Docket Number: EPA-HQ-OPP-2010-0855

www.regulations.gov

Cloransulam-Methyl Summary Document 

Registration Review: Initial Docket

December 2010

3

TABLE OF CONTENTS

Page 

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 11

________________________________________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position on cloransulam-methyl based on the following documents: 

1. Registration Review: Problem Formulation for Environmental Fate, Ecological Risk, 

Endangered Species, and Drinking Water Exposure Assessments for Cloransulam-Methyl 

(PC Code 129116). (DP Barcode: D379667, December 10, 2010).

2. Cloransulam-Methyl. Registration Review Scoping Document for Human Health 

Assessments (DP Barcode: D378194, November 4, 2010).

3. BEAD Chemical Profile for Registration Review: Cloransulam-methyl (129116). 

(November 29, 2010)

4. Cloransulam: Review of Human Incidents (DP Barcode: D381109, August 24, 2010)

These and other supporting documents for the cloransulam-methyl registration review case may 

be found in the docket EPA-HQ-OPP-2010-0855 at www.regulations.gov.
4

I. Preliminary Work Plan

Introduction:

The Food Quality Protection Act of 1996 (FQPA) 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 at: 

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

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 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 and commit to a final work plan and schedule for the registration review of 

cloransulam-methyl. 

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. 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.

Anticipated Risk Assessment and Data Needs:

During registration review the Agency anticipates conducting comprehensive human health and 

ecological risk assessments, including an endangered species assessment, for cloransulammethyl. 

Ecological Risk:

The most recent comprehensive cloransulam-methyl ecological risk assessment 

was conducted for the initial chemical assessment in 1997.

Environmental fate data on cloransulam-methyl are anticipated to be needed to 

better understand, for example, its biotic degradation. Also, environmental effects 

data are anticipated to be needed to complete the Agency’s understanding of the 

potential acute effects to freshwater invertebrates as well as chronic effects to 
5

freshwater and estuarine/marine fish and invertebrates for which no effects data is 

available.

The Agency anticipates needing the following data in order to conduct a

comprehensive ecological risk and endangered species assessment for 

cloransulam-methyl.

o (GLN 835.4200) Anaerobic Soil Metabolism

o (GLN 835.4300) Aerobic Soil 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 835.4200) Anaerobic Soil Metabolism

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 Study (vascular

plants) 

o (GLN 850.5400) Algal Toxicity Study, Tier II

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. 
6

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, a more detailed discussion of the 

anticipated ecological risk assessment and data needs available in the docket.

Human Health Risk:

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

assessment in 1997.

The Agency anticipates requiring 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) 90 day Neurotoxicity - rat

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 revised 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. 

The Agency’s residue chemistry database for cloransulam-methyl is complete and 

sufficient for risk assessment purposes. 

There are no residential uses associated with cloransulam-methyl registrations, therefore,

the anticipated aggregate risk assessment will include only dietary exposure (food + 

drinking water).
7

The Agency anticipates conducting an occupational handler and post-application risk 

assessment during the registration review of cloransulam-methyl to incorporate current 

assessment methodologies.

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

Document for Human Health Assessments a more detailed discussion of the anticipated 

human health risk assessment and data needs, available in the docket.

Other Data Needs:

GLDN 830.7050 UV/Visible Light Absorption – this study is a new data requirement 

under 40 CFR part 158 (Product Chemistry Data Requirements) for registration of a 

pesticide (food and non-food uses). The Agency anticipates requiring this study to obtain 

basic information about the compound’s identity/composition and the wavelengths at 

which the compound may be susceptible to photochemical degradation.

Endocrine Disruptor Screening Program:

For all pesticides that result in residues in foods, EPA reviews numerous studies that bear on a 

pesticide's potential endocrine effects. (71 FR at 43921). These include data on developmental 

toxicity, reproductive toxicity, subchronic toxicity, chronic toxicity, and cancer. Developmental 

studies evaluate several endpoints susceptible to endocrine influence including effects on 

maternal animal fertility and pregnancy rates and on pup viability and sex ratios in pups. (71 FR 

at 43921). As part of the 1997 registration, EPA reviewed these data and concluded that the most 

appropriate and conservative regulatory endpoint was based on increased levels of alkaline 

phosphatase in the liver. However, as required by FFDCA section 408(p), cloransulam-methyl

will be subject to endocrine screening part of the Endocrine Disruptor Screening Program 

(EDSP)

As required under FFDCA section 408(p), 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.

EPA has announced that it would begin to expedite the required EDSP testing of pesticides by 

conducting the testing in parallel or as part of the OPP Registration Review program. Recently, 

EPA published a list of candidate chemicals based, in part, on pesticides that were scheduled for 
8

Registration Review during fiscal years 2007 and 2008. Cloransulam-methyl was not on that 

list. But as part of the Registration Review of cloransulam-methyl EPA will issue an EDSP test 

order/data call in to require that testing. Once all required Tier 1 and Tier 2 data have been 

received and reviewed, the points of departure and safety factors used for risk assessment 

purposes should be reexamined and a new risk assessment performed if necessary.

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 2010 – December

Close Public Comment Period 2011 – February

Case Development

Develop Final Work Plan (FWP) 2011– May

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

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the cloransulam-methyl case.

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. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (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. 
9

Water Quality

Cloransulam-methyl is not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88

5. In addition, no Total Maximum Daily Loads (TMDL) have been developed for cloransulammethyl, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id

=885&p_pollutant_group_name=PESTICIDES. More information on impaired water bodies and 

TMDLs can be found at http://www.epa.gov/owow/tmdl/. 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 Process (see: 

http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm) 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 many 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 cloransulam-methyl, 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.

Other Information

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including any species-specific ecological effects 

determinations. 

The Agency is interested in receiving the following information: 

1. use history

2. directly acquired county-level usage data (not derived from state level data)

a. total pounds per year (county level)

b. the year the pesticide was last used in the county/sub-county area

c. the years in which the pesticide was applied in the county/sub-county area

3. typical interval (days)

4. state or local use restrictions

5. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, insect 

(e.g., honey bees) and mammalian mortalities) not already reported to the Agency.

6. monitoring data
10

Next Steps:

After the 60-day 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 cloransulam-methyl 

registration review case.
11

II. FACT SHEET

Background Information:

The cloransulam-methyl PC Code is 129116 and the CAS# is 147150-35-4.

The technical registrant is Dow Argosciences, LLC. 

Cloransulam-methyl was first registered as an end-use product in 1997.

The September 19, 1997 final rule (40 CFR 180.514) established a tolerance for 

cloransulam-methyl use on soybean (forage, hay and seed). 

There are eight active section 3 product registrations for cloransulam-methyl: one

technical product and seven end-use products.

Cloransulam-methyl belongs to the triazolopyrimidine sulfonamide class of herbicides.

The Pesticide Re-evaluation Division Chemical Review Manager (CRM) is James 

Parker: parker.james@epa.gov.

Product Manager (PM) is James Tompkins: tompkins.jim@epa.gov.

Use & Usage Information: 

Cloransulam-methyl is an herbicide registered for use on soybeans to control various 

broad leaf weeds.

Cloransulam-methyl is applied pre- and/or post-emergent to soybean (hull, seed and 

forage). End-use products are formulated as a suspension concentrate, in water soluble 

packages, and as a wettable powder.

Recent Actions:

There are no pending or recent actions associated with cloransulam-methyl.

Ecological Risk Assessment Status:

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 in the registration review docket for a detailed summary of 

the key findings of the most recent environmental fate and effects assessment. A summary

follows:

The initial cloranaulam-methyl ecological risk assessment identified risks to non-target 

terrestrial plants based on Risk Quotients (RQs) ranging from <1 to 12.

The Agency’s Level of Concern (LOC) was not exceeded for non-target aquatic plants, 

nor federally threatened and endangered (listed) or non-listed terrestrial or aquatic 

organisms.

Risk to federally listed (i.e., threatened or endangered) or non-listed terrestrial, aquatic 

organisms, or beneficial insects was not identified at the time of the initial ecological 

review in 1997.
12

Human Health Risk Assessment Status:

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

Human Health Assessments in the registration review docket for a detailed summary of the key 

findings of the most recent human health assessment. A summary follows:

Hazard Characterization:

The most consistent toxicological effect of cloransulam-methyl was in the liver, indicated 

by increased levels of alkaline phosphatase and increased liver weight. 

Cloransulam-methyl is categorized as Toxicity Category III via the dermal and inhalation 

routes. It is neither a skin irritant nor a skin sensitizer and is moderately toxic (toxicity 

category III) based on oral and dermal toxicity studies, in addition to eye irritation 

studies.

Cloransulam-methyl is classified as “not likely” to be a carcinogen based on lack of 

carcinogenicity in rat and mice studies.

Dietary (Food and Drinking Water):

An acute dietary assessment was not conducted because no acute endpoint was identified

in the toxicity data base.

A screening level chronic dietary risk assessment (including a screening level drinking 

water assessment) indicated that dietary exposure is below the Agency’s level of concern 

(LOC).

Residential:

Cloransulam-methyl registrations do not contain residential uses. Therefore, a residential 

assessment was not conducted.

Aggregate:

For cloransulam-methyl, neither residential exposure exists, nor does an acute dietary 

scenario exist. Hence, the previous aggregate risk assessment consisted of [chronic] food 

plus drinking water exposures only. The results were below the Agency’s level of concern.

Occupational:

Occupational handler (i.e., mixers, loaders and applicators) risks were below the Agency’s 

LOC.

Cumulative:

The Agency does not currently have data to determine whether cloransulam-methyl shares a 

common mechanism of toxicity with other substances. As a result, the Agency has not made 

a common mechanism of toxicity finding for cloransulam-methyl and any other substances,

and cloransulam-methyl does not appear to produce a toxic metabolite that is produced by 

other substances which have tolerances in the U.S. Therefore, EPA has not assumed that 

cloransulam-methyl has a common mechanism of toxicity with other substances. 
13

Agricultural Health Study:

Cloransulam-methyl is among several agricultural chemicals included in the Agricultural 

Health Study (AHS). The AHS began in 1993 and is a collaboration of the National 

Institute of Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), 

the EPA, and the National Institute for Occupational Safety and Health (NIOSH). 

Designed as a large long-term epidemiological study, the AHS collects and analyzes data 

on the health and work practices of nearly 90,000 farmers and their families in Iowa and 

North Carolina who enrolled in the study before any disease developed. The study 

focuses particularly on farmers' exposure to 50 chemicals including many of the most 

widely used pesticides. As data are collected over a period of years, scientists can 

compare overall health outcomes for people who differ in whether they have had 

exposure to various chemicals. While these comparisons cannot conclusively 

demonstrate how exposure affects health, they can show some statistical associations. 

More information on the AHS can be found at: http://aghealth.nci.nih.gov. EPA is 

monitoring the results of the AHS and will consider this study in the registration review 

of cloransulam-methyl as appropriate. 

Past cloransulam-methyl 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), the Agricultural Reentry Task Force (ARTF) Database and the 

Outdoor Residential Exposure Task Force (ORETF) 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.

Incident Reports:

The Agency’s Incident Database System (IDS) identified two low severity (minor, 

unknown or no effects) incidents associated with human incidents involving cloransulammethyl. IDS also identified one moderate high severity cloransulam-methyl incident. 

This incident involved an adult male who got cloransulam-methyl on his hands and then 

washed his hands 30 minutes later, which resulted in a full body rash on the following 

day. 

Preliminary reviews of the Ecological Incident Information System (EIIS, version 2.1) 

and the Avian Incident Monitoring System (AIMS) identified several plant incidents 

between 1998 and 2005, with affected areas ranging from 5 acres to 677.5 acres. No 

incidents involving birds were reported in the AIMS database for cloransulam-methyl.
14

Tolerances and International Harmonization:

MRL’s for cloransulam-methyl have been established for U.S. (0.02ppm), Mexico 

(0.02ppm), Canada (0.01ppm), and Japan (0.06ppm). No CODEX MRLs have been set 

for cloransulam-methyl. The Agency will work to harmonize tolerances/MRLs, where 

possible, during registration review

 

Data Call-In Status:

No previous data call-in (DCI) was issued for cloransulam-methyl. 

Labels:

Cloransulam-methyl labels can be obtained from the Pesticide Label System (PPLS) 

website: http://oaspub.epa.gov/pestlabl/ppls.home. A summary of cloransulam-methyl 

labels is provided in the table below.

Cloransulam-methyl Products

Registration

Number

Product Name Active Ingredient

228-380 RIVERDALE 565 SELECTIVE 

HERBICIDE

84%

279-3231 GAUNTLET 42%

279-3246 GAUNTLET 70 DF HERBICIDE 7.9%

279-3247 GAUNTLET 70 WP HERBICIDE 7.9%

59639-131 GANGSTER HERBICIDE 84%

62719-274 CLORANSULAM-METHYL 

TECHNICAL

97.5%

62719-275 FIRSTRATE 84%

62719-299 FRONTROW 84%