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INTRODUCTION

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of carboxin and oxycarboxin. This work plan addresses public comments 

received concerning the Preliminary Work Plan (PWP), which were posted in the carboxin and 

oxycarboxin registration review docket (EPA-HQ-OPP-2015-0144). 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. 

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

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

Information on this program is provided on the Agency’s website.

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The FWP begins with any updates since the PWP was issued. Next is a summary of substantive 

comments received during the public comment period for the PWP concerning anticipated data 

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a 

summary of the Agency’s responses to those comments. This section is followed by registration 

review planned data needs, risk assessments expected to be conducted, and the projected

registration review timeline for carboxin and oxycarboxin. Lastly, there is a discussion of next 

steps.

UPDATES SINCE THE PWP WAS ISSUED

Since the issuance of the May 2015 National Strategy to Promote the Health of Honey Bees and 

Other Pollinators2 in conjunction with the June 2014 Guidance for Assessing Pesticide Risks to 

Bees3, some of the names, study duration timeframes, and test substance have changed for some 

of the pollinator studies. These changes are reflected in Table 1 of this document, but no 

additional pollinator studies have been required. 

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

2 https://www.whitehouse.gov/sites/default/files/microsites/ostp/Pollinator%20Health%20Strategy%202015.pdf

3

 http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf
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SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the Carboxin and Oxycarboxin Preliminary Work 

Plan (PWP), which opened on March 30, 2015 and closed on May 29, 2015, the Agency received 

5 public comments. Comments were submitted by non-profit organizations including the Center 

for Biological Diversity, Physicians for Responsible Medicine, and FIRFRA Endangered Species 

Task Force; a registrant, MacDermid Agricultural Solutions; and a registrant task force, the 

Creosote Council. The comments do not address the timeline described in the PWP, but they do 

address the planned ecological and human health risk assessments and data requirements. In the 

PWP, EPA also solicited comments on the specific topics of environmental justice, water quality 

concerns, and trade irritants, but no comments or information were received on those issues.

Comments from the Creosote Council (EPA-HQ-OPP-2015-0144-0013) were mistakenly 

associated with the carboxin and oxycarboxin docket, and responses to comments on the creosote 

case do not appear in this document. The creosote docket is available at www.regulations.gov

(EPA-HQ-OPP-2014-0823).

This section does not capture every comment made about the PWP nor all of the Agency’s 

responses. Summarized below are public comments are of a broad regulatory nature. There 

were no comments that resulted in changes to the regulatory timeline, anticipated risk 

assessments, or data requirements. Public comments and EPA responses in their entirety are 

located in the docket, EPA-HQ-OPP-2015-0144. Summarized public comments and Agency 

responses related to the anticipated ecological risk assessment or data needs are in the EFED 

Response to Comments on the Problem Formulation for the Registration Review of 

Carboxin/Oxycarboxin. There were no comments relevant to the anticipated human health risk 

assessment. 

Comments submitted by FESTF in EPA-HQ-OPP-2015-0144-0010

Comment: FESTF noted that the registrant, MacDermid Agricultural Solutions, is member of 

the task force and is entitled to make use of the FESTF database on species proximity to use

sites. 

Response: The Agency is aware of the data developed by FESTF and will use those data to 

evaluate risks to listed species, as appropriate.

Comments submitted by MacDermid Agricultural Solutions in EPA-HQ-OPP-2015-0144-

0011

Comment: The comments submitted by MacDermid Agricultural Solutions focused on their 

intentions regarding the data requirements specified in the problem formulation, including 

waivers, and the implications of a proposal to amend their label.

Response: Data submitted in support of the data requirements will be reviewed and, if found to 

fulfill the Agency’s needs, may be used to fulfill or waive the data requirements. Proposals for 
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data waivers will be considered when submitted after the Data Call-In has been issued and the 

official 90-day response has been submitted to the Agency. 

MacDermid Agricultural Solutions also indicated their intent to amend the label for oxycarboxin 

to read "for use in enclosed commercial greenhouses'', which would eliminate the need to 

conduct many ecological toxicity studies for oxycarboxin. The Agency agrees with this label 

language clarification and, if implemented, will waive the requirements for applicable studies.

Comments submitted by CBD in EPA-HQ-OPP-2015-0144-0012

Comment: CBD’s comments focus on the EPA’s independent duty under the Endangered 

Species Act (ESA) to consult with the U.S. Fish and Wildlife Service and the National Marine 

Fisheries Service (the Services) on the registration review of carboxin and oxycarboxin.

Response: EPA plans to address the concerns raised by CBD as part of the implementation plan 

for assessing the risks of pesticides to listed species, which will be based on the 

recommendations of the April 2013 National Academy of Sciences (NAS) report. EPA will 

address concerns specific to carboxin’s and oxycarboxin’s effects on listed species in connection 

with the development of its registration review decision.

At this time, EPA has not fully developed its risk assessment process for listed species. In 

November 2013, the EPA, along with the Services and the U.S. Department of Agriculture, 

released a summary of their joint Interim Approaches for assessing risks to listed species from 

pesticides. The Interim Approaches were developed jointly by the Agencies in response to the 

NAS recommendations and reflect a common approach to risk assessment shared by the 

Agencies as a way of addressing scientific differences between the EPA and the Services.

The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344, outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the ESA and FIFRA. The joint Interim Approaches were released prior to a 

stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint 

Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and 

State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings, allowing additional 

opportunities for stakeholders to comment on the Interim Approaches. As part of a phased, 

iterative process for developing the Interim Approaches, the Agencies will also consider public 

comments on the Interim Approaches in connection with the development of upcoming 

Registration Review decisions. The details of the joint Interim Approaches are contained in the 

white paper “Interim Approaches for National-Level Pesticide Endangered Species Act 

Assessments Based on the Recommendations of the National Academy of Sciences April 2013 

Report,” dated November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html.

Comments submitted by Physicians for Responsible Medicine in EPA-HQ-OPP-2015-0144-

0014.
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Comment: Comments submitted by the Physicians for Responsible Medicine focused on the 

conduct of the acute avian oral toxicity study for oxycarboxin and the acute toxicity study for 

estuarine and marine fish for carboxin and oxycarboxin, including alternative test methods. 

Response: The Agency will consider these comments when evaluating the registrant-submitted 

protocols, data waivers, and studies in response to the Data Call-In once issued.

PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for carboxin based on the Registration 

review—Preliminary Problem Formulation for the Drinking Water and Ecological Risk 

Assessments of Carboxin and Oxycarboxin, Carboxin and Oxycarboxin: Human Health Scoping 

Document in Support of Registration Review, and EFED Response to Comments on the Problem 

Formulation for the Registration Review of Carboxin/Oxycarboxin. The table has been updated 

since the PWP to reflect changes to the names and study duration timeframes for some of the 

pollinator studies, but the planned data needs have not changed from what was included in the 

PWP.

Table 1: Planned Data Needs for the Carboxin Registration Review

Guideline 

Number4 Study Title4

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

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 (Tier II) TEP 24

870.3465 90-Day Inhalation toxicity - rat5 TGAI 24

 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 5 Study may be reduced to a 28-day duration. 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 subchronic

inhalation study. For additional information, please see Carboxin and Oxycarboxin: Human Health Scoping 

Document in Support of Registration Review.
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Table 1: Planned Data Needs for the Carboxin Registration Review

Guideline 

Number4 Study Title4

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

NonGuideline

(OECD 

213)

Honey bee adult acute oral toxicity (Tier I)

TGAI 12

NonGuideline

OECD

237)

Honey bee larvae acute oral toxicity (Tier I)

TGAI 12

NonGuidelineHoney bee adult chronic oral toxicity (Tier I) TGAI 12

NonGuidelineHoney bee larvae chronic oral toxicity (Tier 

I) TGAI 12

NonGuidelineResidues in pollen and nectar/field residue 

analysis (Tier II) TEP 24

NonGuideline

(OECD 

75)

Semi-field testing for pollinators (tunnel or 

colony feeding studies) (Tier II) 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 labelled 

use of oxycarboxin (i.e., shadehouses)6. As discussed in the document EFED Response to 

Comments on the Problem Formulation for the Registration Review of Carboxin/Oxycarboxin, 

applicable requirements may be waived if the label for oxycarboxin is amended to read "for use 

in enclosed commercial greenhouses.” 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.

 6 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. 
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Table 2: Anticipated Data Needs for the Oxycarboxin Registration Review

Guideline 

Number7 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

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

NonGuideline

(OECD 

237)

Honey bee larvae acute oral toxicity (Tier 

I) TGAI 12

NonGuidelineHoney bee adult chronic oral toxicity (Tier 

I) TGAI 12

NonGuidelineHoney bee larvae chronic oral toxicity (Tier 

I) TGAI 12

NonGuideline

(OECD 75)

Semi-field testing for pollinators (tunnel or 

colony feeding studies) (Tier II) TEP 24

 7 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
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RISK ASSESSMENTS FOR 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 3 below summarizes the planned registration review risk assessments based on the EFED 

Problem Formulation and HED Scoping Document and the planned assessments have not 

changed from what was included in the PWP.
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Table 3: Planned 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.
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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.

TIMELINE

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

oxycarboxin registration review in Table 4 below. The projected timeline has not changed since 

the PWP. 

Table 4: Registration Review for Carboxin and Oxycarboxin – Projected Registration 

Review Timeline

Activities Estimated Date

Opening the Docket

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

Completed

Close Public Comment May 2015 –

Completed

Case Development

Final Work Plan August – Completed

Issue DCI 2015 Oct. – Dec.

Data Submission 2017 Oct. – Dec.

60-day Public Comment Period for Draft Risk Assessments8 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

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate, ecological effects, 

and human health studies for carboxin and oxycarboxin through a Data Call-In Notice, expected 

to be issued in 2015. 

 8 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.