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 

Prepared by:

 

Catherine Aubee, Biologist 

Chuck Peck, Environmental Engineer

U. S. Environmental Protection Agency 

Office of Pesticide Programs 

Environmental Fate and Effects Division 

Environmental Risk Branch IV

1200 Pennsylvania Ave., NW 

Mail Code 7507P 

Washington, DC 20460

Reviewed by: 

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 ........................................................................................................ 21

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. ............................................................ 39

Appendix 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 ......................................................................................... 58

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 

carboxin1

 and oxycarboxin2. 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 use4. 

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, carboxin. Report dated November 24, 1992. See SAN R2004634. 2

 US EPA. 1992. Data requirements for the fungicide, oxycarboxin. Memo from D. Urban to W. Waldrop. May 5, 1992. 3

 Uniroyal Chemical Co., Inc. 1994. Letter from W.F. Cummings to C. Childress, Special Review and Reregistration Branch, US EPA Office of 

Pesticide Programs. May 24, 1994. 

4

 For example, see “Action Code Interpretation” for registration 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 metabolism 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 

Nonguideline9 Honeybee adult acute oral toxicity study 

(TGAI) Needed 

Nonguideline9 Honeybee adult chronic oral toxicity study 

(TGAI) Needed 

Nonguideline9 Honeybee larval acute toxicity (TGAI) Needed 

Nonguideline9 Honeybee larval chronic toxicity (TGAI) Needed 

Nonguideline9 Honey bee semi-field (tunnel or colonyfeeding) test –TGAI and TEP Needed10 

Nonguideline9 Field trial of residues in pollen and nectar 

– TGAI and TEP Needed11 

850.3040 Field testing for pollinators – TGAI and 

TEP Needed12 

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 assessment for oxycarboxin because the 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 honey 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 carboxin14. 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 chain15; 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 cancellation16. 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. 2004b. 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 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

16 USEPA. 2014. Federal Register Notice on the Product Cancellation 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 memo17

that addressed human health occupational risks of oxycarboxin use in greenhouses was issued in 

September 2004. 

a. Ecological Risk Assessment 

The 2004 RED18 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 degradate 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 memo19) as part of the 2004 RED20. 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 2004b. 19 USEPA. 2001. Conclusions of the 11/27/2001 Meeting of the Metabolism Assessment Review Committee 20 Ibid USEPA 2004b
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 μg/L, less than 

the chronic drinking water level of concern (DWLOC) of 26 μg/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 μg/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 200421 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 not 

exceed 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 Benchmarks22 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 environment23. 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 2004c 22 USEPA 2014c. Office of Pesticide Programs’ Aquatic Life Benchmarks. 

http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm#benchmarks 23 Ibid USEPA 2004b. 
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 Kow=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 (25qC) 1.8 x 10-7 torr -- 42493703 

Aqueous solubility 

(pH 7; 20qC) 195 mg/L -- 47687404 

Henry’s Law Constant (20°C) 2.86 x 10-10 atm/m3/mol Calculated 

Log octanol-water partition 

coefficient (log KOW) 2.17 -- 42493705 

Persistence 
11 

Parameter Value Description Source

Hydrolysis half-life 

 pH 5, 25qC 

 pH 7, 25qC 

 pH 9, 25qC 

stable 

stable 

stable 

 

00141213 

Aqueous photolysis half-life 

(25qC) 

0.06 d Supplemental (only one 

ring radiolabelled) 

42192801 

Soil photolysis half-life (25qC) NA 

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

1.35 

< 1 

< 1 

1.24 

1.36 

98 

57 

28 

NA2

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 (25qC) 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 (25qC) 1

C C/CS Soil Supplemental (only one 

ring radiolabelled) 

42600801 

34.4 32.7 SiL 

Anaerobic aquatic metabolism 

half-life (25qC)1

C C/CS Soil Supplemental (uncertainty 

in anaerobic system) 

42600803 

239 250 SiL 

Mobility

Freundlich soil-water 

distribution coefficient (KF) 

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+carboxin 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, Koc values estimated using EPISuite (18-20 L/kgoc) 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. 
13 

Table 5. Carboxin and Its Major Environmental Transformation Products and Degradates 

Chemical Name Chemical Structure Study type Ref. (MRID) Maximum % AR (day) Final % AR (study length) 

Parent

Carboxin 

-- -- -- -- 

Major Transformation Products 

Carboxin sulfoxide Aqueous photolysis 

Aerobic soil Aerobic soil Aerobic soil Aerobic soil Aerobic soil Anaerobic soil Aerobic aquatic Anaerobic aquatic 

42192801 00003225 00005540 00005540 41224504/41252501 41224503 41224508/41725501 42600801 42600803 

20.4 (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 (Carboxin sulfone) 

Aerobic soil Anaerobic soil Anaerobic soil Aerobic aquatic Anaerobic aquatic 

00003225 41224507/41286601 41224508/41725501 42600801 42600803 

2.9 (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-oxathiin 

Anaerobic soil 41224508/41725501 13.9 (60) 13.9 (60) 

S-[2-(acetyloxy)-ethyl]-2-oxo2-(phenylamino)ethanethioate Aerobic aquatic Anaerobic aquatic 42600801 42600803 17.1 (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) 

LC50 = 1.2 mg/L 

(NR, 1.0 – 1.4 mg/L)c

Moderately toxic 

00003004 

00053731 

Acc. No. 224935 

Acceptable 

LC50 = 28.1 mg/L 

(NR, 22.6 – 35.1 mg/L)d

Slightly toxic 

SAN R2004683 

Acceptable 

Rainbow trout 

(Onchorhynchus 

mykiss) 

LC50 = 2.0 mg/L 

(NR, 1.6 – 2.5 mg/L)e

Moderately toxic 

053731 

Acceptable 

LC50 = 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) 

EC50 = 84.4 mg/L 

(NR, 73.1-97.6 mg/L) 

Slightly toxic 

00053730 

Acc. No. 235236 

Acceptable 

EC50 = 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

IC50 = 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 

IC50 = 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 LD50 values of 2,410 mg/kg and greater 

than 10,000 mg/kg, respectively. Additionally, toxicity testing with Vitavax® SP in bobwhite 

quail (LC50 >5,620 mg/kg of diet) and mallard ducks (Anas platyrhynchos; LC50 >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 (LD50 = 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) 

LD50 > 2,150 mg/kg-bw (NA) 

Practically nontoxic 

43582301 

Acceptable 

NA 

Mallard duck 

(Anas platyrhynchos) 

LD50 > 2,000 mg/kg-bw (NA) 

Practically nontoxic 

00072744 

Acceptable 

LD50 = 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) 

LC50 > 4,110 mg/kg diet 

(NA)36

Practically nontoxic 

43582303 

Acceptable 

LC50 > 10,000 mg/kg 

diet (NA) 

Practically nontoxic 

SAN R2004683 

Acceptable 

Mallard duck 

(Anas platyrhynchos) 

LC50 > 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 

Supplemental38

NA 

Mallard duck 

(Anas platyrhynchos) 

NOAEL = 70 mg/kg diet 

LOAEL = 700 mg/kg diet39

Numbers of 

eggs set, 

female body weight 

44240102 

Acceptable 

NA 

Acute oral toxicity to 

mammals 

Laboratory rat 

(Rattus norvegicus) 

LD50 = 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) 

 LC50 > 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) 

LD50 = 2 μg/bee 

Moderately toxic 

00018842 

Acceptable 

LD50 = 5.9 μg/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 (AIMS40) or the 

National Pesticide Information Center (NPIC41). 

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 AIMS42 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 (t1/2 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 sulfoxide43), 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 

(ECOTOX44), 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 effects 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 2004b. 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. 123045) 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 Kow 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). EPA 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 

Acceptable1

Acceptable1

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 

Supplemental1

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 Data 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 

be 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 

be 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 (Kf<1, log Kow<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). Exposure 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 LC50--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) 
39

Appendix A. Summary of endpoints and review classifications for available ecological effects studies, with annotations for internal document tracking. Table A.1. Summary of Endpoints from Aquatic Toxicity Studies for Carboxin and Oxycarboxin. 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax®

Technical)

Acute toxicity to freshwater fish 

Bluegill sunfish 

(Lepomis 

macrochirus)

LC50 = 3.6 mg/L 

(NR, 2.7 – 4.3 mg/L)46

Moderately toxic 

43582304 

Acceptable 

224935 

Invalid47

LC50 = 11.2 mg/L 

(NR) 

Slightly toxic 

224935 

Acceptable48

LC50 = 0.56 mg/L 

(NR) 

Highly toxic 

224935 

Acceptable49

LC50 = 28.1 mg/L 

(NR, 22.6 – 35.1 

mg/L)50

Slightly toxic 

SAN R2004683 

Acceptable 

LC50= 1.2 mg/L 

(NR, 1.0 – 1.4 mg/L)51

Moderately toxic 

00003004 00053731 

Acc. No. 224935 

Acceptable 

SAN R2004606 

Invalid52

46 Based 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, mean 

measured) 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. 

47 Multiple 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 

absence of purity information (see SAN R2004608). The study was reviewed again and classified as invalid (not upgradeable) due to the use of polyethylene liners in tanks and because the data were pooled from separate tests to generate a single mortality curve (see SAN R2005002; February 27, 1981). 

48 Multiple 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 the 

absence of purity information (see SAN R2004608). 

49 Multiple 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 the 

absence of purity information (see SAN R2004608). 

50 Based on nominal treatment concentrations. 51 Based on nominal treatment concentrations.52 Study classified as invalid (but upgradeable) in DER dated October 25, 1979, due to the absence of purity information and lack of data on size and weight of fish. 
40

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax®

Technical)

Rainbow trout 

(Onchorhynchus 

mykiss)

LC50 = 2.3 mg/L (NR, 1.5 – 

2.4 mg/L)53

Moderately toxic 

43582305 

Acceptable 

224935 

Invalid54

LC50 = 6.6 mg/L 

(NR) 

Moderately toxic 

224935 

Acceptable55

LC50 = 0.38 mg/L 

(NR) 

Highly toxic 

224935 

Acceptable56

LC50 = 19.9 mg/L 

(NR, 14.5 – 27.4 

mg/L)57

Slightly toxic 

SAN R2004683 

Acceptable

LC50 = 2.0 mg/L (NR, 1.6 – 

2.5 mg/L)58

Moderately toxic 

053731 

Acceptable 

SAN R2004607 

Invalid59

Early life stage toxicity to freshwater fish 

Not submitted NA NA NA NA NA 

Full life cycle toxicity to freshwater fish 

Not submitted NA NA NA NA NA 

Acute toxicity to freshwater invertebrates 

Water flea 

(Daphnia 

magna)

EC50 = 84.4 mg/L (NR, 

73.1-97.6 mg/L) 

NA NA NA 

53 Based on mean measured concentrations. 54 Multiple 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 absence 

of purity information (see SAN R2004608). The study was reviewed again and classified as invalid (not upgradeable) due to the use of polyethylene liners in tanks and because data were pooled from 

separate tests to generate a single mortality curve (see SAN R2005002; February 27, 1981). 

55 Multiple 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 the 

absence of purity information (see SAN R2004608). 

56 Multiple 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 the 

absence of purity information (see SAN R2004608). 

57 Based on nominal treatment concentrations. 58 Based on nominal treatment concentrations. 59 Study classified as invalid (but upgradeable) in DER dated October 29, 1979, due to the absence of purity information and lack of data on size and weight of fish.
41

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax®

Technical)

Slightly toxic 

00053730 

Acc. No. 235236 

Acceptable60

EC50 = 69.1 mg/L 

(NR, 54.2 – 88.2 

mg/L)61

Slightly toxic 

SAN R2004683 

Acceptable 

EC50 > 57 mg/L62 (NA) 

No more than slightly toxic 

43582306 

Supplemental63

Life cycle toxicity to freshwater invertebrates 

Not submitted NA NA NA NA NA 

Acute toxicity to estuarine/marine fish 

Not submitted NA NA NA NA NA 

Early life stage toxicity to estuarine/marine fish 

Not submitted NA NA NA NA NA 

Full life cycle toxicity to estuarine/marine fish 

Not submitted NA NA NA NA NA 

Acute toxicity to estuarine/ marine invertebrates 

Pink shrimp 

(Penaeus 

duorarum)

NA NA NA 

LC50 = 14 mg/L 

(NR, 5.0 – 41 

mg/L) 

Slightly toxic 

NA 

60 Study classification is reported on branch copy of study report accompanying letter from Uniroyal Chemical Co., dated April 27, 1982. 61 Based on nominal treatment concentrations. 62 Based on mean-measured treatment concentrations. 63 Study classified as supplemental due to poor recovery (approx. 1⁄2 nominal concentration) attributed to limited solubility at higher treatment levels.
42

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax®

Technical)

00003704 

Acc. No. 224935 

Supplemental64

Fiddler crab 

(Uca pugilator) NA NA NA 

LC50 = 964 mg/L 

(NR, 502 – 1,860 

mg/L) 

Practically

nontoxic 

Acc. No. 224935 

Supplemental65

NA 

Acute toxicity to estuarine/marine molluscs 

Not submitted NA NA NA NA NA 

Life cycle toxicity to estuarine/marine invertebrates 

Not submitted NA NA NA NA NA 

Toxicity to aquatic vascular plants (14-day) 

Duckweed 

(Lemna gibba)

NOAEL = 0.15 mg/L 

LOAEL = 0.30 mg/L

IC50 = 0.67 mg/L (NR, 

0.60 – 0.76 mg/L)66

Frond number 

41493802 

Acceptable 

NA NA NA NA 

Toxicity to aquatic Green algae NOAEL = 0.11 mg/L LOAEL = 0.22 mg/L NA NA NA NA 

64Study 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 test 

temperature (see SAN R2004599). 

65 Study 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 test 

temperature (see SAN R2004599).

66 Based on mean-measured treatment concentrations. 
43 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax®

Technical)

nonvascular plants (120-hr) 

(Pseudokirchner

iella 

subcapitata) 

IC50 = 0.37 mg/L (NR, 

0.33 – 0.42 mg/L)67

Cell density 

41493801 

Acceptable 

Toxicity to aquatic nonvascular plants (72-hr) 

Alga 

(Chlorella 

pyrenoidosa) 

NOAEL = 1.0 mg/L 

LOAEL = 1.8 mg/L 

IC50 = 2.6 mg/L 

(4.1, 2.34 – 2.77 mg/L)68

Cell density 

41317801 

Supplemental 

NA NA NA NA 

Table A.2. 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.) 

Carboxin EP (75% 

a.i.) 

Carboxin 

(38.7%) + Captan 

(37.5%) 

Carboxin (17%) 

+ Thiram (17%) 

Oxycarboxin 

TGAI (Plantvax 

Technical)

Acute oral toxicity to birds 

Bobwhite quail 

(Colinus virginianus) 

LD50 > 2,150 mg/kgbw (NA) 

Practically nontoxic 

43582301 

Acceptable 

NA 224935 

Invalid69

224935 

Invalid70 NA 

67 Based on mean-measured treatment concentrations. 68 Based on nominal treatment concentrations.69 Study 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). 

70 Classified 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). 
44 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax 

Technical)

Mallard duck 

(Anas platyrhynchos) 

LD50 > 2,000 mg/kgbw (NA) 

Practically nontoxic 

00072744 

Acceptable71

NA NA NA 

LD50 = 1,250 

mg/kg-bw 

(NR, 852-1,835 

mg/kg-bw) 

Slightly toxic 

SAN R2004683 

Acceptable 

Subacute dietary toxicity to birds 

Bobwhite quail 

(Colinus virginianus) 

LC50 > 4,110 mg/kg 

diet (NA)72

Practically nontoxic 

43582303 

Acceptable 

LC50 > 5,620 mg/kg 

diet (NA) 

Practically nontoxic 

00029175 

Acc. No. 224935 

Supplemental73

NA NA 

LC50 > 10,000 

mg/kg diet (NA) 

Practically 

nontoxic 

SAN R2004683 

Acceptable 

LC50 > 4,640 mg/kg 

diet (NA) 

Practically nontoxic 

00003037 00072745 

Acceptable74

Mallard duck 

(Anas platyrhynchos) 

LC50 > 4,110 mg/kg 

diet (NA)75

Practically nontoxic 

NA NA NA NA 

71 See review and classification in SAN R2004626 and R2004650.72 Based on mean-measured treatment concentrations. 73 Study classified as supplemental in DER dated October 22 1979 (see SAN R2004604). 74 Study classified as acceptable in SAN R2004651 but identified as unacceptable and not fulfilling guideline requirements in SAN R2004597. It is unclear whether these reviews refer to two studies 

using 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 the 

test material. 

75 Based on mean-measured treatment concentrations.
45 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax 

Technical)

43582302 

Acceptable 

LC50 > 4,640 mg/kg 

diet (NA) 

Practically nontoxic 

00003139 

Acc. No. 224935 

Acceptable 

Ring-necked pheasant (Phasianus colchicus) NA 

LC50 > 4,464 mg/kg 

diet (NA)76

Practically nontoxic 

SAN R2004605 

Supplemental 

NA NA NA 

Avian reproduction 

Bobwhite quail 

(Colinus virginianus) 

NOAEL = 1,000 mg/kg 

diet 

LOAEL > 1,000 mg/kg 

diet 

No effects 

44240101 

Supplemental77

NA NA NA NA 

Mallard duck 

(Anas platyrhynchos) 

NOAEL = 70 mg/kg 

diet

LOAEL = 700 mg/kg 

diet78

NA NA NA NA 

76 The LC50 value is inferred from mortality observations. One of twelve pheasants died in the 2 oz/bushel wheat (~2,232 mg/kg diet) 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 when compared to environmentally relevant concentrations. 

78 Based on nominal treatment rates.
46 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax 

Technical)

Numbers of 

eggs set, 

female body weight 

44240102 

Acceptable 

Acute oral toxicity to mammals 

Laboratory rat 

(Rattus norvegicus) LD50 = 2,588 (1,450-

4,622) mg/kg bw 

Practically nontoxic 

43171401 

Acceptable 

NA NA 

LD50 = 6,250 

(4,880 – 8,000) 

mg/kg bw 

Practically 

nontoxic 

00003012 

Acceptable 

NA 

Acute inhalation toxicity to mammals 

Laboratory rat 

(Rattus norvegicus) LC50 > 20 mg/L 

Toxicity Category IV 

00003116 

Acceptable 

NA NA 

LC50 > 20 mg/L 

Toxicity Category 

IV 

00003011 

Acceptable 

NA 

Chronic (twogeneration reproduction) toxicity to mammals 

Laboratory rat 

(Rattus norvegicus) 

NOAEL = 1 mg/kg 

bw/day

LOAEL = 10 mg/kg 

bw/day 

NOAEC = 20 mg/kg 

diet

LOAEC = 200 mg/kg 

diet 

Reduced parental body 

weight 

41922601/ 

NA NA NA NA 
47 

Study Type Species 

Test 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%) 

Oxycarboxin 

TGAI (Plantvax 

Technical)

42391107 

Acceptable 

Acute contact toxicity 

Honey bee 

(Apis mellifera) 

LD50 = 2 μg/bee 

Moderately toxic 

00018842 

Acceptable79

NA NA NA 

LD50 = 5.9 μg/bee 

Moderately toxic 

00018842 

Acceptable80

Seedling emergence of terrestrial plants 

Not submitted NA NA NA NA NA 

Vegetative vigor of terrestrial plants Not submitted NA NA NA NA NA 

79 Identified as scientifically sound in the DER (February 4, 1981), but not otherwise classified. 80 Identified 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 Date: 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 Type: 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 Type: 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 MINIMUM 
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: 

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 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 that 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: minimum 
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: 

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) 1326 

(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-1992 
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: 

51 

In an acute oral toxicity study (MRID 43171401), fasted Sprague Dawley rats (5/sex/dose) were given a single oral dose by gavage 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 observed 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 observed at 

necropsy included: intestinal tract filled with yellow contents (13/30 animals) and focal discoloration of the stomach glandular 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 the 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 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 that 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 report 
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: 

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 that 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 Type: 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 inhalation 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 the 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 nose, 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 estimated 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 administered

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 the F2a 

and F2b litters. 

No treatment-related findings were observed in the 20 ppm males and females. Mortality, clinical signs, pup development, were unaffected 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 males 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 examination 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 gestation 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 gains were 

observed in the P adults throughout the F1a phase and in the F1b adults throughout the F2a phase. Macroscopic examination of the 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 affect 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 compared 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 controls 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 males 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 decrease in the

number of pregnancies in the F2b generation, resulting in decreased fertility indices for the F1b parental males and females. The 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 females. 

CLASSIFICATION: The submitted study is classified as acceptable/guideline (§83-4) and satisfies the requirements for a multigenerational 

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).