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CLORANSULAM-METHYL FINAL WORK PLAN

Introduction:

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

for the registration review of cloransulam-methyl. This FWP includes the expected registration 

review timeline. The work plan also addresses public comments received concerning the 

Preliminary Work Plan in the Summary Document, dated December 17, 2010, which was 

posted in the cloransulam-methyl registration review docket (EPA-HQ-OPP-2010-0855). The 

Summary Document provided information on what EPA knows about the pesticide and what 

additional risk analyses or information the Agency believes are needed to make a registration 

review decision.

The Agency is implementing the new registration review program, and will review each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices will 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 that statutory standard. The public 

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

on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/.

Cloransulam-methyl is a triazolopyrimidine sulfonamide herbicide which is currently registered 

for use solely on soybeans to control broad leaf weeds by way of plant enzyme inhibition. 

Cloransulam-methyl is not registered for use in residential or public recreational areas. There are 

seven end-use registrations and one technical product containing cloransulam-methyl. 

Cloransulam-methyl was first registered in 1997 and, therefore, was not subject to the 

reregistration requirements of FIFRA.

Comments Received on Preliminary Work Plan:

The Agency received one submission during the 60-day public comment period for the 

Cloransulam-methyl Preliminary Work Plan (PWP), which began on December 22, 2010 and 

ended on February 22, 2011 (EPA-HQ-OPP-2010-0855). The single submission from Dow

AgroSciences (DAS) included comments regarding technical corrections, anticipated human 

health data requirements, and earlier data submissions for cloransulam-methyl. These comments

did not change the work plan or timeline established in the PWP. Further, this document makes 

final the work plan for the cloransulam-methyl registration review process. A summary of the 

submitted comments and the EPA’s responses are presented in the “Summary of Comments and 

Agency Responses” section of this document. 

In the PWP, EPA also solicited comment on the specific topics of environmental justice, water 

body impairment, and trade irritants. No comments were received during the public comment 

period concerning these issues. 
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Risk Assessment and Data Needs:

The Agency anticipates conducting a comprehensive ecological risk assessment, including an 

endangered species assessment, for all uses of cloransulam-methyl and it’s degradates of 

concern. A drinking water assessment will be conducted in order to support future human health 

risk assessments. Below is a summary of the issues relevant to the registration review of 

cloransulam-methyl and (human health and ecological) data which will be required by the 

Agency during registration review.

Ecological Risk:

The most recent comprehensive cloransulam-methyl ecological risk assessment 

was conducted for the initial chemical assessment in 1997.

The Agency will require the following data in order to conduct an updated

comprehensive ecological risk and endangered species assessment for 

cloransulam-methyl. 

o (GLN 835.4200) Anaerobic Soil Metabolism

o (GLN 835.4300) Aerobic Aquatic Metabolism 

o (GLN 835.4400) Anaerobic Aquatic Metabolism

o (GLN 835.6100) Freezer Storage Stability and Analytical 

Method - sediment (with Independent Laboratory 

Validation) for Residues

o (GLN 850.1010) Acute Freshwater Invertebrate Toxicity Test

o (GLN 850.1300) Freshwater Invertebrate Life Cycle Toxicity Test 

o (GLN 850.1400) Fish Early-Life Stage Toxicity Test, Freshwater 

o (GLN 850.2100) Avian Acute Oral Toxicity (passerine species)

o (GLN 850.2300) Avian Reproduction Test (Bobwhite quail)

o (GLN 850.4225) Terrestrial Plant Seedling Emergence, Tier II 

o (GLN 850.4250) Terrestrial Plant Vegetative Vigor, Tier II 

o (GLN 850.4400) Aquatic Plant Growth Tier II (vascular plants) 

o (GLN 850.5400) Algal Toxicity, Tier II
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The Agency has not conducted an ecological risk assessment that supports a complete 

endangered species determination for cloransulam-methyl. The ecological risk 

assessment planned during registration review will allow the Agency to determine 

whether the use of cloransulam-methyl 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 (FWS) and/or National Marine Fisheries Service (NMFS) (the Services), as 

appropriate.

Please refer to the document: Registration Review: Preliminary Problem Formulation for 

Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water 

Exposure Assessments for Cloransulam-methyl, dated December 10, 2010 located in the 

docket for a more detailed discussion of the anticipated ecological risk assessment and 

data needs.

Human Health Risk:

A comprehensive human health risk assessment was conducted for the initial chemical 

assessment in 1997.

The Agency will require the following studies, in accordance with the revised 40CFR, 

Part 158, to conduct a comprehensive human health risk assessment for the registration 

review of cloransulam-methyl.

o (GLN 870.6200) Acute Neurotoxicity 

o (GLN 870.7800) Immunotoxicity

Based upon the anticipated data, and changes to various science policy and assessment 

methodologies implemented since the completion of the previous human health risk 

assessment for cloransulam-methyl, the Agency will examine the toxicological database 

as a whole including all points of departure and uncertainty factors during the registration 

review of cloransulam-methyl. 

A drinking water assessment will be conducted and incorporated into a revised dietary

risk assessment. The assessments will reflect current models and methodologies, as well 

as any updated hazard information.

The tolerance expression in 40 CFR §180.514 will be reviewed during registration review 

to ensure that it appropriately covers the metabolites and degradates of cloransulammethyl, and that it specifies the residues to be measured for each commodity. 

Because there are no residential uses, the aggregate human health risk assessment for 

cloransulam-methyl will include only dietary exposure (food + drinking water).
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The Agency will conduct an occupational handler and post-application risk assessment 

during the registration review of cloransulam-methyl to incorporate any updates to the 

toxicological database, or updates to OPP assessment methodologies. 

Please refer to the document: Cloransulam-Methyl. Registration Review Scoping 

Document for Human Health Assessments dated November 4, 2010 in the docket for a 

more detailed discussion of the anticipated human health risk assessment and data needs.

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, sub-chronic 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 cyclist, 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, 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), cloransulam-methyl is 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. Cloransulammethyl is not among the group of 58 pesticide active ingredients on the initial list to be screened 

under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP 

orders/data call-ins, requiring the submission of EDSP screening assays for cloransulam-methyl. 

For further information on the status of the EDSP, the policies and procedures, the list of 67
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chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

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

Timeline:

EPA has created the following estimated timeline for the completion of the registration review of 

cloransulam-methyl. 

Registration Review for Cloransulam-methyl – Projected Registration Review Timeline

Activities Estimated Date

Opening the docket

Open Public Comment Period for the Cloransulam-methyl Docket Dec. 22, 2010

Close Public Comment Period Feb. 22, 2011

Case Development

Develop Final Work Plan (FWP) 2011– June

Issue DCI 2012 – Jan. – Mar. 

Data Submission 2014 – Jan. – Mar. 

Open Public Comment Period for Preliminary Risk Assessments 2015 – Jul. – Sept. 

Close Public Comment Period 2015 – Oct. – Dec.

Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision 2016 – Jan. – Mar. 

Close Public Comment Period 2016 – Apr. – June

Registration Review Decision and Begin Post-Decision Follow-up 2016

 Total (years) 6

Summary of Comments and Agency Responses:

The cloransulam-methyl registration review docket was open for a 60-day comment period 

beginning on December 22, 2010. During the comment period, Dow AgroScience submitted 

several comments which identified technical errors within the preliminary work plan and support 

documents, and provided rationales for the Agency to reconsider the need for certain data. The 

following is a summary of the comments and EPA’s responses. 

1. Comment 

Dow AgroScience identified several technical errors within the cloransulam-methyl 

Preliminary Work Plan document.

EPA Response

The EPA will work with the registrant to ensure that the associated cloransulam-methyl 

background data is accurate in the upcoming human health and environmental risk 

assessments for the registration review decision.
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2. Comment 

Dow AgroScience requested that the Agency reconsider requesting the immunotoxicity 

data requirement (GLN 870.7800) because it believes that the Agency has established an 

overall weight-of-the evidence suggesting that cloransulam methyl does not target the 

immune system, and therefore immunotoxicity data are not necessary.

EPA Response

The Agency agrees in part with Dow AgroScience’s comments, where data from existing 

structural immune parameters provide useful toxicological information. However, the 

Agency points out that these data do not provide sufficient endpoints upon which to 

predict potential immunotoxicity. Therefore, at this time, the Agency anticipates 

requiring the immunotoxicity data requirement (GLN 870.7800). 

3. Comment 

Dow AgroScience identified a correction to table 7.4 of the Cloransulam-methyl Problem 

Formulation for guideline 850.4225, Terrestrial Plant Toxicity: Tier II Seedling 

Emergence and guideline 850.4250, Terrestrial Plant Toxicity: Tier II Vegetative Vigor. 

DAS noted that EPA’s comment for both of these guidelines was that “the study was 

conducted using the TGAI (typical grade active ingredient) instead of the required TEP 

(typical end-use product).” DAS indicated to EPA that this is incorrect. MRID 44744516 

applies to a study of three metabolites, not cloransulam-methyl and MRID 43715404, 

which is not included in Table 7.4, reports results for cloransulam-methyl. 

EPA Response

The Agency concurs with Dow AgroScience in that MRID 43715404 should replace 

MRID 44744516 for guideline 850.4225 (Terrestrial Plant Toxicity: Tier II Seedling 

Emergence) in table 7.4 of the Cloransulam-methyl Problem Formulation document. 

However, EPA notes that submission of both a seedling emergence, and vegetative vigor 

study conducted with the TEP remains a data gap for cloransulam methyl. 

4. Comment 

Dow AgroScience requested that as part of the registration review of cloransulammethyl, the Agency review the three prospective groundwater monitoring studies and 

associated modeling scenarios which were required as a condition of registration. Label 

advisory statements have been in place since the requirement of these data.

EPA Response

The Agency agrees that these data will be reviewed as part of the Registration Review 

process. Following review of these data, the Agency anticipates being able to 

recommend appropriate updates to advisory statements now on cloransulam-methyl 

product labels. 
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5. Comment 

Dow AgroScience indicated that the study classification for the chemical 5-

hydroxycloransulam-methyl for the taxon duckweed was changed from core to 

supplemental due to test material instability. However, DAS notes that solutions in the 

absence of the plants were stable, and that data reflect actual exposure conditions in the 

presence of plants.

EPA Response

The Agency notes that the test substance declined to less than 70% of the initial 

concentrations by study termination. The study therefore was not able to provide reliable 

information on the concentration to which the test organisms were exposed. The Agency 

therefore maintains the “supplemental” classification for this study and its requirement

for the Tier II, Aquatic Plant Growth data (OCSPP 850.4400). 

Please refer to the documents: Cloransulam- Methyl – Waiver request for Immunotoxicity and 

Subchronic Neurotoxicity testing (4/12/11) and Revised Environmental Fate and Effects Division 

Response to Comments on the Public Docket from Dow AgroSciences LLC on Registration 

Review Problem Formulation for Cloransulam-methyl (5/05/11) in the docket for a more detailed 

discussion of the Agency’s response to comments received from Dow AgroScience.

Summary of Data Gaps – Cloransulam-methyl:

The table below summarizes all data needs for cloransulam-methyl as listed in the CloransulamMethyl. Registration Review Scoping Document for Human Health Assessments, dated 

November 04, 2010, and the Registration Review: Preliminary Problem Formulation for 

Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure 

Assessments for Cloransulam-methyl, dated December 10, 2010.

Guideline 

Number

Data Requirement Test Material

835.4200 Anaerobic Soil Metabolism TGAI or PAIRA

835.4300 Aerobic Aquatic Metabolism TGAI or PAIRA

835.4400 Anaerobic Aquatic Metabolism TGAI or PAIRA

835.6100 Terrestrial Field Dissipation TEP

850.1010 Acute Freshwater Invertebrate Toxicity Test TGAI, TEP

850.1300 Freshwater Invertebrate Life Cycle Toxicity TGAI

850.1400 Fish Early-Life Stage Toxicity Test,

Freshwater 

TGAI

850.2100 Avian Acute Oral Toxicity TGAI, TEP

850.2300 Avian Reproduction Test TGAI
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Guideline 

Number

Data Requirement Test Material

850.4225 Terrestrial Plant, Seedling emergence, Tier II TEP

850.4250 Terrestrial Plant, Vegetative Vigor, Tier II TEP

850.4400 Aquatic Plant Growth, Tier II TEP or TGAI

850.5400 Algal Toxicity, Tier II TEP or TGAI

870.6200 Acute Neurotoxicity - rat TGAI

870.7800 Immunotoxicity TGAI

Footnote: Technical End-use Product (TEP), Technical Grade Active Ingredient (TGAI) and “Pure” Active Ingredient-Radio Labeled (PAIRA)

Next Steps:

The Agency plans to require several ecological effects and human health studies through a 

generic data call-in, which is expected to be issued in early 2012. This new information will be 

used to conduct human health and ecological risk assessments for all registered uses of 

cloransulam-methyl.