Docket Number: EPA-HQ-OPP-2011-0663

www.regulations.gov

Bensulfuron methyl Final Work Plan

Registration Review

February 2012

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BENSULFURON 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 bensulfuron methyl. The FWP includes the expected registration

review timeline. The FWP also addresses public comments received concerning the 

Preliminary Work Plan (PWP) in the Summary Document, which was posted in the bensulfuron

methyl registration review docket (EPA-HQ-OPP-2011-0663), and any other comments 

concerning the initial docket postings. The Summary Document provided information on what

EPA knows about this pesticide and what additional risk analyses and data or information the

Agency believes are needed to make a registration review decision. 

The Agency’s implementation of the registration review program requires review of 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/.

Bensulfuron methyl is a sulfonylurea herbicide with a mode of action of inhibiting acetolactate 

synthase, a pathway. Bensulfuron methyl is registered for use to control broadleaf weeds and 

sedges in aquatic rice production. Due to the use pattern, tolerances have been established for 

crayfish, rice, and rice straw. There are no registered residential uses of bensulfuron methyl. 

Bensulfuron methyl was first registered in 1989; therefore, it was not subject to the 

reregistration requirements of FIFRA.

Comments Received on the Preliminary Work Plan

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

beginning on September 30, 2011. During the public comment period, the Agency received 

comments from the Physicians Committee for Responsible Medicine. The comments received 

did not change the planned risk assessment, data needs, or the timeline detailed in the 

bensulfuron methyl PWP. EPA also solicited comments, through the PWP, on three specific 

topics: environmental justice, water body impairment, and trade irritants. No comments or 

information were received during the comment period on these topics. 

A general overview of the comments and the Agency’s responses to the comments are 

presented in the “Summary of Comments and Agency Responses” section of this document. 
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Risk Assessment and Data Needs

The Agency will require data and will conduct a comprehensive ecological risk assessment, 

including an endangered species assessment, and will require data and conduct human exposure 

risk assessments for all uses of bensulfuron methyl. Below is a summary of the issues relevant 

to the registration review of bensulfuron methyl.

Ecological Risk:

• No comprehensive ecological risk assessment has been conducted for bensulfuron 

methyl. A screening level risk assessment was conducted in 1988 for registration. 

Estimates of ground and surface water concentrations were included as part of a risk 

assessment completed in 1997 in order to add new tolerances.

• An ecological risk assessment of all registered uses of bensulfuron methyl will be 

conducted during registration review. The new assessment will incorporate the most 

up-to-date modeling methodologies, updated toxicological endpoints, and data 

submitted under the registration review data call-in (DCI).

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for bensulfuron methyl. The ecological risk assessment planned 

during registration review will allow the Agency to determine whether bensulfuron 

methyl’s use 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.

• Update Since the Preliminary Work Plan was Issued: In the document Registration 

Review– Preliminary Problem Formulation for the Environmental Fate, Ecological 

Risk, and Endangered Species and Drinking Water Assessments for Bensulfuron methyl, 

September 11, 2011, a previously submitted photodegradation on soil study (MRID 

40089330) was misclassified as a photodegradation in water study. This 

photodegradation on soil study is acceptable and fulfills this data requirement 

(Guideline 835.2410). However, the data requirements listed in the Preliminary Work 

Plan do not change, as these data were not identified for the proposed DCI.

• All data listed in the Preliminary Work Plan will be required to complete ecological and 

human health risk assessments during the registration review of bensulfuron methyl.

• The Agency anticipates requiring the following data for parent bensulfuron methyl to 

conduct the planned ecological risk assessment, including an endangered species 

assessment:
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• GDLN 835.4100 – Aerobic Soil Metabolism

• GDLN 835.4400 – Anaerobic Aquatic Metabolism

• GDLN 835.6200 – Aquatic Field Dissipation

• GDLN 850.2100 – Avian Acute Oral Toxicity Test (passerine)

• GDLN 850.2300 – Avian Reproduction (bob white quail)

• GDLN 850.4100 – Seedling Emergence (Tier II)

• GDLN 850.4150 – Vegetative Vigor (Tier II)

• GDLN 850.4400 – Aquatic Plant Growth: vascular plants (Tier II)

• GDLN 850.5400 – Aquatic Plant Growth: algae (pinnate and centric diatom) 

(Tier II)

• NON-GDLN – Special Study for Non-Target Plant Reproductive Toxicity

• The Agency anticipates needing the following data for the major bensulfuron methyl

degradates: 2-amino-4,6-dimethoxyprimidine and methyl 2-(aminosulfonylmethyl)benzoate. The data will be used in conducting a complete ecological risk 

assessment, including an endangered species assessment:

• GDLN 850.4100 – Seedling Emergence (Tier II)

• GDLN 850.4400 – Aquatic Plant Growth: vascular plants (Tier II)

• GDLN 850.5400 – Aquatic Plant Growth: algae (green algae, cyanobacteria, 

pinnate and centric diatom) (Tier II)

• Please refer to Registration Review– Preliminary Problem Formulation for the 

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

Assessments for Bensulfuron methyl, September 11, 2011, located in docket EPA-HQOPP-2011-0663, for a detailed discussion of these anticipated risk assessment and data 

needs.

Human Health Risk:

• The most recent human health risk assessment for bensulfuron methyl was completed in 

1997 for the establishment of tolerances on rice straw and crayfish. 

• The Agency anticipates requiring the following data for bensulfuron methyl for use in 

conducting a complete human health risk assessment:

• GDLN 870.3200 – Dermal Toxicity

• GDLN 870.4200 – Carcinogenicity Study (rats only)

• GDLN 870.6200 – Acute and Subchronic Neurotoxicity Battery 

• GDLN 870.7800 – Immunotoxicity
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• After the required toxicology studies are submitted and reviewed, EPA will re-evaluate 

endpoints and safety/uncertainty factors for bensulfuron methyl. 

• During registration review, the Agency will update the dietary risk assessment using

revised estimated drinking water concentrations, toxicological endpoints, and 

incorporating any degradates that are determined to be of human toxicological concern.

• There are no residential uses of bensulfuron methyl. However, residential bystander 

exposures might occur as a result of aerial application and off-site transport (e.g., spray 

drift or volatilization). The Agency will consider the need for a bystander inhalation 

risk assessment for bensulfuron methyl during registration review.

• The Agency will revise the aggregate assessment to include changes in dietary exposure 

estimates and any residential bystander exposure estimates, if applicable.

• The Agency will conduct new occupational handler and post-application assessments as 

necessary, based on updated doses, endpoints, and procedures for both dermal and 

inhalation endpoints.

• The Agency will modify tolerances as needed, and work to harmonize tolerance/MRLs 

where possible in key export markets during registration review.

• For more information please refer to Bensulfuron methyl: Human Health Assessment 

Scoping Document in Support of Registration Review, July 6, 2011, located in the 

docket (EPA-HQ-OPP-2011-0663). 

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 bensulfuron methyl 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), 

bensulfuron methyl is subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

Endocrine Disruptor Screening Program
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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. Bensulfuron

methyl 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 bensulfuron

methyl. For further information on the status of the EDSP, the policies and procedures, the list 

of 67 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 bensulfuron methyl

registration review.

Registration Review for Bensulfuron methyl – Projected Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and Public Comment Period 2011 – September

Close Public Comment 2011 – November

Case Development

Final Work Plan 2012 – February

Issue DCI 2012 – Oct. – Dec.

Data Submission 2016 – Oct. – Dec.

Open Public Comment Period for Draft Risk Assessments 2018 – April – June

Close Public Comment Period 2018 – July – Sept.

Registration Review Decision
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Open Public Comment Period for Proposed Registration Review 

Decision

2018 – Oct. – Dec.

Close Public Comment Period 2019 – Jan. – March

Registration Review Decision and Begin Post-Decision Follow-up 2019

Total (years) 8

Summary of Comments and Agency Responses

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

beginning on September 30, 2011. During the comment period, a comment was submitted by 

the Physicians’ Committee for Responsible Medicine (PCRM). The comments received do not 

change the risk assessment, data needs, or the timeline detailed in the bensulfuron methyl PWP. 

A general summary of these comments and the Agency’s response to comments is provided 

below. 

Physicians Committee for Responsible Medicine Comment: PCRM encourages the Agency to 

revise its position on potentially accepting the Organization for Economic Co-operation and 

Development (OECD) test guideline (TG223) for the acute avian oral toxicity test for passerine 

species.

Agency Response: The Agency recently completed its review of the OECD validation report 

to determine if the TG223 effects endpoints and dose/response information adequately address 

the purposes of the avian acute oral data requirement as described in 40 CFR Part 158 and 40 

CFR Part 161. The Agency determined that a study conducted using TG223 may be classified 

as acceptable if it is scientifically valid, is conducted using the LD50- slope test or limit dose 

test guidelines (the LD50 - only test is not adequate for fulfilling data requirements), and meets 

all of the following criteria:

• The study is conducted using bobwhite quail (other test species may be acceptable if they

have low background mortality in the laboratory and do not regurgitate during the study). The 

background mortality data for the species in question should be available from the submitting 

laboratory at the time of the Agency review.

• The chemical being tested does not cause delayed effects.

• For a limit dose test, it is conducted at 2,000 mg a.i./kg-bw or the environmentally

relevant concentration (whichever is greater).

• For the LD50 - slope test, the raw data and results are submitted electronically using the

SEquential DEsign Calculator (SEDEC) (the Excel calculator that determines the

placement of doses during testing and is used to estimate the LD50, slope and confidence

limits for TG223 studies).

• The study meets the same validity requirements as 850.2100 (e.g., a study should be

invalidated if more than 10% of the controls die).

• Control birds are not added during the course of the study.
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Studies that deviate from the above criteria may be classified as acceptable or supplemental if 

they are considered adequate for use in risk assessment or invalid if they are not scientifically 

sound; however, any TG223 study that deviates from the above criteria will need additional 

evaluation by the Agency to confirm the study’s classification.

Comment: PCRM recommends that the Agency allow the data requirement for guideline 

870.3250 (21/28 day dermal toxicity) be fulfilled using in-vitro or in-silico dermal penetration 

models. One example of such a model that could be used to assess the extent of dermal 

penetration likely for bensulfuron methyl is OECD Test Guideline 428.

Agency Response: The Agency currently utilizes in-vitro dermal penetration models in 

conjunction with in-vivo dermal absorption data. HED will consider the comments from the 

PCRM as the risk assessment is developed for bensulfuron-methyl registration review. 

Although we will accept studies using OECD guidelines, at present OPP does not use in-vitro

studies alone to estimate dermal absorption. An in-vivo dermal absorption study is needed as 

well.

Comment: PCRM suggests that the Agency should not require acute and subchronic 

neurotoxicity (GL 870.6200(a)(b)) and immunotoxicity (GL 870.7800) studies because 

bensulfuron methyl shows no indication of neurotoxicity or immunotoxicity. 

Agency Response: Although there was no evidence of neurotoxicity or immunotoxicity in the 

bensulfuron-methyl toxicology database, the studies the Agency currently has on file are not 

designed to specifically assess neurotoxicity parameters and histopathology or to assess 

functions of the immune system. Because of this, we will require these studies at this time. 

Nonetheless, HED will consider the comments from the PCRM as risk assessment is developed 

for bensulfuron methyl registration review. Additionally, the Agency is currently working on a 

retrospective analysis to determine whether or not the immunotoxicity study will be required 

and the decision may affect bensulfuron methyl registration review.

Next Steps

The Agency will require several ecological effects and human health studies through a data 

call-in, which is expected to be issued in late 2012. This new information will be used to 

conduct risk assessments for bensulfuron methyl uses. 
Summary of Data Gaps – Bensulfuron methyl

The table below summarizes all anticipated data needs for bensulfuron methyl in Section I, of this 

document (Preliminary Work Plan), the Registration Review– Preliminary Problem Formulation for the 

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

Bensulfuron methyl, dated September 2, 2011, and the Bensulfuron methyl: Human Health Assessment 

Scoping Document in Support of Registration Review, dated July 6, 2011.

Guideline 

Number Anticipated Data Requirement Test 

Material

Study Duration 

(months)

835.4100 Aerobic Soil Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

835.6200 Aquatic Field Dissipation (including Environmental 

Chemistry Methods and ILV for Water) TGAI 24

850.2100 Avian Acute Oral Toxicity1 TGAI 12

850.2300 Avian Reproduction2 TGAI 24

850.4100 Seedling Emergence, Tier II2,3 TEP, 

degradate4 12

850.4150 Vegetative Vigor, Tier II2, 3 TEP, 12

850.4400 Aquatic Plant Toxicity Test using Lemna spp. Tier II2,3 TEP, 

degradate4 12

850.5400 Algal Toxicity, Tier II2, 3 TGAI

Degradate4 12

870.3200 21/28-Day Dermal Toxicity TGAI 24

870.4200 Carcinogenicity Study (rats only) TGAI 48

870.6200 Neurotoxicity Screening Battery (Acute and Subchronic) TGAI 24

870.7800 Immunotoxicity TGAI 12

NON-GDLN Special Study for Non-target Plant Reproductive Toxicity1 TEP 24

 1

The anticipated DCI is expected to require that a protocol be submitted for review and approval by the Agency prior to initiation of this study. 2 Study is currently under review. 

3 A Tier II study is expected to be required. A Tier I plant study may be conducted in lieu of a Tier II study with the understanding that any adverse effects 

observed by the Tier I study would necessitate conduct and submission of a Tier II study as well. 4 The anticipated DCI is expected to require this study for the major degradates 2-amino-4,6-dimethoxyprimidine, methyl 2-(aminosulfonyl-methyl)benzoate, 

and any other major degradates (degradates occurring at 10% or greater than the parent) found.