Carboxin and Oxycarboxin Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY................................................................... 8

CHEMICAL FACTS ...................................................................................................................... 8

USE AND USAGE INFORMATION............................................................................................ 9

RECENT ACTIONS..................................................................................................................... 11

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW.............................. 11

TIMELINE.................................................................................................................................... 13

NEXT STEPS ............................................................................................................................... 14

Appendix – Additional Areas Considered in the Carboxin and Oxycarboxin Registration 

Review ...................................................................................................................................... 15

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Registration review—Preliminary Problem Formulation for the Drinking Water and 

Ecological Risk Assessments of Carboxin and Oxycarboxin. Aubee, C. and Peck, C. March 

11, 2015.

2. Carboxin and Oxycarboxin: Human Health Scoping Document in Support of Registration 

Review. Kidwell, J., Khasawinah, A., Cropp-Kohlligian, B., Hummel, S., and Nieves, I. 

February 24, 2015.

3. Carboxin and Oxycarboxin: Tier I Review of Human Incidents. Recore, S., and E. Evans.

November 20, 2014.

4. BEAD Chemical Profile (BCP) for Registration Review: Carboxin (090201) and 

Oxycarboxin (090202). Yourman, L.. Atwood, D., and Ranville, M. March 11, 2015.

2
5. Carboxin SLUA. July 28, 2014.

6. EFED Table 1 Report for Carboxin. May 12, 2014.

7. HED Master Label Report for Carboxin. May 12, 2014.

These and other supporting documents for the carboxin and oxycarboxin registration review case 

may be found in the docket EPA-HQ-OPP-2015-0144 at http://www.regulations.gov.

3
OVERVIEW

The docket for carboxin and oxycarboxin is now open, initiating the first public comment period 

for this registration review (docket number EPA-HQ-OPP-1015-0144). Carboxin is a systemic 

fungicide with products registered for application to seeds prior to planting for control of various 

fungi that cause seed and seedling diseases (smut, rot, and blight) on crops including wheat, 

barley, oats, corn, cotton, soybeans, safflower, beans, and ornamental bulbs. The seed treatment 

uses of carboxin are considered food/feed uses based on data that demonstrate uptake of 

detectable residues in crops. Carboxin degrades to carboxin sulfoxide and carboxin sulfone, 

which is known as oxycarboxin. Oxycarboxin is also a registered active ingredient and is 

therefore included in this registration review case. Products containing oxycarboxin are

registered for foliar application for control of rust diseases on ornamentals grown in enclosed 

commercial structures such as greenhouses, shadehouses, and interiorscapes. There are no 

residential uses for either carboxin or oxycarboxin. 

This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs

knows about carboxin and oxycarboxin highlighting anticipated data and assessment needs, 

identifying the types of information that would be especially useful to the Agency in conducting 

the review, and providing an anticipated timeline for completing the registration review for these 

chemicals

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about carboxin and oxycarboxin and what types of 

new data or other information would be helpful for the Agency to receive as it moves toward a 

decision on these chemicals. The Agency encourages all interested stakeholders to review the 

PWP and Appendix and to provide comments and additional information that will help the 

Agency’s decision-making process for these chemicals. In addition to general areas on which 

persons may wish to comment, there are some areas identified in the PWP and Appendix about 

which the Agency specifically seeks comments and information. Interested stakeholders could 

include: environmental non-profit or interest groups; pesticide manufacturers; agricultural labor 

or commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for carboxin and 

oxycarboxin. Next, it discusses the statutory and regulatory authority for registration review. 

Then the document provides chemical facts, use and usage information, recent actions, the 

anticipated risk assessments, and a projected registration review timeline for carboxin and 

oxycarboxin. Finally, the Appendix to this document includes identification and discussion of 

some areas that are considered generally in registration review along with some additional 

chemical case-specific information.

4
ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for carboxin. For additional discussion of the 

anticipated data needs, see the Registration review—Preliminary Problem Formulation for the 

Drinking Water and Ecological Risk Assessments of Carboxin and Oxycarboxin and Carboxin 

and Oxycarboxin: Human Health Scoping Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Carboxin Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Carboxin

835.1230 Leaching and adsorption/desorption – sediment 

leaching and soil adsorption/desorption TGAI 12

850.1025 Acute toxicity estuarine and marine organisms --

oyster TGAI 12

850.1035 Acute toxicity estuarine and marine organisms --

Mysid TGAI 12

850.1075 Acute toxicity estuarine and marine organisms –

estuarine/marine fish TGAI 12

850.2100 Avian oral toxicity - passerine TGAI 12

850.4100 Seedling emergence and seedling growth (Tier I)

– 10 species TGAI or TEP 12

850.4550 Cyanobacterial Toxicity TGAI 12

850.3040 Field testing for pollinators TGAI and TEP 12

870.3465 28-Day Inhalation toxicity - rat2 TGAI 24

NonGDLN Field trial of residues in pollen and nectar TGAI and TEP 18

NonGDLN Pollinator Acute Oral Toxicity – honeybee adult TGAI 18

NonGDLNPollinator Chronic Oral Toxicity – honeybee 

adult TGAI 18

NonGDLN Pollinator Acute Oral Toxicity – honeybee larvae TGAI 18

NonGDLNPollinator Chronic Oral Toxicity – honeybee

larvae TGAI 18

1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 2 Please note that additional PPE (ie., a PF5 respirator) on registered labels for carboxin corn seed treatment 

involving multiple activities and for oxycarboxin mixing/loading/applying with a mechanically pressurized 

handgun will mitigate the risk concern prompting the inclusion of the subacute inhalation study. For additional 

information, please see Carboxin and Oxycarboxin: Human Health Scoping Document in Support of Registration 

Review.

5

 
Table 1: Anticipated Data Needs for the Carboxin Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

NonGDLN Semi-Field Toxicity Test with Honeybee TGAI and TEP 24

Anticipated Data Needs for the Carboxin Sulfoxide Degradate

850.1300 Aquatic invertebrate life cycle (freshwater) 

toxicity Degradate 12

850.1350 Aquatic invertebrate life cycle (saltwater) Degradate 12

850.1400 Fish early-life stage toxicity (freshwater and 

marine/estuarine) Degradate 12

TGAI = technical grade active ingredient; TEP = typical end-use product

Table 2 below summarizes anticipated data needs for oxycarboxin based on the current 

understanding of the oxycarboxin use pattern (i.e., shadehouses)3. For additional discussion of 

the anticipated data needs, see the Registration review—Preliminary Problem Formulation for 

the Drinking Water and Ecological Risk Assessments of Carboxin and Oxycarboxin and 

Carboxin and Oxycarboxin: Human Health Scoping Document in Support of Registration 

Review.

Table 2: Anticipated Data Needs for the Oxycarboxin Registration Review

Guideline 

Number4 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Oxycarboxin

850.1025 Acute toxicity estuarine and marine organisms --

oyster TGAI 12

850.1035 Acute toxicity estuarine and marine organisms --

Mysid TGAI 12

850.1075 Acute toxicity estuarine and marine organisms –

estuarine/marine fish TGAI 12

3 The current oxycarboxin label provides for use of this ingredient in shadehouses. The EPA’s current 

understanding of this use is that the enclosure may be made of permeable material, and that the sides of the structure 

may be opened. Given this understanding, the data in table 2 are needed to support a quantitative risk assessment for 

registration review of oxycarboxin. 4 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; 

OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028

6

 
Table 2: Anticipated Data Needs for the Oxycarboxin Registration Review

Guideline 

Number4 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

850.1300 Aquatic invertebrate life cycle (freshwater) 

toxicity TGAI 12

850.1350 Aquatic invertebrate life cycle (saltwater) TGAI 12

850.1400 Fish early-life stage toxicity (freshwater and 

marine/estuarine) TGAI 12

850.2100 Avian oral toxicity (upland gamebird and 

passerine) TGAI 12

850.2200 Avian dietary toxicity (waterfowl species) TGAI 12

850.2300 Avian reproduction toxicity (upland gamebird 

and waterfowl species) TGAI 12

850.4100 Seedling emergence and seedling growth (Tier I)

– 10 species TEP 12

850.4150 Vegetative vigor (Tier I)) TEP 12

850.4400 Aquatic plant growth (aquatic vascular plant 

toxicity) (Tier I) TGAI or TEP 12

850.4550 Cyanobacterial Toxicity TGAI 12

NonGDLNPollinator Chronic Oral Toxicity – honeybee 

adult TGAI 18

NonGDLN Pollinator Acute Oral Toxicity – honeybee larvae TGAI 18

NonGDLNPollinator Chronic Oral Toxicity – honeybee

larvae TGAI 18

NonGDLN Semi-Field Toxicity Test with Honeybee TGAI and TEP 24

7
STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website.

5

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of carboxin and oxycarboxin.

CHEMICAL FACTS

Table 3 provides a summary of the chemical facts for carboxin 

Table 3: Chemical Facts for Carboxin and Oxycarboxin

Carboxin Oxycarboxin

PC code 090201 090202

Case Number 0012 0012

CAS Number 5234-68-4 5259-88-1

Year first registered 1968 1971

Pesticide Type Fungicide Fungicide

Chemical class Oxathiin Oxathiin

Reregistration 

Eligibility Decision 

(RED)

2004 2004

5 http://www.epa.gov/oppsrrd1/registration_review/

8

 
Table 3: Chemical Facts for Carboxin and Oxycarboxin

Tolerance 

Reassessment 

Eligibility Decision 

(TRED)

2002 Not applicable. There were no 

food-uses of oxycarboxin to 

necessitate a TRED.

Cumulative group Not applicable. Carboxin has not 

been identified as a member of a 

cumulative group that shares a 

common mechanism of toxicity.

Not applicable. Oxycarboxin 

has not been identified as a 

member of a cumulative group 

that shares a common 

mechanism of toxicity.

40 CFR Citation Tolerances for carboxin and its 

metabolites convertible to aniline 

(which includes oxycarboxin as a 

minor metabolite) and expressed as 

carboxin are established in 40 

CFR§180.301.

There are no food-uses of 

oxycarboxin as an active 

ingredient, however, the 

tolerance expression for 

carboxin includes the 

metabolite oxycarboxin.

Dual-use Carboxin is registered for 

conventional pesticidal uses only and 

has no registered antimicrobial or 

biopesticidal uses.

Oxycarboxin is registered for 

conventional pesticidal uses 

only and has no registered 

antimicrobial or biopesticidal 

uses.

Non-pesticidal uses There are no identified non-pesticidal 

uses of carboxin.

There are no identified nonpesticidal uses of oxycarboxin.

Pesticide Reevaluation 

Division, Chemical 

Review Manager

Dana L. Friedman, friedman.dana@epa.gov, 703-347-8827

Registration 

Division, Product 

Manager

Hope Johnson, johnson.hope@epa.gov, 703-305-5410

USE AND USAGE INFORMATION

Table 4 summarizes the use and usage information for carboxin. Please see the BEAD Chemical 

Profile (BCP) for Registration Review: Carboxin (090201) and Oxycarboxin (090202) in the 

registration review docket for more details.

Table 4: Carboxin Use and Usage Information

Summary of Use Carboxin is a systemic fungicide registered for use as a seed 

treatment prior to planting for control of various fungi that cause 

seed and seedling disease. Carboxin is applied both by 

commercial seed treaters and on-farm applicators.

Use Sites Carboxin is registered for use on the following agricultural use 

sites: barley, beans, canola, corn, cotton, mustard seed, oats, 

9
Table 4: Carboxin Use and Usage Information

onions, peas, rice, rye, safflower, sorghum, soybeans, triticale, 

and wheat. Carboxin is also registered for use as a dip application 

on ornamentals in some locations.

Summary of Usage Based on USDA-NASS (United States Department of 

Agriculture's National Agricultural Statistics Service), Private 

Pesticide Market Research, and California DPR (Department of 

Pesticide Regulation), carboxin use as a seed treatment for wheat 

is the most extensive use of this chemical at 44,000 pounds of 

active ingredient per year, which is less than 2.5% of the wheat 

crop. 

Formulation Type(s) Wettable powder, dust, flowable concentrate, ready-to-use liquid. 

Several products are co-formulated with other active ingredients.

Application Method(s) Mechanical, slurry, or mist-type seed-treatment equipment.

Technical Registrant(s) Macdermid Agricultural Solutions, Inc. 

No. of Registrations 15 Section 3 products6, 7 Section 24c products

Restricted Use No

Table 5 summarizes the use and usage information for oxycarboxin. Please see the BEAD 

Chemical Profile (BCP) for Registration Review: Carboxin (090201) and Oxycarboxin 

(090202)in the registration review docket for more details.

Table 5: Oxycarboxin Use and Usage Information

Summary of Use Oxycarboxin is registered for control of rust diseases by foliar use 

on ornamentals grown in enclosed commercial structures.

Use Sites Use is limited to ornamentals in enclosed commercial structures 

such as greenhouses, shadehouses, and interiorscapes. 

Summary of Usage EPA has no usage data for oxycarboxin.

Formulation Type(s) Wettable powder

Application Method(s) Products can be applied by aerosol cans, handheld sprayers, 

foggers, and mechanical sprayers.

Technical Registrant(s) Macdermid Agricultural Solutions, Inc.

No. of Registrations 2 Section 3 products6

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• The oxycarboxin label is unclear with respect to “shadehouses.” Without further 

information, EPA expects to use conservative assumptions to approximate these 

parameters in order to conduct a quantitative risk assessment. However, the Agency will

work with registrants to clarify information on oxycarboxin product labels.

6 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home).

10

 
• The maximum application rate should be specified in terms of mass active ingredient 

(a.i.) per unit area (e.g., lbs a.i./acre).

• Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use.

• Use distribution (e.g., acreage and geographical distribution of relevant use sites).

• Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county.

• Typical application timing (date of first application and application intervals) – national, 

state, and county.

• Usage/use information for non-agricultural uses.

• Typical application interval (days).

• State or local use restrictions.

• Foreign technical registrants not listed above who supply technical carboxin and/or 

oxycarboxin to the US market.

RECENT ACTIONS

There are no recent actions for carboxin or oxycarboxin.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for carboxin and oxycarboxin was 

completed in 2004 in preparation for the Reregistration Eligibility. The most recent ecological 

and environmental fate risk assessment was completed in 2004 for carboxin for the same 

purpose, and for oxycarboxin when it was initially registered. Findings and conclusions from 

these risk assessments are summarized in the Registration review—Preliminary Problem 

Formulation for the Drinking Water and Ecological Risk Assessments of Carboxin and 

Oxycarboxin and Carboxin and Oxycarboxin: Human Health Scoping Document in Support of 

Registration Review.

During registration review, the Agency anticipates the need to conduct a comprehensive

ecological risk assessment, including an endangered species assessment, for all uses of carboxin 

and oxycarboxin. For human health, EPA anticipates the need to conduct revised dietary and 

occupational risk assessments during registration review. If toxicological endpoints or points of 

departure are revised based on the data that are anticipated to be required for registration review, 

they will be considered in the new assessments, as well as any changes to the standard operating 

procedures or default exposure assumptions.

Table 6 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document.

11
Table 6: Anticipated Risk Assessments for the Carboxin and Oxycarboxin Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Yes A comprehensive ecological risk assessment is 

needed for carboxin and oxycarboxin. 

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

carboxin and oxycarboxin, see page 18 of the 

Problem Formulation.

Human Health

Dietary

Food Yes A dietary assessment may be needed if changes are 

made to the toxicological endpoints or uncertainty 

factors.

Drinking water No A drinking water assessment is not needed as the uses 

of carboxin and oxycarboxin have not changed since 

the previous assessment.

Occupational

Handlers (mixers, loaders, 

applicators)

Yes The risk assessment will include updated handler risk 

estimates based on current policies and if any changes 

are made to the toxicological endpoints or uncertainty 

factors.

Post-application Yes The risk assessment will include updated postapplication risk estimates based on current policies 

and if any changes are made to the toxicological 

endpoints or uncertainty factors.

Residential

Handlers No There are no residential uses of carboxin or 

oxycarboxin.

Post-application/bystander Yes The need for spray drift and volatilization risk 

assessment will be examined during registration 

review.

Other

Aggregate No There are no residential uses of carboxin or 

oxycarboxin so an aggregate assessment is not 

needed.

Cumulative No EPA has not made a common mechanism of toxicity 

finding for carboxin, oxycarboxin, and any other 

active ingredients.

Tolerances Yes Tolerances in/on cotton gin byproducts, mustard seed, 

peas, and rye will need to be established.

12
Incidents Will check for 

updates

For a discussion of reported human incidents for 

carboxin and oxycarboxin, see page 10 of the Scoping 

Document and the Carboxin and Oxycarboxin: Tier I 

Review of Human Incidents.

Guidance for Commenters: Additional ecological information requested for this 

registration review, and of particular interest to EPA, is described below.

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency.

• Water quality monitoring data (see Appendix for further details).

TIMELINE

EPA has created the following estimated timeline for the completion of the carboxin and 

oxycarboxin registration review in Table 7 below.

Table 7: Projected Carboxin and Oxycarboxin Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2015 – March

Close Public Comment 2015 – May

Case Development

Final Work Plan 2015 – August

Issue DCI 2015 Oct. – Dec.

Data Submission 2017 Oct. – Dec.

60-day Public Comment Period for Draft Risk 

Assessments7

2019 April - June

Registration Review Decision

60-day Public Comment Period for Proposed 

Registration Review Decision

2020 Jan. - March

Registration Review Decision and Begin Post-Decision 

Follow-up

2021

Total (years) 6

7 The regulations governing registration review generally require the Agency to provide a public comment period of 

at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.

13

 
NEXT STEPS

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of carboxin and oxycarboxin. 

14
Appendix – Additional Areas Considered in the Carboxin and Oxycarboxin 

Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality:

Carboxin and oxycarboxin are not identified as a cause of impairment for any water bodies listed 

as impaired under section 303(d) of the Clean Water Act.

8

 In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for carboxin or oxycarboxin.

9

 More information on 

impaired water bodies and TMDLs can be found at the Agency’s website.

10 The Agency invites 

submission of water quality data for this pesticide. To the extent possible, data should 

conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: 

Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review 

Risk Assessment and Management Process11 in order to ensure they can be used quantitatively or 

qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to carboxin or oxycarboxin compared to the general 

population. Please comment if you are aware of any sub-populations that may have 

atypical, unusually high exposure compared to the general population.

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

9

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

group_name=PESTICIDES 10 http://www.epa.gov/owow/tmdl/ 11 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

15

 
ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been 

conducted for carboxin and oxycarboxin. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether use of carboxin and oxycarboxin

has “no effect” or “may affect” federally listed threatened or endangered species (listed species) 

or their designated critical habitats. When an assessment concludes that a pesticide’s use “may 

affect” a listed species or its designated critical habitat, the Agency will consult with the U.S. 

Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as 

appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for carboxin and its 

reregistration decision for oxycarboxin, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. However, as 

required by FFDCA section 408(p), carboxin and oxycarboxin are subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 201312 and includes some 

12 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

16

 
pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.13

HUMAN STUDIES:

Occupational

Past carboxin and oxycarboxin risk assessments rely in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database 

(PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the 

studies supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies.

13 http://www.epa.gov/endo/

17