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Environmental Fate and Ecological Risk Assessment for the 

Registration of

Carboxin:

5,6 dihydro-2-methyl-1,4-oxathiin-3-carboxanilide

Prepared by:

R. David Jones, Ph.D., Senior Agronomist

Thomas M. Steeger, Ph.D., Senior Biologist

Environmental Risk Branch 4

 

United States Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch IV

Ariel Rios Building, 1200 Pennsylvania Ave., NW.

Mail Code 7507C

Washington, DC 20004

DP Barcode: D288407, D289830

PC Code: 090201

Reviewed by:

Elizabeth Behl, Branch Chief
090201 D295494 RED (Revised Carboxin).wpd 2

EXECUTIVE SUMMARY

Carboxin is a systemic fungicide used as a seed protectant on a variety of crops. The fungicide

is frequently co-formulated with other fungicides and insecticides to broaden the spectrum of

effectiveness. Carboxin is a mobile compound (Kd = 0.78 L (kg-soil)-1) that degrades rapidly in the

environment; however, its primary degradates, i.e., carboxin sulfoxide and carboxin sulfone, are more

likely to persist. The primary routes of degradation of carboxin are via aerobic soil metabolism (mean

half life (T1⁄2) = 1.25 days) and aqueous photolysis (T1⁄2 = 1.5 hours). 

Carboxin is practically nontoxic to birds (LD50 >2,150 mg kg-1) and mammals (LD50 =2,588 mg

kg-1) on an acute exposure basis; however, chronic exposure can result in reproductive effects in birds

(no observable adverse effect concentration [NOAEC]=70 mg Kg of diet-1) and reduced growth and

survival in mammals (NOAEC = 200 mg kg of diet-1). Carboxin is moderately toxic to freshwater fish

(LC50 = 1.2 mg L-1) and slightly toxic to freshwater invertebrates (LC50 range: 14 - 84 mg L-1) on an acute

exposure basis; however, there are no data available with which to gauge the chronic toxicity of the

fungicide to aquatic animals. Both vascular duckweed (Lemna gibba; IC50 = 0.67 mg L-1) and

nonvascular green algae (Pseudokirchneriella subcapitata IC50 = 0.37 mg L-1) plants appear to be the

most sensitive species tested to carboxin. Since the core structure of the carboxin molecule remains

intact in major degradates, we have assumed, in the absence of data, that the toxicity of degradates is

similar to that of the parent.

At maximum seed application rates across all of the uses evaluated acute risk levels of concern

(RQ $0.5) are exceeded for mammals (RQ range 9 - 92). The chronic risk level of concern (RQ $1.0) is

exceeded for both birds (RQ range: 10 - 107) and mammals (RQ range: 3.5 - 39) exceed the level of

concern for avian chronic risk. Even when based on the lowest observed effect concentration rather than the no

observed effect concentration, avian (RQ range: 1 to 11) and mammalian (RQ range: 1.8 to 19) exceed chronic LOC’s.

While the chronic avian risk is above the level of concern in this screening assessment, risks may be reduced if the

duration of exposure is short as a result of dissipation processes and birds rely on other food sources in untreated areas.

 Additionally, the practice of planting seeds 0.5 to 1-inch deep in the soil reduces exposure, and thus risk. 

Although acute and chronic endangered species levels of concern are exceeded for mammals, only the

Delmarva fox squirrel (Sciurus niger cinereus) is likely to be impacted since its diet consists primarily of seeds and it

may occur near field crops in Delaware, Maryland and Virginia.

Although aquatic animals were more sensitive to the effects of carboxin than terrestrial animals,

no acute risk LOC’s are exceeded based on estimated environmental concentrations. The potential for

chronic risk could not be evaluated since no chronic toxicity data were available for review. 

Drinking water estimated environmental concentrations (EEC) were developed using screening

level models, FIRST and SCIGROW for the crop with the maximum seed application rate. The acute

surface water EEC (total residue of carboxin plus the sulfoxide degradate) is 29.6 μg L-1; the chronic is

0.63 μg L-1. The ground water EEC’s are 0.09 μg L-1 for both acute and chronic. We are not aware of any

monitoring data for carboxin or degradates.
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TABLE OF CONTENTS

EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Use Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

ENVIRONMENTAL FATE ASSESSMENT ....................................................... 7

Aqueous Photolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Soil Photolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Aerobic soil metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Anaerobic soil metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Aerobic aquatic metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Anaerobic aquatic metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Soil column leaching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Batch equilibrium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Terrestrial Field Dissipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

DRINKING WATER EXPOSURE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

AQUATIC EXPOSURE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

TERRESTRIAL EXPOSURE ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

ECOLOGICAL EFFECTS ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

ECOLOGICAL RISK ASSESSMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Terrestrial Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Birds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Mammals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Aquatic Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Aquatic Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Aquatic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

RISK CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Endocrine Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Endangered Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

LITERATURE CITED . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

APPENDIX I. USE CLOSURE MEMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Rotational Crop Restrictions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Crops/Formulations/Use Sites Not Being Supported . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

APPENDIX II. GENEEC 2 MODEL OUTPUT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
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APPENDIX III. ECOLOGICAL TOXICITY DATA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Toxicity to Terrestrial Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Acute and Subacute Toxicity to Birds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Chronic Toxicity to Birds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Acute and Chronic Toxicity to Mammals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Toxicity to Insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Toxicity to Freshwater Aquatic Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Acute Toxicity to Freshwater Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Chronic Toxicity to Freshwater Fish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Acute Toxicity to Freshwater Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Chronic Toxicity to Freshwater Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Toxicity to Estuarine and Marine Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Acute and Chronic Toxicity to Estuarine and Marine Fish . . . . . . . . . . . . . . . . . . . . . . . . . 46

Acute Toxicity to Estuarine and Marine Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Chronic Toxicity to Estuarine and Marine Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Toxicity to Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Toxicity to Terrestrial Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Toxicity to Aquatic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

APPENDIX IV . EXPOSURE AND RISK TO NONTARGET ANIMALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

APPENDIX V. SEEDING RATES FOR ASSESSED CROPS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
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INTRODUCTION

Carboxin, (IUPAC: 5,6 dihydro-2-methyl-1,4-oxathiin-3-carboxanilide; CAS: 5,6-dihydro-2-methyl-Nphenyl-1,4-oxathiin-3-carboximide), is a systemic fungicide belonging to both the anilide and oxathiin class

fungicides and is used as a seed protectant on a variety of crops (Table 1). Carboxin’s primary site of action

is in the mitochondria where the chemical inhibits the succinate-ubiquinone oxidoreductase system of the

mitochondrial electron transfer chain (Schewe and Lyr 1987). According to the use closure memo (Appendix

I), carboxin is predominately used as a cereal seed treatment for systemic control of smut (Ustilago spp.) and

bunt diseases. Carboxin is frequently co-formulated with contact fungicides such as thiram, captan and

pentachloronitrobenzene (PCNB) to control a broader spectrum of fungal pests (Rhizoctonia, Rhizopus,

Helminthosporium, Fusarium and Penicillium) such as in Vitavax® (carboxin 10%, captan 45% and PCNB

15%). Carboxin is also formulated with other fungicides in combination with insecticides such as in Vitavax

Thiram Lindane® (carboxin 14%, thiram 12%, lindane 8%).

Use Characterization

Carboxin is registered for commercial use as a seed protectant fungicide on a variety of crops

(Table 1). The application rate onto the field depends both on the application rate to the seed, and the seeding

rate. According to the use closure memo, the highest registered application rate is on beans which have a

seeding rate of 120 to 160 lbs. seed/acre which is corresponds to 0.051 to 0.167 lbs active ingredient (a.i.)/acre.

However, EFED’s assessment of the current maximum labeled rates (Table 2) indicates that peanuts have the

highest application rate with at seeding rate of 135 lbs. seed/acre treated 0.06 lb carboxin per 100 lb of seed

which is equivalent to 0.380 lbs a.i./acre. Peanuts also represent the largest total poundage of seeds ranging

from 96.8 to 121 million pounds. On average, maximum equivalent (lbs a.i./acre) application rates reported in

the use closure memo were 28% lower (range -11% to 84% lower) than those projected in EFED’s analysis. The

discrepancy between maximum equivalent application rates results from EFED’s use of maximum reported

seeding rates (APPENDIX V), which the Special Review and Reregistration Division (SRRD) has agreed are

accurate. 

Carboxin is applied in both a liquid flowable and a dust formulation as a seed treatment with most of

the seed crops subsequently incorporated into the soil. According to the use closure memo, carboxin-treated

seed is generally applied once per growing season. Since treated seeds do not flow as freely as untreated

seeds, the label recommends that drills be adjusted accordingly to compensate for restricted seed flow to

prevent lower than desired seeding rates. For a few small seeded crops such as rape and canola, the seed may

not be buried, but broadcast on the surface and then worked into the surface using a drag chain.
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Table 1. Commercial seed application rates and equivalent application rates of carboxin by crop.

Crop Range of Seed Application Rates

lbs seed/acre

Equivalent

lbs a.i./acre

Barley 50 - 80 0.0179 - 0.063

Bean 120 - 160 0.051 - 0.167

Canola 4 - 8 0.0037 - 0.0075

Corn 11 - 25 0.005 - 0.031

Cotton 10 - 18 0.0066 - 0.038

Oats 48 - 128 0.0173 - 0.1002

Onion 1 - 15 0.0075 - 0.1125

Peanuts 90 - 120 0.023 - 0.0815

Rice 67 - 160 0.0201 - 0.096

Rye 75 - 150 0.029 - 0.078

Safflower 20 - 100 0.010 - 0.052

Sorghum 5 - 8 --

Soybeans 50 - 85 0.021 - 0.0887

Triticale 70 - 90 0.022 - 0.070

Wheat 45 - 120 0.0162 - 0.0939
090201 D295494 RED (Revised Carboxin).wpd 7

Table 2. Maximum application rates for carboxin based on current labels and U.S. Department of

Agriculture crop profiles.

Crop Maximum Seed Application Rates

lbs seed/acre

Equivalent

lbs a.i./acre

Barley 100 0.141

Bean 160 0.15

Canola 8 0.008

Corn 25 0.034

Cotton 18 0.068

Oats 128 0.213

Onion 15 0.113

Peanuts 135 0.380

Rape 8 0.008

Rice 160 0.12

Soybeans 100 0.094

Triticale

90 0.063

Wheat 135 0.190

ENVIRONMENTAL FATE ASSESSMENT

 Carboxin is mobile compound that degrades rapidly in the environment. However, the primary

metabolites formed, carboxin sulfoxide and carboxin sulfone, tend to be much more persistent than the parent

and may have similar pesticidal activity. 

Carboxin parent degrades rapidly in soil by aerobic metabolism with a mean half-life from two studies

of 1.25 days. Carboxin degraded much more slowly in anaerobic soil with a half-life of 128 days. In both aerobic

and anaerobic soil studies, the predominant degradate was carboxin sulfoxide (Figure 1). The degradates were

otherwise similar , except that "-vinyl sulfinyl acetanilide (Figure 2) is an additional degradate in the

anaerobic soil metabolism study. There was no evidence of degradation by hydrolysis at any pH. Aqueous

photolysis is rapid with a half-life of 1.5 hours under a xenon arc lamp. A submitted soil photolysis study could

not be interpreted. Photolysis is not expected to be a major route of dissipation in the field as planted seed is

generally buried some depth below the surface, but may contribute to dissipation after it has entered surface

water bodies. Degradation in the anaerobic phase of the anaerobic soil metabolism was much slower with a

mean degradation half-life from two studies of 129 days. While a definitive statement cannot be made, there

is some evidence that carboxin may degrade by direct oxidation in aqueous systems when dissolved oxygen

is present. Limited information on aquatic metabolism show slower degradation rates anaerobically (245 days)

than aerobically (31 days). Interestingly, in two anaerobic soil metabolism studies conducted for carboxin

sulfoxide the major degradate formed was carboxin, indicating that thus carboxin can reform from the

sulfoxide under anaerobic conditions. Maximum degradate concentrations for all major degradates in each of

the degradation studies are found in Table 3.

Table 3. Maximum degradate amounts as a fraction of the nominal parent applied in laboratory

degradation studies for carboxin. The duration of the study is in parentheses next to the study name.
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Study Degradate

A BCDEF

Hydrolysis (30 d) – – – – – –

Aqueous Photolysis (8 h) 20.4 – – 54.9 – –

Aerobic Soil Metabolism (48 d) 59.9 – – – – –

Anaerobic Soil Metabolism (60 d) 30.8 4.9 10.0 – 13.9 –

Aerobic Aquatic Metabolism (30 d) 16.4 0.6 – – – 17.1

Anaerobic Aquatic Metabolism (30 d) 12.9 0.8 – – – 10.6

A: carboxin sulfoxide

B: carboxin sulfone

C: "-vinyl sulfinyl acetanilide

D: oxo (phenylamino) acetic acid

E: 2,3-dihydro-5-carboxy-6-methyl-1,4-oxathiin

F: S-[2-(acetyloxy)-ethyl]-2-oxo-2-(phenylamino)ethanethioate
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Figure 1. Carboxin sulfoxide

Figure 2. "-vinyl sulfinyl acetanilide
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 Carboxin is very mobile. A single measured Fruendlich partition coefficient (Kf) in a Manchester sandy loam

with 1.89% organic matter content was 0.78 with a curvature term (1/n) of 0.93 indicating that the isotherm was fairly

linear. This data is consistent with several aged soil column leaching studies that showed substantial leaching. Greater

than 40% applied radioactivity of carboxin and degradates was eluted from a 12 inch column by somewhat less than four

void volumes of water, thus the parent is unlikely to be a substantial groundwater threat because of the rapid aerobic

degradation rate in soil. However, carboxin sulfoxide, which is substantially more persistent than the parent and is also

mobile, as shown in the aged column leaching study, may, in fact, reach groundwater. A summary table of the

environmental fate data is Table 4.

Table 4. Environmental fate data for carboxin.

Parameter Value Source

CAS Number 5234-68-4

Molecular Mass 235.3 g @mol-1 One-liner

Aerobic Soil Metabolism Half-life 1.24 d

1.26 d

parent + sulfoxide: 23 d

MRID’s 41242503

41242504, 41252501

Anaerobic Soil Metabolism Half-life 146 d

114 d

MRID’s 41224507, 41286601, 41224508,

41314303, and 41725501

Aerobic Aquatic Metabolism Half-life 34.4 d

parent + sulfoxide: 31.2 d

42600801

Anaerobic Aquatic Metabolism Half-life 239 d

parent + sulfoxide: 250 d

42600803

Kf 0.78 MRID 00005541

Solubility in water 195 mg L-1 at 7°C EFED One-liner

Vapor Pressure 1.8 x 10-7 torr EFED One-liner

Henry's Law Constant (calculated) 2.86 x 10 -10 atm. @m3 @mol-1 EFED One-liner

Hydrolysis half life at pH 5 parent: stable

sulfone: stable (pH 3)

Acc. No. 254339

Hydrolysis half-life at pH 7 parent: stable

sulfone: 36 d (pH 6)

Acc. No. 254339

Hydrolysis half-life at pH 9 parent: stable

sulfone: < 4 h (pH 9)

Acc. No. 254339

Aqueous Photolysis Half-life 1.54 h MRID 42192801

Soil Photolysis Constant not available
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Aqueous Photolysis

A supplemental aqueous photolysis study showed that carboxin degraded with a half-life of 1.54 hours as

estimated by linear regression on log transformed concentration data, when irradiated under a xenon arc lamp at 25° C.

Twelve degradates were isolated of which two were identified, oxo(phenyl amino) acetic acid (Figure 4), reached 54.9%

of the applied at 8 hours of irradiation, which was the end of the study. Carboxin sulfoxide reached a maximum of 20.4%

of the applied at 7 hours and then decreased. None of the unidentified degradates exceeded 10% of the applied. There

was no pattern of degradation observed in the dark control. 

Soil Photolysis

Data submitted to fulfill this data requirement were not interpretable because of anomalies in the dark

controls (MRID 41992101) as the concentration of parent carboxin increased during the experiment. However,

as noted above, soil photolysis should not be a significant route of dissipation of for a seed treatment and the

absence of the data does not impact the risk assessment. If the registrant wished to pursue uses other than

seed treatments, an acceptable soil photolysis study will need to be submitted. 

Hydrolysis

Carboxin is stable to hydrolysis at pH’s 5, 7, and 9. (Acc. No. 254339), Carboxin sulfone degrades slowly

or not at all at pH 3, but degrades with a half-life of 36 days at pH 6 and less than 4 hours at pH 9. The primary

degradate at both pH’s 6 and 9 was 3-oxo-N-phenyl-thiomorpholine-1,1-dioxide with a peak of 49.3 percent of

the applied at pH 6 on day 72, and 74.9% for pH 9 on day 1. The data requirement is satisfied.

Aerobic soil metabolism

Two studies, reported in three documents, (MRID’s 41252501, 41224503, 41242504) describe the

degradation of carboxin under aerobic conditions in the soil. Both studies were conducted at 25° C and a

moisture content of 75% of 1/3 bar. Carboxin which was radiolabeled on the aniline ring degraded with a halflife of 1.26 d, with 95% confidence bounds at 1.01 and 1.68 days estimated by linear regression. Oxathiin-labeled

carboxin degraded with a half-life of 1.24 d (95% CI: 1.10-1.41 d). Both studies were conducted in an unidentified

sandy loam soil. The primary degradate was carboxin sulfoxide which reached a maximum of 51.6% of the

applied in the first study and 59.7% in the second study. In both cases the maximum was reached at the study

termination at 48 d. Less than 2% of the radioactivity was mineralized to carbon dioxide at the end of the

studies. Fifteen to seventeen percent of radioactivity was unidentified material bound to the soil at the end of

the studies. A linear regression for a first order decay model was used on the sum of carboxin and carboxin

sulfoxide. While there appeared to have been a decrease in the sum in the aniline labeled study, the linear

regression was not significant. A half-life of 23 days was estimated for the sum for the oxathiin labeled study

with 95% confidence bounds of 12 to 742 days. The wide confidence bound is an indication that the first order

model did not describe the degradation of the sum particularly well.

There were also two studies (MRID’s 41224501, 41224502) that looked at degradation of the

degradation of carboxin sulfoxide directly. In both cases, the studies were conducted in an unidentified sandy

loam soil. In the aniline-ring labeled study, carboxin sulfoxide degraded with a half-life of 92 days while in the

oxathiin-ring labeled study the half-life was 82 days. Both studies were conducted at 25° C and a moisture

content of 75% of 1/3 bar. The primary degradate in both studies was carboxin sulfone with a maximum amount

of 15.2% of the applied radioactivity found in the aniline-labeled study and 14.4% in the oxathiin-labeled study,

in both cases at 120 days which was at the termination of the study. Carbon dioxide was also found at

maximum at the end of the study with 10.2 and 8.2% of the applied in the aniline and oxathiin labeled studies
090201 D295494 RED (Revised Carboxin).wpd 12

respectively. A substantial amount of material was unidentified bound residue at 120 d, 34.5% in the aniline

labeled study and 26.7% in the oxathiin labeled study.

Anaerobic soil metabolism

This study is necessary to support the rice use of carboxin. Two studies describe the degradation of

carboxin in soil under anaerobic conditions. ( MRID’s 41224507, 41286601, 41224508, 41314303, and 41725501).

Both studies were conducted in an unidentified sandy loam at 25° C and followed the EPA guideline for

anaerobic soil metabolism studies. In the study in which the aniline ring was labeled, carboxin degraded with

a half-life of 146 days with a 95% confidence limits ranging from 106 to 232 days. In the oxathiin ring labeled

study, the half life was 114 days with 95% confidence interval from 83 to 181 days. There were two major

degradates, carboxin sulfoxide which was 30.7% of the applied radioactivity at the initiation of anaerobic

conditions in the aniline labeled study and decreased to 9.4% at 60 days which was the conclusion of the study.

In the oxathiin labeled study, the sulfoxide was 30.8% of the applied at the start of anaerobic conditions and

decreased to 8.9 percent at the conclusion of the study. One other degradate exceeded 10% of the applied, 2,3-

dihydro-5-carboxy-6-methyl-1,4-oxathiin was at 13% of the applied radioactivity at 60 days in the oxathiin

labeled study. Carboxin sulfone was a minor degradate peaking 4.9% of the applied at 31days in the aniline

labeled study and 1.7% at 31 days in the oxathiin labeled study.

Two anaerobic soil metabolism studies were conducted for carboxin sulfoxide as well. Both were

conducted under the same conditions as for the parent, with one aniline-ring radiolabeled and one oxathiin-ring

radiolabeled. These aniline-labeled degraded with a half-life of 29 days while the oxathiin-ring labeled study

had a 30.9 day half-life. Surprisingly, the major degradate formed in both studies was carboxin which 38% and

36% of the applied in the aniline- and oxathiin-ring labeled studies respectively at the conclusion of the study,

thus carboxin can reform from the sulfoxide under anaerobic conditions. Carboxin sulfone also formed but did

not exceed 10% of the applied in either study. There were up to nine unidentified compounds representing up

to 3.4% of the radioactivity on an individual basis formed in the two studies.

Aerobic aquatic metabolism

Carboxin degraded with a half-life of 34.4 days in flooded silt loam soil that was incubated in the dark

at 25° C under aerobic conditions (42600801). A 95% confidence interval for the half-life ranges from 26 to 50

days. The major degradates were carboxin sulfoxide which peaked at 16.4% of the applied radioactivity one

day after treatment and S-[2-(acetyloxy)-ethyl]-2-oxo-2-(phenylamino)ethanethioate (Figure 5). Identified minor

degradates were carboxin sulfone, –phenyl-1-hydroxy-[2-[2-[1-hydroxypropanoxy] ethylthio]] acetamide,

–phenyl-1-hydroxy-[2-[2-propanoxy]ethyl]thioacetamide, and CO2. The last two metabolites were tracked

during the course of the study as single values because they co-eluted in TLC. Nine minor metabolites could

not be identified.

For the purposes of modeling for risk assessment, the half-life for the sum of carboxin plus carboxin

sulfoxide was estimated using linear regression. The sum degraded with a half-life of 31.2 days in a flooded

silt loam soil from Mississippi under aerobic conditions which is 3 days shorter than the half-life of parent. The

reason for the apparent decrease in half-life for the sum is the noisy nature of the data. This result is not

unexpected given that there is a redox gradient with some anaerobic conditions in the sediment. Hence, the

carboxin sulfoxide would be converting back to carboxin the sediment, a sort of pseudo-equilibrium state. This

would result in the half-life of the sum being approximately the same as for the parent alone.
090201 D295494 RED (Revised Carboxin).wpd 13

Figure 3. S[2-acetyloxy)ethyl]-2-oxo-2-

(phenylamino)ethanethioate.

Anaerobic aquatic metabolism

Carboxin degraded with a half-life of 239 days in flooded silt loam soil that was incubated in the dark

at 25 C under anaerobic conditions (MRID 42600803). A 95% confidence interval for the half-life ranges from

128 to 388 days. The major degradates were carboxin sulfoxide and S-[2-(acetyloxy)-ethyl]-2-oxo-2-

(phenylamino)ethanethioate (Figure 3). Identified minor degradates were carboxin sulfone, –phenyl-1-hydroxy-

[2-[2-[1-hydroxypropanoxy]ethylthio]] acetamide; –phenyl-1-hydroxy-[2-[2-propanoxy]ethyl]thioacetamide;

2,3 dihydro-5-carboxy-6-methyl-1,4-oxathiin; 2,3 dihydro-5-carboxy-6-methyl-1,4-oxathiin-4-oxide, and CO2.

There were 12 minor degradates that were not identified. None exceeded 5% of the nominal concentration of

the parent at any point during the study. In addition a small amount of radioactivity was found at the origin.

For modeling purposes to support risk assessment, the half-life for the sum of the parent plus carbon sulfoxide

was estimated by linear regression. The sum of carboxin plus carboxin sulfoxide degraded with a half-life of

250 days.

Soil column leaching

Twenty inches of water was eluted through a 12 inch column of a clay loam soil (MRID 00003227).

Fifty-two percent of the applied radioactivity and 41% of the applied carboxin were found in the leachate.

Thirty-eight percent of the radioactivity remained in the column with ten percent of the radioactivity could not

be accounted for at the end of the study. This study indicates that carboxin is highly mobile.

An aged soil column leaching study conducted on a Willston sand (MRID 0003229) had 17% of the

applied radioactivity leach through a 12 inch column with 22.5 inches of water with 0.5 inches of water applied

each day for 45 days. The column was aged for 33 days prior to the initiation of leaching. Carboxin, carboxin

sulfoxide and carboxin sulfone were found in the leachate at 0.3, 3.3 and 0.5% of the applied respectively. The

remainder of the radioactivity in the leachate was not identified. Of the remaining radioactivity about one third

was found in the top three inches of the column and 60% was found in the top 6 inches. This study indicates

that the degradates also are mobile and have the potential to leach.

Batch equilibrium

Carboxin adsorption and desorption isotherms were estimated in a Manchester sandy loam (MRID

00005541). An adsorption Fruendlich coefficient of 0.78 with a 1/n value of 0.93 was estimated from the

adsorption data using linear regression on log transformed data. The desorption isotherm had an estimate

Fruendlich coefficient of 1.1 with 1/n of 0.94. The organic carbon content was 1.09%, so a point estimate of the

Koc can be made as 71 L (kg-OC)-1. It cannot be determined whether there is actually a relationship between

carboxin binding to soil and organic carbon as there is only a single estimate of the isotherm 

available.
090201 D295494 RED (Revised Carboxin).wpd 14

Terrestrial Field Dissipation

Uncharacterized carboxin residues dissipated with a half-life of 14 days from the top 6 inches of a

sandy loam soil in Donalsonville, GA after the second of two 1.5 lb acre-1 applications (41259401-A). Carboxin

did not appear to leach below 6 inches. The study could not be used to characterize degradates as a common

moiety method was used to convert all residues to aniline for analysis. 

DRINKING WATER EXPOSURE ASSESSMENT

The drinking water assessment uses the FQPA (Food Quality Protection Act) Index Reservoir

Screening Tool (FIRST) model for estimating the upper bound on the concentrations that could occur in

surface-water-source drinking water, and Screening Concentration in Ground Water (SCIGROW) model to

estimate the concentrations in ground water used for drinking. Output from both models is contained in Table

5. There are no monitoring data for carboxin in water resources so monitoring data are not considered in this

assessment. The use pattern assessed was peanuts, as this is the crop which receives the highest application

rate, a single application of 0.375 lb acre-1.

Table 5. Tier 1 EEC's for carboxin on peanuts for surface water and ground water as estimated by

FIRST and SCIGROW respectively.

Source Acute Chronic Cancer

Surface Water 29.6 :g @L-1 0.63 :g @L-1 0.63 :g @L-1

Ground Water 0.0947 :g @L-1 0.0947 :g @L-1 0.0947 :g @L-1

FIRST is a screening model of the Office of Pesticide Programs to estimate the concentrations found

in drinking water from surface water sources for use in human health risk assessment (EFED, 2001a). As

such, it provides upper bound values on the concentrations that might be found in drinking water due to the

use of a pesticide. It was designed to be simple to use and to only require data which are typically available

early in the pesticide registration process. FIRST is a single event model (one runoff event), but can account

for spray drift from multiple applications. FIRST is hardwired to represent the Index Reservoir, a standard

water body used by the Office of Pesticide Programs to assess drinking water exposure (Hetrick et al, 1998).

It is based on an actual reservoir located in Illinois; the model reservoir is known to be vulnerable to pesticide

contamination. The single runoff event moves a maximum of 8% of the applied pesticide into the reservoir. This

amount can be reduced due to degradation on the field and the effects of binding to soil in the field. 

SCIGROW (EFED, 2001b) is a regression model used as a screening tool for ground water used as

drinking water. SCIGROW was developed by regressing the results of Prospective Ground Water studies

against the Relative Index of Leaching Potential (RILP). The RILP is function of aerobic soil metabolism and

the soil-water partition coefficient. The output of SCIGROW (Table 5) represents the concentrations that might

be expected in shallow unconfined aquifers under sandy soils.

Table 6. FIRST and GENEEC2 input parameters for carboxin. Metabolism reflect the combined

degradation of parent carboxin and carboxin sulfoxide.
090201 D295494 RED (Revised Carboxin).wpd 15

Chemical carboxin

Solubility 195 mg L-1 at 7°C

Hydrolysis stable

Photolysis 0.064 d 

Aerobic Soil Metabolism T1/2 = 71.2 d; rate for sum of carboxin + carboxin sulfoxide, single study

Aerobic Aquatic Metabolism T1/2 = 93.6 d; rate for sum of carboxin + carboxin sulfoxide, single study

Soil Water Partitioning (Kd) Kd: 0.78 L (kg-soil)-1;

The chemistry input values for FIRST and GENEEC2 are listed in Table 6 and for SCIGROW in Table

7. The metabolism values represent those for first-order degradation model fit to the sum of the carboxin and

carboxin sulfoxide concentrations using linear regression on log-transformed data. This was not done for

aqueous photolysis as there was little carboxin sulfoxide formed in the study. The aerobic soil metabolism

value of 23.9 d is an estimate from a single study. This value was used directly in SCIGROW and multiplied

by three to account for the uncertainty due to the single measurement for FIRST. FIRST assumes a percent

cropped area adjustment factor (PCA) of 0.87, as a default. The partition coefficient is also from a single study

(Smyser, 1979). No information was available on the binding potential, i.e. partition coefficient (Kd) of the soil,

of carboxin sulfoxide, so the value for carboxin was used to represent both. The organic carbon partition

coefficient (Koc) value for SCIGROW was estimated from the Kd by dividing by the organic carbon content in the

original study.

Table 7. SCIGROW input parameters for carboxin.

Aerobic soil metabolism half-life 23.9 days

Soil Water Partition Coefficient (Koc) 71 L (kg-OC)-1

The use pattern selected to generate the recommended EEC’s was for the seed treatment on peanuts

from the Vitavax® label (Reg. No.400-106) as this is the use pattern expected to generate the largest EEC’s

(Table 8). 

Table 8. Carboxin maximum use practices for peanuts.

Crop Registration

Number Product Application

Rate to Seed Seeding Rate Application

Rate Per Acre

Incorporation

Depth (cm)

peanuts 400-106 Vitavax .28 lb/100 lb seed 135 lb acre-1 0.37 lb acre-1 1 cm

Both FIRST and SCIGROW are screening models. This means that when the output value does not

exceed the level of concern, there can be reasonable certainty that the consumption of the compound in

drinking water poses little or no risk to human health. Conversely, when the level of concern is exceeded, it

could be either that the EEC’s are greater than those actually seen in the environment or that the risks from

the compound are actually greater than the level of concern. However, at this tier, it is not possible to

distinguish the two cases. Generally exceedances of the risk thresholds with two models will result in a further

refinement of the drinking water exposure by more sophisticated modeling approaches, monitoring data, field

studies, or some combination of these. 

There is currently no direct information on the removal of carboxin from water during drinking water

treatment. Because carboxin is stable to hydrolysis, processes which alter pH like softening, will not impact

the concentration in water. The low partition coefficients suggest that it will not be removed easily by

flocculation and sedimentation.
090201 D295494 RED (Revised Carboxin).wpd 16

AQUATIC EXPOSURE ASSESSMENT

A screening aquatic risk assessment was conducted using Generic Estimated Environmental

Concentration (GENEEC) model to estimate the aquatic exposure (Parker et al., 1995) GENEEC is a

metamodel of PRZM and EXAMS which are used in tandem by the Office of Pesticide Programs to estimate

exposure at Tier 2. GENEEC is a screening model used to estimate the concentrations found in water for use in

ecological risk assessment. As such, it provides upper bound values on the concentrations that might be found

in the ecologically sensitive environments due to the use of a pesticide. It was designed to be simple to use and

to only require data which is typically available early in the pesticide registration process. GENEEC is a single

event model (one runoff event), but can account for spray drift from multiple applications. GENEEC is

hardwired to represent a 10-ha field immediately adjacent to a 1-ha pond, 2-m deep with no outlet. The pond

receives a spray drift event from each application plus one runoff event. The runoff event moves a maximum

of 10% of the applied pesticide into the pond. This amount can be reduced due to degradation on the field and

the effects of binding to soil in the field. The version of GENEEC used is 2.0 dated May 1, 2001.

The chemistry input parameters for carboxin are listed in Table 6. Chemistry input parameters were generated

according to current guidance for model parameter estimates (USEPA, 2002). The aerobic soil metabolism input

represents three times a single value and was estimated by linear regression on the sum of carboxin and carboxin

sulfoxide. Two studies were available, but a first order model was not statistically significant for one of the studies, so

it provided no basis for estimating a half-life. The input parameter of aerobic aquatic metabolism also was estimated

by multiplying the single value by three as only a single study was available. Multiplying the single value by three

protects against uncertainty in the half-life estimate and is intended to approximate an upper 90% confidence bound on

the mean. Metabolism values are highly variable, and there is a substantial chance in overestimating the degradation

significantly when only a single value is available. Table 9 contains peak and 21-day average estimated pond water

concentrations of carboxin; output from GENEEC for major carboxin seed treatments can be found in Appendix II.

Table 9. GENEEC model estimated carboxin concentrations in surface water.

Crop Peak

μg/L

21-day Average

μg/L

Barley 6.95 4.32

Bean 7.39 4.60

Canola 2.27 1.41

Corn 1.68 1.04

Cotton 1.87 1.17

Oats 10.49 6.53

Onion 5.57 3.46

Peanuts 18.72 11.65

Rape 2.27 1.41

Rice 5.91 3.68

Soybean 4.63 2.88

Triticale 3.10 1.93

Wheat 9.36 5.83
090201 D295494 RED (Revised Carboxin).wpd 17

TERRESTRIAL EXPOSURE ASSESSMENT

Birds and mammals in the field may be exposed to seed treated with pesticides by ingesting material directly

with the diet. They also may be exposed by other routes, such as incidental ingestion of contaminated soil, dermal contact

with treated seed surfaces and soil during activities in the treated areas, preening activities, inhalation of pesticide vapor

and contaminated particulate, and ingestion of drinking water contaminated with pesticide. In this assessment, only

ingestion of the treated seed was considered.

For the purposes of this assessment, terrestrial estimated environmental concentrations and subsequent risk acute

risk quotient values have been calculated in two different ways. The first way looks at the dietary dose assuming that

an organism has been eating only treated seed. This approach uses the acute oral toxicity for the toxicity endpoint

(LD50). The second method also uses the acute oral dose for toxicity and compares it to the available concentration of

pesticide on the basis of pesticide per square foot. The first and approach assumes that the carboxin is localized around

the seed coat and, hence, similar to a granular formulation. 

ECOLOGICAL EFFECTS ASSESSMENT

Toxicity testing reported in this section does not represent all species of bird, mammal, or aquatic organism.

Only a few surrogate species for both freshwater fish and birds are used to represent all freshwater fish (2000+) and bird

(680+) species in the United States. For mammals, acute studies are usually limited to Norway rat or the house mouse.

Estuarine/marine testing is usually limited to a crustacean, a mollusc, and a fish. Also, neither reptiles nor amphibians

are tested. The assessment of risk or hazard makes the assumption that avian and reptilian toxicities are similar. The

same assumption is used for fish and amphibians. 

Appendix III summarizes the ecological toxicity studies of technical grade (purity >90%) carboxin: 70% were

classified as core and as having complied with guideline recommendations. The remaining studies (30%) were classified

as supplemental. Although supplemental studies did not completely comply with guideline recommendations, they do

provide information useful in characterizing the ecological effects of carboxin.

Based on the ecological effect studies, carboxin is practically nontoxic to terrestrial animals (Table 10) and

ranges from moderately to slightly toxic to aquatic animals (Table 11) on an acute exposure basis. No data were

available to gauge the acute toxicity of carboxin to estuarine/marine fish. Following chronic exposure, mallard ducks

(Anas platyrhynchos) exhibited reductions in the number of eggs laid, viable embryos, live 3-week embryos, normal

hatchlings and 14-day survivors at 700 mg kg-1 d-1. Chronic exposure to rats (Rattus norvegicus) resulted in reduced

growth (decreased body weight) of offspring. No chronic toxicity data were available for aquatic animals. 

Similar to technical grade carboxin, the formulated products Vitavax 75 W (38.7% carboxin plus 37.5% thiram)

and Vitavax SP 38.7% carboxin plus 37.5% captan) were practically nontoxic to bobwhite quail with acute oral LD50

values of 2,410 mg kg-1 and greater than 10,000 mg kg-1, respectively. Additionally, subacute dietary toxicity testing

with Vitavax SP in bobwhite quail (LC50 >5,620 mg kg-1 of diet) and mallard ducks (LC50 >4,640 mg kg-1 f diet) indicated

that the formulated product was practically nontoxic to birds.

Table 12 summarizes toxicity data on aquatic plants; both vascular (Lemna gibba) and nonvascular

(Pseudokirchneriella subcapitata) plants were relatively sensitive to carboxin with EC50 values of 0.67 and 0.37 mg L-1,

respectively. No data were available on which to gauge either terrestrial or semiaquatic plant phytotoxicity 
090201 D295494 RED (Revised Carboxin).wpd 18

Table 10 . Summary of acute and chronic toxicity data for terrestrial organisms exposed to carboxin.

Species

Acute Toxicity Chronic Toxicity

LD50

(ppm)

Acute Oral

Toxicity

(MRID)

5-day

LC50

(ppm)

Subacute Dietary

Toxicity

(MRID)

NOAEC/LOAEC

(ppm)

(MRID)

Affected

Endpoints

Bobwhite quail

(Colinus virginicus) >2,150

practically

nontoxic

(435823-01)

>4,110 practically nontoxic

(435823-03) -- --

Mallard duck

(Anas platyrhynchos) 6094 -- -- -- 70 / 700

reduced

numbers of

eggs hatched,

reduced

survival

Honey bee

(Apis meliferus) 2 μg/bee

practically

nontoxic

(no MRID)

-- -- -- --

Laboratory rat

(Rattus norvegicus) 2,588

practically

nontoxic

(431714-01)

-- -- 200 / 300 reduced growth

nephrititis

Table 11. Summary of acute aquatic animal toxicity estimates using technical grade carboxin.

Species

Acute Toxicity Chronic Toxicity

96-hr LC50

(mg/L)

48-hr EC50

(mg/L)

Acute Toxicity

(MRID)

NOAEC /

LOAEC

(mg/L)

Affected Endpoints

(MRID)

Bluegill sunfish

(Lepomis macrochirus) 1.2 -- moderately toxic(224935) -- --

Water flea

(Daphnia magna) -- 84.4 slightly toxic(235236) -- --

Pink shrimp

(Panaeus duorarum) 14 -- slightly toxic(165048A) -- --

Table 12. Summary of acute phytotoxicity data for aquatic plants exposed to carboxin.

Species

Acute Toxicity

96-hr LC50

(mg/L)

Acute Toxicity

(MRID)

Duckweed

(Lemna gibba) 0.67 (414938-02)

Green algae

(Pseudokirchneriella subcapitata) 0.37 (414938-01)
090201 D295494 RED (Revised Carboxin).wpd 19

F

BW

W = −

0 648

1

0 651 . *

( )

.

Adj LD LD AW

TW .

(1. )

50 50

15 1

= 



 





−

ECOLOGICAL RISK ASSESSMENT

Terrestrial Animals

Birds

For the first type of assessment, for screening purposes we just consider the smallest birds that eat seeds, which

weigh about 20 g. Small birds tend to eat more per unit body weight, so they will be the most vulnerable. Exposure is

estimated from the concentration of carboxin on treated seed. For example, the maximum application rate to peanuts (0.38

lbs a.i. per 135 lbs seed) is equivalent to 2,815 (mg a.i.) kg-1 of seed. Using daily food intake as estimated by Nagy

(1987), a 20 g bird will consume about 5.1 g of food based on the allometric equation:

where F is the food intake in grams of fresh weight, BW is the body mass of the organism, and W is the mass fraction of

water in the food. For this assessment W is assumed to be 0.1. This results in a dose of carboxin of 14.4 mg a.i. day-1 (5.1

g seed day-1* 0.001 kg g-1 * 2,815 mg a.i. kg-1 ). In addition, extrapolations from one bird to another need to consider

differences the scaling of toxicity for difference in body weight. The LD50 can be adjusted for body weight based on the

formula recommended by Mineau et al. 1996:

where adjusted LD50 is the median 50% lethal dose for the species being assessed, LD50 is the median lethal dose in the

test organism, AW is the body weight of the assessed organism and TW is the body weight for the test organism. Since

we are assessing a small songbird, 20 g is a suitable value for AW. The test organism is a sub-adult mallard weighing

about 2000 g. With a test LD50 of 6094 mg kg-1, the adjusted LD50 is 3054 mg kg-1. The risk quotient for peanuts is then

4.7 x 10-3 (14.4 mg ÷ 3054 mg) which is, along with all of the other uses evaluated, well below all acute levels of concern

for endangered species (RQ $ 0.1).

For the second type of assessment, it is assumed that 100% of the seed is available for consumption. This is

reasonable as the seed is tiny and is not planted deeply, a half-inch deep at most. Seed can either planted by drill, or

broadcast followed by a drag chain. With either method it will be near the surface and generally available to wildlife. The

amount of carboxin available is then the seed application rate of 135 lbs of seed acre-1 (0.38 lbs a.i./acre). This is

equivalent to 3.96 mg ft-2. Using the same daily dose rate of carboxin (3054 mg kg-1) as above for peanuts, based on a 20

g granivorous bird, the risk quotient (3.96 ÷ 3054) for this method is 0.0013. For all of the uses evaluated, all of the risk

quotients are below acute risk levels of concern. The results of the two methods for seed treatments using carboxin are

summarized in Table 13. 

The chronic avian risk was estimated using the peak concentration on the seed (e.g., peanuts: 2,815 mg kg-1),

as well as the NOAEC from the avian reproduction study (mallard duck NOAEC = 70 mg (kg of diet)-1) (Table 13).

Chronic RQ values (range 10 - 108) exceed the chronic risk LOC (RQ $1.0). If risk quotients were based on the lowest

observed effect concentration (LOAEC = 700 mg/kg of diet) rather than the NOAEC, RQ’s would range from 1 to 11 and

would still exceed the chronic LOC.

Table 13. Summary of avian acute and chronic risk quotients for carboxin based on three methods of estimating

exposure based on a mallard duck acute oral toxicity of 6,094 mg kg-1 and a chronic NOAEC of 70 mg kg-1 of diet.
090201 D295494 RED (Revised Carboxin).wpd 20

F

BW

W = −

0 621

1

0 564 . *

( )

.

Adj LD LD

AW

TW .

(. )

50 50

0 75

10 = 



 





Crop Acute RQ Method 1a Acute RQ Method 2b Chronic RQc

Barley <0.01 <0.01 20d

Bean <0.01 <0.01 13d

Canola <0.01 <0.01 14d

Corn <0.01 <0.01 19d

Cotton 0.006 <0.01 54d

Oats <0.01 <0.01 24d

Onion 0.013 <0.01 108d

Peanuts 0.005 <0.01 40d

Rape <0.01 <0.01 14d

Rice <0.01 <0.01 11d

Soybeans <0.01 <0.01 13d

Triticale <0.01 <0.01 10d

Wheat <0.01 <0.01 20d

a

 Acute RQ Method 1 = mg•kg-1day-1 / LD50 b

 Acute RQ Method 2 = mg•ft-2 / LD50 c Chronic RQ = mg•kg-1 seed / NOAEC d

 Exceeds chronic risk (RQ $ 1.0) level of concern. 

Mammals

 A similar approach as that used for birds in calculating exposure was used for mammals. Equations

used for calculating the daily food intake and the adjusted toxicity value for a 20 g. mammal are provided

below (Nagy 1987; USEPA 1995). The analysis assumed that small mammals would weigh 20 g and would

consume roughly 3.7 g of food per day. Also, similar to the approach used for birds, the LD50 was adjusted

to reflect the differential in toxicity to a 20-g mammal versus the rough average weight (200 g) of the rats used

in the acute oral toxicity study; the adjusted LD50 was determined to be 81.84 mg kg-1. Based on exposures

calculated using Method 1, acute risk levels of concern (RQ$0.5) are exceeded (RQ range: 9 - 92) at

maximum seed application rates used across all of the uses evaluated (Table 14). 

Compared against the mammalian NOAEC (200 mg/Kg of diet), chronic risk LOC’s are exceeded (RQ

range: 3.5 - 38) for all of the uses modeled (Table 14). If chronic risk quotients were based on LOAEC (300

mg/kg of diet), RQ values would range from 1.8 to 19 and still exceed the chronic LOC by minimally a factor

of two. 
090201 D295494 RED (Revised Carboxin).wpd 21

Table 14. Summary of acute and chronic mammalian RQ values based on an adjusted mammalian

acute LD50 and chronic NOAEC of 81.84 mg kg-1 and 200 mg kg-1 of diet, respectively.

Crop Acute RQ Method 1a Acute RQ Method 2b Chronic RQc

Barley 17 d 0.02 7.1e

Bean 11 d 0.02 4.7e

Canola 12 d <0.01 5e

Corn 17 d <0.01 6.8e

Cotton 46 d <0.01 19e

Oats 20 d 0.03 8.3e

Onion 92 d 0.01 38e

Peanuts 34 d 0.05 14e

Rape 12 d 0.01 5e

Rice 9.2 d 0.02 3.8e

Soybeans 11 d 0.01 4.7e

Triticale 8.6 d 0.01 3.5e

Wheat 17 d 0.02 7.0e

a

 Acute RQ Method 1= mg•kg-1bw-1d-1/LD50 b

 Acute RQ Method 2 = mg•ft-2 / LD50 c

 Chronic RQ = mg• kg-1seed -1 /NOAEC d

 Exceeds acute risk (RQ$0.5), restricted use (RQ$0.2), and acute endangered species LOC (RQ$0.1) dd Exceed acute endangered species (RQ $0.1) levels of concern. e

 Exceeds chronic risk (RQ $ 1.0) level of concern.

Aquatic Risk Assessment

Aquatic Animals

Using a single granular application, broadcast, with no incorporation for the management practice to

represent the seed treatment application, the peak concentration estimated with GENEEC 2.0 was 18.7 μg L-1.

Comparing this to the aquatic endpoints (see Table 15) shows that there is no aquatic risk above the level of

concern (RQ $ 0.05).

.
090201 D295494 RED (Revised Carboxin).wpd 22

Table 15. Summary of acute risk quotients for freshwater fish (bluegill LC50 = 1200 μg/L) and

invertebrates (Daphnia magna EC50= 84,400 μg/L) for carboxin based on estimated environmental

concentrations generated using GENEEC 2 model.

Crop Peak GENEEC Value

μg/L Fish Acute RQa Invertebrate Acute RQ

Barley 6.95 0.0058 <0.01

Bean 7.39 0.0062 <0.01

Canola 0.39 0.0003 <0.01

Corn 1.68 0.0014 <0.01

Cotton 3.35 0.0028 <0.01

Oats 10.5 0.0088 <0.01

Onion 5.57 0.0046 <0.01

Peanut 18.7 0.0156 <0.01

Rape 0.39 0.0003 <0.01

Rice 5.91 0.0049 <0.01

Soybeans 4.63 0.0039 <0.01

Triticale 3.10 0.0026 <0.01

Wheat 9.36 0.0078 <0.01

a

RQ= peak EEC ÷ LC50
090201 D295494 RED (Revised Carboxin).wpd 23

Aquatic Plants

Exposure to non-target aquatic plants may occur through runoff from adjacent treated sites. An

aquatic plant risk assessment for acute risk is usually made for aquatic vascular plants from the surrogate

duckweed Lemna gibba. Non-vascular acute risk assessments are performed using either algae or a diatom,

whichever is the most sensitive species. An aquatic plant risk assessment for acute- endangered species is

usually made for aquatic vascular plants from the surrogate duckweed Lemna gibba. To date, there are no

known non-vascular plant species on the endangered species list. Runoff is computed from environmental

concentrations estimated using GENEEC. The risk quotient is determined by dividing the pesticide's initial

or peak concentration in water by the plant EC50 value. Based on the results of this analysis (Table 16), no

acute levels of concern (RQ $1.0) are exceeded for aquatic plants. Additionally, when NOAEC values for

green algae (NOAEC = 0.11 mg L-1) and duckweed (NOAEC= 0.15 mg L-1) were compared to estimated

environmental concentrations, RQ values ranged from 0.02 to 0.17 for green algae and from 0.01 to 0.12 for

duckweed. None of the RQ values exceed the endangered species LOC (RQ $1) for aquatic plants. 

Table 16. Acute risk quotients for both nonvascular and vascular plants based on green algae

(Pseudokirchneriella subcapitata EC50 = 0.37 mg L-1) and duck weed (Lemna gibba EC50 = 0.67 mg L-1)

toxicity tests.

Crop Peak GENEEC Value

μg/L

Nonvascular Plant

 Acute RQb

Vascular Plant

Acute RQ

Barley 6.95 0.02 0.01

Bean 7.39 0.02 0.01

Canola 0.39 0.001 <0.01

Corn 1.68 0.01 <0.01

Cotton 3.35 0.01 <0.01

Oats 10.5 0.03 0.02

Onion 5.57 0.02 0.01

Peanut 18.7 0.05 0.03

Rape 0.39 0.001 <0.01

Rice 5.91 0.02 0.01

Soybeans 4.63 0.01 0.01

Triticale 3.10 0.01 0.01

Wheat 9.36 0.03 0.01

RISK CHARACTERIZATION

Based on two different methods of estimating exposure to birds, no acute LOC’s are exceeded for

small-sized (20 g) birds that are most likely to ingest seeds as part of their normal diet. However, chronic risk

LOC’s (RQ $1.0) were exceeded for birds (RQ range: 10 to 107) for all of the uses evaluated. While the

RQ’s exceed the chronic level of concern LOC by as much as 100-fold, there are a number of reasons why this
090201 D295494 RED (Revised Carboxin).wpd 24

is likely an overstatement of the risk. First, the LOAEC (700 mg/kg of diet) is a factor of ten higher than the

NOAEC, and based on the type of experiment and data analysis done to estimate these values, we can only

say the “true” LOEC lies somewhere between these values; RQ values based on the LOAEC range from 1 to

11. Additionally, treated seed is available for consumption for only about 10 days before the seed germinates

and becomes unavailable. Furthermore, carboxin should diffuse out of the seed coat and into the soil to some

extent which will reduce the concentration. Carboxin parent degrades rather rapidly which will also reduce

exposure. It is not known, however, whether the primary degradates, which are more persistent, have similar

toxicity to the parent. While the chronic avian risk is above the level of concern in this screening assessment,

risks may be reduced if the duration of exposure is short as a result of dissipation processes and birds rely on

other food sources in untreated areas. Usual planting practice is to plant the seed one-half to one inch deep

in the soil. This practice reduces exposure, and thus risk. 

Although carboxin is classified as practically nontoxic to mammals on an acute oral exposure basis

 (LD50 = 2,588 mg Kg-1), acute risk LOC’s are exceeded (RQ range: 9 - 92) at the maximum seed application

rates for all of the uses evaluated. Similar to birds, the chronic risk level of concern is exceeded by a wide

margin with RQ values ranging from 3.5 to 38. The chronic mammalian LOAEC (300 mg/Kg of diet) is only

a factor of 1.5 higher than the NOAEC and suggests the use of a NOAEC in the risk calculation does not

provide a large margin of safety; risk quotients based on the LOAEC range from 1.8 to 19. While the other

mitigating factors that applied to the avian chronic assessment apply here, the magnitude of the exceedance

makes it more likely that the residues consumed in the field may in fact result in impacts on mammalian

wildlife and that effects may be elicited by consuming relatively few carboxin-treated seeds. It is worth noting

that while parent carboxin is not expected to be persistent, the carboxin sulfoxide degradate is much more

persistent than the parent. Since the core structure of the molecule is intact there is some basis for assuming

the toxicity of this degradate could be similar to the parent.

Based on environmental concentrations in surface water estimated using GENEEC, no acute LOCs

are exceeded for aquatic animals. Since no chronic toxicity data were available for EFED to review, it is not

possible for EFED to gauge the potential for chronic risk to aquatic animals at this time. Additionally, no

acute LOC’s are exceeded for aquatic plants.

Endocrine Disruption

There are data indicating that carboxin exposure may impact endocrine-mediated processes in

terrestrial animals. Chronic dietary exposure of mallard ducks to carboxin resulted in reproductive effects

including reduced number of eggs laid, reduced number of normal hatchlings, and reduced numbers of 14-day

survivors. At this time it is not possible to determine whether similar reproductive effects may have been

elicited in aquatic animal since no chronic data were available for review. 

EPA is required under the Federal Food, Drugs, and Cosmetics Act (FFDCA), as amended by FQPA,

to develop a screening program to determine whether certain substances (including all pesticide active and

other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally-occurring

estrogen, or other such endocrine effects as the Administrator may designate.” Following the

recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA

determined that there was scientific basis for including, as part of the program, the androgen- and thyroid

hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC’s recommendation

that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use

FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect
090201 D295494 RED (Revised Carboxin).wpd 25

in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow,

screening of additional hormone systems may be added to the Endocrine Disruptor Screening Program. 

When the appropriate screening and or testing protocols being considered under the Agency’s

Endocrine Disruptor Screening Program have been developed, it is recommended that carboxin be subjected

to additional screening and or testing to better characterize effects related to endocrine disruption.

Endangered Species

Acute risk LOC’s for endangered/threatened mammals are exceeded (RQ range: 9 - 92) based on

maximum seed application rates for all of the uses evaluated while chronic risk LOC’s have been exceeded

for both avian (RQ range 10 - 107) and mammalian species (RQ range: 3.5 - 38). The Agency has developed

the Endangered Species Protection Program to identify pesticides whose use may cause adverse impacts on

endangered and threatened species, and to implement mitigation measures that address these impacts. The

Endangered Species Act requires federal agencies to ensure that their actions are not likely to jeopardize listed

species or adversely modify designated critical habitat. To analyze the potential of registered pesticide uses

to affect any particular species, EPA puts basic toxicity and exposure data developed for RED’s into context

for individual listed species and their locations by evaluating important ecological parameters, pesticide use

information, the geographic relationship between specific pesticide uses and species locations, and biological

requirements and behavioral aspects of the particular species. This analysis will take into consideration any

regulatory changes recommended in this RED that are being implemented at this time. A determination that

there is a likelihood of potential impact to a listed species may result in limitations on use of the pesticide,

other measures to mitigate any potential impact, or consultations with the Fish and Wildlife Service and/or the

National Marine Fisheries Service as necessary.

 

Carboxin is used exclusively to treat seeds and its affects on mammals are likely limited to seedingeating mammals. Based on discussions with the Field and External Affairs Division (FEAD; personal comm.

Larry Turner, FEAD Senior Biologist 2003), only the Delmarva fox squirrel (Sciurus niger cinereus) in

Delaware, Maryland, and Virginia and six species of kangaroo rats (Dipodomys spp.) in California are

endangered seed-eating mammals associated with agricultural crops. Kangaroo rats are not expected in

agricultural fields but may occur around them. However, the Delmarva fox squirrel may be near fields with

treated seeds. Thus, only the Delmarva fox squirrel would be likely to encounter seeds treated with carboxin.

The Endangered Species Protection Program as described in a Federal Register notice (54 FR 27984-

28008, July 3, 1989) is currently being implemented on an interim basis. As part of the interim program, the

Agency has developed County Specific Pamphlets that articulate many of the specific measures outlined in

the Biological Opinions issued to date. The Pamphlets are available for voluntary use by pesticide applicators

on EPA’s website at www.epa.gov/espp. A final Endangered Species Protection Program, which may be

altered from the interim program, is scheduled to be proposed for public comment in the Federal Register in

2002.
090201 D295494 RED (Revised Carboxin).wpd 26

LITERATURE CITED

Accession No. 254339 (in part) . Dzialo, D. G. and M. R. Lengen. 1983. [

14C] carboxin hydrolysis study.

Project N. 8304. Unpublished study received Aug. 8 1984 under 400-81 submitted by Uniroyal

Chemical, Bethany, CT. 

Accession No. 254339 (in part). Smilo, A. R., J. A. Lacadie, and R. A. Cardona. 1977. Hydrolysis of Plantvax

at various pH’s and temperatures. Project No. 7627. Unpublished study received August 8, 1984.

under 400-81; submitted by Uniroyal Chemical, Bethany, CT.

MRID 00003227. Lacadie, J. A., D. R. Gerecke and R. A. Cardona. 1978. Vitavax® 14C laboratory column

leaching study in clay loam. Project No. 7758. Unpublished study received Dec 27, 1978.

Performed and submitted by Uniroyal Chemical, Bethany, CT.

MRID 00003229. Lacadie, J. A., D. G. Dzialo and I. E. Dannae. 1978. Vitavax® 14C aged laboratory column

leaching study in sandy soil. Project No. 7832. Unpublished study received Dec 27, 1978.

Performed and submitted by Uniroyal Chemical, Bethany, CT.

MRID 00005541. Smyser, B. P. 1979. Adsorption-Desorption of Vitavax 14C on a Manchester sandy

loam. Project no. 7659. Unpublished study received March 28, 1979 un 400-81. submitted

by Uniroyal Chemical, Bethany, Connecticut. 

MRID 41224502. Dzialo, D. 1989b. [

14C-oxathiin] carboxin sulfoxide aerobic soil metabolism study.

Completed in September 1989. Performed and submitted by Uniroyal Chemical Company,

Middlebury, CT. Project No. 8916.

MRID 41224503. Dzialo, D. G., 1989c. [C14-aniline] carboxin aerobic soil metabolism on sandy loam soil.

Project no. 8915. Unpublished study performed and submitted by Uniroyal Chemical Company,

Inc., Middlebury, CT.

MRID 41224504. Dzialo, D. 1989d. [

14C-oxathiin] carboxin aerobic soil metabolism study-status report.

Completed in September 1989. Performed and submitted by Uniroyal Chemical Company,

Middlebury, CT. Project No. 8916.

MRID 41224507. Gaydosh, K. A. 1989a. [C14-aniline] Vitavax anaerobic soil metabolism - interim report.

Project no. 8978. Unpublished study performed and submitted by Uniroyal Chemical Company,

Inc., Middlebury, CT.

MRID 41224508. Gaydosh, K. A. 1989b. [C14-oxathiin] Vitavax anaerobic soil metabolism - status report.

Project no. 8977. Unpublished study performed and submitted by Uniroyal Chemical Company,

Inc., Middlebury, CT.

MRID 412525-01. Dzialo, D. 1989e. [

14C-oxathiin] carboxin aerobic soil metabolism study final report.

Completed in September 1989. Performed and submitted by Uniroyal Chemical Company,

Middlebury, CT. Project No. 8916.
090201 D295494 RED (Revised Carboxin).wpd 27

MRID 412594-01A. Scruggs, J. W. , and S. O. Guy. 1989. Carboxin (Vitavax 3F) field dissipation -

Terrestrial study on peanuts in Donalsonville, GA. WRLA Protocol no 1641-88-115-02-07C-01.

Unpublished study performed by Landis Associates, Inc., Valdosta, GA, and Southern Agricultural

Research, Inc., Donalsonville, GA; and submitted by Uniroyal Chemical Company, Middlebury, CT.

MRID 413143-03. Gaydosh, K. A. 1989. [

14C-oxathiin] Vitavax anaerobic soil metabolism. Uniroyal Project

8978. Unpublished study performed and submitted by Uniroyal Chemical Company, Middlebury,

CT.

MRID 417255-01. Beerbaum, C. M. 1990. Vitavax - identification of peak in [14C-oxathiin] Vitavax

anaerobic soil metabolism in study 8978. Uniroyal Project No. 89143. Unpublished study performed

and submitted by Uniroyal Chemical Company, Inc. Middlebury, CT.

MRID 419921-01. White, C. K. 1991. Vitavax soil photolysis. Laboratory Project No. 9115. Unpublished

study performed and submitted by Uniroyal Chemical Company, Inc. Middlebury, CT.

MRID 421928-01. Horree, D. J. 1992. Aqueous photolysis of Vitavax. Uniroyal Project No. 9040. Unpublished

study performed and submitted by Uniroyal Chemical Company, Middlebury. CT. 

MRID 426008-01. Wu, D. 1992. Aerobic aquatic metabolism of 14C-carboxin. XBL Study No. XBL 92036;

XBL Report No. RPT00110; Uniroyal Study No. 9260. Unpublished study performed by XenoBiotic

Laboratories, Inc., Princeton, NJ, and submitted by Uniroyal Chemical Company, Middlebury, CT.

MRID 426008-03. Wu, D. 1993. Anaerobic aquatic metabolism of 14C-carboxin. XBL Study No. XBL

92037; XBL Report No. RPT00143; Uniroyal Study No. 9269. Unpublished study performed by

XenoBiotic Laboratories, Inc., Princeton, NJ, and submitted by Uniroyal Chemical Company,

Middlebury, CT.

D187842. Jones, R. David. January 31, 2002. Carboxin aerobic aquatic metabolism study review. Internal

EPA memorandum to Stephanie Nguyen. 

D197786. Jones, R. David. January 31, 2002. Carboxin anaerobic aquatic metabolism study review.

Internal EPA memorandum to Stephanie Nguyen. 

D258134. Parker, Ronald. 1999. Expected Maximum Drinking Water Concentrations for Carboxin as a Seed

Treatment. Internal EPA memorandum to Mary Waller and Margarita Collantes dated October 28,

1999.

D261852. Lee, Richard. 2000. Section 3 Registration (Label Amendment) for the New-use of Carboxin as

Seed Treatment on Onion. Internal EPA memorandum to Marry Waller dated April 5, 2000.

D279190. Budd, Ed, Douglas Dotson, and R. David Jones. November 21, 2001. PP#’s 9F3777 and 9F6036.

Carboxin. Metabolism Assessment Review Committee Briefing and Memorandum. Internal EPA

Memorandum to Richard Loranger and Norm Birchfield. 

Bragg, David and Burns, J. W. 2001. Crop Profile for Canola in Washington.

http://pestdata.ncsu.edu/cropprofiles/docs/wacanola.html
090201 D295494 RED (Revised Carboxin).wpd 28

Environmental Fate and Effects Division. 2001a. FIRST (F)IFRA (I)ndex (R)eservoir (S)creening

(T)ool. Tier 1 Model for Drinking Water Exposure: User’s Manual.

http://www.epa.gov/oppefed1/models/water/first_users_manual.htm

Environmental Fate and Effects Division. 2001b. SCI-GROW - (S)creening (C)oncentration (I)n (GRO)und

(W)ater: User’s Manual. http://www.epa.gov/oppefed1/models/water/scigrow_users_manual.htm

Mineau, P, B. T. Collins, and A. Baril, 1996. On the use of scaling factors to improve interspecies

extrapolation of acute toxicity in birds. Regulatory Toxicology and Pharmacology. 24:24-29.

Nagy, K. A. 1987. Field metabolic rate and food requirement scaling in mammals and birds. Ecological

Monographs 57:111-128.

Nelson, Jennifer, 2000. Crop Profile for Canola in Minnesota.

http://pestdata.ncsu.edu/cropprofiles/docs/mncanola.html

Parker, Ronald D., Henry P. Nelson and R. David Jones. 1995. GENEEC: A Screening Model for Pesticide

Environmental Exposure Assessment. The International Symposium on Water Quality Monitoring,

April 2-5 1995. American Society of Agricultural Engineers. p 485.

Schewe, T. and H. Lyr. 1987. Mechanism of action of carboxin fungicides and related compounds. In H. Lyr

(Editor) Modern Selective Fungicides, Properties, applications and mechanisms of action. Longman

Scientific & Technical (John Wiley & Sons, Inc.), New York. Pages 133 - 142 

United States Environmental Protection Agency. 2002. Guidance for Selecting Input Parameters in Modeling

the Environmental Fate and Transport of Pesticides, Version II.

http://www.epa.gov/oppefed1/models/water/input_guidance2_28_02.htm

USEPA 1995. Great Lakes Water Quality Technical Support Document for Wildlife Criteria. Washington

DC Office of Water. Document Number EPA-820-B095-009
090201 D295494 RED (Revised Carboxin).wpd

APPENDIX I. USE CLOSURE MEMO

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF 

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

Date: June 9, 2003

To: Carboxin RED Team

From: Dirk Helder, Chemical Review Manager

Special Review and Reregistration Division

Subject: Carboxin Use Closure Memo

This memo serves as the carboxin use closure memo and clarifies carboxin uses for the Reassessment

Eligibility Decision (RED) risk assessment.

Background:

The SMART meeting for carboxin was held on March 27, 2003. During the SMART meeting,

Crompton and Gustafson presented current carboxin use and usage information as requested by the Agency.

Carboxin is a systemic fungicide used to treat seeds. Carboxin is predominantly used as cereal seed

treatments for systemic control of smut and bunt diseases. The addition of contact fungicides such as thiram

and captan to carboxin in formulations allows control of a much broader spectrum of seedling diseases and

crops. Insecticides may also be included to protect tender developing rootlets of cereal seedlings against

wireworms and leatherjackets. Carboxin is registered for commercial use on barley, beans, canola, corn,

cotton, oats, onions, peanuts, rice, rye, safflower, sorghum, soybeans, sugar beet, triticale, wheat, flower bulbs,

corms, and grass seed for export. In addition, carboxin is registered for on-farm use on barley, bean, corn,

cotton, oats, rice, soybeans, triticale, and wheat.

Applications:

Carboxin is only applied as a seed treatment with most of the seed crops subsequently incorporated

into the soil. It is applied in both a liquid flowable and a dust formulation. Carboxin is applied in commercial

seed treatment operations and also in on-farm situations where it is applied by hand. Carboxin treated seed

is generally applied once per growing season, but may be seeded a second time due to dry conditions at

planting or winterkill in fall plantings. 

The table below represents the carboxin labeled use rates that are being supported for reregistration.

The risk assessments will be based on these formulations, use rates, and application methods, as presented in

the table below. After the issuance of the RED, all end use products will have to conform with these
090201 D295494 RED (Revised Carboxin).wpd 30

parameters, and other risk mitigation that may be identified through the reregistration process. Updated

labeling may need to be submitted after the RED is issued. 
090201 D295494 RED (Revised Carboxin).wpd 31

 Supported Uses of Carboxin-COMMERCIAL

Crop Range of Seed

Application Rates 

Pounds seed/Acre

Equivalent

(lbs. A.I./Acre)

Apps.

Per

Year

Application

Method

Total lbs. Treated Seeds Current 

REI

(hours)

Barley 50-80 0.0179-0.063 1 Flowable 4,370,644 - 5,828,013 12

Bean 120-160 0.051 – 0.167 1 Flowable 5,377,110 - 7,134,971 12

Canola 4-8 0.0037 – 0.0075 1 Flowable None Sold 12

Corn 11-25 (15) 0.005 – 0.031 1 Flowable 1,440,000 - 2,880,000 12

Cotton 10-18 (15) 0.0066 – 0.038 1 Flowable 17,372,460 - 26,139,112 12

Oats 48-128 (60) 0.0173 – 0.1002 1 Flowable 1,280 - 65,280 12

Onion 1-15 (2) 0.0075 – 0.1125 1 Dust 53,147 12

Peanuts 90-120 (90) 0.023 – 0.0815 1 Dust &

Flowable

D: 96,800,000 -

121,000,000

F: 1,237,333

12

Rice 67-160 0.0201 – 0.096 1 Flowable 8,163,390 - 10,896,128 12

Rye 75-150 0.029 – 0.078 1 Flowable 1,040,096 - 1,386,794 12

Safflower 20-100 0.010 – 0.052 1 Flowable None Sold 12

Sorghum 5-8 (6) None Sold

Not On Labels Yet

1 None Sold

Not On

Labels Yet

None Sold

Not On Labels Yet

12
Crop Range of Seed

Application Rates 

Pounds seed/Acre

Equivalent

(lbs. A.I./Acre)

Apps.

Per

Year

Application

Method

Total lbs. Treated Seeds Current 

REI

(hours)

090201 D295494 RED (Revised Carboxin).wpd 32

Soybeans 50-85 (60) 0.021 – 0.0887 1 Flowable 24,946,668 12

Sugar Beet 2-8 None Sold None

Sold

None Sold None Sold 12

Triticale 70-90 0.022 – 0.070 1 Flowable 94,118 - 128,000 12

Wheat 45-120 (90) 0.0162 – 0.0939 1 Flowable 43,218,328 - 57,829,452 12

Flower Bulbs Use So Low, No Sales Information Available

Corms

Use So Low, No Sales Information Available

Grass Seed

(Export Only) No Export Sales Information Available

( ) = Actual seeding rate reflects the seeding rate of carboxin-treated seed or the average seeding rate to the best of the registrants knowledge based

on sales info and an understanding of the use practices.
090201 D295494 RED (Revised Carboxin).wpd 33

 Supported Uses of Carboxin-ON FARM

Crop Range of Seed

Application Rates 

Pounds seed/Acre

Equivalent

(lbs. A.I./Acre)

Apps. Per

Year

Application

Method

Total lbs. Treated

Seeds

Current 

REI

(hours)

Barley 50-80 0.00975 – 0.0417 1 Flowable 2,763,367 - 7,492,174 12

Bean 120-160 0.03375 – 0.06 1 N/A None Sold

Not On Labels Yet

12

Corn 11-25 (15) 0.0028 – 0.0168 1 Dust 100,134,133 12

Cotton 10-18 (15) 0.0075 – 0.027 1 Dust 3,423,000 12

Oats 48-128 (60) 0.0141 – 0.1 1 Flowable 24,320 12

Rice 67-160 0.0139 – 0.0748 1 Flowable 1,305,882 - 1,776,000 12

Soybeans 50-85 (60) 0.01289 – 0.05315 1 Dust 3,561,997 12

Triticale 70-90

0.025 - 0.044

1 Flowable 282,353 - 384,000 12

Wheat 45-120 (90) 0.0105 – 0.06 1 Dust & Flowable D: 25,958,836

F: 29,844,368 

12

Rotational Crop Restrictions

None

Crops/Formulations/Use Sites Not Being Supported

All labeled uses are being supported at the maximum labeled rate. In addition, six products (Vitavax

Maneb (7501-37), Vitavax Plus (7501-37-42056), Vitavax Thiram (7501-44), Vitavax Pour-On (7501-95),

Enhance V-M-L (7501-152), RTU Vitavax Extra (7501-166)) will be voluntarily cancelled by the registrant.

These products are not included in the carboxin risk assessment.

The risk assessment for carboxin will be based on the use sites listed in this memorandum,

information from the Biological and Economic Analysis Division (BEAD), current carboxin labels, as well

as other pertinent use information provided by the registrant and maintained within the Agency’s database

systems. 
090201 D295494 RED (Revised Carboxin).wpd 34

APPENDIX II. GENEEC 2 MODEL OUTPUT

 RUN No. 1 FOR CARBOXIN ON BARLEY * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .141( .141) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 6.95 6.43 4.32 2.17 1.50

 RUN No. 2 FOR CARBOXIN ON BEAN * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .150( .150) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 7.39 6.84 4.60 2.31 1.59
090201 D295494 RED (Revised Carboxin).wpd 35

 RUN No. 3 FOR CARBOXIN ON CANOLA * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) (FT) (IN)

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

 .008( .008) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) 

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 394.14 328.06 171.00 69.10 46.21

 RUN No. 4 FOR CARBOXIN ON CORN * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .034( .034) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 1.68 1.55 1.04 .52 .36

 RUN No. 5 FOR COTTON ON COTTON * INPUT VALUES *
090201 D295494 RED (Revised Carboxin).wpd 36

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) (FT) (IN)

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

 .068( .068) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) 

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 3.35 2.79 1.45 .59 .39

 RUN No. 6 FOR CARBOXIN ON OATS * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .213( .213) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 10.49 9.72 6.53 3.28 2.26
090201 D295494 RED (Revised Carboxin).wpd 37

 RUN No. 7 FOR CARBOXIN ON ONION * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .113( .113) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 5.57 5.16 3.46 1.74 1.20

 RUN No. 8 FOR CARBOXIN ON PEANUTS * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .380( .380) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 18.72 17.34 11.65 5.85 4.04
090201 D295494 RED (Revised Carboxin).wpd 38

 RUN No. 9 FOR CARBOXIN ON RAPE * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) (FT) (IN)

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

 .008( .008) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) 

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 394.14 328.06 171.00 69.10 46.21

 RUN No. 11 FOR CARBOXIN ON RICE * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .120( .120) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 5.91 5.47 3.68 1.85 1.27
090201 D295494 RED (Revised Carboxin).wpd 39

 RUN No. 12 FOR CARBOXIN ON SOYBEAN * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .094( .094) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 4.63 4.29 2.88 1.45 1.00

 RUN No. 13 FOR CARBOXIN ON TRITICALE * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .063( .063) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 3.10 2.87 1.93 .97 .67
090201 D295494 RED (Revised Carboxin).wpd 40

 RUN No. 14 FOR CARBOXIN ON WHEAT * INPUT VALUES *

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

 RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

 ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

 .190( .190) 1 1 .8 195.0 GRANUL( .0) .0 .0

 FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) 

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

 METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

 (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

 71.20 2 N/A .06- 7.94 93.60 7.32

 GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

 PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

 GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

 9.36 8.67 5.83 2.92 2.02

 

 
090201 D295494 RED (Revised Carboxin).wpd 41

APPENDIX III. ECOLOGICAL TOXICITY DATA

Toxicity to Terrestrial Animals

Acute and Subacute Toxicity to Birds

The acute oral toxicity of carboxin to 19 week-old Bobwhite quail (Colinus virginianus) was

assessed over 14 days (MRID 43582301). Carboxin (Vitavax Technical) was administered to the birds by

oral doses of 464, 681, 1000, 1470 or 2150 mg carboxin/kg body weight (bw) in gelatine capsules without

any carrier. The 14-day acute oral LD50 was greater than the highest dose tested (>2,150 mg a.i/kg bw)

(Table III-1). The 14-day NOEL of carboxin to Colinus virginianus, based on lethality was 1,000 mg a.i/kg

bw. Carboxin is categorized as practically nontoxic to Colinus virginianus on an acute oral basis. This

toxicity study is scientifically sound, is classified as core, and meets guideline 71-1 acute oral toxicity testing

requirements for birds. Additionally, an 8-day acute oral toxicity study was conducted using mallard ducks;

the study resulted in an LD50 of 6,094 mg/kg bw and was classified as core.

Table III-1. Summary of avian acute oral toxicity test on bobwhite quail (Colinus virginianus) exposed

to carboxin.

Species Study Type % active

ingredient

LD50

mg/kg bw

MRID No.

Author Year Toxicity Category Fulfills GuidelineRequirement

Bobwhite quail

Colinus virginianus oral 97.39 >2,150 435823-01

Pederson, 1994 Practically nontoxic Core

Mallard duck

Anas platyrhynchos oral 99 6,094

no MRID

Beavers and Fink,

1997

Practically nontoxic Core

Acute toxicity testing with Vitavax 75W® (37.5% carboxin/37.5% thiram) indicated that the

formulated product was practically nontoxic (LD50 = 2,410 mg/kg) to Bobwhite quail on an acute exposure

basis (Accession Number 224935). No raw data were provided to verify the study conclusions; therefore,

these data are supplemental. 

Acute toxicity testing with Vitavax SP (37.5% carboxin; 37.5% captan) using Bobwhite quail

indicated the formulated product was practically nontoxic (LD50 >10,000 mg/kg bw). However, no raw data

were available to substantiate the study results (Accession Number 224935). 

Two subacute dietary studies using the technical grade active ingredient (TGAI) are required to

establish the toxicity of carboxin to birds (Table III-2). The preferred test species are the bobwhite quail and

the mallard duck. For the quail study (MRID 435823-03), no abnormal findings were noted. Body weights

and feed consumption values were similar between treatment and control. The LC50 was greater than the

highest dietary concentration tested, i.e., >4,110 mg (kg of diet)-1, and the NOAEC was 4,110 mg kg-1. In

the subacute dietary toxicity study of mallard ducks (MRID 435823-02), no abnormal effects were noted on

243 arbitrarily selected birds. However, at 4,110 mg kg-1 group birds were lethargic, sat huddled in one

corner of the brooder and only moved when prodded. By the fourth day of the study, these birds appeared

to be normal and active. The LC50 was greater than 4,110 mg kg-1 and the NOAEC was 1,050 mg kg-1. From

the results of both studies, carboxin is categorized as practically nontoxic on a subacute dietary exposure
090201 D295494 RED (Revised Carboxin).wpd 42

basis. Both the bobwhite quail and mallard duck studies are classified as core and meet guideline 71-2

subacute dietary toxicity testing requirements for birds. 

Additionally, in a 8-day subacute dietary toxicity study of Vitavax technical (99% a.i.) using

bobwhite quail, the LC50 was greater than the highest concentration (10,000 mg (kg of diet)-1) tested. At the

highest concentration tested though, two birds out of ten were found dead.

Table III-2. Summary of subacute dietary toxicity studies with mallard ducks (Anas platyrhynchos)

and bobwhite quail (Colinus virginianus) for carboxin.

Species Study Type % active

ingredient

LC50 

mg/L

MRID No.

Author

Year

Toxicity Category Fulfills Guideline

Requirement

Bobwhite quail

Colinus virginianus dietary 97.4 >4,110 435823-03

Pederson, 1995 Practically nontoxic Core

Mallard duck

Anas platyrhynchos dietary 97.4 >4,110 435823-02

Pederson, 1995 Practically nontoxic Core

Subacute dietary toxicity data were also available for Vitavax SP (75% a.i.). The 8-day dietary LC50

values for Bobwhite quail and mallard ducks were higher than the maximum dietary concentrations tested,

i.e., >5620 mg/kg of diet (Fiche ID 00003037; MRID 029175) and >4,640 mg (kg of diet)-1 (Fiche ID

00003139), respectively. Since no raw data were available to verify the study results, these study results are

classified as supplemental. Based on these data, the formulated end-product is practically nontoxic to birds

on a subacute dietary exposure basis.

Chronic Toxicity to Birds

Two avian reproduction studies were submitted for review (Table III-3). In the study with bobwhite

quail (MRID 442401-01), no significant treatment related effects on any parameters measured at any

concentration tested were noted. This study is scientifically sound, however it does not meet the guideline

requirements for an avian reproduction study using bobwhite quail since it is not clear whether the maximum

dietary concentration tested, i.e., 1000 mg kg-1 d-1 , is above the maximum field residue level and the study

is classified as supplemental. Based on the results of this test, the NOAEC is 1000 mg kg-1 d-1. In a study with

mallard ducks (MRID 442401-02), there was no treatment related mortality or overt signs of toxicity at any

test concentration. However, there appeared to have been treatment-related effects on reproductive

parameters. There were significant reductions in the number of eggs laid, eggs set, viable embryos, live 3-

week embryos, normal hatchlings and 14-day survivors at the 700 mg kg-1 d-1 concentration level when

compared to the control. There was also a significant difference (p>0.05) in the number of eggs set at the

1,000 mg kg-1 d-1 treatment level. The NOAEC and LOAEC were determined to be 70 and 700 mg kg-1 d-1,

respectively. The mallard duck study is scientifically sound, is classified as core, and meets Guideline 71-4

chronic avian reproductive toxicity testing requirements. 
090201 D295494 RED (Revised Carboxin).wpd 43

Table III-3. Summary of avian reproduction study with mallard ducks (Anas platyrhynchos) and

bobwhite quail (Colinus virginianus) for carboxin.

Species % active

ingredient

NOAEL &

LOAEL

mg/kg

LOAEL

 endpoint

MRID No.

Author

Year

Fulfills Guideline

Requirement

Bobwhite Quail

Colinus virginianus 97.3 1000 / >1,000 None reported

442401-01

Mitchell et al.,

1997

Supplemental

Mallard Duck

Anas platyrhynchos 97.3 70 & 700

Number of eggs laid/set,

viable embryos, live at 3-

wk, normal hatchlings

and female body weight

442401-02

Mitchell et al.,

1997

Core

Acute and Chronic Toxicity to Mammals

Wild mammal testing may be required on a case-by-case basis, depending on the results of lower tier

laboratory mammalian studies, intended use pattern and pertinent environmental fate characteristics. In

almost all cases, rat or mouse toxicity values obtained from the Office of Pesticide Programs’ Health Effects

Division (HED) substitute for wild mammal testing; these toxicity values are summarized in Table III-4.

Carboxin is classified as practically nontoxic to mammals on an acute exposure basis (LD50=2,588 mg/kg).

Chronic toxicity data from a 2-generation rat reproduction study indicated that decreased body weight in

second generation pups (NOAEL = 200 mg kg d-1) was the primary chronic effect of carboxin in rats.

Additionally, chronic nephritis was also observed in both males and females; however, the study was not able

to determine the statistical significance of this endpoint.

Table III-4. Acute and chronic toxicity of carboxin to the rat.

Species % a.i. LD50 (mg/kg) MRID

Author, year Study Classification

Rat

102.2% 2,588 (males)

3,080 (females)

431714--01

Goldenthal 1992 core

Rat

98% NOAEL = 200 ppm (males)

NOAEL = 300 ppm (females)

419226-01

Kehoe 1991

423911-07

Kehoe 1992

core

Toxicity to Insects

A honeybee acute contact study using the TGAI was required for carboxin because its use may result

in honeybee exposure. Acute oral toxicity testing indicated a 96-hr LD50 of 2.0 μg/bee. The 96-hr contact

toxicity value is 181.29 μg/bee. Based on these results, carboxin is categorized as practically nontoxic to bees

on an acute contact and an acute oral exposure basis (Table E4). The acute contact studies are scientifically

sound and are classified as core; the acute oral study is classified as supplemental. 
090201 D295494 RED (Revised Carboxin).wpd 44

Table III-4. Summary of acute contact and oral 48-hr toxicity tests with the honey bee (Apis mellifera)

for carboxin.

Species % active ingredient LD50

:g/bee

MRID No.

Author/Year Toxicity Category Fulfills GuidelineRequirement

Honey Bee >95% 2.0 00018842

Toxicity to Freshwater Aquatic Animals

Acute Toxicity to Freshwater Fish

Two freshwater fish toxicity studies using the TGAI are required to establish the toxicity of carboxin

to fish. The preferred test species are the cold-water (Guideline 72-1c) rainbow trout (Onchorynchus mykiss)

and the warm-water (Guideline 72-1a) bluegill sunfish (Lepomis macrochirus). Rainbow trout exposed to

the four highest concentration levels (0.93, 1.5, 2.4, and 4.1 mg L-1 ) demonstrated partial to complete loss

of equilibrium, lethargy, darkened pigmentation and swimming on the surface. The 96-h LC50 for rainbow

trout exposed to carboxin was determined to be 2.3 mg L-1 and the NOAEC was 0.6 mg L-1. The rainbow

trout acute LC50 test (MRID 435823-05) was classified as core (Table III-5). An additional rainbow trout

study (Accession No. 224935) reported a 96-hr LC50 value of 2.0 mg L-1; the study is classified as

supplemental since fish were smaller than recommended.

Bluegill sunfish exposed to the three highest concentrations, i.e., 2.7, 4.3, and 7.5 mg L-1, also

demonstrated partial to complete loss of equilibrium, lethargy, darkened pigmentation and swimming on the

surface. After 96 hours, there were detectable amounts of degradates (0.5 to 0.8 mg/L) found in the two

highest treatment concentrations. The 96-h LC50 was determined to be 3.6 mg L-1 and the NOAEC was 1.8

mg L-1. The bluegill sunfish study (MRID 435823-04) is scientifically sound, is classified as core and meets

Guideline 72-1a requirements. An additional 96-hr acute toxicity of carboxin with bluegill sunfish reported

a 96-hr LC50 of 1.2 mg/L. 

Table III-5. Summary of acute 96-hr toxicity tests on rainbow trout (Onchorynchus mykiss) and

bluegill sunfish (Lepomis macrochirus) exposed to carboxin.

Species % active

ingredient

LC50 

mg/L

MRID No.

Author

Year

Toxicity Category Fulfills Guideline

Requirement

Rainbow Trout 97.39 2.3 435823-05

Bettencourt, 1994 Moderately toxic Core

Rainbow Trout 99% 2.0 224935

Kuc and Cary, 1977 Moderately toxic Supplemental

Bluegill Sunfish 97.39 3.6 435823-04

Bettencourt, 1994 Moderately toxic Core

Bluegill Sunfish 99% 1.2 224935

Kuc and Cary, 1977 Moderately toxic Core

Static 96-hr acute toxicity testing of rainbow trout with Vitavax® SP (seed protectant; 37.5% carboxin

and 37.5% captan) indicated that the formulated product is moderately toxic (LC50 = 4.5 mg/L) on an acute

exposure basis (Accession Number 224935). Similarly, static 96-hr acute toxicity testing of the Vitavax SP
090201 D295494 RED (Revised Carboxin).wpd 45

using bluegill sunfish indicated that the formulated product was moderately toxic (LC50 = 2.9 mg/L) to warmwater fish on an acute exposure basis (Accession Number 224935).

Static 96-hr acute toxicity testing of rainbow trout and bluegill sunfish with Vitavax SP/Captan

(37.5% carboxin / 37.5% captan) indicated that the formulated product is moderately toxic to rainbow trout

(LC50 = 6.6 mg L-1) and slightly toxic (LC50 = 11.2 mg L-1) on an acute exposure basis (Accession Number

224935).

Static 96-hr acute toxicity testing of rainbow trout and bluegill sunfish with Vitavax SP/Thiram

(37.5% carboxin /37.5% thiram) indicated the formulated product is highly toxic to both rainbow (LC50 = 0.38

mg L-1) and bluegill sunfish (LC50 = 0.56 mg L-1). 

Chronic Toxicity to Freshwater Fish

No chronic toxicity data were available for freshwater fish.

Acute Toxicity to Freshwater Invertebrates

In a static acute toxicity of carboxin (Vitavax technical; 99% a.i.) using Daphnia magna (Acc. No.

235236) the 48-hr EC50 and NOAEC were determined to be 84.4 mg L-1 and mg L-1, respectively (Table III7). There was 10 and 70 % mortality in the 56 and 100 mg L-1 (highest) test concentrations after 48 hours.

This study is scientifically sound, is classified as core, and meets Guideline 72-3 testing requirements for an

acute toxicity study with a freshwater invertebrate.

A flow-through freshwater aquatic invertebrate toxicity test using TGAI was also submitted (MRID

435823-06, flow through) to establish the toxicity of carboxin to aquatic invertebrates. The EC50 was

determined to be greater than the highest concentration tested, (>57 mg L-1). This study is scientifically sound,

but was classified as supplemental since mean-measured concentrations were approximately half of nominal

due to poor solubility of the compound at higher exposure concentrations. However, because of the

chemical’s low solubility and apparent low toxicity, the requirement for a new study is waived. Based on the

results of both the static and flow-through acute toxicity studies, carboxin is categorized as slightly toxic to

freshwater invertebrates on an acute exposure basis.

Table III-7. Summary of acute 48-hr toxicity tests on water fleas (Daphnia magna) for carboxin. 

Species % active

ingredient

LC50

mg/L

MRID No.

Author/Year

Toxicity Category Fulfills Guideline

Requirement

Daphnia magna,

flow-through

97.39 >57 43582306

Putt, 1994

slightly toxic Supplemental

Daphnia magna,

static

99 84.4 235236

Vilkas, 1977

slightly toxic core

Chronic Toxicity to Freshwater Invertebrates

No chronic toxicity data were available for freshwater invertebrates.
090201 D295494 RED (Revised Carboxin).wpd 46

Toxicity to Estuarine and Marine Animals

Acute and Chronic Toxicity to Estuarine and Marine Fish

No acute or chronic toxicity data were available for estuarine/marine fish.

Acute Toxicity to Estuarine and Marine Invertebrates

Acute toxicity tests were conducted using the formulated end-product Vitavax-R Flowable (carboxin

17%, thiram 17%) with estuarine/marine pink shrimp (Penaeus duorarum) and fiddler crabs (Uca pugilator)

(Table III-). After 96 hours, fiddler crabs exhibited partial loss of equilibrium in the 320 mg/L exposure

group and up to 70% mortality in the highest exposure concentration (1,000 mg L-1); the 96-hr LC50 was

964 mg L-1. Pink shrimp were considerably more sensitive to the formulated product with an LC50 value of

14 mg L-1. Based on these studies (Accession Number 165048A), formulated product ranged from being

slightly to practically nontoxic to estuarine/marine invertebrates. These studies are classified as supplemental

though and acute toxicity testing using technical grade active ingredient should be made available for

evaluation.

Table III-. Summary of acute 96-hr toxicity tests on marine invertebrates exposed to formulated endproduct Vitavax R flowable fungicide (17% carboxin and 17% thiram). 

Species % active

ingredient

LC50

mg/L

MRID/Accession No.

Author/Year

Toxicity Category Study

Classification

Pink Shrimp

Penaeus duorarum

17 14 165048A

Heitmuller, 1975

slightly toxic Supplemental

Fiddler crab

Uca pugilator

17 964 165048A

Heitmuller, 1975

practically

nontoxic

Supplemental

Chronic Toxicity to Estuarine and Marine Invertebrates

No chronic toxicity data were available for estuarine/marine invertebrates. 

Toxicity to Plants

Toxicity to Terrestrial Plants

Terrestrial plant testing (seedling emergence and vegetative vigor) is required for pesticides that have

terrestrial non-residential outdoor use patterns and that may move off the application site through

volatilization (vapor pressure > 1.0 x 10-5 mm Hg at 25o C) or drift (aerial or irrigation) and/or that may have

endangered or threatened plant species associated with the application site. In many cases, the registrants

elect to proceed directly to Tier II testing. However, according to a memo dated April 4, 1989, since only

seed treatments exist for carboxin, terrestrial phytotoxicity studies are no longer required. 
090201 D295494 RED (Revised Carboxin).wpd 47

Toxicity to Aquatic Plants

Aquatic plant testing is required for any pesticide that has outdoor non-residential terrestrial uses that

may move off-site by runoff or by drift from aerial applications or ground spray. The vascular duckweed,

Lemna gibba, and nonvascular green algae, Pseudokirchneriella subcapitata, should be tested at Tier I.

(Table III-14). The 14-day EC50 for duckweed was 0.67 mg a.i./L, based on mean-measured concentrations

while the NOAEC and LOAEC values were 0.15 and 0.30 mg a.i./L, respectively (MRID 414938-02). This

study is scientifically sound and meets Guideline 123-2 testing requirements for a Tier-2 non-target aquatic

plant study. The freshwater green algae test (Pseudokirchneriella subcapitata, MRID 414938-01) exhibited

a 5-day EC50 of 0.37 mg ai/l; the NOAEC and LOAEC values were 0.11 and 0.22 mg a.i./L, respectively.

This study is scientifically sound and will be useful in risk assessment purposes. A additional green algae

tested was Chlorella pyrenoidosa (MRID 413178-01) and exhibited a 3-day NOAEC, LOAEC and EC50 of

1.0, 1.8 and 2.55 mg a.i./l, respectively. This study is scientifically sound but does not meet the guideline

requirements for a Tier 2 non-target plant study due to the use of a non-guideline species; however, the data

are useful for risk assessment purposes. 

Table III-14. Summary of vascular and nonvascular acute aquatic plant toxicity tests with

carboxin.

Species % active

ingredient

EC50/IC50

mg/L

Most Sensitive

Endpoint

MRID No.

Author

Year

Fulfills

Guideline

Requirement

Duckweed

Lemna gibba

(static)

97.5 0.67 Frond number 414938-02

Hughes, 1990 Core

Green algae

Chlorella pyrenoidosa

(non-guideline species)

97 2.55

(nominal) biomass, growth rate 413178-01Bogers, 1989 Supplemental

Green algae

Pseudokirchneriella subcapitata1 97.5 0.37 Cell density 41493801

Hughes, 1990

Core

1

 Formerly Selenastrum capricornutum
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APPENDIX IV . EXPOSURE AND RISK TO NONTARGET ANIMALS

Risk Assessment

A means of integrating the results of exposure and ecotoxicity data is called the quotient method.

For this method, risk quotients (RQ’s) are calculated by dividing exposure estimates by ecotoxicity values,

both acute and chronic. 

RQ = EXPOSURE/TOXICITY 

Risk quotients are then compared to OPP's levels of concern (LOC’s). These LOC’s are criteria used by OPP

to indicate potential risk to non-target organisms and the need to consider regulatory action. The criteria

indicate that a pesticide used as directed has the potential to cause adverse effects on non-target organisms.

LOC’s currently address the following risk presumption categories: (1) acute high - potential for acute risk

is high, regulatory action may be warranted in addition to restricted use classification; (2) acute restricted

use - the potential for acute risk is high, but this may be mitigated through restricted use classification; (3)

acute endangered species - the potential for acute risk to endangered species is high, regulatory action may

be warranted; and (4) chronic risk - the potential for chronic risk is high, regulatory action may be warranted.

 Currently, EFED does not perform assessments for chronic risk to plants, acute or chronic risks to non-target

insects, or chronic risk from granular/bait formulations to mammalian or avian species.

The ecotoxicity test values (i.e., measurement endpoints) used in the acute and chronic risk quotients are

derived from the results of required studies. Examples of ecotoxicity values derived from the results of shortterm laboratory studies that assess acute effects are: (1) LC50 (fish and birds); (2) LD50 (birds and mammals);

(3) EC50 (aquatic plants and aquatic invertebrates); and (4) EC25 (terrestrial plants). Examples of toxicity test

effect levels derived from the results of long-term laboratory studies that assess chronic effects are: (1)

LOAEC (birds, fish, and aquatic invertebrates); (2) NOAEC (birds, fish and aquatic invertebrates); and (3)

MATC (fish and aquatic invertebrates). For birds, mammals, and all aquatic organisms, the NOAEC is the

ecotoxicity test value used in assessing chronic risk. Other values may be used when justified. Risk

presumptions, along with the corresponding RQ’s and LOC’s are summarized in Tables E1 through E3.
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Table E1. Risk presumptions for terrestrial animals

Risk Presumption RQ LOC

Birds

Acute High Risk EEC1

/LC50 or LD50/ft2 or LD50/day3 0.5

Acute Restricted Use EEC/LC50 or LD50/ft2

 or LD50/day (or LD50 < 50 mg/kg) 0.2

Acute Endangered Species EEC/LC50 or LD50/ft2

 or LD50/day 0.1

Chronic Risk EEC/NOAEC 1

Wild Mammals

Acute High Risk EEC/LC50 or LD50/ft2

 or LD50/day 0.5

Acute Restricted Use EEC/LC50 or LD50/ft2

 or LD50/day (or LD50 < 50 mg/kg) 0.2

Acute Endangered Species EEC/LC50 or LD50/ft2

 or LD50/day 0.1

Chronic Risk EEC/NOAEC 1

1

 abbreviation for Estimated Environmental Concentration (ppm) on avian/mammalian food items 2

 mg/ft2 3 mg of toxicant consumed/day

 LD50 * wt. of bird LD50 * wt. of bird 

Table E2. Risk presumptions for aquatic animals

Risk Presumption RQ LOC

Acute High Risk EEC1

/LC50 or EC50 0.5

Acute Restricted Use EEC/LC50 or EC50 0.1

Acute Endangered Species EEC/LC50 or EC50 0.05

Chronic Risk EEC/NOAEC 1

1

 EEC = (ppm or ppb) in water

Table E3. Risk presumptions for plants

Risk Presumption RQ LOC

Terrestrial and Semi-Aquatic Plants 

Acute High Risk EEC1

/EC25 1

Acute Endangered Species EEC/EC05 or NOAEC 1

Aquatic Plants

Acute High Risk EEC2

/EC50 1

Acute Endangered Species EEC/EC05 or NOAEC 1 1

 EEC = lbs ai/A 

2

 EEC = (ppb/ppm) in water 
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APPENDIX V. SEEDING RATES FOR ASSESSED CROPS

In the process of assessing the pesticide carboxin, which is solely used as a seed treatment pesticide,

it was necessary to estimate the maximum likely seeding rates for a large number of crops for use in the risk

assessment. Since this information would be useful for other seed treatment pesticides, and in order to ensure

consistency across Division products, these maximum estimated rates and their sources are gathered Table

1.

Table 1. Maximum and typical seeding rates for selected crops in the United States

Crop Typical Rate (lb/acre) Maximum Rate (lb acre) Source

Barley 100 Colorado crop profile

Beans, Dry 160 registrant

Canola 8 registrant,

Minnesota crop profile

Corn 15 25 registrant

Cotton 15 18 registrant

Oats 60 128 registrant

Onions 2 15 registrant

Peanuts 90 135 Florida peanuts crop profile

Rape 8 registrant,

Minnesota crop profile

Rice 160 registrant

Rye 150 registrant

Safflower 100 registrant

Sorghum 6 8 registrant

Soybeans 60 100 registrant (typical)

crop profile (max)

Sugar beets 8 registrant

Triticale 90 registrant

Wheat 90 135 Kansas wheat crop profile

Crop profiles are at http://pestdata.ncsu.edu/cropprofiles/cplist.cfm?org=crop. The maximum seeding

rate for winter wheat was listed as “900,000 to 1,350,000 seeds per acre for irrigated wheat” in the Kansas

crop profile for wheat. This was converted to pounds per acre by assuming 1000 seeds per pound which was

the rate used for conversion in the Colorado wheat crop profile.
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In addition to the seeding rates from the crops profiles, some seeding rates were identified by the

registrants, Crompton and Gustafson in their submissions at the SMART meeting (Crompton Manufacturing

Corporation,2003; Gustafson, 2003). These values were used to support the use closure memo. When these

values were higher than those found in the Crop Profiles, they were used preferentially.

Coors Brewing Company. Crop Profile for Barley in Colorado. 2000.

http://pestdata.ncsu.edu/cropprofiles/cplist.cfm?org=crop

Colorado Wheat Administrative Committee. Crop Profile for Wheat (Winter) in Colorado. 2000.

http://pestdata.ncsu.edu/cropprofiles/cplist.cfm?org=crop

Crompton Manufacturing Corporation, Inc. 2003. CARBOXIN (VITAVAX) Usage Meeting. Submitted to the

U. S. Environmental Protection Agency March 27, 2003.

Gustafson. 2003. VITAVAX Seed Treatment Use Information. Submitted to U. S. Environmental Protection

Agency March 27, 2003.

University of Florida. Crop Profile for Peanuts in Florida. 2000.

http://pestdata.ncsu.edu/cropprofiles/docs/Flpeanuts.html

Kansas State University. Crop Profile for Wheat in Kansas. 1999.

http://pestdata.ncsu.edu/cropprofiles/cplist.cfm?org=crop