2 C LORANSULAM

- 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 i ncludes 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 implement ing 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, publi c 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 statutor y 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/registra tion_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 reside ntial 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 FIFR A.

Comments Received on Preliminary Work Plan :

The Agency received one submission during the 60

- day public comment period for the Cloransulam

- methyl Preliminary W ork P lan (PWP), which began on December 22, 2010 and ended on February 22, 20 1 1 (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 cloransula m

- methyl

. These comment s 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

.3

Risk Assessment and Data Needs:

The Agency anticipates conduct ing 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 regis tration 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 comprehensiv e 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 Stabil ity and Analytical Method

- sediment (with Independent Laboratory Validation) for Residues

o (GLN 850.1010) Acute Freshwater Invertebrate Tox icity Test

o (GLN 850.1300) Freshwater Invertebrate Life Cycle Tox icity Test

o (GLN 850.1400) Fish Earl y

- Life Stage Toxicity Test, Freshwater

o (GLN 850.2100) Avian Acute Oral Tox icity (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) Terre strial Plant Vegetative Vigor, Tier II

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

o (GLN 850.5400) Algal Toxicity, Tier II4

The Agency has not conducted an ecological risk assessment that supports a complete endangered species de termination 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 Nati onal 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 fo r 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 A gency 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 re view ed during registration review to ensure that it appropriately covers the metabolites and degradates of cloransulam

methyl, 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).5

The Agency will conduct an occupational handler and post

- application risk assessment during the registration review of cloransulam

- methyl to incorporate any update s to the toxicological database, or updates to OPP assessm ent 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 an d 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 toxici ty, 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 histopa thology, 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 r eproductive 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 r equired 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 i ngredients) 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 re quired 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 ide ntify 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. C loransulam

methyl is not among the group of 58 pesticide active ingredients on the initia l 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 EDS P, the policies and procedures, the list of 676

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 foll owing 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 f or the Cloransulam

- methyl Docket Dec

. 22, 2010
Close Public Comment Period Feb

. 2 2 , 2011 Case Development Develop Final Work Plan (FWP) 2011

– June
Issue DCI 2012

– Jan.

– Mar.
Data Submission 2014

– Jan.

– Mar. Open Public Comment Period f or 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

- d ay comment period beginning on December 22, 2010. During th e comment period , Dow AgroScience submitted several comment s which iden tified technical errors within the preliminary work plan and support documents

, and provided rationales for the Agency to rec onsider 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 wor k 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.7

2 . Comment Dow AgroScience requested that the Agency reconsider requesting the immunotoxicity data requirement (GLN 870.7800) because it believes th at the Agency has established an overall weight

- of

- the evidence suggesti ng that cloransulam methyl does not target the
immune system, and therefore immunotoxici ty 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 provi de 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 t he 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 guideline s was that “t he 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 cloransula m

- 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 Toxi city: 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 me thyl

.

4

. Comment Dow AgroScience requested that as part of the registration review of cloransulam

methyl, the Agency review the three prospective groundwater monitoring studies and associated modeling scenarios which were required as a condition of r egistration. 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 anticip ates being able to recommend appropriate updates to advisory statements now on cloransulam

- methyl product labels.8

5

. Comment Dow AgroScience indicated that the study classification for the chemical 5

- hydroxycloransulam

- methyl for the taxon duckweed w as changed from core to supplemental due to test material instability. However, DAS notes that solutions in the

a bsence of the plants were stable, and that d ata reflect actual exposure conditions in the presence of plants.

EPA Response The Agency notes that t he 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 mai ntains the “supplemental” classification for this study and its requirement for the Tier II, Aquatic Plant Growth data ( OCSPP 850.4400 )

.

Please refer to the document s : 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 discussi on 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 Cloransulam

Methyl. 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 Dissipatio n 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 Av ian Reproduction Test TGAI9

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 A cute Neurotoxicity

- rat TGAI 870.7800 Immunotoxicity TGAI

Footnote : T echnical E nd

- use P roduct (TEP), T echnical G rade A ctive I

ngredient (TGAI) and “ P ure ” A ctive I ngredient

- R adio L abeled (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 201 2 . This new information will be used to conduct human health and ecological risk assessments for all registered uses of cloransulam

- methyl.