### 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON D.C., 20460

March 11, 2015

PC Code: 090201/090202

DP Barcode: D423826

MEMORANDUM

Subject: Registration Review – Preliminary Problem Formulation for the Drinking Water and Ecological Risk Assessments of Carboxin and Oxycarboxin

To: Dana Friedman, Chemical Review Manager Cathryn Britton, Team Leader Risk Management Branch 2 Pesticide Re-evaluation Division (7508P)

From: Catherine Aubee, Biologist Chuck Peck, Environmental Engineer

Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

Reviewed by: Jim Carleton, Ph.D., Senior Fate Scientist Thomas Steeger, Ph.D., Senior Science Advisor

Environmental Risk Branch IV

Environmental Fate and Effects Division

Through: Jean Holmes, DVM, Branch Chief

Environmental Risk Branch IV

Environmental Fate and Effects Division 2015.03.11 12:54:27

-04'00' 2015.03.11

12:57:39

-04'00'

### 2 

# REGISTRATION REVIEW

DRAFT PROBLEM FORMULATION FOR DRINKING WATER

AND ECOLOGICAL RISK ASSESSMENTS OF

Carboxin and Oxycarboxin

5,6 dihydro-2-methyl-1,4-oxathiin-3-carboxanilide and 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide 4,4-dioxide

CAS Registry Number: 5234-68-4 and 5259-88-1

PC Code: 090201 and 090202

Carboxin Oxycarboxin

P

repared by:

Catherine Aubee, Biologist Chuck Peck, Environmental Engineer U. S. Environmental Protection Agency Office of Pesticide Programs

E nvironmental Fate and Effects Division

E nvironmental Risk Branch I V 1200 Pennsylvania Ave., NW

M

ail Code 7507P Washington, DC 20460 R eviewed by:

Jim Carleton, Ph.D., Senior Scientist Thomas Steeger, Ph.D., Senior Science Advisor Jean Holmes, DVM, Branch Chief

### 3 

# Table of Contents

1. Executive Summary ............................................................................................................. ... 4
2. Introduction .................................................................................................................. ........... 6
3. Use Characterization .......................................................................................................... ..... 7
4. Conclusions from Previous Risk Assessments ....................................................................... 8

a. Ecological Risk Assessment ................................................................................................ 8

b. Drinking Water Exposure Assessments ............................................................................... 8

c. Clean Water Act Programs .................................................................................................. 9

5. Environmental Fate and Transport.......................................................................................... 9

a. Parent Compound................................................................................................................ . 9

b. Transformation Products .................................................................................................... 11
6. Receptors...................................................................................................................... ......... 14

a. Effects to Aquatic Organisms ............................................................................................ 14

b. Effects to Terrestrial Organisms ........................................................................................ 17

c. Ecological Incidents .......................................................................................................... . 19
7. Exposure Pathways of Concern ............................................................................................ 20
8. Analysis Plan ................................................................................................................. ....... 20

a. Stressors of Concern .......................................................................................................... 20

i. Ecological Risk Assessment ........................................................................................... 20

ii. Drinking Water ........................................................................................................... 21

b. Measures of Exposure ........................................................................................................ 2 1

c. Available Monitoring Data ................................................................................................ 21

d. Measures of Effect ............................................................................................................ . 21
9. Endangered Species Assessment .......................................................................................... 22
10. Endocrine Disruptor Screening Program (EDSP) ................................................................. 22
11. Preliminary Identification of Data Gaps ............................................................................... 22

a. Environmental Fate ............................................................................................................ 22

b. Effects ....................................................................................................................... ......... 23
12. References .................................................................................................................... ......... 29

a. Fate Studies .................................................................................................................. ...... 30

b. Effects Studies for Carboxin .............................................................................................. 32

c. Effects Studies for Oxycarboxin ........................................................................................ 37 Appendix A. Summary of endpoints and review classifications for available ecological effects studies, with annotations for internal document tracking. ............................................................ 39Appendix B. Toxicology one-liners for mammalian (rat) acute oral, acute inhalation, and twogeneration reproduction data reviewed by HED. .......................................................................... 48 1. Acute oral toxicity ....................................................................................................... ........ 48 2. Acute inhalation toxicity ................................................................................................. ..... 54 3. Two-generation rat reproduction ......................................................................................... 5 8 Appendix C. Screening Tool for Inhalation Risk (v. 1.0). ........................................................... 62

### 4 

## 1. Executive Summary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of carboxin and oxycarboxin. Oxycarboxin, commonly referred to a carboxin sulfone, occurs as a transformation product of carboxin and is also a separately registered pesticide active ingredient (a.i.). The problem formulation describes the methods planned to be used during the completion of drinking water and ecological risk assessments in support of registration review and provides an overview of the environmental fate, ecological effects, potential risks and uncertainties associated with the use of carboxin and oxycarboxin. This document also identifies additional studies that would be beneficial to the conduct of an ecological risk assessment.

In support of previous risk assessments, EFED identified fate and ecological data gaps for

carboxin 1 

### and oxycarboxin 2 

### . In lieu of submitting ecotoxicity data for oxycarboxin, the registrant elected to voluntarily cancel various outdoor terrestrial nonfood uses and limit remaining uses of oxycarboxin to “ornamentals grown in enclosed commercial structures such as greenhouses, shadehouses, and interiorscapes.” 3 

### However, this language is ambiguous by current standards because the Agency currently considers shadehouse use to be an outdoor use 4



### . Therefore, in the absence of label clarification, EFED will assess risk from oxycarboxin use on shadehouse ornamentals as an outdoor use. The data recommendations for oxycarboxin reflect this assumption. However, if the label is clarified to indicate only indoor use, then no additional guidelines studies are needed to support the oxycarboxin ecological risk assessment.

Exposure of pollinators to carboxin and oxycarboxin is expected to be limited. Nonetheless, exposure may occur as a result of carboxin seed treatment uses through contact ( e.g. , for soildwelling bees) and through ingestion of residues in plants germinated from treated seeds. Additionally, as oxycarboxin may be applied at bloom and is systemic, there is uncertainty with regards to exposure of pollinators to residues in pollen and nectar of ornamentals treated with oxycarboxin. Carboxin and oxycarboxin showed similar acute toxicity through contact exposure in laboratory tests with the honey bee; therefore, the data from pollinator studies requested for carboxin will be considered representative of toxicity from oxycarboxin. If data are provided to demonstrate that residues in flowers/ornamentals are below the limit of detection (<LOD) when bees might be foraging or that ornamentals treated with oxycarboxin are cultivated to prevent pollination, then EFED will consider these data in determining whether additional pollinator studies are needed.

To support a quantitative ecological risk assessment for oxycarboxin, the maximum application rate needs to be specified in terms of mass a.i. per unit area ( e.g ., lbs a.i./A) and the maximum number of applications per year. Current labels specify the dilution ratio (1.6 to 2.4 oz product per 10 gallons water) and retreatment interval (two-to-four sprays per season at approximately

1 US EPA. 1992. Data requirements for the fungicide, car boxin. Report dated November 24, 1992. See SAN R2004634.

2 US EPA. 1992. Data requirements for the fungicide, oxycarboxi n. Memo from D. Urban to W. Waldrop. May 5, 1992.

3 Uniroyal Chemical Co., Inc. 1994. Letter from W.F. Cummings to C. Childress, Sp ecial Review and Reregistration Branch, US EP A Office of Pesticide Programs. May 24, 1994.

4 For example, see “Action Code Interpretation” for registrati on of a non-food outdoor use under PRIA 3. Available online at http://www2.epa.gov/pria-fees/r060-pria-fee-category . Last updated November 17, 2014.

### 5 two week intervals), but do not identify the maximum amount of oxycarboxin that may be applied in a given area.

Based on current risk assessment methodology, data requirements, and the use patterns of these pesticide active ingredients, EFED recommends submission of the fate and ecotoxicity data in

Table 1 and Table 2 . For ecotoxicity tests, Table 2 specifies whether each study should be conducted with technical grade active ingredient (TGAI), typical end-use product (TEP), or a transformation product ( e.g. , carboxin sulfoxide). As appropriate, EFED will consider submissions of other relevant data ( e.g., non-guideline submissions) to address uncertainties in the ecotoxicity profile of oxycarboxin and its toxicity relative to carboxin.

Table 1. Environmental Fate Data Recommendations for the Fungicide Active Ingredients Carboxin and Oxycarboxin.


### OCSPP

Guideline Study Type Carboxin Oxycarboxin

835.1230 Batch equilibrium (adsorption/desorption) Needed

Table 2. Ecotoxicity Data Recommendations for the Fungicide Active Ingredients Carboxin and Oxycarboxin.



### OCSPP

Guideline Study Type Carboxin Oxycarboxin
(to assess outdoor use - shadehouse)



### 850.2100 Avian acute oral toxicity, upland game bird species (TGAI) Needed

850.2100 Avian acute oral toxicity, passerine species (TGAI) Needed Needed

850.2200 Avian dietary toxicity, waterfowl species (TGAI) Needed

850.2300 Avian reproduction, waterfowl species (TGAI) Needed

850.2300 Avian reproduction, upland game bird species (TGAI) Needed

850.1025 Estuarine/Marine mollusc acute toxicity (TGAI) Needed Needed

850.1035 Estuarine/Marine crustacean acute toxicity (TGAI) Needed Needed

850.1075 Estuarine/Marine fish acute toxicity (TGAI) Needed Needed

850.1300 Freshwater invertebrate, reproduction test (using carboxin sulfoxide) 5 

### Needed Needed

850.1350 Estuarine/marine invertebrate, reproduction test (using carboxin sulfoxide) 6 

### Needed Needed

5 The carboxin ecological risk assessment will rely upon chronic toxicity data to be submitted for aquatic organisms exposed to the transformation product carboxin sulfoxide because carboxin from treated seeds is expected to be largely transformed through aerobic soil me tabolism before reaching surface water.

6 Ibid.

### 6 OCSPP

Guideline Study Type Carboxin Oxycarboxin
(to assess outdoor use - shadehouse)



### 850.1400 Freshwater fish, early life stage test (using carboxin sulfoxide) 7 

### Needed Needed

850.1400 Estuarine/marine fish, early life stage test (using carboxin sulfoxide) 8 

### Needed Needed

Nonguideline 9 

### Honeybee adult acute oral toxicity study (TGAI) Needed

Nonguideline 9 

### Honeybee adult chronic oral toxicity study (TGAI) Needed

Nonguideline 9 

### Honeybee larval acute toxicity (TGAI) Needed Nonguideline 9 

### Honeybee larval chronic toxicity (TGAI) Needed

Nonguideline 9 

### Honey bee semi-field (tunnel or colonyfeeding) test –TGAI and TEP Needed 10



### Nonguideline 9 

### Field trial of residues in pollen and nectar

– TGAI and TEP Needed 11



### 850.3040 Field testing for pollinators – TGAI and

TEP Needed 12



### 850.4100 Seedling emergence (10 species) (TGAI or TEP) Needed Needed

850.4150 Vegetative vigor (10 species) (TEP) Needed

850.4400 Aquatic plant growth, vascular plant (TGAI or TEP) Needed

850.4500 Aquatic Plant, freshwater green alga species (TGAI or TEP) Needed

850.4500 Aquatic Plant, freshwater diatom (TGAI) Needed Needed 850.4500 Aquatic Plant, marine diatom (TGAI) Needed Needed 850.4550 Aquatic Plant, cyanobacterium (TGAI) Needed Needed



## 2. Introduction

7 Ibid.

8 Ibid.

9 Carboxin data will be used in the a ssessment for oxycarboxin because th e acute contact toxicity values for honey bees exposed to carboxin and oxycarboxin are similar.

10 Higher tier insect pollinator testing ( e.g ., semi-field and field trials) may be conducted after the Agency has

evaluated the lower tier h oney bee toxicity studies ( e.g ., acute and chronic toxicity to honey bee larvae and adults).

11 Ibid.

12 Ibid.

### 7 EFED evaluated the most recent ecological risk assessments for carboxin and oxycarboxin in association with the updated toxicity, exposure, and usage information to determine if sufficient data are available and if further updates are needed to support registration review. The most recent risk assessment (DP Barcode 295494) 13 

### was prepared for the 2004 Registration Eligibility

Document for carboxin 14 

### . In addition, EFED considered the latest Agency science policies and risk assessment methodologies.

Carboxin (CAS 5234-68-4) and oxycarboxin (CAS 5259-88-1) are members of the oxathiin class of systemic fungicides. 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 15 

### ; oxycarboxin is presumed to have a similar mode of action.



## 3. Use Characterization

Carboxin is used to control seed and seedling fungal diseases (smut, rot, blight) on barley, beans, canola, corn, cotton, oats, onions, peanuts, rice, rye, safflower, sorghum, soybeans, triticale, and wheat. It is formulated in 12 active end-use products as a wettable powder, dust, flowable concentrate, emulsifiable concentrate, and ready-to-use liquid. Carboxin is applied to seeds prior to planting, both by commercial seed treaters and by on-farm applicators. In August 2014, seven carboxin products were cancelled following a Federal Register (FR) notice announcement of voluntary cancellation 16 

### . Based on maximum treated seed application rates and maximum seed planting rates, the range of application rates to fields is 0.01 to 0.4 lbs a.i./acre.

Oxycarboxin, also known as carboxin sulfone, is formulated as a wettable powder fungicide and is used as a foliar spray for control of rust diseases of ornamentals grown in enclosed commercial structures such as greenhouses, shadehouses and interiorscapes. It is formulated in one active end-use product. Oxycarboxin is also a minor transformation product of carboxin in anaerobic environments, and a major transformation product of carboxin sulfoxide, a major transformation product of carboxin, in aerobic soil metabolism studies.

The chemical profiles produced by BEAD, located in the docket for this registration review action, list the use patterns of maximum exposures for the current uses of carboxin and oxycarboxin. For risk assessment purposes, EFED will utilize application scenarios that result in maximum exposure for a given use. In the absence of information on maximum single application rate, application interval, annual maximum rate (lbs a.i./year), or application method conservative assumptions may be employed by EFED to support the risk assessment.

13 USEPA. 2004. Final ecological risk assessment in support of the Reregistration Eligibility Decision for carboxin. September 10, 2004. Environmental Fate and Effects Division, Office of Pesticide Programs, Washington, DC 20460. Available online at http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0081-0119 . DP Barcode 295494 et seq

. 14 USEPA. 2004 b . Reregistration Eligibility Decision for Carboxin. Office of Chemical Safety and Pollution Prevention formerly the Office of Prevention, Pesticides and Toxic Substances . (7508C). EPA 738-R-04-015. September 2004. http://www.epa.gov/pesticides/reregistration/REDs/0012red_carboxin.pdf

15 Schewe, T. and H. Lyr. 1987. Mechanism of action of carboxin fung icides and related compounds. In H. Lyr (Editor) Modern Selec tive Fungicides, Properties, applications and mechanisms of action. Longman Scientific & Technical (John Wiley & Sons, Inc.), New Yo rk. Pages

133 - 142

16 USEPA. 2014. Federal Register Notice on the Product Cancella tion Order for Certain Pesticide Registrations. EPA-HQ-OPP-2010- 0014. Federal Register Volume 79, Number 136 (Wednesday, July 16, 2014. http://www.gpo.gov/fdsys/pkg/FR-2014-07-16/html/2014-16458.htm

### 8 

## 4. Conclusions from Previous Risk Assessments

In 2004, carboxin completed re-registration and a registration eligibility decision (RED) document was issued. Oxycarboxin was not assessed for ecological risks at that time. A memo 17 

### that addressed human health occupational risks of oxycarboxin use in greenhouses was issued in September 2004.

a. Ecological Risk Assessment

The 2004 RED 18 

### indicated that carboxin risk quotients (RQs) exceeded the chronic risk level of concern (LOC) for birds that were likely to ingest seeds as part of their normal diet. For mammals, RQs also exceeded the Agency’s LOCs for acute and chronic risk ( Table 3 ). Life history data for potentially affected listed species were used to characterize the risk. The RED concluded that seed treatment uses of carboxin may affect one listed species of seed-eating bird, the Attwater prairie chicken ( Tympanuchus cupido attwateri ). However, it determined that with soil incorporation/discing of treated seeds, exposure may be significantly reduced. To support further analysis, the assessment noted that additional data were needed on the efficiency of soil incorporation efforts and the extent to which alternative food sources may exist in and around cotton fields where carboxin-treated seed is planted. The likelihood of adverse effects from chronic exposure of aquatic animals and the potential for adverse effects to non-target terrestrial plants were not assessed due to a lack of toxicity data.

In the absence of data for oxycarboxin, ecological risk was not previously assessed. Ecological exposure from registered greenhouse and shadehouse uses of oxycarboxin was considered possible, though limited.

The major ecological risk conclusions for carboxin in the RED were as follows:

Table 3. Summary of Risks and Concerns Identified for Carboxin in Previous Assessments

Birds Mammals Terr.

Plants Terr.

Inverts Fish BCF Aquatic

Inverts Aquatic

Plants Groundwater

contamination Persistence Degradates

of concern

Yes Yes Not

Assessed No No* No No* No No No Yes**

Yes = at least one LOC has been exceeded in previous assessments; No = LOCs have not been exceeded in previous assessments; NA = RQs have not been calculated previously. *Chronic risk not previously assessed due to lack of data. No conclusions were presented for chronic risk. ** Carboxin sulfoxide was identified as a degradat e product of concern in previous assessments.



### b. Drinking Water Exposure Assessments

A human drinking water exposure assessment was conducted for carboxin residues (carboxin and

carboxin sulfoxide as identified in a 2001 HED memo 19 

### ) as part of the 2004 RED 20 

### . The use pattern selected for both the surface and groundwater assessment was the carboxin seed

17 USEPA. 2004c. Reregistration Eligibility Decision for Oxycarboxin. http://www.epa.gov/opp00001/chem_search/reg_actions/reregistration/red_G-20_30-Sep-04.pdf

18 Ibid USEPA 2004 b

. 19 USEPA. 2001. Conclusions of the 11/27/2001 Mee ting of the Metabolism Assessment Review Committee

20 Ibid USEPA 2004 b

### 9 treatment on peanuts, as this was expected to represent a reasonable worst case situation. The chronic surface water estimated drinking water concentration (EDWC) was 0.63 μ g/L, less than the chronic drinking water level of concern (DWLOC) of 26 μ g/L, indicating that chronic exposure to carboxin in food and drinking water from surface water sources was below the Agency’s DWLOC. The groundwater drinking water concentration (0.095 μ g/L) was also less than the chronic DWLOC, indicating that chronic exposure to carboxin in both food and drinking water from groundwater sources was below the Agency’s LOC. No mitigation measures were necessary to reduce risks from drinking water exposure.

Oxycarboxin was not included in the carboxin RED, but a subsequent memorandum in September 2004 21 

### addressed occupational risks (in greenhouses). The oxycarboxin memorandum indicated that since there was no residential use of oxycarboxin, no dietary, residential, or environmental risk assessment was performed. The Agency recognized that limited residential exposure could occur if treated ornamentals were obtained from an enclosed commercial structure, such as a nursery or greenhouse, and then brought back to a residence. However, the Agency determined that residential risk of exposure from oxycarboxin did notexceed LOCs for the following reasons: oxycarboxin was believed not to persist on plants postapplication; there was low likelihood of sustained potential exposure; the occupational margin of exposure (MOE) was not exceeded assuming baseline levels of protection; and a 12-hour applicators and handlers re-entry interval (REI) was considered protective.

c. Clean Water Act Programs

Carboxin and oxycarboxin were not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Loads (TMDL) or ambient water quality criteria have been developed for carboxin or oxycarboxin. Office of Pesticide Program (OPP) Aquatic Life Benchmarks 22 

### have been established for carboxin; however, given the indoor use, similar benchmarks have not been developed for oxycarboxin. Any data submitted or otherwise located as part of the registration review process may be used to update Aquatic Life Benchmarks if applicable.



## 5. Environmental Fate and Transport

a. Parent Compound

Based on previous assessments, carboxin is characterized as a mobile compound that degrades rapidly in the environment 23 

### . However, the primary transformation products formed, carboxin sulfoxide and oxycarboxin, tend to be much more persistent than the parent and, based on their structures, may have similar pesticidal activity. Fate properties of carboxin are provided in

Table 4 . Half-lives are calculated for carboxin and carboxin plus carboxin sulfoxide in the event that they need to be used in the risk assessments.

21 Ibid USEPA 2004 c

22 USEPA 2014 c . Office of Pesticide Programs’ Aquatic Life Benchmarks. http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm#benchmarks

23 Ibid USEPA 2004 b

.

### 10 Carboxin is not considered persistent as it degraded rapidly in aerobic soil, with a mean half-life from four studies of 1.19 days. Carboxin degraded much more slowly in anaerobic soil with a half-life of 128 days. In both aerobic and anaerobic soil studies, the predominant transformation product was carboxin sulfoxide, with oxycarboxin occurring as a minor transformation product. The degradates in both aerobic and anaerobic studies were otherwise similar, except that Į -vinyl sulfinyl acetanilide was an additional major degradate in the anaerobic soil metabolism study. Carboxin did not degrade via hydrolysis at any of the pH values studied (pH 5, 7, and 9).

Aqueous photolysis was rapid with a half-life of 1.5 hours. No soil photolysis data were available; however, 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. Photolysis may however contribute to dissipation after carboxin has entered surface water bodies.

There was some evidence that carboxin may degrade in aqueous systems when dissolved oxygen is present. Limited information on aquatic metabolism showed slower degradation rates in an anaerobic metabolism study (239 days) than in the aerobic metabolism study (34.4 days).

In a terrestrial field dissipation study (41259401-A), 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 applications. Carboxin residues were below 0.14 ppm in the 6-12 inch layer, and were not detected at depths greater than 12 inches. The study cannot be used to characterize degradates formed in the field, as a common moiety method was used to convert all residues to aniline for analysis.

Bioconcentration studies have been submitted for carboxin, but have been deemed unacceptable. However, given the logarithmic octanol-water partition coefficient (log K ow 

### =2.17) for carboxin, the compound is not expected to bioaccumulate.

For oxycarboxin, fate studies have been submitted to fulfill the hydrolysis (OCSPP Guideline 835.2120), aerobic soil metabolism (OCSPP Guideline 835.4100), and batch equilibrium (OCSPP Guideline 835.1240) requirements for pesticides used in greenhouses, but the reviews for these studies have not been finalized; therefore, persistence and mobility of the compound

has not been characterized.

Table 4. Chemical Properties and Environmental Fate Parameters of Carboxin

Parameter Value Description Source

Selected Physical/Chemical Parameters

Molecular mass (molecular formula) 235.3g/mol -- --

Vapor pressure (25 q C) 1.8 x 10 -7 torr -- 42493703

Aqueous solubility (pH 7; 20 q C) 195 mg/L -- 47687404

Henry’s Law Constant (20°C) 2.86 x 10 -10 atm/m 3 /mol Calculated

Log octanol-water partition coefficient (log K O W ) 2.17 -- 42493705

Persistence

### 11 Parameter Value Description Source

Hydrolysis half-life pH 5, 25 q C pH 7, 25 q C pH 9, 25 q C stable

stable

stable 00141213

Aqueous photolysis half-life (25 q C) 0.06 d Supplemental (only one ring radiolabelled) 42192801

Soil photolysis half-life (25 q C) NA

Aerobic soil metabolism halflife (25 q C) 1 C C/CS Soil

1.35

< 1

< 1

1.24

1.36 98

57

28

NA 2

23 S

LS

SiL

SL

SL Aniline ring labeled Aniline ring labeled Aniline ring labeled Aniline ring labeled Oxathiin ring labeled 00003225

00005540

00005540

41224503

41224504/41252501

Anaerobic soil metabolism half-life (25 q C) 1 C C/CS Soil

109

104 51

65 SL

SL Aniline ring labeled Oxathiin ring labeled 41224507/41286601

41224508/41725501

Aerobic aquatic metabolism half-life (25 q C) 1 C C/CS Soil Supplemental (only one ring radiolabelled) 42600801

34.4 32.7 SiL

Anaerobic aquatic metabolism half-life (25 q C) 1 C C/CS Soil Supplemental (uncertainty in anaerobic system) 42600803

239 250 SiL

Mobility

Freundlich soil-water distribution coefficient (K F ) 0.78 (sandy loam)

1/n = 0.93 00005541

Field Dissipation

Terrestrial field dissipation half-life, leaching depth 14 d; leached to < 6” depth 41259401

Fish Bioconcentration

Fish Bioconcentration Factor NA
1. C – carboxin, C/CS – carboxin+carb oxin sulfoxide, S – sand, LS – Loamy sand, SiL – silt loam, SL – sandy loam 2. Study was unavailable for estimation of half-life at the time of the development of the problem formulation.



### b. Transformation Products

Table 5 lists the major transformation products and degradates formed in the environmental fate studies. The primary transformation products formed during the biotic and abiotic metabolism studies were carboxin sulfoxide and oxycarboxin (carboxin sulfone). There is uncertainty as to the extent to which these transformation products may have pesticidal activity similar to that of the parent. Carboxin sulfoxide is considered mobile, based on information provided in an aged column leaching study (MRID 47137502). The mobility, fate, and transformation products for oxycarboxin have yet to be evaluated, as the aerobic soil and hydrolysis studies are under review.
However, K oc 

### values estimated using EPISuite (18-20 L/kg oc 

### ) indicate that oxycarboxin is also

mobile.

### 12 There were two aerobic soil metabolism studies (MRID’s 41224501 and 41224502) that examined the degradation of carboxin sulfoxide. Carboxin sulfoxide degraded with a half-life of 82-92 days, with the primary transformation product in both studies being oxycarboxin (maximum of 14.4-15.2% at study termination at 120 days). Approximately 27-35% of the material was unidentified bound residue at 120 days. Two anaerobic soil metabolism studies (MRIDs 41224505 and 41224506) were also conducted for carboxin sulfoxide. Carboxin sulfoxide degraded with a half-life of 29-31 days. The major transformation product formed in both studies was carboxin at 36-38% at the conclusion of the study, indicating that carboxin can reform from the sulfoxide under anaerobic conditions. Oxycarboxin also formed but did not exceed 10% of the applied in either study.13Table 5. Carboxin and Its Major Environmental Transformation Products and DegradatesChemical NameChemical StructureStudy typeRef. (MRID)Maximum % AR(day)Final % AR(study length)ParentCarboxin-- -- -- --Major Transformation ProductsCarboxin sulfoxideAqueous photolysisAerobic soilAerobic soilAerobic soilAerobic soilAerobic soilAnaerobic soilAerobic aquaticAnaerobic aquatic4219280100003225000055400000554041224504/412525014122450341224508/41725501426008014260080320.4 (0.3)54.3 (7)50.7 (1)52.4 (1)59.5 (2)52 (2)30.8 (0)16.4 (1)12.9 (30)20.4 (0.3)19 (154)27.5 (30)43.6 (30)59.5 (2)52 (2)8.9 (60)4.2 (30)3.9 (365)Oxycarboxin (Carboxinsulfone)Aerobic soilAnaerobic soilAnaerobic soilAerobic aquaticAnaerobic aquatic0000322541224507/4128660141224508/4172550142600801426008032.9 (154)4.9 (31)0.6 (0)0.6 (30)0.8 (30)2.9 (154)1.5 (60)ND (60)0.6 (30)ND (365)Į-vinyl sulfinyl acetanilide Anaerobic soil 41224507/41286601 10.0 (60) 10.0 (60)oxo (phenylamino) acetic acid Aqueous photolysis 42192801 54.9 (0.33) 54.9 (0.33)2,3-dihydro-5-carboxy-6-methyl-1,4-oxathiinAnaerobic soil 41224508/41725501 13.9 (60) 13.9 (60)S-[2-(acetyloxy)-ethyl]-2-oxo2-(phenylamino)ethanethioateAerobic aquaticAnaerobic aquatic426008014260080317.1 (21)10.6 (0.5)15.4 (30)3.8 (365)

### 14 

## 6. Receptors

A detailed description of the available ecotoxicity data for carboxin is provided in the final risk assessment in support of the RED (US EPA 2004, DP Barcode 295494) 24 

### . No additional data

have been submitted and/or reviewed since that time. Table 6 and Table 7 provide a summary of the aquatic and terrestrial species tested to characterize the potential acute and chronic effects of carboxin and oxycarboxin. Several early reviews recorded in data evaluation records (DERs) lacked clearly identifiable Accession Numbers or Master Record Identifiers (MRIDs); thus, alternative document identifiers are provided where needed for internal tracking purposes. Also

as noted in the footnotes to Tables 6 and 7 , the classification of some studies has changed based

on the extent to which uncertainties identified in the initial DER have been addressed.

a. Effects to Aquatic Organisms

Based on the ecological effect studies, carboxin and its end-use products range from slightly to highly toxic to freshwater fish and invertebrates on an acute exposure basis. Freshwater fish are most sensitive to carboxin co-formulated with the dithiocarbamate fungicide thiram (CAS 137- 26-8; PC Code 079801) as compared to carboxin alone or co-formulated with phthalimide fungicide captan (CAS 133-06-2; PC Code 081301). Technical grade oxycarboxin is slightly toxic to freshwater fish on an acute exposure basis. No guideline-compliant data have been submitted for chronic toxicity to freshwater fish and invertebrates or for acute and chronic toxicity to estuarine/marine animals. Technical grade carboxin reduced frond number and cell density in aquatic plants. Only carboxin data are available for one of the four recommended nonvascular plant groups (green alga; Pseudokirchneriella subcapitata 

### ); additional data are needed to evaluate carboxin toxicity to freshwater and estuarine/marine diatoms and cyanobacteria and oxycarboxin toxicity to all aquatic plant groups. The most sensitive aquatic toxicity endpoints from scientifically sound studies with carboxin and oxycarboxin TGAI are summarized in Table

6 . A summary of all available studies, including formulation-specific (TEP) data, is presented in Appendix A

.

24 Ibid US EPA. 2004.

### 15 Table 6. Summary of Endpoints from Aquatic Toxicity Studies for Carboxin and Oxycarboxin TGAI.

Study Type Species Test Item (Purity or Product Name)

Carboxin TGAI

(97-99% a.i.) a Oxycarboxin TGAI (Plantvax ® Technical) b

Acute toxicity to

freshwater fish Bluegill sunfish ( Lepomis

macrochirus ) LC 50 = 1.2 mg/L (NR, 1.0 – 1.4 mg/L) c

Moderately toxic

00003004

00053731

Acc. No. 224935 Acceptable LC 50 = 28.1 mg/L (NR, 22.6 – 35.1 mg/L) d

Slightly toxic

SAN R2004683

Acceptable

Rainbow trout ( Onchorhynchus mykiss ) LC 50 = 2.0 mg/L (NR, 1.6 – 2.5 mg/L) e

Moderately toxic

053731 Acceptable LC 50 = 19.9 mg/L (NR, 14.5 – 27.4 mg/L) f Slightly toxic

SAN R2004683

Acceptable

Early life stage toxicity to freshwater

fish Not submitted NA NA

Full life cycle toxicity

to freshwater fish Not submitted NA NA

Acute toxicity to

freshwater

invertebrates Water flea ( Daphnia magna ) EC 50 = 84.4 mg/L (NR, 73.1-97.6 mg/L)

Slightly toxic

00053730

Acc. No. 235236 Acceptable EC 50 = 69.1 mg/L (NR, 54.2 – 88.2 mg/L) g

Slightly toxic

SAN R2004683

Acceptable

Life cycle toxicity to

freshwater

invertebrates Not submitted NA NA

Acute toxicity to

estuarine/marine fish Not submitted NA NA

Early life stage toxicity to

estuarine/marine fish Not submitted NA NA

a Bolded values represent endpoints to be used in risk estimation.

b Bolded values represent endpoints to be used in risk estimation.

c Based on nominal treatment concentrations.

d Based on nominal treatment concentrations.

e Based on nominal treatment concentrations.

f Based on nominal treatment concentrations.

g Based on nominal treatment concentrations.

### 16 Study Type Species Test Item (Purity or Product Name)

Carboxin TGAI

(97-99% a.i.) a Oxycarboxin TGAI (Plantvax ® Technical) b Full life cycle toxicity

to estuarine/marine

fish Not submitted NA NA

Acute toxicity to

estuarine/ marine

invertebrates Not submitted NA NA

Acute toxicity to

estuarine/marine

molluscs Not submitted NA NA

Life cycle toxicity to

estuarine/marine

invertebrates Not submitted NA NA

Toxicity to aquatic vascular plants (14- day)

Duckweed ( Lemna gibba ) NOAEL = 0.15 mg/L LOAEL = 0.30 mg/L
IC 50 = 0.67 mg/L (NR, 0.60 – 0.76 mg/L) h

Frond number

41493802 Acceptable NA

Toxicity to aquatic nonvascular plants (120-hr) Green algae ( Pseudokirchneriella subcapitata ) NOAEL = 0.11 mg/L LOAEL = 0.22 mg/L

IC 50 = 0.37 mg/L (NR, 0.33 – 0.42 mg/L) i

Cell density

41493801 Acceptable NA

h Based on mean-measured treatment concentrations.

i Based on mean-measured treatment concentrations.

### 17 b. Effects to Terrestrial Organisms

Carboxin is practically nontoxic to terrestrial animals on an acute exposure basis. Similar to technical grade carboxin, the formulated products Vitavax ® 

### 75 W (38.7% carboxin plus 37.5% thiram) and Vitavax ® 

### SP 38.7% carboxin plus 37.5% captan) are practically nontoxic to bobwhite quail ( Colinus virginianus ) with acute oral LD 50 

### values of 2,410 mg/kg and greater than 10,000 mg/kg, respectively. Additionally, toxicity testing with Vitavax ® 

### SP in bobwhite quail (LC 50 

### >5,620 mg/kg of diet) and mallard ducks ( Anas platyrhynchos ; LC 50 

### >4,640 mg/kg of diet) indicated that the formulated product is practically nontoxic to birds on a subacute dietary exposure basis. Oxycarboxin is slightly toxic to mallard duck (LD 50 

### = 1,250 mg/kg bw) on an acute oral exposure basis. Chronic exposure in the avian diet at 700 mg/kg diet caused reductions in female mallard duck body weight and in the number of eggs set (NOAEC = 70 mg/kg diet). Chronic exposure to rats ( Rattus norvegicus ) resulted in reduced growth (lower body weight) of offspring. Technical grade carboxin and oxycarboxin are moderately toxic to the adult honey bee ( Apis mellifera ) on an acute contact exposure basis. No data were submitted for terrestrial plant toxicity. The most sensitive terrestrial toxicity endpoints from scientifically sound studies with carboxin and oxycarboxin TGAI are summarized in Table 7 . A summary of all available studies, including formulation-specific (TEP) data, is presented in Appendix A

.

Table 7. Summary of Endpoints from Terrestrial Toxicity Studies for Carboxin and Oxycarboxin.

Study Type Species Test Item (Purity or Product Name)

Carboxin TGAI (97-99% a.i.) 34 Oxycarboxin TGAI (Plantvax Technical) 35

Acute oral toxicity to

birds Bobwhite quail ( Colinus virginianus ) LD 50 > 2,150 mg/kg-bw (NA)

Practically nontoxic

43582301 Acceptable NA

Mallard duck ( Anas platyrhynchos ) LD 50 > 2,000 mg/kg-bw (NA)

Practically nontoxic

00072744 Acceptable LD 50 = 1,250 mg/kgbw (NR, 852-1,835

mg/kg-bw)

Slightly toxic

SAN R2004683

Acceptable

Passerine (Not submitted) NA NA

34 Bolded values represent endpoints to be used in risk estimation.

35 Bolded values represent endpoints to be used in risk estimation.

### 18 Study Type Species Test Item (Purity or Product Name)

Carboxin TGAI (97-99% a.i.) 34 Oxycarboxin TGAI (Plantvax Technical) 35

Subacute dietary toxicity to birds Bobwhite quail ( Colinus virginianus ) LC 50 > 4,110 mg/kg diet (NA) 36

Practically nontoxic

43582303 Acceptable LC 50 > 10,000 mg/kg diet (NA)

Practically nontoxic

SAN R2004683

Acceptable

Mallard duck ( Anas platyrhynchos ) LC 50 > 4,110 mg/kg diet (NA) 37

Practically nontoxic

43582302 Acceptable NA

Avian reproduction Bobwhite quail ( Colinus virginianus ) NOAEL = 1,000 mg/kg diet LOAEL > 1,000 mg/kg diet

No effects

44240101 Supplemental 38 NA

Mallard duck ( Anas platyrhynchos ) NOAEL = 70 mg/kg diet LOAEL = 700 mg/kg diet 39

Numbers of

eggs set, female body weight

44240102 Acceptable NA

Acute oral toxicity to

mammals Laboratory rat ( Rattus norvegicus ) LD 50 = 2,588 mg/kg bw (1,450-4,622 mg/kg bw)

Practically nontoxic

43171401 Acceptable NA

Acute inhalation toxicity to mammals Laboratory rat ( Rattus norvegicus ) LC 50 > 20 mg/L

Toxicity Category IV

00003116 Acceptable NA

Chronic toxicity to

mammals Laboratory rat ( Rattus norvegicus ) NOAEL = 1 mg/kg bw/day LOAEL = 10 mg/kg bw/day NA

36 Based on mean-measured treatment concentrations.

37 Based on mean-measured treatment concentrations. 38 Classified as scientifically sound but supplemental because it was uncertain whether treatment levels were high enough when compared to environmentally relevant concentrations.

39 Based on nominal treatment rates.

### 19 Study Type Species Test Item (Purity or Product Name)

Carboxin TGAI (97-99% a.i.) 34 Oxycarboxin TGAI (Plantvax Technical) 35 (two-generation reproduction) NOAEC = 20 mg/kg diet LOAEC = 200 mg/kg diet

Reduced parental body weight

41922601/

42391107 Acceptable

Acute contact toxicity Honey bee ( Apis mellifera ) LD 50 = 2 μ g/bee

Moderately toxic

00018842 Acceptable LD 50 = 5.9 μ g/bee

Moderately toxic

00018842 Acceptable Seedling emergence of terrestrial plants Not submitted NA NA

Vegetative vigor of terrestrial plants Not submitted NA NA



### c. Ecological Incidents

The risk assessment will incorporate information from reports of ecological incidents associated with carboxin and oxycarboxin use. This information may come from sources such as the Agency’s Ecological Incident Information System (EIIS), OPP’s aggregate incident report database, or external portals such as the Avian Incident Monitoring System (AIMS 40 

### ) or the National Pesticide Information Center (NPIC 41 

### ).

The EIIS is an internal OPP database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure. A search of the EIIS for ecological incidents run on September 17, 2014, identified two incidents associated with carboxin. One report was of a honey bee decline outside the United States in which the Slovenian Agricultural Inspection Service determined that more than 2,500 hives (or 10% of beekeepers) in the Mura region were affected during maize sowing time (Incident ID I023225-006). Multiple pesticide residues were detected in various media from the affected area, including carboxin in maize samples. In 1999, a Wisconsin farmer reported that 142 acres of soybean yield were reduced as a result of seed

treatment with Kernel ® 

### Guard Supreme, which contains both carboxin and permethrin (Incident ID I009544-001). Other incidents may have occurred due to carboxin or oxycarboxin exposures but may not have been reported due to various factors, such as a lack of reporting or a lack of

40 American Bird Conservancy. 2013 Avian Incident Monitoring System Available at: http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm

41 National Pesticide Information Center. http://npic.orst.edu/

### 20 observation of effects. Therefore, the lack of incident reports does not necessarily indicate the

absence of incidents.

No plant or wildlife incidents have been reported through OPP’s aggregate incident report database and no avian incidents have been captured in the AIMS 42 

### as of January 5, 2015. The AIMS database contains publicly available reports on pesticide-related avian incidents through

2005.



## 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of carboxin indicate that leaching to ground water and runoff are potential transport mechanisms to aquatic and terrestrial environments and non-target biological receptors. Given that carboxin is applied as a seed treatment and degrades fairly rapidly in aerobic soil (~1.2 days) to carboxin sulfoxide, which has been shown to degrade at a much slower rate (t 1/2 

### around 87 days), EFED believes the main residue of concern for chronic exposure in the runoff and receiving waterbodies would be the carboxin sulfoxide transformation product, which may further transform into carboxin sulfone (oxycarboxin).

Drinking water and inhalation exposure pathways for carboxin were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods and were found to be exposure pathways of low concern (no LOC exceedances are expected). Example inputs and outputs for STIR are presented in Appendix C . SIP and STIR

are described in detail a http://www.epa.gov/oppefed1/models/terrestriallindex.htm

.

As oxycarboxin is used in greenhouses and shadehouses, exposure is possible for visiting terrestrial organisms and for aquatic organisms if used irrigation water containing oxycarboxin residues is released into nearby aquatic habitats. Oxycarboxin was not screened using SIP and STIR because there were insufficient data to serve as inputs: the maximum application rate for oxycarboxin is not specified on the label and no mammalian toxicity data for oxycarboxin have

been reviewed.



## 8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

The stressors of ecological concern for both aquatic and terrestrial organisms are carboxin and its main transformation products carboxin sulfoxide and oxycarboxin. For chronic exposure in surface water habitats, the transformation products are the stressors of concern. Oxycarboxin has demonstrated slightly greater toxicity than parent carboxin in acute toxicity tests with freshwater invertebrates and with birds. Additional data are needed to support a comparative assessment of hazard and risk across taxonomic groups.

42 Ibid American Bird Conservancy. 2013.

### 21 ii. Drinking Water

The previous drinking water assessment conducted in support of the RED human health risk assessment of carboxin incorporated model estimates for carboxin residues of concern ( i.e.

, carboxin and carboxin sulfoxide 43 

### ), in surface and ground waters. The 2001 Metabolism Assessment Review Committee (MARC) identified the residues of concern considering available fate, toxicity, and structural data. The carboxin residues of concern may be reevaluated pending receipt and review of additional environmental fate and toxicity data for carboxin and its degradates. Given that oxycarboxin is used only on ornamental plants in greenhouses, the risk assessment conducted in 2004 determined that there was no dietary risk from oxycarboxin uses and, as the uses of oxycarboxin have not changed since the previous risk assessment, a drinking water assessment will not be conducted for oxycarboxin uses. As oxycarboxin is only a minor transformation product of carboxin and not likely to contribute significantly to estimated drinking water concentrations for carboxin and is no more toxic than carboxin, it is not included as a residue of concern for the carboxin drinking water assessment.

b. Measures of Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm . In addition, the Exposure and Fate Assessment Screening Tool (E-FAST; version 2014) and any additional available exposure models may be used to assess use in drains, drain lines, irrigation supply systems, waste water systems, sewage systems, sewer lines, and storm sewers. E-FAST

is described in detail at: http://www.epa.gov/oppt/exposure/pubs/efast.htm

.

c. Available Monitoring Data

The Agency is aware of monitoring conducted by federal and state agencies and this data will be considered in the assessment to the extent that data on carboxin and oxycarboxin are available.

d. Measures of Effect

The most sensitive, definitive ecotoxicity endpoints for carboxin and oxycarboxin TGAI presented in Section 3 of this problem formulation will be used to calculate risk quotients. Ecotoxicity data for carboxin formulations ( Appendix A ) and additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment may also be considered. The open literature studies are identified using EPA's ECOTOXicology database (ECOTOX 44 

### ), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effe cts of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional

characteristics of the affected communities.

43 Ibid USEPA 2004 b

. 44 USEPA. 2014. ECOTOXicology data (ECOTOX). Office of Research and Development, National Health and Environmental Effects Research Laboratory Mid-Continent Ecology Division (MED). http://cfpub.epa.gov/ecotox/

### 22 

## 9. Endangered Species Assessment

Consistent with the Agency's responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and/or endangered (listed) species from registered uses of pesticides in registration review. The process for evaluating potential risks to listed species is further described at: http://www.epa.gov/oppfead1/endanger/litstatus

/riskasses.htm

.


## 10. Endocrine Disruptor Screening Program (EDSP)

Carboxin and oxycarboxin were not included in the first group of 67 chemicals issued an order to conduct Tier 1 EDSP testing. For additional information the EDSP program, visit http://www.epa.gov/endo/.



## 11. Preliminary Identification of Data Gaps

a. Environmental Fate

Table 8 identifies environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. Batch equilibrium studies (835. 1230 45 

### ) should be conducted using five soils comparable to those in the United States where the product is used. The available study (MRID 47137501) was conducted using four European studies, where insufficient information was provided on the soils to make a comparison to those in the United States. As such, either the registrant can provide supplemental to address the deficiencies in the study, or can submit a new batch equilibrium study. Although an acceptable bioconcentration factor study has not been submitted for carboxin, EFED is not requesting one, given that the K ow 

### is indicative of a compound that does not bioaccumulate.

Table 8. Summary of Submitted Fate Studies for Carboxin

OCSPP

Guideline # Data Requirement Sufficient

for EFED? Submitted Studies (MRID/Acc. #) Classification Current Additional

Data Need

835.2120 Hydrolysis Yes 00254339

05002176 Acceptable Unacceptable

835.2240 Aqueous photolysis Yes 00003088

00145679

00162078

42192801 Unacceptable Unacceptable Unacceptable Supplemental

835.2410 Soil photolysis Yes 00118422

00145679

00162078

40567901

41992101 Unacceptable Supplemental Unacceptable Unacceptable Unacceptable

45 USEPA. 2008. Fate, Transport and Transformation Test Guidelines, OPPTS 835.1230. Adsorption/Desorption (Batch Equilibrium). Office of Chemical Safety and Pollution Prevention (OCSPP) formerly the Office of Prevention, Pesticides and Toxic Substances (OPPTS). EP A 712-08-

009. October 2008.

### 23 OCSPP

Guideline # Data Requirement Sufficient

for EFED? Submitted Studies (MRID/Acc. #) Classification Current Additional

Data Need

835.4100 Aerobic soil

metabolism Yes 00002935

00003225

00003041

00005540

05002176

41224501

41224502

41224503

41224504

41252501 Unacceptable Acceptable Unacceptable Acceptable Unacceptable Acceptable 1 Acceptable 1 Acceptable Acceptable Acceptable

835.4200 Anaerobic soil

metabolism Yes 00148101

41224505

41224506

41224507

41224508

41286601

41314301

41314302

41314303

41427101

41725501

41817801 Unacceptable Unacceptable Unacceptable Acceptable Acceptable Acceptable Acceptable Unacceptable Unacceptable Unacceptable Acceptable Supplemental

835.4300 Aerobic aquatic

metabolism Yes 42600801 Supplemental

835.4400 Anaerobic aquatic

metabolism Yes 43040303 Supplemental

835.1230

835.1240 Aged leaching/ adsorption/ desorption No 00003114

00003229

00003227

47137501

47137502

47137503 Unacceptable Supplemental Supplemental Supplemental Supplemental 1 Unacceptable Study 00003227 – one

soil Study 00003229 – aged,

one soil 47137501 carboxin, one US soil, 4 European soils

835.6100 Terrestrial field dissipation Yes 00003087

00005542

00005543

00118422

41259401

41314304

41591001

41725502

41725503

41725504

42192802 Supplemental Unacceptable Unacceptable Unacceptable Supplemental

No DER

No DER Supplemental Supplemental Supplemental Supplemental

850.1730 Fish

bioaccumulation Yes 00005544

00005545 Unacceptable Unacceptable 1. MRIDs 41224501, 41224502, and 47137502 were conducted for carboxin sulfoxide, a degradate of carboxin.



### b. Effects

Table 9 identifies ecological effects studies with carboxin and oxycarboxin, by MRID (or by Accession number or other reference), for each guideline requirement, as well as study

### 24 classifications and whether or not additional data are needed in order to support the risk assessment. The rationale for any additional data requested is presented in the comments field. The data needs presented for oxycarboxin reflect consideration of the labeled use on shadehouse ornamentals as a terrestrial outdoor use. If oxycarboxin is limited to strictly indoor use, these data are not needed for the current registration review.

Table 9. Submitted Ecological Effects Da ta for Carboxin (1) and Oxycarboxin (2).

Guideline Description—Test

Substance MRID, Acc. No., or SAN ID (R) Study

Classification

1. Carboxin
2. Oxycarboxin Are data

Needed for

Risk

Assessment? Comments (Justification and Assumptions

EPA will Make in Absence of Data)

Avian and Mammalian Testing

71-1 (850.2100) Avian acute oral toxicity, waterfowl

—TGAI 00072744

R2004683 1. Acceptable 2. Acceptable No

71-1 (850.2100) Avian acute oral toxicity, upland game bird species

—TGAI 43582301

NA 1. Acceptable

2. NA Yes: Oxycarboxin Oxycarboxin was more toxic than carboxin in the acute oral toxicity

test with mallard duck. In the

absence of data for bobwhite quail, EFED will be unable to

estimate acute risk to birds from exposure to oxycarboxin.

850.2100 Avian acute oral toxicity, passerine

species—TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin In the absence of data, EFED will

be unable to assess risk to passerine birds.

Nonguideline Avian acute inhalation toxicity,

most sensitive species from oral

toxicity tests –

TGAI NA

NA 1. NA

2. NA No Screening-level exposure analysis using the STIR tool did not identify inhalation as a significant exposure pathway for

birds.

850.2200 Avian dietary toxicity, waterfowl

species—TGAI 43582302

NA 1. Acceptable

2. NA Yes : Oxycarboxin Oxycarboxin was more toxic than carboxin in the acute oral toxicity

test with mallard duck. In the absence of data, EFED will be

unable to estimate acute risk to birds from exposure to oxycarboxin.

Avian dietary toxicity, upland game bird—TGAI 43582303

R2004683 1. Acceptable 2. Acceptable No

71-4 (850.2300) Avian reproduction,

waterfowl species—TGAI 44240102

NA 1. Acceptable

2. NA Yes : Oxycarboxin In the absence of data, EFED will

be unable to assess chronic risk to birds from exposure to oxycarboxin.

71-4 (850.2300) Avian reproduction, upland game bird

species—TGAI 44240101

NA 1. Supplemental
2. NA Yes : Oxycarboxin In the absence of data, EFED will

be unable to assess chronic risk to birds from exposure to oxycarboxin.

### 25 Guideline Description—Test

Substance MRID, Acc. No., or SAN ID (R) Study

Classification

1. Carboxin

2. Oxycarboxin Are data

Needed for

Risk

Assessment? Comments (Justification and Assumptions

EPA will Make in Absence of Data)

850.2400 Wild mammal toxicity—TGAI NA

NA 1. NA

2. NA No EFED will evaluate risk to mammals based on toxicity data for laboratory rat or other

mammals tested. EFED will

consult with HED to identify the most appropriate acute and chronic toxicity endpoints.

850.2500 Simulated or actual field testing—TEP NA

NA 1. NA

2. NA No Not triggered based on ecotoxicity data, predicted EECs,

fate properties, and use pattern

criteria.

Aquatic Animal Testing

72-2 (850.1010) Freshwater invertebrate, acute

toxicity—TGAI 00053730

43582306

R2004683 1. Acceptable 1. Supplemental 2. Acceptable No

72-3 (850.1025) Estuarine/Marine

mollusc acute toxicity—TGAI NA

NA 1. NA

2. NA Yes:
Carboxin and Oxycarboxin In the absence of data, EFED will

be unable to assess risk to

molluscs.

72-3 (850.1035) Estuarine/Marine

crustacean acute toxicity—TGAI NA

NA 1. NA

2. `NA Yes:
Carboxin and Oxycarboxin In the absence of data, EFED will

be unable to assess risk to

estuarine/marine invertebrates.

850.1075 Freshwater fish, acute toxicity,

warm water species—TGAI 00053731

R2004683 1. Acceptable 2. Acceptable No

850.1075 Freshwater fish, acute toxicity, cold

water species—

TGAI 00053731

R2004683 1. Acceptable 2. Acceptable No

850.1075 Estuarine/Marine

fish acute toxicity—TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin In the absence of data, EFED will

be unable to assess risk to

estuarine/marine fish.

72-4 (850.1300) Freshwater invertebrate, reproduction test—

TGAI NA

NA 1. NA

2. NA Yes : Carboxin

sulfoxide and Oxycarboxin In the absence of data, EFED will

b e unable to assess chronic risk to

freshwater invertebrates. The carboxin ecological risk assessment will rely upon chronic toxicity data to be submitted for

aquatic organisms exposed to

carboxin sulfoxide because

carboxin from treated seeds is expected to be largely transformed through aerobic soil

metabolism before reaching

surface water.

### 26 Guideline Description—Test

Substance MRID, Acc. No., or SAN ID (R) Study

Classification

1. Carboxin

2. Oxycarboxin Are data

Needed for

Risk

Assessment? Comments (Justification and Assumptions

EPA will Make in Absence of Data)

850.1350 Estuarine/marine invertebrate, reproduction test—

TGAI NA

NA 1. NA

2. NA Yes : Carboxin

sulfoxide and Oxycarboxin If acceptable data are submitted for acute toxicity to

estuarine/marine invertebrates and for life cycle (reproduction) toxicity to freshwater invertebrates, EFED may use an

acute-to-chronic ratio to estimate

a chronic toxicity endpoint for

estuarine/marine invertebrates.

The carboxin ecological risk assessment will rely upon chronic toxicity data to be submitted for

aquatic organisms exposed to

carboxin sulfoxide.

850.1400 Freshwater fish, early life stage

test—TGAI NA

NA 1. NA

2. NA Yes : Carboxin

sulfoxide and Oxycarboxin In the absence of data, EFED will

b e unable to assess chronic risk to fish. The carboxin ecological risk assessment will rely upon chronic toxicity data to be submitted for

aquatic organisms exposed to

carboxin sulfoxide.

850.1400 Estuarine/marine fish, early life stage

test—TGAI NA

NA 1. NA

2. NA Yes : Carboxin

sulfoxide and Oxycarboxin If acceptable data are submitted for acute toxicity to

estuarine/marine fish and for

early life stage toxicity to freshwater fish, EFED may use an

acute-to-chronic ratio to estimate

a chronic toxicity endpoint for

estuarine/marine fish. The

carboxin ecological risk assessment will rely upon chronic toxicity data to be submitted for

aquatic organisms exposed to

carboxin sulfoxide.

850.1500 Freshwater fish life cycle test NA

NA 1. NA

2. NA Reserved There are insufficient data at this

time to determine whether a fish

full life cycle test is triggered.

Estuarine/marine fish life cycle test NA

NA 1. NA

2. NA Reserved There are insufficient data at this

time to determine whether a fish

full life cycle test is triggered.

850.1950 Simulated or actual field testing for aquatic organisms NA

NA 1. NA

2. NA No Not triggered based on ecotoxicity data, predicted EECs,

fate properties, and use pattern

criteria.

### 27 Guideline Description—Test

Substance MRID, Acc. No., or SAN ID (R) Study

Classification

1. Carboxin

2. Oxycarboxin Are data

Needed for

Risk

Assessment? Comments (Justification and Assumptions

EPA will Make in Absence of Data)

Sediment Testing

850.1735 Whole sediment 10-

d freshwater

invertebrate—

TGAI NA

NA 1. NA

2. NA No

Carboxin and oxycarboxin are not expected to partition to or

accumulate in sediment based on

their measured and predicted (EpiSuite) physico-chemical characteristics (K f <1, log K

ow <3) 850.1740 Whole sediment 10-

d estuarine/marine

invertebrate—

TGAI NA

NA 1. NA

2. NA No

Agency-wide

guideline Whole sediment

chronic freshwater

estuarine/marine invertebrate (three species) —TGAI NA

NA 1. NA

2. NA No

Insect Pollinator Testing

850.3020 Honey bee acute contact toxicity—

TGAI 00018842

00018842 1. Acceptable 2. Acceptable No

Nonguideline* Honeybee acute oral toxicity study—TGAI NA

NA 1. NA

2. NA Yes : Carboxin In the absence of data, EFED will be unable to complete a risk

assessment for terrestrial invertebrates (specifically, insect pollinators). Exposu re to bees is

expected to be limited for both

carboxin and oxycarboxin. Nonetheless, exposure may occur

as a result of carboxin seed treatment uses through contact ( e.g ., for soil-dwelling bees) and through ingestion of residues in plants germinated from treated seeds. Bees may be exposed to

oxycarboxin as a result of its registered uses when visiting

shadehouses or other structures that are not completely enclosed, or when brought into greenhouses intentionally for pollination services. Nonguideline* (protocol required) Honeybee adult chronic oral toxicity study—TGAI NA

NA 1. NA

2. NA Yes : Carboxin

Nonguideline* (protocol required) Honey bee acute larval toxicity —

TGAI NA

NA 1. NA

2. NA Yes : Carboxin

Nonguideline* (protocol required) Honey bee chronic larval toxicity —

TGAI NA

NA 1. NA

2. NA Yes : Carboxin

850.3030 Honey bee toxicity

of residues on foliage—TEP NA

NA 1. NA

2. NA No Not triggered at this time based on ecotoxicity data, predicted EECs, fate properties, and use pattern criteria.

Nonguideline* (protocol required) Honey bee semifield (tunnel or colony-feeding) test

–TGAI and TEP NA

NA 1. NA

2. NA Yes : Carboxin May be triggered based on results of lower tier honey bee toxicity

studies.

### 28 Guideline Description—Test

Substance MRID, Acc. No., or SAN ID (R) Study

Classification

1. Carboxin

2. Oxycarboxin Are data

Needed for

Risk

Assessment? Comments (Justification and Assumptions

EPA will Make in Absence of Data)

Nonguideline* (protocol required) Field trial of residues in pollen

and nectar – TGAI

and TEP NA

NA 1. NA

2. NA Yes : Carboxin May be triggered based on results of lower tier honey bee toxicity

studies.

850.3040 Field testing for pollinators – TGAI

and TEP NA

NA 1. NA

2. NA Yes : Carboxin May be triggered based on results of lower tier honey bee toxicity

studies.

Terrestrial Plant Testing

850.4100 Seedling emergence (10 species)—TEP

or TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin Seed treatment uses of carboxin and greenhouse/shadehouse discharges of oxycarboxin may result in exposure to non-target

plants through root uptake. Without these data, EFED will be unable to assess risk to non-target

terrestrial and wetland plants.

850.4150 Vegetative vigor (10 species)—TEP NA

NA 1. NA

2. NA Yes: Oxycarboxin Seed treatment uses of carboxin are not expected to result in foliar

exposure to non-target plants. However, uses of oxycarboxin in

shadehouses or in greenhouses where non-target plants are also present may result in exposure to non-target plants. Without these

data, EFED will be unable to assess risk to non-target plants

from foliar applications of oxycarboxin.

Aquatic Plant Testing

850.4400 Aquatic plant growth, vascular plant

—TGAI or TEP 41493802

NA 1. Acceptable

2. NA Yes : Oxycarboxin Without these data, EFED will be unable to assess risk to aquatic vascular plants from oxycarboxin.

850.4500** Aquatic Plant, freshwater green

alga species—

TGAI or TEP 41493801

NA 1. Acceptable

2. NA Yes : Oxycarboxin Without these data, EFED will be unable to assess risk to aquatic nonvascular plants (algae and diatoms) from oxycarboxin.

Aquatic Plant,

freshwater diatom

—TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin Without these data, EFED will be unable to assess risk to aquatic nonvascular plants (algae and diatoms). Aquatic Plant,

marine diatom

—TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin

850.4550 † Aquatic Plant, cyanobacterium—

TGAI NA

NA 1. NA

2. NA Yes : Carboxin and Oxycarboxin

TGAI = Technical Grade Active Ingredient

### 29 TEP = typical end-use product * Carboxin data will be used in the assessment for oxycarboxin because the acute contact toxicity values for honey bees exposed to carboxin and oxycarboxin are similar. ** Algal toxicity tests are now under guideline OCSPP 850.4500 (formerly 850.5400)

† Cyanobacterium tests are now under guideline 850.4550 (formerly 850.5400)



## 12. References

Jones, R.D. et al., 2000. Guidance for use of the Index Reservoir and Percent Crop Area Factor in Drinking Water Assessments (March 21, 2000). Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

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

USEPA. 1999. Guidance for Use of the Index Reservoir in Drinking Water Exposure Assessments. Arlington, VA.

USEPA. 2000. Drinking Water Screening Level Assessment. Part A: Applying a Percent Crop Area Adjustment to Tier II Surface Water Model Estimates for Pesticide Drinking Water Exposure Assessments. FQPA Science Policy Document .Public Comment Draft September 1, 2000. Federal Register: October 11, 2000 (volume 65, number 197). Electronic copy available

at http://www.epa.gov/pesticides/trac/science/

USEPA. 2001. Conclusions of the 11/27/2001 Meeting of the Metabolism Assessment Review Committee. December 19, 2001

USEPA. 2002a. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version II (February 28, 2002). Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington,

VA.

U.S. EPA. 2003a. Use of Regional Percent Crop Area Factors in Refined Drinking Water Assessments. US EPA Office of Pesticide Programs (OPP), Environmental Fate and Effects Division (EFED), Water Quality Technical Team (WQTT). Arlington, VA

USEPA, 2003b. SCI-GROW 2.3: Windows Version of SCI-GROW. September 30, 2003. Office of Pesticide Programs, Environmental Fate and Effects Division, U.S. Environmental Protection Agency. Arlington, VA.

USEPA. 2004a. Reregistration Eligibility Decision for Carboxin. United States Environmental Protection Agency (USEPA). Office of Prevention, Pesticides and Toxic Substances. EPA 738- R-04-015, September 2004. Available at http://www.epa.gov/pesticides/reregistration/REDs/0012red_carboxin.pdf

### 30 USEPA. 2004b. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. United States Environmental Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

.

USEPA. 2004c. Reregistration Eligibility Decision for Oxycarboxin. United States Environmental Protection Agency (USEPA). Office of Prevention, Pesticides and Toxic Substances. September 2004. Available at http://www.epa.gov/opp00001/chem_search/reg_actions/reregistration/red_G-20_30-Sep-04.pdf

a. Fate Studies

MRID: 00005541 Smyser, B.P. (1979) Adsorption-Desorption of Vitavax (R)I-14C by Manchester Sandy Loam: Project No. 7859. (Unpublished study received Mar 28, 1979 under 400-81; submitted by Uniroyal Chemical, Bethany, Conn.; CDL:098029-B)

MRID: 00141213 Dzialo, D.; Lengen, M. (1983) Carbon 14 Carboxin Hydrolysis Study: Project No. 8304. Unpublished study prepared by Uniroyal Chemical. 18 p.

MRID: 41224501 Dzialo, D. (1989) Carbon 14|-Aniline Carboxin Sulfoxide Aerobic Soil Metabolism: Project No. 8908. Unpublished study prepared by Uniroyal Chemical Co. 20 p.

MRID: 41224502 Dzialo, D. (1989) Carbon 14|-Oxathiin Carboxin Sulfoxide Aerobic Soil Metabolism on Sandy Loam Soil: Project No. 88107. Unpublished study prepared by Uniroyal Chemical Co. 20 p.

MRID: 41224503 Dzialo, D. (1989) Carbon 14|-Aniline Carboxin Aerobic Soil Metabolism on Sandy Loam Soil: Project No. 8915. Unpublished study prepared by Uniroyal Chemical Co. 20 p.

MRID: 41252501 Dzialo, D. (1989) [Carbon 14-Oxattin] Carboxin Aerobic Soil Metabolism on Sandy Loam Soil: Proj. No. 8916. Unpublished study prepared by Uniroyal Chemical Co., Inc. 20 p.

MRID: 41224507 Gaydosh, K. (1989) (Carbon 14)-Aniline Vitavax Anaerobic Soil Metabolism: Project No. 8977. Unpublished study prepared by Uniroyal Chemical Co. 13 p.

MRID: 41224508 Gaydosh, K. (1989) (Carbon 14)-Oxathiin Vitavax Anaerobic Soil Metabolism: Project No. 8978. Unpublished study prepared by Uniroyal Chemical Co. 11 p.

MRID: 41259401

### 31 Scruggs, J.; Guy, S. (1989) Carboxin (Vitavax 3F) Field Dissipation-terrestrial Study on Peanuts in Donalsonville, GA: NCL Study No. 20-003: Project No. 8831. Unpublished study prepared by North Coast Laboratories, Inc. 263 p.

MRID: 41286601 Gaydosh, K. (1989) Carbon-14-aniline Vitavax Anaerobic Soil Metabolism: Lab Project Number 8977. Unpublished study prepared by Uniroyal Chemical Co., Inc. 25 p.

MRID: 41725501 Beerbaum, C. (1990) Vitavax: Identification of Peak in Carbon 14|- Oxathin: Vitavax Anaerobic Soil Metabolism in Study 8978: Lab Project Number: 89143. Unpublished study prepared by Uniroyal Chemical Co., Inc. 20 p.

MRID: 42192801 Horree, D. (1992) Aqueous Photolysis of Vitavax: Lab Project Number: 9040. Unpublished study prepared by Uniroyal Chemical Co., Inc. 45 p.

MRID: 42493703 Cranor, W.; Freeman, J. (1984) Determination of Ambient Vapor Pressure of Vitavax: Lab Project Number: 30702. Unpublished study prepared by ABC Labs, Inc. 109 p.

MRID: 42493705 De Vera, N. (1987) Octanol/Water Partition Coefficient of Carboxin: Lab Project Number: 87107. Unpublished study prepared by Uniroyal Chemical Co., Inc. 16 p.

MRID: 42600801 Wu, D. (1992) Aerobic Aquatic Metabolism of (carbon 14)-Carboxin: Lab Project Number: XBL 92036: RPT00110: 9260. Unpublished study prepared by XenoBiotic Laboratories, Inc. 127 p.

MRID: 43040303 Wu, D. (1993) Anaerobic Aquatic Metabolism of (carbon 14)-Carboxin: Lab Project Number: XBL/92037: RPT00143: 9269. Unpublished study prepared by XenoBiotic Labs, Inc. 129 p.

MRID: 47137501 Wanner, U. (2003) [Carbon 14]-Carboxin: Adsorption to Five Soils. Project Number: 2002/103. Unpublished study prepared by Crompton Corp. and Agvise Inc. 158 p.

MRID: 47687404 Riggs, A. (2001) The Solubility of Purified Carboxin in Water and Aqueous Buffers: Final Report. Project Number: GRL/11755, 2001/085, GRL/FR/11755. Unpublished study prepared by Crompton Co. 36 p.

### 32 b. Effects Studies for Carboxin

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference

3037 Weir, R.J. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received Jun 14, 1969 under 9G0819; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091420-O) 3139 Fink, R. (1974) Final Report: Eight-Day Dietary LC 50 

### --Mallard Ducks: Project No. 117-102. (Unpublished study including official analytical report, received Mar 11, 1974 under 400-106; prepared by Truslow Farms, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:128723-A)

3308 Mastalski, K. (1970) Report to Uniroyal Chemical, Division of Uniroyal, Inc.: Acute Oral Toxicity Study on Vitavax Seed Protectant with Thiram in Bobwhite Quail: IBT No. J8584. (Unpublished study received May 8, 1972 under 2F1191; prepared by Industrial Bio-Test Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091003-C) 3309 Mastalski, K. (1970) Report to Uniroyal Chemical, Division of Uniroyal, Inc.: Acute Oral Toxicity Study on Vitavax Seed Protectant with Captan in Bobwhite Quail: IBT No. J8584. (Unpublished study received May 8, 1972 under 2F1191; prepared by Industrial Bio-Test Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091003-D) 72744 Fink, R.; Beavers, J.B.; Brown, R. (1977) Final Report: Acute Oral LD50-- Mallard Duck: Project No. 117-117. (Unpublished study received Jan 24, 1978 under 400-81; prepared by Wildlife International, Ltd. in cooperation with Washington College, sub- mitted by Uniroyal Chemical, Bethany, Conn.; CDL:235237-J) 43582301 Pedersen, C. (1994) 14-Day Acute Oral LD50 Study with Vitavax Technical in Bobwhite Quail: Lab Project Number: 109-018-03. Unpublished study prepared by Bio-Life Associates, Ltd. 53 p.

71-2 Avian Dietary Toxicity

MRID Citation Reference

3038 Robinson, D.; Shillam, K.W.G. (1968) The Palatability to the Young Pheasant of Grain Dressed with Vitavax and Its Effects on Mortality and Growth: 2469/68/346. (Unpublished study received Jun 14, 1969 under 9G0819; prepared by Huntingdon Research Centre, Eng. for Uniroyal International, submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091420-P)

### 33 10348 Weir, R.J. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received Nov 16, 1967 under 400-75; prepared by Hazleton Laboratories, Inc. for United States Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:132110-B) 29175 Weir, R.J.; Hopkins, M. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received Dec 12, 1967 under 400-49; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL: 009021-H) 72745 Fink, R.; Beavers, J.B.; Brown, R. (1977) Final Report: Eight-Day Dietary LC50--Bobwhite Quail: Project No. 117-116. (Unpublished study received Jan 24, 1978 under 400-81; prepared by Wildlife International, Ltd. in cooperation with Washington College, submitted by Uniroyal Chemical, Bethany, Conn.; CDL: 235237-K) 88429 Weir, R.J.; Hopkins, M. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received May 5, 1969 under 400-85; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:101785-C) 122630 Weir, R.; Hopkins, M. (1967) Acute Dietary Toxicity: Bobwhite Quail: Project No. 798-100. Final rept. (Unpublished study received Dec 26, 1967 under 8F0682; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:092988-G) 43582302 Pedersen, C. (1995) 8-Day Acute Dietary LC50 Study with Vitavax Technical in Mallard Ducklings: Lab Project Number: 109-017-02. Unpublished study prepared by Bio-Life Associates, Ltd. 113 p. 43582303 Pedersen, C. (1995) 8-Day Acute Dietary LC50 Study with Vitavax Technical in Bobwhite Quail: Lab Project Number: 109-016-01. Unpublished study prepared by Bio-Life Associates, Ltd. 114 p.

71-4 Avian Reproduction

MRID Citation Reference

44240101 Mitchell, L.; Martin, K.; Beavers, J. et al . (1997) Vitavax Technical: A Reproduction Study with the Northern Bobwhite ( Colinus virginianus ): (Final Report): Lab Project Number: 117-168: 117/022896/QR.WC/SUB117: VIT 136-05. Unpublished study prepared by Wildlife International Ltd. 206 p.

44240102 Mitchell, L.; Martin, K.; Beavers, J. et al . (1997) Vitavax Technical: A Reproduction Study with the Mallard ( Anas platyrhynchos ): (Final Report): Lab Project Number: 117-169: 117/022796/MR.WC/SUB117: VIT 136-04. Unpublished study prepared by Wildlife International Ltd. 200 p.

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

### 34 3036 Weir, R.J. (1967) Final Report: Acute Toxicity in Aqueous Exposure to Rainbow Trout: Project No. 798-100. (Unpublished study received Jun 14, 1969 under 9G0819; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091420-M) 3059 Weir, R.J. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Dec 14, 1966 under 400-EX-27; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:123429-B) 76405 Weir, R.J.; Rathbun, F. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Apr 10, 1967 under 400-82; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:090718-G) 88428 Weir, R.J.; Hopkins, M. (1967) Final Report: Acute Toxicity in Aqueous Exposure to Rainbow Trout: Project No. 798-100. (Unpublished study received May 5, 1969 under 400-85; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:101785-B) 112368 Weir, R.; Rathbun, F. (1966) Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Alar 85 and Other Compounds|: Project No. 798-100. Final rept. (Unpublished study received May 29, 1967 under 7F0614; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:092906-C) 122629 Weir, R.; Hopkins, M. (1967) Acute Toxicity in Aqueous Exposure to Rainbow Trout: Seven Test Materials: Project No. 798-100. Final rept. (Unpublished study received Dec 26, 1967 under 8F0682; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:092988-F) 139122 Pitcher, F. (1973) ?Vitavax-75W: Bluegill|: Test No. 627. (Pre- pared by U.S. Environmental Protection Agency, Pesticides Regulation Div., Animal Biology Laboratory). 139123 U.S. Environmental Protection Agency (1977) Toxicity of Vitavax Seed Protectant: Brook Trout, Rats, Rabbits|. 41142005 Pitcher, F. (1973) Fish Toxicity Laboratory Report: Vitavax - 75W. Unpublished study prepared by Animal Biology Laboratory, EPA-PR, ARC. 5

p. 41142007 McCann, J. (1977) Biological Report of Analysis: Vitavax Technical: Sample No. 143966. Unpublished study prepared by Animal Biology Laboratory, U.S.

EPA. 2 P. 43582304 Bettencourt, M. (1994) Vitavax Technical--Acute Toxicity to Bluegill Sunfish ( Lepomis macrochirus ) Under Flow-through Conditions: Final Report: Lab Project Number: 94-1-5135: 41.0793.6141.105. Unpublished study prepared by Springborn Labs, Inc. 74 p. 43582305 Bettencourt, M. (1994) Vitavax Technical--Acute Toxicity to Rainbow Trout ( Oncorhynchus mykiss ) Under Flow-through Conditions: Final Report: Lab Project Number: 94-2-5159: 41.793.6142.108. Unpublished study prepared by Springborn Labs, Inc. 74 p.

### 35 72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

2875 Frear, D.E.H.; Boyd, J.E. (1967) Use of Daphnia magna for the microbioassay of pesticides: I. Development of standardized techniques for rearing Daphnia and preparation of dosage- mortality curves for pesticides. Journal of Economic Entomology. 60(5):1228-1236. (Also in unpublished submission received May 11, 1977 under 239-2458; submitted by Chevron Chemical Co., Richmond, Calif.; CDL:230225-A) 84745 Cheah, M.L.; Avault, J.W., Jr.; Graves, J.B. (1978) Some Effects of Thirteen

Rice Pesticides on Crawfish Procambarus clarkii and P. acutus acutus

. (Unpublished paper presented at the 4th international symposium of the International Association of Astacology; Aug 28-31, 1978, Thonon les Bains, France; unpublished study received Oct 8, 1981 under 476-2107; prepared by Louisiana State Univ., Dept. of Entomology and Fisheries Section, submitted by Stauffer Chemical Co., Richmond, Calif.; CDL:246020-L) 43582306 Putt, A. (1994) Vitavax Technical--Acute Toxicity to Daphnids ( Daphnia

magna ) Under Flow-through Conditions: Final Report: Lab Project Number: 94-2-5154: 41.0893.6143.115. Unpublished study prepared by Springborn Labs, Inc. 75 p.

72-3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference

3074 Heitmuller, T. (1975) Acute Toxicity of Vitavax to Pink Shrimp ( Penaeus

duorarum ) and Fiddler Crabs ( Uca pugilator ). (Unpublished study received May 16, 1975 under 400-116; prepared by Bionomics--EG&G, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:165048-A)

72-4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference

9733 Weir, R.J. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Nov. 16, 1966 under unknown admin. no.; prepared by Hazleton Laboratories, Inc. for United States Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:104902-A) 10347 Weir, R.J. (1967) Final Report: Acute Toxicity in Aqueous Exposure to Rainbow Trout: Project No. 798-100. (Unpublished study received Dec 11, 1967 under 400-75; prepared by Hazleton Laboratories, Inc. for United States

### 36 Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:132110- A) 21610 Mastri, C. (1970) Report to Uniroyal Chemical, Division of Uniroyal, Inc.: Four-Day Fish Toxicity Study on Three Samples of Vitavax Seed Protectants: IBT No. A8585. (Unpublished study received Feb 18, 1972 under 400-81; prepared by Industrial Bio- Test Laboratories, Inc., submitted by Uniroyal Chemical, Beth- any, Conn.; CDL:003261-D) 21615 Weir, R.J. (1967) Final Report: Acute Toxicity in Aqueous Exposure to Rainbow Trout: Project No. 798-100. (Unpublished study received Jun 13, 1967 under 400-EX-30; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:123433-R) 29174 Weir, R.J.; Rathbun, F.; Hopkins, M. (1967) ?Acute Toxicity in Aqueous Exposure to Bluegill Sunfish and Rainbow Trout|: Project No. 798-100. Final rept. (Unpublished study received Dec 12, 1967 under 400-49; prepared by Hazleton Laboratories, Inc., sub- mitted by Uniroyal Chemical, Bethany, Conn.; CDL:009021-G) 53731 Kuc, W.J. (1977) Acute Toxicity of Vitavax Technical, Lot BL 8108 to the Bluegill Sunfish, Lepomis macrochirus Rafinesque and Rainbow Trout, Salmo gairdneri Richardson: UCES Project # 11506- A29-01. (Unpublished study received Jan 24, 1978 under 400-81; prepared by Union Carbide Environmental Services, submitted by Uniroyal Chemical, Bethany, Conn.; CDL:235237-I) 57460 Pitcher, F.G. (1973) Vitavax-75W: Bluegill ( Lepomis macrochirus ): Test No. 627. (U.S. Environmental Protection Agency, Pesticides Regulation Div., Animal Biology Laboratory, unpublished study; CDL:128524-A)

81-1 Acute oral toxicity in rats

MRID Citation Reference

139123 U.S. Environmental Protection Agency (1977) Toxicity of Vitavax Seed Protectant: Brook Trout, Rats, Rabbits|.

81-4 Primary eye irritation in rabbits

MRID Citation Reference

139123 U.S. Environmental Protection Agency (1977) Toxicity of Vitavax Seed Protectant: Brook Trout, Rats, Rabbits|.

### 37 c. Effects Studies for Oxycarboxin

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference

3037 Weir, R.J. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received Jun 14, 1969 under 9G0819; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:091420-O)

71-2 Avian Dietary Toxicity

MRID Citation Reference

10348 Weir, R.J. (1967) Final Report: Acute Dietary Toxicity--Bobwhite Quail: Project No. 798-100. (Unpublished study received Nov 16, 1967 under 400-75; prepared by Hazleton Laboratories, Inc. for United States Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:132110-B)
29175 Weir, R.J.; Hopkins, M. (1967) Final Report: Acute Dietary Toxicity-- Bobwhite Quail: Project No. 798-100. (Unpublished study received Dec 12, 1967 under 400-49; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL: 009021-H)

88429 Weir, R.J.; Hopkins, M. (1967) Final Report: Acute Dietary Toxicity-- Bobwhite Quail: Project No. 798-100. (Unpublished study received May 5, 1969 under 400-85; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:101785-C)

122630 Weir, R.; Hopkins, M. (1967) Acute Dietary Toxicity: Bobwhite Quail: Project No. 798-100. Final rept. (Unpublished study received Dec 26, 1967 under 8F0682; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:092988-G)

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

3059 Weir, R.J. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Dec 14, 1966 under 400-EX-27; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:123429-B)

### 38 76405 Weir, R.J.; Rathbun, F. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Apr 10, 1967 under 400-82; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:090718-G)

112368 Weir, R.; Rathbun, F. (1966) Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Alar 85 and Other Compounds|: Project No. 798-100. Final rept. (Unpublished study received May 29, 1967 under 7F0614; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:092906-C) 140204 Weir, R.; Hopkins, M. (1966) Acute Aqueous Exposure: Rainbow Trout: Alar-85 and F461-75W: Project No. 798-100. Final rept. (Unpublished study received Dec 3, 1969 under 400-90; prepared by Hazleton Laboratories, Inc., submitted by Uniroyal Chemical, Bethany, CT; CDL:003277-E)

72-4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

MRID Citation Reference

9732 Weir, R.J. (1966) Final Report: Acute Aqueous Exposure--Rainbow Trout: Project No. 798-100. (Unpublished study received Nov 30, 1966 under unknown admin. no.; prepared by Hazleton Laboratories, Inc. for United States Rubber Co., submitted by Uniroyal Chemical, Bethany, Conn.; CDL:104900-A) 9733 Weir, R.J. (1966) Final Report: Acute Toxicity in Aqueous Exposure to Bluegill Sunfish: Project No. 798-100. (Unpublished study received Nov. 16, 1966 under unknown admin. no.; prepared by Hazleton Laboratories, Inc. for United States Rubber Co., sub- mitted by Uniroyal Chemical, Bethany, Conn.; CDL:104902-A)
29174 Weir, R.J.; Rathbun, F.; Hopkins, M. (1967) ?Acute Toxicity in Aqueous Exposure to Bluegill Sunfish and Rainbow Trout|: Project No. 798-100. Final rept. (Unpublished study received Dec 12, 1967 under 400-49; prepared by Hazleton Laboratories, Inc., sub- mitted by Uniroyal Chemical, Bethany, Conn.; CDL:009021-G)39Appendix A. Summary of endpoints and review classifications for available ecological effects studies, withannotations for internal document tracking.Table A.1. Summary of Endpoints from Aquatic Toxicity Studies for Carboxin and Oxycarboxin.Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) +Captan (37.5%)Carboxin (17%) +Thiram (17%)OxycarboxinTGAI (Plantvax®Technical)Acute toxicity tofreshwater fishBluegill sunfish(Lepomismacrochirus)LC50= 3.6 mg/L(NR, 2.7 – 4.3 mg/L)46Moderately toxic43582304Acceptable224935Invalid47LC50= 11.2 mg/L(NR)Slightly toxic224935Acceptable48LC50= 0.56 mg/L(NR)Highly toxic224935Acceptable49LC50= 28.1 mg/L(NR, 22.6 – 35.1mg/L)50Slightly toxicSAN R2004683AcceptableLC50= 1.2 mg/L(NR, 1.0 – 1.4 mg/L)51Moderately toxic0000300400053731Acc. No. 224935AcceptableSAN R2004606Invalid5246Based on mean-measured treatment concentrations. Detectable amounts of the sulfoxide degradate (0.5-0.8 mg/L) were found in the two highest treatment concentrations (4.3 and 7.5 mg/L, meanmeasured) and were not added to the concentrations of carboxin parent. This should be considered if comparing to EECs generated using parent plus the sulfoxide degradate.47Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due toabsence of purity information (see SAN R2004608). The study was reviewed again and classified as invalid (not upgradeable) dueto the use of polyethylene liners in tanks and because the data werepooled from separate tests to generate a single mortality curve (see SAN R2005002; February 27, 1981).48Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due to theabsence of purity information (see SAN R2004608).49Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due to theabsence of purity information (see SAN R2004608).50Based on nominal treatment concentrations.51Based on nominal treatment concentrations.52Study classified as invalid (but upgradeable) in DER datedOctober 25, 1979, due to the absence of purity information and lackof data on size and weight of fish.40Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) +Captan (37.5%)Carboxin (17%) +Thiram (17%)OxycarboxinTGAI (Plantvax®Technical)Rainbow trout(Onchorhynchusmykiss)LC50= 2.3 mg/L (NR, 1.5 –2.4 mg/L)53Moderately toxic43582305Acceptable224935Invalid54LC50= 6.6 mg/L(NR)Moderately toxic224935Acceptable55LC50= 0.38 mg/L(NR)Highly toxic224935Acceptable56LC50= 19.9 mg/L(NR, 14.5 – 27.4mg/L)57Slightly toxicSAN R2004683AcceptableLC50= 2.0 mg/L (NR, 1.6 –2.5 mg/L)58Moderately toxic053731AcceptableSAN R2004607Invalid59Early life stagetoxicity tofreshwater fishNot submitted NA NA NA NA NAFull life cycletoxicity tofreshwater fishNot submitted NA NA NA NA NAAcute toxicity tofreshwaterinvertebratesWater flea(Daphniamagna)EC50= 84.4 mg/L (NR,73.1-97.6 mg/L)NA NA NA53Based on mean measured concentrations.54Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due absenceof purity information (see SAN R2004608). The study was reviewed againand classified as invalid (not upgradeable) due to the use of polyethylene liners in tanks and because data were pooled fromseparate tests to generate a single mortality curve (see SAN R2005002; February 27, 1981).55Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due to theabsence of purity information (see SAN R2004608).56Multiple tests are associated with Acc. No, 224935. The study classification pertains only to this test. Previously classified as invalid (but upgradeable) in DER dated October 29, 1979, due to theabsence of purity information (see SAN R2004608).57Based on nominal treatment concentrations.58Based on nominal treatment concentrations.59Study classified as invalid (but upgradeable) in DER datedOctober 29, 1979, due to the absence of purity information and lackof data on size and weight of fish.41Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) +Captan (37.5%)Carboxin (17%) +Thiram (17%)OxycarboxinTGAI (Plantvax®Technical)Slightly toxic00053730Acc. No. 235236Acceptable60EC50= 69.1 mg/L(NR, 54.2 – 88.2mg/L)61Slightly toxicSAN R2004683AcceptableEC50> 57 mg/L62(NA)No more than slightly toxic43582306Supplemental63Life cycletoxicity tofreshwaterinvertebratesNot submitted NA NA NA NA NAAcute toxicity toestuarine/marinefishNot submitted NA NA NA NA NAEarly life stagetoxicity toestuarine/marinefishNot submitted NA NA NA NA NAFull life cycletoxicity toestuarine/marinefishNot submitted NA NA NA NA NAAcute toxicity toestuarine/ marineinvertebratesPink shrimp(Penaeusduorarum)NA NA NALC50 =14 mg/L(NR, 5.0 – 41mg/L)Slightly toxicNA60Study classification is reported on branch copy of study report accompanying letter from Uniroyal Chemical Co., dated April 27, 1982.61Based on nominal treatment concentrations.62Based on mean-measured treatment concentrations.63Study classified as supplemental due to poor recovery (approx. 1⁄2 nominal concentration) attributed to limited solubility at higher treatment levels.42Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) +Captan (37.5%)Carboxin (17%) +Thiram (17%)OxycarboxinTGAI (Plantvax®Technical)00003704Acc. No. 224935Supplemental64Fiddler crab(Uca pugilator)NA NA NALC50 =964 mg/L(NR, 502 – 1,860mg/L)PracticallynontoxicAcc. No. 224935Supplemental65NAAcute toxicity toestuarine/marinemolluscsNot submitted NA NANA NA NALife cycletoxicity toestuarine/marineinvertebratesNot submitted NA NA NA NA NAToxicity toaquatic vascularplants (14-day)Duckweed(Lemna gibba)NOAEL = 0.15 mg/LLOAEL = 0.30 mg/LIC50= 0.67 mg/L(NR,0.60 – 0.76 mg/L)66Frond number41493802AcceptableNA NA NA NAToxicity toaquaticGreen algaeNOAEL = 0.11 mg/LLOAEL = 0.22 mg/LNA NA NA NA64Study classification inferred from DER which stated that the test could be used to support the formulation, but noted the use of a nonguideline species and deviation from recommended testtemperature (see SAN R2004599).65Study classification inferred from DER which stated that the test could be used to support the formulation, but noted the useof a nonguideline species and deviation from recommended testtemperature (see SAN R2004599).66Based on mean-measured treatment concentrations.43Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) +Captan (37.5%)Carboxin (17%) +Thiram (17%)OxycarboxinTGAI (Plantvax®Technical)nonvascularplants (120-hr)(Pseudokirchneriellasubcapitata)IC50= 0.37 mg/L(NR,0.33 – 0.42 mg/L)67Cell density41493801AcceptableToxicity toaquaticnonvascularplants (72-hr)Alga(Chlorellapyrenoidosa)NOAEL = 1.0 mg/LLOAEL = 1.8 mg/LIC50= 2.6 mg/L(4.1, 2.34 – 2.77 mg/L)68Cell density41317801SupplementalNA NA NA NATable A.2. Summary of Endpoints from Terrestrial Toxicity Studies for Carboxin and Oxycarboxin.Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) + Captan(37.5%)Carboxin (17%)+ Thiram (17%)OxycarboxinTGAI (PlantvaxTechnical)Acute oral toxicityto birdsBobwhite quail(Colinus virginianus)LD50> 2,150 mg/kgbw (NA)Practically nontoxic43582301AcceptableNA224935Invalid69224935Invalid70NA67Based on mean-measured treatment concentrations.68Based on nominal treatment concentrations.69Study classified as invalid due to lack of information on percent active ingredients and the absence of raw data (see DER dated October 17, 1979; SAN R2004603). A separate review identified the %a.i. (SAN R2004599).70Classified as invalid due to lack of information on percent active ingredients and the absence of raw data (see DER dated October 11, 1979; SAN R2004602). A separate review identified the % a.i.(SAN R2004599).44Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) + Captan(37.5%)Carboxin (17%)+ Thiram (17%)OxycarboxinTGAI (PlantvaxTechnical)Mallard duck(Anas platyrhynchos)LD50> 2,000 mg/kgbw(NA)Practically nontoxic00072744Acceptable71NA NA NALD50= 1,250mg/kg-bw(NR, 852-1,835mg/kg-bw)Slightly toxicSAN R2004683AcceptableSubacute dietarytoxicity to birdsBobwhite quail(Colinus virginianus)LC50> 4,110 mg/kgdiet (NA)72Practically nontoxic43582303AcceptableLC50> 5,620 mg/kgdiet (NA)Practically nontoxic00029175Acc. No. 224935Supplemental73NA NALC50> 10,000mg/kg diet (NA)PracticallynontoxicSAN R2004683AcceptableLC50> 4,640 mg/kgdiet (NA)Practically nontoxic0000303700072745Acceptable74Mallard duck(Anas platyrhynchos)LC50> 4,110 mg/kgdiet(NA)75Practically nontoxicNA NA NA NA71See review and classification in SAN R2004626 and R2004650.72Based on mean-measured treatment concentrations.73Study classified as supplemental in DER dated October 22 1979 (see SAN R2004604).74Study classified as acceptable in SAN R2004651 but identified as unacceptable and not fulfilling guideline requirements in SANR2004597. It is unclear whether these reviews refer to two studiesusing different products (Vitavax®technical, 99% a.i., and Vitavax®EP 75% a.i.) but achieving the same outcome (LC50> 4,640 mg/kg diet), or if there was an administrative error in documenting thetest material.75Based on mean-measured treatment concentrations.45Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) + Captan(37.5%)Carboxin (17%)+ Thiram (17%)OxycarboxinTGAI (PlantvaxTechnical)43582302AcceptableLC50> 4,640 mg/kgdiet (NA)Practically nontoxic00003139Acc. No. 224935AcceptableRing-necked pheasant(Phasianus colchicus)NALC50> 4,464 mg/kgdiet (NA)76Practically nontoxicSAN R2004605SupplementalNA NA NAAvianreproductionBobwhite quail(Colinus virginianus)NOAEL = 1,000 mg/kgdietLOAEL > 1,000 mg/kgdietNo effects44240101Supplemental77NA NA NA NAMallard duck(Anas platyrhynchos)NOAEL = 70 mg/kgdietLOAEL = 700 mg/kgdiet78NA NA NA NA76 The LC50 value is inferred from mortality observations. One of twelve pheasants died in the 2 oz/bushel wheat (~2,232 mg/kgdiet) treatment and three of twelve birds died in the 4 oz/bushel wheat(~4,464 mg/kg diet) treatment.77 Classified as scientifically sound but supplemental because it was uncertain whether treatment levels were high enough whencompared to environmentally relevant concentrations.78 Based on nominal treatment rates.46Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) + Captan(37.5%)Carboxin (17%)+ Thiram (17%)OxycarboxinTGAI (PlantvaxTechnical)Numbers ofeggs set,female body weight44240102AcceptableAcute oral toxicityto mammalsLaboratory rat(Rattus norvegicus) LD50= 2,588 (1,450-4,622) mg/kg bwPractically nontoxic43171401AcceptableNA NALD50= 6,250(4,880 – 8,000)mg/kg bwPracticallynontoxic00003012AcceptableNAAcute inhalationtoxicity tomammalsLaboratory rat(Rattus norvegicus)LC50> 20 mg/LToxicity Category IV00003116AcceptableNA NALC50> 20 mg/LToxicity CategoryIV00003011AcceptableNAChronic (twogenerationreproduction)toxicity tomammalsLaboratory rat(Rattus norvegicus)NOAEL = 1 mg/kgbw/dayLOAEL = 10 mg/kgbw/dayNOAEC = 20 mg/kgdietLOAEC = 200 mg/kgdietReduced parental bodyweight41922601/NA NA NA NA47Study TypeSpeciesTest Item (Purity or Product Name)Carboxin TGAI(97-99% a.i.)Carboxin EP (75%a.i.)Carboxin(38.7%) + Captan(37.5%)Carboxin (17%)+ Thiram (17%)OxycarboxinTGAI (PlantvaxTechnical)42391107AcceptableAcute contacttoxicityHoney bee(Apis mellifera)LD50= 2μg/beeModerately toxic00018842Acceptable79NA NA NALD50= 5.9μg/beeModerately toxic00018842Acceptable80Seedlingemergence ofterrestrial plantsNot submitted NA NA NA NA NAVegetative vigorof terrestrial plantsNot submitted NA NA NA NA NA79Identified as scientifically sound in the DER (February 4, 1981), but not otherwise classified.80Identified as scientifically sound in the DER (February 4, 1981), but not otherwise classified.

### 48 

## Appendix B. Toxicology one-liners for mammalian (rat) acute oral, acute inhalation, and two-generation reproduction data reviewed by HED.

1. Acute oral toxicity

EPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Dat e: 27-Jan-2015 Last Updated: 16-Aug2013 Page: 1

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 27-Jan-1978

TXR: 0000750 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14-Day observation period Study Classified

as: Minimum

MRID: 00003081 Species: Strain: Rat : Long-Evans Material (material; batch; %ai): Formulation; BL8229; Vitavax Flowable Fungicide, 34% a.i. Laboratory: Food & Drug Research Laboratories,

Inc. Study No; Report

Date: 5481A; 28-Jun-1977 LD50 > 5.0 ml/kg (2/10 animals succumbed) Toxic Signs: ataxia, decreased activity, emaciation Necropsy: not performed Toxicity Category: IV Classification: Core - Minimum

This study in conjunction with the study performed on 9/9/77 [MRID 00003082], adequately demonstrate the LD50 to be in excess of 5 ml/kg. No further testing is necessary.

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 27-Jan-1978 TXR: 0000750 Study Typ e : Acute, Oral, Treatment Duration: 1 Dose Study Classified as: Minimum

MRID: 00003082 Species: Strain: rat : Not Specified Material (material; batch; %ai): Formulation; BL8599; Vitavax Flowable Fungicide, 34 % a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5481A; 9-Sep-1977 LD50 > 5 ml/kg (3/20 animals succumbed) Toxic Signs: ataxia, urinary incontinence, nasal discharge. Necropsy: mottled lungs, liver and kidneys; vascularization of skin; congested and vascularized G.I. tract Tox. Category: IV

Classification: Core - Minimum Data

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 2-Aug-1978 TXR: 0000752 Study Typ e : Acute, Oral, Treatment Duration: 1 Dose Study Classified as: Minimum

MRID: 00058241 Species: Strain: rat : Not Specified Material (material; batch; %ai): Formulation; 5495c; Vitavax-17 Flowable Fungicide, 17.1% a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5495C; 9-Sep-1977 A total of 4 of the 20 rats died, therefore the product is category IV. Symptoms observed during the test period were decreased activity, ataxia, urinary maintenance. Necropsy findings were mottled lungs, and liver and pale kidneys.

This test is CORE MINIMUMEPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 49 Guideline: 81-1 Acute oral toxicity in rats Memo Date: 22-Aug-1978 TXR: 0000753 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14-Day observation period Study Classified as: Minimum

MRID: 00003012 Species: Strain: Rat : Long-Evans Material (material; batch; %ai): Formulation; not in DER; Vitavax-200 (Carboxin, Thiram): not in DER Laboratory: Pharmakon Laboratories Study No; Report Date: ; 30-May-1973 Vitavax-200 (Carboxin, Thiram): LD50 = 6.25 (4.88 - 8.00) g/kg Toxic Signs: Decreased body tone, prostration chromaturia. Necropsy: Test compound present in the stomach, irritation and hemorrahage of the gastrointestinal tract.
Classification: Core Minimum Data
Tox. Cat. : IV

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 26-Jan-1979 TXR: 0000755 Study Type: Acute, Oral, Treatment Duration: 1 Dose; also Acute Dermal, Eye and Dermal irritation Study Classified as: Minimum

MRID: 00021645 Species: Strain: Rabbit : New Zealand White,Rat : Sprague-Dawley Material (material; batch; %ai): Formulation; not in DER; Evershield RTU 1050 seed protectant: thiram (10.15%); vitavax (5.16%) Laboratory: Hill Top Research Study No; Report Date: 78/427/21; 29-Jun-1978 Three formulations tested: 1. Evershield RTU 1000 - 10% Thiram; 2. Evershield RTU 1050 - 10% Thiram + 5% Vitavax; 3. Evershield RTU
1010 - 10% Thiram + 10% Vitavax.

Acute Oral: All three formulations: LD50 > 10.0 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Acute Dermal: All three formulations: LD50 > 21.5 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Primary Eye Irritation: Formulation 1.: It is uncertain from the report whether the staining effect of the test material interf ered with the animals' vision or whether the staining effect interfered with complete evaluation of corneal opacity. Classification: Supplementary. Primary Dermal Irritation: All three formulations: Although the staining effect precluded complete evaluation, the data show th at the test material is not corrosive or a severe irritant. Tox Category IV. Classification: Core-Minimum Data.

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 23-Apr-1979 TXR: 0000756 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14 day observation period Study Classified as: Minimum

MRID: 00005549 Species: Strain: Rat : Not Specified Material (material; batch; %ai): Formulation; not in DER; Vitavax 10G (% ai not in DER) Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5480A; 28-Jun-1977 LD50 > 5 g/kg bw. Decreased activity and ataxia.; Toxicity catagory IV.
Classification: minimumEPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 50 Guideline: 81-1 Acute oral toxicity in rats Memo Date: 3-Aug-1979 TXR: 0000759 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14 day observation period Study Classified as: Minimum

MRID: 00030110 Species: Strain: Rat : Long-Evans Material (material; batch; %ai): Formulation; not in DER; Vitavax HBM-25: Carboxin, 12.5% a.i.; Captan, 12.5% a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5483; 28-Jun-1977 Vitavax HBM-25 (Carboxin, Captan): LD50 = 5.4 ±0.8 gm/kg (both sexes). Toxicity category IV. Classified: minimum.

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 2-Oct-1979 TXR: 0000761 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14 day observation period Study Classified as: Minimum

MRID: 00024924 Species: Strain: Rat : Not Specified Material (material; batch; %ai): Formulation; # 8901161V and 8520157V; 32.9% ai Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 6135; 1-Jan-1979 LD50 > 5/ g/kg. Toxicity category IV.
Classified: minimum

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 2-Aug-1982 TXR: 0005383 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 15 day observation period Study Classified as: Guideline

MRID: 00105982 Species: Strain: Rat : Not Specified Material (material; batch; %ai): Formulation; not in DER; 25% ai Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 7211A; 6-Apr-1982 Signs of toxicity: ataxia, decreased activity, lacrimation. At necropsy: intestines contained bloodlike viscous liquid

. acute oral LD50 (95% CI) for males: 4 g/kg (1.8-8.87 g/kg); for females: 6.69 g/kg (3.43-19.36 g/kg); combined: 5.18 g/kg (3.36 -8.47 g/kg); Toxicity category III Study classification: Guideline

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 13-Sep-1989 TXR: 0007488 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 15 day observation period Study Classified as: Minimum

MRID: 40997302 Species: Strain: Rat : Sprague-Dawley Material (material; batch; %ai): Formulation; not in DER; 30% Carboxin; 50% Thiram Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 9275A; 3-Dec-1986 Pro-Gro (thiram, carboxin):LD50 = (M) 1530 (1039-2915) mg/kg; slope = 4.15; (F) 1139 (858-1620) mg/kg;slope 7.67; (combined) 13 26 (1065-1676); slope = 5.15. Toxicity category III.
Classified Minimum

Guideline: 81-1 Acute oral toxicity in rats Memo Date: 5-Mar-2002 TXR: 0050129 Study Type: Acute, Oral, Treatment Duration: 1 Dose; 14 day observation period Study Classified as: Acceptable/Guideline

MRID: 43171401 Species: Strain: Rat : Sprague-Dawley Crl:CD BR VAF/Plus Material (material; batch; %ai): Technical; Lot/Batch #: 111N624EZ; Carboxin (Vitavax technical):102.2% ai Laboratory: International Research & Development Corp. Study No; Report Date: 399/127; 21-Oct-1992EPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 51 In an acute oral toxicity study (MRID 43171401), fasted Sprague Dawley rats (5/sex/dose) were given a single oral dose by gavag e of carboxin (102.2% a.i., Lot #: 111N624EZ) in 0.5% carboxymethylcellulose at dose levels of 2430, 3500, or 5040 mg/kg. All animals were ob served for clinical signs of toxicity and mortality for up to 14 days post-dosing.

During the study, mortality was observed at 2430 (2/5 males and 1/5 females), 3500 (4/5 males and 4/5 females), and 5040 mg/kg (4/5 males and 4/5 females). Clinical signs of toxicity observed included the following: decreased activity, ptosis, and ataxia, no stool, cold to touch, decreased defecation, prostration, impaired limb function, chromodacryorrhea, ataxia, material around eye, and emaciation. All surviving animals appeared normal by Day 11. No treatment-related effects on survivor body weight were observed. Gross abnormalities obse rved at necropsy included: intestinal tract filled with yellow contents (13/30 animals) and focal discoloration of the stomach glandula r mucosa (7/30 animals).

Oral LD50 Males = 2588 (1450-4622) mg/kg (calculated) Females = 3080 (2259-4199) mg/kg (calculated) Combined = 2864 (2156-3803) mg/kg (calculated)

Carboxin is classified as TOXICITY CATEGORY III. This study is classified acceptable/guideline (§81-1) and does satisfy the guideline requirements for an acute oral study in th e rat.

Guideline: 81-2 Acute dermal toxicity in rabbits or rats Memo Date: 26-Jan-1979 TXR: 0000755 Study Type: Acute, Oral, Treatment Duration: 1 Dose; also Acute Dermal, Eye and Dermal irritation Study Classified as: Minimum

MRID: 00021645 Species: Strain: Rabbit : New Zealand White,Rat : Sprague-Dawley Material (material; batch; %ai): Formulation; not in DER; Evershield RTU 1050 seed protectant: thiram (10.15%); vitavax (5.16%) Laboratory: Hill Top Research Study No; Report Date: 78/427/21; 29-Jun-1978 Three formulations tested: 1. Evershield RTU 1000 - 10% Thiram; 2. Evershield RTU 1050 - 10% Thiram + 5% Vitavax; 3. Evershield RTU
1010 - 10% Thiram + 10% Vitavax.

Acute Oral: All three formulations: LD50 > 10.0 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Acute Dermal: All three formulations: LD50 > 21.5 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Primary Eye Irritation: Formulation 1.: It is uncertain from the report whether the staining effect of the test material interf ered with the animals' vision or whether the staining effect interfered with complete evaluation of corneal opacity. Classification: Supplementary. Primary Dermal Irritation: All three formulations: Although the staining effect precluded complete evaluation, the data show th at the test material is not corrosive or a severe irritant. Tox Category IV. Classification: Core-Minimum Data.

Guideline: 81-5 Primary dermal irritation Memo Date: 26-Jan-1979 TXR: 0000755 Study Type: Acute, Oral, Treatment Duration: 1 Dose; also Acute Dermal, Eye and Dermal irritation Study Classified as: Minimum

MRID: 00021645 Species: Strain: Rabbit : New Zealand White,Rat : Sprague-Dawley Material (material; batch; %ai): Formulation; not in DER; Evershield RTU 1050 seed protectant: thiram (10.15%); vitavax (5.16%) Laboratory: Hill Top Research Study No; Report Date: 78/427/21; 29-Jun-1978 Three formulations tested: 1. Evershield RTU 1000 - 10% Thiram; 2. Evershield RTU 1050 - 10% Thiram + 5% Vitavax; 3. Evershield RTU
1010 - 10% Thiram + 10% Vitavax.

Acute Oral: All three formulations: LD50 > 10.0 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Acute Dermal: All three formulations: LD50 > 21.5 gm/kg, Classification: Core-Minimum Data, Tox Category: IV Primary Eye Irritation: Formulation 1.: It is uncertain from the reportEPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 52 whether the staining effect of the test material interfered with the animals' vision or whether the staining effect interfered with complete evaluation of corneal opacity. Classification: Supplementary. Primary Dermal Irritation: All three formulations: Although the staining effect precluded complete evaluation, the data show th at the test material is not corrosive or a severe irritant. Tox Category IV. Classification: Core-Minimum Data.

OneLiner Report Updated: 01/27/2015

### 53 EPA Chemical Code: - Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: Print Date: 27-Jan-2015 Last Updated: Page: 6

No reports were found in IHAD for the following pccodes: 090202;

Start Time: 01/27/2015 08:18:03 AM
End Time: 01/27/2015 08:21:21 AM

OneLiner Report Updated: 01/27/2015

### 54 2. Acute inhalation toxicity

EPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27 -Jan-2015 Last Updated: 16-Aug-2013 Page: 1

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 27-Jan-1978 TXR: 0000750 Study Type: Acute, Inhalation, Treatment Duration: 1 Hour; 14-Day Observation Period Study Classified as: Minimum

MRID: 00003083 Species: Strain: rat : Sprague-Dawley Material (material; batch; %ai): Formulation; BL8229; Vitavax Flowable Fugicide, 34% a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5481A; 15-Sep-1977 LC50 > 20 mg/l (no deaths occurred) Toxic Signs: decreased activity and ataxia during exposure. Necropsy: not performed Tox. Category: IV

Classification: Core - Minimum Data

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 14-Apr-1978 TXR: 0000751 Study Type: Acute, Inhalation, Treatment Duration: 1 Hour; 14-Day observation period Study Classified as: Minimum

MRID: 00003116 Species: Strain: rat : Long-Evans Material (material; batch; %ai): Technical; 891; Vitavax, no a.i. given Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5495A; 18-Oct-1977 No deaths LC50>20 mg/L Toxic Signs: ataxia, urinary incontinence Necropsy: not performed Body weight: not reported Classification: Core - Minimum Data Tox Category:
IV CAUTION

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 2-Aug-1978 TXR: 0000752 Study Typ e : Acute, Inhalation, Treatment Duration: 1 Hour Study Classified as: Minimum

MRID: 00073210 Species: Strain: rat : Not Specified Material (material; batch; %ai): Formulation; 5481B; Vitavax-17 Flowable Fungicide, 17.1% a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5481B; 25-Sep-1977 None of the 10 rats died. No note worthy symptoms developed during or after exposure. The product is Category IV. This test is Core Minimum. The particle size was not determined nor was the chamber periodically sampled.EPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 55 Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 22-Aug-1978 TXR: 0000753 Study Type: Acute, Inhalation, Treatment Duration: 1 Hour; Whole body, 14-Day observation period Study Classified as: Minimum

MRID: 00003011 Species: Strain: Rabbit : New Zealand White Material (material; batch; %ai): Formulation; not in DER; Vitavax-200 (Carboxin, Thiram): not in DER Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5480B; 15-Sep-1977 Vitavax-200 (Carboxin, Thiram):
Classification: Core Minimum Data
Tox. Cat. IV LC50 > 20 mg/L 1 hour

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 3-Aug-1979 TXR: 0000759 Study Type: Acute, Inhalation, Treatment Duration: 1 Dose; 14 day observation period Study Classified as: Minimum

MRID: 00029650 Species: Strain: Rat : Long-Evans Material (material; batch; %ai): Formulation; not in DER; Vitavax HBM-25: Carboxin, 12.5% a.i.; Captan, 12.5% a.i. Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: 5483; 18-Oct-1977 Vitavax HBM-25 (Carboxin, Captan):LC50 > 20 mg/L. Toxicity category IV. Classified: minimum.

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 2-Oct-1979 TXR: 0000761 Study Type: Acute, Inhalation, Treatment Duration: 1 Hour; 14 day observation period Study Classified as: Minimum

MRID: 00024923 Species: Strain: Rat : Not Specified Material (material; batch; %ai): Formulation; # 8901161V and 8520157V; 32.9% ai Laboratory: Food & Drug Research Labs Study No; Report Date: 6135; 1-Jan-1979 LC50 > 5.6 mg/L. Toxicity category III.
Classified: minimum

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 8-Jul-1983 TXR: 0000162 Study Type: Acute, Inhalation, Treatment Duration: 4 Hours; whole body, 14 day observation period Study Classified as: Minimum

MRID: 00128468 Species: Strain: Rat : Sprague-Dawley Material (material; batch; %ai): Technical; not in DER; not in DER Laboratory: Food & Drug Research Laboratories, Inc. Study No; Report Date: NO PROJNR; 13-Oct-1982 LC50 > 5.5 mg/L. Toxicity Category III.
Classified minimum

Guideline: 81-3 Acute inhalation toxicity in rats Memo Date: 5-Mar-2002 TXR: 0050129 Study Type: Acute, Inhalation, Treatment Duration: 4 Hours; whole body, 14 day observation period Study Classified as: Acceptable/Guideline

MRID: 43171403 Species: Strain: Rat : Sprague-Dawley Crl:CD BR VAF/Plus Material (material; batch; %ai): Technical; 111N624EZ; Carboxin (Vitavax technical):102.2% ai Laboratory: International Research & Development Corp. Study No; Report Date: 399/132; 5-Feb-1993 In an acute inhalation toxicity study (MRID 43171403), 10 young adult Sprague-Dawley rats (5/sex) were exposed by whole-body in halation to carboxin dust (102.2% a.i., Lot # 111N624EZ) at an analytically-determined concentration of 4.7 mg/L for 4 hours. The MMAD of t he particles was 6.8 microns; the smallest obtainable particle size. Animals were observed for clinical signs of toxicity for up to 14 days post-exposure and all animals were subject to gross necropsy.EPA Chemical Code: 090201-Carboxin Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page:



### 56 No mortalities occurred during the study. Clinical signs were limited to material matted fur, red/brown material around the nos e, increased salivation, corneal opacity, and labored breathing with all affected animals recovering by post-exposure day 4. There were no treatment-related effects on body weight. No gross lesions were observed during necropsy.

Inhalation LC50: Males greater than 4.7 mg/L; Females greater than 4.7 mg/L

Carboxin is classified as TOXICITY CATEGORY IV based on the LC50 values in males and females.

This study is classified acceptable/guideline (§81-3) and does satisfy the guideline requirements for an acute inhalation study in the rat.

OneLiner Report Updated: 01/27/2015

### 57 EPA Chemical Code: - Studies for Display: Studies that satisfy guideline requirements alone or with another CAS Number: Print Date: 27-Jan-2015 Last Updated: Page: 4

No reports were found in IHAD for the following pccodes: 090202;

Start Time: 01/27/2015 08:08:47 AM
End Time: 01/27/2015 08:11:50 AM

OneLiner Report Updated: 01/27/2015

### 58 3. Two-generation rat reproduction

EPA Chemical Code: 090201-Carboxin Studies for Display: All CAS Number: 5234-68-4,125225-28-7 Print Date: 27-Jan-2015 Last Updated: 16-Aug-2013 Page: 1

Guideline: 83-4 2-generation repro.-rat Memo Date: 17-Jun-1969 TXR: 0000747 Study Type: Reproduction, Oral, Treatment Duration: 3 Generations Study Classified as: Not Classified

MRID: 00003032 Species: Strain: Rat : Charles River CD(SD) Material (material; batch; %ai): Technical; not in DER; Vitavax Technical, D735, 95% a.i. Laboratory: Hazleton Laboratories, Inc. Study No; Report Date: 798/104; 9-Aug-1968

Guideline: 83-4 2-generation repro.-rat Memo Date: 17-Jan-1989 TXR: 0007742 Study Type: Reproduction, Oral, Treatment Duration: 3 Generations Study Classified as: Supplementary

MRID: 00003032 Species: Strain: Rat : Not Specified Material (material; batch; %ai): Technical; not in DER; % ai not in DER Laboratory: Hazleton Laboratories, Inc. Study No; Report Date: 798/104; 9-Aug-1968 Based on the moderated growht depression noted among the pups at the 600 ppm level, a no-effect level of 200 ppm can be estimat ed for D735 from this 3-generation rat reproduction study. NOEL = 200 ppm. LEL = 600 ppm (depression of pup growth) Classified: supplementary

### 59 Guideline: 83-4 2-generation repro.-rat Memo Date: 27-Nov-1991 TXR: 0008862 Study Type: Reproduction, Oral, Treatment Duration: 2 Generations Study Classified as: Supplementary

MRID: 41922601 Species: Strain: Rat : Crl:CD BR Material (material; batch; %ai): Technical; LOT: 812N465FZ; 97.55 - 98.05 % ai Laboratory: Hazleton Laboratories America, Inc. Study No; Report Date: HLA/6111/128; 11-Apr-1991

Guideline: 83-4 2-generation repro.-rat Memo Date: 1-Dec-1992 TXR: 0009868 Study Type: Reproduction, Oral, Treatment Duration: 2 Generations Study Classified as: Minimum

MRID: 41922601 Species: Strain: Rat : CrL:CD(SD)BR Material (material; batch; %ai): Technical; not in DER; not in DER Laboratory: Hazleton Laboratories America, Inc. Study No; Report Date: HLA/6111/128; 1-Dec-1991

MRID: 42391107 Species: Strain: Rat : CrL:CD(SD)BR Material (material; batch; %ai): Technical; not in DER; not in DER Laboratory: Study No; Report Date: HLA/611/128; 1-Dec-1992

Guideline: 83-4 2-generation repro.-rat Memo Date: 5-Mar-2002 TXR: 0050129 Study Type: Reproduction, Oral, Treatment Duration: 2 Generations Study Classified as: Acceptable/Guideline

MRID: 41922601 Species: Strain: Rat : CrL:CD BR Material (material; batch; %ai): Technical; 812N465FZ; carboxin (97.55-98.05% a.i.,) Laboratory: Hazleton Laboratories America, Inc. Study No; Report Date: HLA/6111/128; 11-Apr-1991

MRID: 42391107 Species: Strain: Rat : Crl:CD BR Material (material; batch; %ai): Technical; 812N465FZ; carboxin (97.55-98.05% a.i.,) Laboratory: Study No; Report Date: HLA/611/128; 12-Jun-1992 In a two-generation reproduction study (MRIDs 41922601 and 42391107), carboxin (97.55-98.05% a.i., Lot# 812N465FZ) was administ ered continuously in the diet to Crl:CD BR rats (25/sex/group) at nominal dose levels of 0, 20, 200, or 400 ppm in males and 0, 20, 300, or 600 ppm in females. The P animals were mated twice to produce the F1a and F1b litters and the F1b animals were mated twice to produce t he F2a
and F2b litters.

No treatment-related findings were observed in the 20 ppm males and females. Mortality, clinical signs, pup development, were u naffected by

the test substance.

At 200/300 ppm (M/F), body weight gains were decreased (p less than or equal to 0.05) compared to controls in the F1b adult mal es on days 0-63, 0-70, and 0-77 during the F2a phase and on days 0-42, 0-56, 0-63, 0-77, and 0-84 during the F2b phase; increased (p less than or equal to 0.01) food consumption was observed in these animals on days 0-21 and 42-45 during the F2a phase. Macroscopic examinat ion of the kidneys indicated an increased incidence of large pelvis(es) in the F1b adult males.

At 400/600 ppm (M/F) decreased (p less than or equal to 0.05 or 0.01) mean body weights were observed as follows: (i) in the P males during the F1a and F1b phases; (ii) in the F1b males during the F2a and F2b phases; (iii) in the P females during the F1b phase on ges tation day (GD) 0, 7, 14, and 20 and lactation days (LD) 0, 4, and 7; (iv) in the F1b females on days 42, 49, and 70 of the F2a phase and on GDs 0-20 and LD 0, 7, and 14 of the F2b phase. In the males, decreased (p less than or equal to 0.05 or 0.01) cumulative body weight gai ns were observed in the P adults throughout the F1a phase and in the F1b adults throughout the F2a phase. Macroscopic examination of th e kidneys indicated an increased incidence of large pelvis(es) in the P and F1b adult males and females compared to the controls.

Only the kidneys with macroscopic lesions were examined histologically (0-3 P animals/dose and 1-9 F1b animals/dose); the data, while meager, indicate that the test material may have deleterious effects (chronic nephritis and associated changes) on the kidneys of the 200 and 400 ppm F1b males and possibly the 300 and 600 ppm females. However, it is not possible to assess the true incidence of this af fect due to the limited amount of kidney histological data provided in this study.

### 60 A decreasing trend in the number of pregnancies with increasing dose was observed in the F1 females during the F2b phase when c ompared to controls or the F1 females during the F2a phase. Decreased (not statistically significant) fertility indices were observed with increasing dose in the F2b males and females compared to controls, and decreased (p less than or equal to 0.01) pup body weights compared to contr ols were observed in the 400 ppm F2b males on lactation days 7 and 21. A non-statistically significant decrease in pup body weights was also observed in the 200 ppm F2b males.

The LOAEL for parental toxicity is 200 ppm (10 mg/kg/day) for males based on decreased body weight gains in the F1 parental mal es during the F2a and F2b generations and macroscopic and microscopic changes in the kidneys. The LOAEL for females is 300 ppm (15 mg/kg/ day) based on equivocal microscopic changes in the kidneys. The parental NOAEL for both males and females is 20 ppm (1 mg/kg/day).

The LOAEL for reproductive toxicity is 400 ppm (20 mg/kg/day) for males and 600 ppm (30 mg/kg/day) for females, based on a decr ease in the number of pregnancies in the F2b generation, resulting in decreased fertility indices for the F1b parental males and females. T he NOAEL for reproductive toxicity is 200 ppm (10 mg/kg/day) for males and 300 ppm (15 mg/kg/day) for females.

The LOAEL for offspring toxicity is 400 ppm (20 mg/kg/day) for males and 600 ppm (30 mg/kg/day) for females, based on decreased body weiths for F2b male pups. The NOAEL for offspring toxicity is 200 ppm (10 mg/kg/day) for males and 300 ppm (15 mg/kg/day) for f emales.

CLASSIFICATION: The submitted study is classified as acceptable/guideline (§83-4) and satisfies the requirements for a multigen erational reproductive toxicity study in rats.

OneLiner Report Updated: 01/27/2015

### 61 EPA Chemical Code: - Studies for Display: All
CAS Number: Print Date: 27-Jan-2015 Last Updated: Page: 4

No reports were found in IHAD for the following pccodes: 090202;

Start Time: 01/27/2015 09:17:56 AM End Time: 01/27/2015 09:20:04 AM

OneLiner Report Updated: 01/27/2015

### 62 

## Appendix C. Screening Tool for Inhalation Risk (v. 1.0).