impact the Agency’s future decision-making? 

Submission of additional data on cymoxanil degrade toxicity could eliminate the need of having to 

presume risk of degradates to aquatic organisms in the ecological risk assessment.