090201 D295494 RED (Revised Carboxin).wpd 

# 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

### 2 090201 D295494 RED (Revised Carboxin).wpd 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 (K d= 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 degradatio n of carboxin are via aerobic soil metabolism (mean half life (T 1⁄2) = 1.25 days) and aqueous photolysis (T 1⁄2= 1.5 hours). Carboxin is practically nontoxic to birds (LD 50>2,150 mg kg -1 ) and mammals (LD 50=2,588 mg kg -1 ) on an acute exposure basis; however, chronic ex posure 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 (LC 50= 1.2 mg L -1 ) and slightly toxic to freshwater invertebrates (LC 50range: 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; IC 50= 0.67 mg L -1 ) and nonvascular green algae (Pseudokirchneriella subcapitata IC 50= 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 chroni c 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 pro cesses and birds rely on other food sources in untreated areas. Additionally, the practice of planting seeds 0.5 to 1-in ch 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 cons ists 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 estimate d environmental concentrations. The potential for chronic risk could not be evaluated since no chronic toxicity data were available for review. Drinking water estimated environmental concen trations (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.

### 3 090201 D295494 RED (Revised Carboxin).wpd 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

### 4 090201 D295494 RED (Revised Carboxin).wpd 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

### 5 090201 D295494 RED (Revised Carboxin).wpd INTRODUCTION
Carboxin, (IUPAC: 5,6 dihydro-2-methyl-1,4-oxath iin-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). Accord ing 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 contro l a broader spectrum of fungal pests ( Rhizoctonia, Rhizopus, Helminthosporium, Fusarium andPenicillium ) 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 s eed 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 re gistered application rate is on beans which have a seeding rate of 120 to 160 lbs. seed/acre which is corre sponds 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 lb s. 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 equi valent (lbs a.i./acre) application rates reported in the use closure memo were 28% lower (range -11% to 84% lower) than those projecte d 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 Reregist ration 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 so il. 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 a ccordingly to compensate fo r 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 th en worked into the surface using a drag chain.

### 6 090201 D295494 RED (Revised Carboxin).wpd 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

### 7 090201 D295494 RED (Revised Carboxin).wpd 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 ra pidly 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 aerobi c metabolism with a mean half-life from two studies of 1.25 days. Carboxin degraded much more slowly in anae robic 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 evidenceof 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 th e 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 dire ct 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, in dicating 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 inTable 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.

### 8 090201 D295494 RED (Revised Carboxin).wpd 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 sulfinylacetanilide 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

### 9 090201 D295494 RED (Revised Carboxin).wpd 

### Figure 1. Carboxin sulfoxide

Figure 2. 

### " -vinyl sulfinyl acetanilide

### 10 090201 D295494 RED (Revised Carboxin).wpd 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 co lumn leaching studies that showed substantial leaching. Greater than 40% applied radioactivity of carboxin and degradates wa s 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 persistentthan 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

K f 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. @ m 3 @ 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

### 11 090201 D295494 RED (Revised Carboxin).wpd 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 concentrati on 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 e nd 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 signific ant 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-thi omorpholine-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 docu ments, (MRID’s 41252501, 41224503, 41242504) describe the degradation of carboxin under aerobic conditions in the soil. Both studies wereconducted 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 carboxinsulfoxide 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 fo r a first order decay model was used on the sum of carboxin and carboxin sulfoxide. While there appeared to have been a decrea se 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 co nfidence 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 case s, the studies were conducted in an unidentified sandy loam soil. In the aniline-ring labeled study, carboxin su lfoxide 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 anilin e-labeled study and 14.4% in the oxathiin-labeled study, in both cases at 120 days which was at the terminatio n 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

### 12 090201 D295494 RED (Revised Carboxin).wpd 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 condit ions. ( 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 whic h the aniline ring was labeled, carboxin degraded with a half-life of 146 days with a 95% confidence limits ra nging from 106 to 232 days. In the oxathiin ring labeled study, the half life was 114 days with 95% confidenceinterval 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 conduc ted 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 ha lf-life of 29 days while the oxathiin-ring labeled study had a 30.9 day half-life. Surprisingly, the major degrad ate 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 anae robic 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 indi vidual basis formed in the two studies. Aerobic aquatic metabolism Carboxin degraded with a half-life of 34.4 days in fl ooded silt loam soil that was incubated in the dark at 25° C under aerobic conditions (42600801). A 95% confiden ce interval for the half-life ranges from 26 to 50 days. The major degradates were carboxin sulfoxide wh ich peaked at 16.4% of the applied radioactivity one day after treatment and S-[2-(acetyloxy)-ethyl]-2-oxo-2-(p henylamino)ethanethioate (Figure 5). Identified minor degradates were carboxin sulfone, –phenyl-1-hydr oxy-[2-[2-[1-hydroxypropanoxy] ethylthio]] acetamide, –phenyl-1-hydroxy-[2-[2-propanoxy]ethyl]thioacetamide, and CO 2 . The last two metabolites were tracked during the course of the study as single values becaus e 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 ae robic conditions which is 3 days shor ter than the half-life of parent. The reason for the apparent decrease in half-life for the su m is the noisy nature of the data. This result is not unexpected given that there is a redox gradient with so me 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.

### 13 090201 D295494 RED (Revised Carboxin).wpd 

### Figure 3. S[2-acetyloxy)ethyl]-2-oxo-2- (phenylamino)ethanethioate 

### . Anaerobic aquatic metabolism Carboxin degraded with a half-life of 239 days in fl ooded 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 carboxinsulfoxide and S-[2-(ac etyloxy)-ethyl]-2-oxo-2- (phenylamino)ethanethioate ( Figure 3 ). Identified minor degradates were carboxin sulfone, –phenyl-1-hydroxy- [2-[2-[1-hydroxypropanoxy]ethylthio]] acetamide; –p henyl-1-hydroxy-[2-[2-propanoxy]ethyl]thioacetamide; 2,3 dihydro-5-carboxy-6-methyl-1,4-oxathiin; 2,3 dihydr o-5-carboxy-6-methyl-1,4-ox athiin-4-oxide, and CO 2 . There were 12 minor degradates that were not identifi ed. 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 de graded 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 st udy 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 with22.5 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 leac hate at 0.3, 3.3 and 0.5% of the applied respectively. The remainder of the radioactivity in the leachate was not id entified. 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 we re 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 regressi on 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 K

occan 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 th ere is only a single estimate of the isotherm available.

### 14 090201 D295494 RED (Revised Carboxin).wpd 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 coul d 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 (F ood Quality Protection Act) Index Reservoir Screening Tool (FIRST) model for estimating the uppe r 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 re sources so monitoring data are not considered in this assessment. The use pattern assessed was peanuts, as th is 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 Pestic ide Programs to estimate the concentrations found in drinking water from surface water sources for us e in human health risk assessment (EFED, 2001a). As such, it provides upper bound values on the concentratio ns 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 Progra ms to assess drinking water exposure (Hetrick et al, 1998 ). It is based on an actual reservoir located in Illinois; th e 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 unconfi ned aquifers under sandy soils. Table 6. FIRST and GENEEC2 input parameters for carboxin. Metabolism reflect the combined degradation of parent carboxin and carboxin sulfoxide

.

### 15 090201 D295494 RED (Revised Carboxin).wpd Chemical carboxin Solubility 195 mg L -1 at 7°C Hydrolysis stable Photolysis 0.064 d Aerobic Soil Metabolism T 1/2 = 71.2 d; rate for sum of carboxin + carboxin sulfoxide, single study Aerobic Aquatic Metabolism T 1/2 = 93.6 d; rate for sum of carboxin + carboxin sulfoxide, single study Soil Water Partitioning (K d ) 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 regressi on on log-transformed data. This was not done for aqueous photolysis as there was littl e 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 si ngle 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 th e binding potential, i.e. partition coefficient (K d ) of the soil, of carboxin sulfoxide, so the value for carboxin was used to represent both. The organic carbon partition coefficient (K oc ) value for SCIGROW was estimated from the K dby dividing by the organic carbon content in the original study. Table 7. SCIGROW input parameters for carboxin

.

Aerobic soil metaboli sm half-life 23.9 days Soil Water Partition Coefficient (K oc ) 71 L (kg-OC) -1 The use pattern selected to generate the recommend ed 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. Thi s 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 environm ent or that the risks from the compound are actually greater than the level of co ncern. However, at this tier, it is not possible to distinguish the two cases. Generally exceedances of the ri sk thresholds with two models will result in a further refinement of the drinking water exposure by more so phisticated 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 stab le to hydrolysis, processes which alte r pH like softening, will not impact the concentration in water. The low partition coeffi cients suggest that it will not be removed easily by flocculation and sedimentation.

### 16 090201 D295494 RED (Revised Carboxin).wpd AQUATIC EXPOSURE ASSESSMENT A screening aquatic risk assessment was cond ucted 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 tandemby 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 amo unt 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 es timates (USEPA, 2002). The aerobic soil metabolism input represents three times a single value and was estimat ed by linear regression on the sum of carboxin and carboxin sulfoxide. Two studies were available, but a first order mode l 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 a nd 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 fo r major carboxin seed treatments can be found in Appendix II.

Table 9. GENEEC model estimated carb oxin 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

### 17 090201 D295494 RED (Revised Carboxin).wpd 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 tr eated areas, preening activities, inhalation of pesticide vapor and contaminated particulate, and ingestion of drinking wate r 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 appro ach uses the acute oral toxicity for the toxicity endpoint (LD 50 ). The second method also uses the acute oral dose for t oxicity and compares it to the available concentration of pesticide on the basis of pesticide per square foot. The fi rst 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 repres ent all species of bird, mammal, or aquatic organism. Only a few surrogate species for both freshwater fish and bird s are used to represent all freshwater fish (2000+) and bird (680+) species in the United States. For mammals, acute st udies 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 r ecommendations. The remaining studies (30%) were classified as supplemental. Although supplemental studies did not co mpletely 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 pr oducts Vitavax 75 W (38.7% carboxin plus 37.5% thiram) and Vitavax SP 38.7% carboxin plus 37.5% captan) were pr actically nontoxic to bobwhite quail with acute oral LD 50 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 (LC 50>5,620 mg kg -1 of diet) and mallard ducks (LC 50>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 EC 50values of 0.67 and 0.37 mg L -1 , respectively. No data were available on which to gaugeeither terrestrial or semiaquatic plant phytotoxicity

### 18 090201 D295494 RED (Revised Carboxin).wpd Table 10 . Summary of acute and chronic toxicity data for terrestrial organisms exposed to carboxin.

Species Acute Toxicity Chronic Toxicity
LD 50 (ppm) Acute Oral Toxicity (MRID) 5-day LC 50 (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 t oxicity estimates using technical grade carboxin.

Species Acute Toxicity Chronic Toxicity
96-hr LC 50

(mg/L) 48-hr EC 50 (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 da ta for aquatic plants exposed to carboxin.

Species Acute Toxicity 96-hr LC 50

(mg/L) Acute Toxicity (MRID) Duckweed ( Lemna gibba ) 0.67 (414938-02) Green algae ( Pseudokirchneriella subcapitata ) 0.37 (414938-01)

### 19 090201 D295494 RED (Revised Carboxin).wpd 

## 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. Fo r example, the maximum application rate to peanuts (0.38 lbs a.i. per 135 lbs seed) is e quivalent 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 LD 50can be adjusted for body weight based on the formula recommended by Mineau et al. 1996:

where adjusted LD 50is the median 50% lethal dose for the species being assessed, LD 50is the median lethal dose in the test organism, AW is the body weight of the assessed organi sm 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 LD 50of 6094 mg kg -1 , the adjusted LD 50is 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 quo tients 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.

### 20 090201 D295494 RED (Revised Carboxin).wpd 

### F BW W =

− 0 621 1 0 564 

### . * ( ) . 

### Adj LD LD AW TW . (. )
50 50 0 75 

### 10 =       Crop Acute RQ Method 1 a Acute RQ Method 2 b Chronic RQ c Barley <0.01 <0.01 20 d Bean <0.01 <0.01 13 d Canola <0.01 <0.01 14 d Corn <0.01 <0.01 19 d Cotton 0.006 <0.01 54 d Oats <0.01 <0.01 24 d Onion 0.013 <0.01 108 d Peanuts 0.005 <0.01 40 d

Rape <0.01 <0.01 14 d Rice <0.01 <0.01 11 d Soybeans <0.01 <0.01 13 d Triticale <0.01 <0.01 10 d Wheat <0.01 <0.01 20 d

aAcute RQ Method 1 = mg•kg -1 day -1 / LD 50 bAcute RQ Method 2 = mg•ft -2 / LD 50 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 adju sted 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 LD 50

### 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 LD 50

### 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.

### 21 090201 D295494 RED (Revised Carboxin).wpd 

### Table 14. Summary of acute and chronic mamma lian RQ values based on an adjusted mammalian acute LD 50 

### and chronic NOAEC of 81.84 mg kg -1 

### and 200 mg kg -1 

### of diet, respectively. Crop Acute RQ Method 1 a Acute RQ Method 2 b Chronic RQ c Barley 17 d 0.02 7.1 e Bean 11 d 0.02 4.7 e Canola 

### 12 d <0.01 5 e
Corn 17 d <0.01 6.8 e Cotton 46 d <0.01 19 e Oats 20 d 0.03 8.3 e Onion 

### 92 d 0.01 38 e
Peanuts 34 d 0.05 14 e

Rape 12 d 0.01 5 e Rice 9.2 d 0.02 3.8 e Soybeans 11 d 0.01 4.7 e Triticale 8.6 d 0.01 3.5 e Wheat 17 d 0.02 7.0 e

aAcute RQ Method 1= mg•kg -1 bw -1 d -1 /LD 50 bAcute RQ Method 2 = mg•ft -2 / LD 50 c Chronic RQ = mg• kg -1 seed-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.
eExceeds chronic risk (RQ $ 1.0) level of concern.


### Aquatic Risk Assessment Aquatic Animals Using a single granular application, broadcast, w ith no incorporation for the management practice to represent the seed treatment application, the peak con centration 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).

.

### 22 090201 D295494 RED (Revised Carboxin).wpd 

### Table 15. Summary of acute risk quotients for freshwater fish (bluegill LC 50 

### = 1200 μg/L) and invertebrates (Daphnia magna EC 50 

### = 84,400 μg/L) for carboxin based on estimated environmental concentrations generated using GENEEC 2 model. Crop Peak GENEEC Value μg/L Fish Acute RQ a 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 ÷ LC 50

### 23 090201 D295494 RED (Revised Carboxin).wpd 

### 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 usuallymade for aquatic vascular plants from the surrogate duckweed Lemna gibba . Non-vascular acute risk assessments are pe rformed 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 quotie nt is determined by dividing the pesticide's initial or peak concentration in water by the plant EC 50

### 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 nonva scular and vascular plants based on green algae ( Pseudokirchneriella subcapitata EC 50 

### = 0.37 mg L -1 

### ) and duck weed ( Lemna gibbaEC 50 

### = 0.67 mg L -1 

### ) toxicity tests. Crop Peak GENEEC Value μg/L Nonvascular Plant Acute RQ b 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 expos ure to birds, no acute LOC’s are exceeded for small-sized (20 g) birds that are most likely to ingestseeds 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 mu ch as 100-fold, there are a number of reasons why this

### 24 090201 D295494 RED (Revised Carboxin).wpd 

### is likely an overstatement of the risk. First, the LOAE C (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 valu es; RQ values based on the LOAEC range from 1 to 11. Additionally, treated seed is available for consum ption for only about 10 days before the seed germinates and becomes unavailable. Furthermore, carboxin should di ffuse 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 pr actice 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 (LD 50

### = 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 suggest s the use of a NOAEC in the risk calculation does not provide a large margin of safety; risk quotients basedon the LOAEC range from 1.8 to 19. While the other mitigating factors that applied to the avian chroni c 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 pe rsistent, the carboxin sulfoxide degradate is much more persistent than the parent. Since the core structure of the molecule is intact ther e is some basis for assuming the toxicity of this degradate could be similar to the parent. Based on environmental concentrations in surf ace water estimated using GENEEC, no acute LOCs are exceeded for aquatic animals. Since no chronic toxi city data were available for EFED to review, it is not possible for EFED to gauge the potential for chronic riskto aquatic animals at th is 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 ma llard 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 th e 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 horm one system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effect s 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

### 25 090201 D295494 RED (Revised Carboxin).wpd 

### in humans, FFDCA authority to require the wildlife eval uations. As the science develops and resources allow, screening of additional hormone systems may be adde d 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 de veloped, it is recommended that carboxin be subjected to additional screening and or testing to better ch aracterize 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 ev aluated 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 identif y 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 toxic ity and exposure data devel oped for RED’s into context for individual listed species and their locations by evaluating important ecological parameters, pesticide use information, the geographic relationship between speci fic pesticide uses and species locations, and biological requirements and behavioral aspects of the particular speci es. This analysis will take into consideration any regulatory changes recommended in this RED that are be ing implemented at this time. A determination that there is a likelihood of potential impact to a listed sp ecies may result in limitations on use of the pesticide, other measures to mitigate any potential impact, or consu ltations 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 agricu ltural 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 w ould 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.

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

### LITERATURE CITED Accession No. 254339 (in part) . Dzialo, D. G. and M. R. Lengen. 1983. [ 14 

### C] carboxin hydrolysis study. Project N. 8304. Unpublished study receive d 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 ® 14 

### C 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 ® 14 

### C 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 14 

### C 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. [ 14 

### C-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. [C 14 

### -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. [ 14 

### C-oxathiin] carboxin aerobic so il 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. [C 14 

### -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. [ 14 

### C-oxathiin] carboxin aerobic soil metabolism study final report. Completed in September 1989. Performed and submitted by Uniroyal Chemical Company, Middlebury, CT. Project No. 8916.

### 27 090201 D295494 RED (Revised Carboxin).wpd 

### 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. [ 14 

### C-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 [ 14 

### C-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 14 

### C-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 14 

### C-carboxin. XBL Study No. XBL 92037; XBL Report No. RPT00143; Uniroyal StudyNo. 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 aquaticmetabolism study review

. Internal EPA memorandum to Stephanie Nguyen. D258134. Parker, Ronald. 1999. Expected Maximum Drinking Water Con centrations 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

### 28 090201 D295494 RED (Revised Carboxin).wpd 

### 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 f ood 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. Ne lson 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 S upport Document for Wildlife Criteria. Washington DC Office of Water. Document Number EPA-820-B095-009090201 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 a nd 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 te nder developing rootlets of cereal seedlings against wireworms and leatherjackets. Carboxin is register ed 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. Car boxin is applied in commercial seed treatment operations and also in on-farm situati ons 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

### 30 090201 D295494 RED (Revised Carboxin).wpd 

### 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.

### 31 090201 D295494 RED (Revised Carboxin).wpd 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 12Crop 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)



### 32 090201 D295494 RED (Revised Carboxin).wpd 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 re gistrants knowledge based on sales info and an understa nding of the use practices.

### 33 090201 D295494 RED (Revised Carboxin).wpd 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 additi on, 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 regi strant and maintained within the Agency’s database systems.

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

### APPENDIX II. GENEEC 2 MODEL OUTPUT

RUN No. 1 FOR CARBOXIN ON B ARLEY * 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 B EAN * 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

### 35 090201 D295494 RED (Revised Carboxin).wpd 

### RUN No. 3 FOR CARBOXIN ON C ANOLA * 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 C ORN * 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 C OTTON * INPUT VALUES *

### 36 090201 D295494 RED (Revised Carboxin).wpd 

### -------------------------------------------------------------------- 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 O ATS * 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

### 37 090201 D295494 RED (Revised Carboxin).wpd 

### RUN No. 7 FOR CARBOXIN ON O NION * 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

### 38 090201 D295494 RED (Revised Carboxin).wpd 

### 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

### 39 090201 D295494 RED (Revised Carboxin).wpd 

### RUN No. 12 FOR CARBOXIN ON S OYBEAN * 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 T RITICALE * 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

### 40 090201 D295494 RED (Revised Carboxin).wpd 

### RUN No. 14 FOR CARBOXIN ON W HEAT * 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

### 41 090201 D295494 RED (Revised Carboxin).wpd 

### 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 LD 50

### 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 co re, and meets guideline 71-1 acute oral toxicity testing requirements for birds. Additionally, an 8-day acute or al toxicity study was conducted using mallard ducks; the study resulted in an LD 50

### 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 LD 50 mg/kg bw MRID No. Author Year Toxicity Category Fulfills Guideline Requirement 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 (LD 50

### = 2,410 mg/kg) to Bobwhite quail on an acute exposure basis (Accession Number 224935). No raw data were provi ded 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 (LD 50

### >10,000 mg/kg bw). However, no raw data were available to substantiate th e 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 LC 50

### 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 LC 50

### 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

### 42 090201 D295494 RED (Revised Carboxin).wpd 

### 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 toxicitystudy of Vitavax technical (99% a.i.) using bobwhite quail, the LC 50

### 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 LC 50 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 availabl e for Vitavax SP (75% a.i.). The 8-day dietary LC 50 

### 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 fo rmulated end-product is practically nontoxic to birds on a subacute dietary exposure basis.
Chronic Toxicity to Birds Two avian reproduction studies we re submitted for review ( Table III-3 ). In the study with bobwhite quail (MRID 442401-01), no significant treatment relate d effects on any parameters measured at any concentration tested were noted. This study is sci entifically sound, however it does not meet the guideline requirements for an avian reproduction study using bobwh ite 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 num ber 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 scientificallysound, is classified as core, and meets Guideline 71-4 chronic avian reproductive toxicity testing requirements.

### 43 090201 D295494 RED (Revised Carboxin).wpd 

### 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 tes ting; these toxicity values are summarized in Table III-4. Carboxin is classified as practically nontoxic to mammals on an acute exposure basis (LD 50 

### =2,588 mg/kg). Chronic toxicity data from a 2-generation rat repr oduction 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. LD 50 (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 i ndicated 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.

### 44 090201 D295494 RED (Revised Carboxin).wpd 

### Table III-4. Summary of acute contact and oral48-hr toxicity tests with the honey bee ( Apis mellifera ) for carboxin. Species % active ingredient LD 50 : g/bee MRID No. Author/Year Toxicity Category Fulfills Guideline Requirement 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 LC 50

### 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 LC 50

### test (MRID 435823-05) was classified as core ( Table III-5 ). An additional rainbow trout study (Accession No. 224935) reported a 96-hr LC 50

### 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 amount s of degradates (0.5 to 0.8 mg/L) found in the two highest treatment concentrations. The 96-h LC 50

### 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 withbluegill sunfish reported a 96-hr LC 50

### 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 LC 50 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 testi ng of rainbow trout with Vitavax ® 

### SP (seed protectant; 37.5% carboxin and 37.5% captan) indicated that the formulated product is moderately toxic (LC 50

### = 4.5 mg/L) on an acute exposure basis (Accession Number 224935). Similarly, static 96-hr acute toxicity testing of the Vitavax SP

### 45 090201 D295494 RED (Revised Carboxin).wpd 

### using bluegill sunfish indicated that the formulated product was moderately toxic (LC 50

### = 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 sunfis h with Vitavax SP/Captan (37.5% carboxin / 37.5% captan) indicated that the form ulated product is moderately toxic to rainbow trout (LC 50

### = 6.6 mg L -1 

### ) and slightly toxic (LC 50

### = 11.2 mg L -1 

### ) on an acute exposure basis (Accession Number 224935). Static 96-hr acute toxicity testing of rainbow trout and bluegill sunfis h with Vitavax SP/Thiram (37.5% carboxin /37.5% thiram) indicated the formulated product is highly toxic to both rainbow (LC 50

### = 0.38 mg L -1 

### ) and bluegill sunfish (LC 50

### = 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 carboxi n (Vitavax technical; 99% a.i.) using Daphnia magna (Acc. No. 235236) the 48-hr EC 50

### 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 co re, and meets Guideline 72-3 testing requirements for an acute toxicity study with a freshwater invertebrate. A flow-through freshwater aquatic invertebrate toxi city test using TGAI was also submitted (MRID 435823-06, flow through) to establish the toxicity of carboxin to aquatic invertebrates. The EC 50

### 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 c oncentrations 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, th e requirement for a new study is waived. Based on the results of both the static and flow-through acute toxic ity 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 LC 50 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.

### 46 090201 D295494 RED (Revised Carboxin).wpd 

### 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 fo rmulated 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 high est exposure concentration (1,000 mg L -1 

### ); the 96-hr LC 50

### was 964 mg L -1 

### . Pink shrimp were considerably more sen sitive to the formulated product with an LC 50

### 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 i nvertebrates. These studies are classified as supplemental though and acute toxicity testing using technical grad e active ingredient should be made available for evaluation.

Table III-. Summary of acute 96-hr toxicity tests on mari ne invertebrates exposed to formulated endproduct Vitavax R flowable fungicide (17% carboxin and 17% thiram). Species % active ingredient LC 50 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 ve getative 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 25 o 

### C) or drift (aerial or irrigation) and/or that may have endangered or threatened plant speci es associated with the application s ite. 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.

### 47 090201 D295494 RED (Revised Carboxin).wpd 

### 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 EC 50

### 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 EC 50

### 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 EC 50

### 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 nonvascu lar acute aquatic plant toxicity tests with carboxin.
Species % active ingredient EC 50 /IC 50 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 413178-01 Bogers, 1989 Supplemental
Green algae Pseudokirchneriella subcapitata 1 97.5 0.37 Cell density 41493801 Hughes, 1990 Core

1 Formerly Selenastrum capricornutum

### 48 090201 D295494 RED (Revised Carboxin).wpd 

### 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 calculate d 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 th e need to consider regulatory action. The criteria indicate that a pesticide used as di rected 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 ri sk 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 ofecotoxicity values derived from the results of shortterm laboratory studies that assess acute effects are: (1) LC 50

### (fish and birds); (2) LD 50

### (birds and mammals); (3) EC 50

### (aquatic plants and aquatic invertebrates); and (4) EC 25 

### (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) NOAE C (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

.

### 49 090201 D295494 RED (Revised Carboxin).wpd 

### Table E1. Risk presumptions for terrestrial animals Risk Presumption RQ LOC Birds Acute High Risk EEC 1 /LC 50or LD 50 /ft2 or LD 50 /day 3 0.5 Acute Restricted Use EEC/LC 50or LD 50 /ft2 or LD 50 /day (or LD 50< 50 mg/kg) 0.2 Acute Endangered Species EEC/LC 50or LD 50 /ft2 or LD 50 /day 0.1 Chronic Risk EEC/NOAEC 1 Wild Mammals Acute High Risk EEC/LC 50or LD 50 /ft2 or LD 50 /day 0.5 Acute Restricted Use EEC/LC 50or LD 50 /ft2 or LD 50 /day (or LD 50< 50 mg/kg) 0.2 Acute Endangered Species EEC/LC 50or LD 50 /ft2 or LD 50 /day 0.1 Chronic Risk EEC/NOAEC 1

1 abbreviation for Estimated Environmental Con centration (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 EEC 1 /LC 50or EC 50 0.5 Acute Restricted Use EEC/LC 50or EC 50 0.1 Acute Endangered Species EEC/LC 50or EC 50 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 EEC 1 /EC 25 1 Acute Endangered Species EEC/EC 05 or NOAEC 1 Aquatic Plants Acute High Risk EEC 2 /EC 50 1 Acute Endangered Species EEC/EC 05 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, whic h is solely used as a seed treatment pesticide, it was necessary to estimate the maximum likely seeding rat es 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 rate s for selected crops in the United States Crop Typical Rate (lb/acre) M aximum 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 prof iles, some seeding rates were identified by the registrants, Crompton and Gustafson in their submi ssions 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 Cr op 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