Docket Number: EPA

- HQ

- OPP

- 2011

- 0663 www.regulations.gov



## Bensulfuron methyl Final Work Plan Registration Review February 201 23 BENSULFURON METHYL FINAL WORK PLAN

Introducti on

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 con cerning the Preliminary Work Plan (PWP) in the Summary Document

, which was posted i n the bensulfuron methyl registration review docket ( EPA

- HQ

- OPP

- 2011

- 0663 )

, and any other comments concerning the initial docket postings

. The Summary Document provided inf ormation 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 r egistration r eview program requires revi ew 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 o ver 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 revi ew 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 synth ase , a pathway. Bensulfuron methyl is registered for use to control broadleaf weeds and sedges in aquatic rice production. Due to the use pattern, tolerance s have been established for crayfis h, rice, and rice straw . There are no registered residential uses of bensulfuron methyl

. Bensulfuron methyl was first registered in 198 9 ; therefore

, it was not subject to the reregistration requirements of FIFRA.

Comments Received on the Preliminary Wor k 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

, t he Agency received

comment s from the Physicians Committee for Responsible Medicine

. The com ments 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

.4 R isk 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 us es of bensulfuron methyl

. Below is a summary of the issues relevant to the registration review of bensulfuron methyl

.

E cological R isk :

**•** No comprehensive ecological risk assessment has been conducted for bensulfuron methyl. A screening level risk assessme nt 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 bensulfuro n methyl will be conducted during registration review. The new assessment will incorporate the most

up

- to

- date modeling methodologies, updated toxicological endpoint s, and data
submitted under the registration review data call

- in (DCI)

.

**•** The Agency has no t 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 e ffect” 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 Agen cy 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 th e 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 stud y 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 :5 **•** GDLN 835.4100

– Aerobic Soil Metabolism

**•** GDLN 835.4400

– Anaerobic Aquatic Metabolism

**•** GDLN 835.6200

– Aquatic Field Dissipation

**•** GDLN 850.2100

– Avian Acute Oral Toxi city 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 me thyl 2

- (aminosulfonyl

methyl)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 plan ts (Tier II)

**•** GDLN 850.5400

– Aquatic Plant Growth: a lgae ( 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 Sp ecies and Drinking Water Assessments for Bensulfuron methyl

, September 11, 2011 , located in docket EPA

- HQ

OPP

- 2011

- 0663 , for a detailed discussion of these anticipated risk assessment and data
needs.

Human Health Risk:

**•** The most recent human health risk a ssessment 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 assessmen t:

**•** GDLN 870.3200

– Dermal Toxicity

**•** GDLN 870.4200

– Carcinogenicity Study (rats only)

**•** GDLN 870.6200

– Acute and Subchronic Neurotoxicity Battery

**•** GDLN 870.7800

– Immunotoxicity6 **•** After the required toxicology studies are submitted and reviewed, EPA will re

- evaluate endpoints and safety/uncertainty factors for bensulfuron methyl.

**•** During registratio n review, the Agency will update the dietary risk assessment using
revised estimated drinking water concentrations

, toxicological endpoints, and incorporat ing an y degradates that are determined to be of human toxicological concern.

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

expos ures might occur as a result of aerial application and off

- site transport (e.g., spray
drift o r 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 re sidential 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 Registr ation 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 sys temic toxicity. These studies include endpoints which may be susceptible to endocrine inf luence, 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 test s 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 rele vant 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 Program7 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 d esignate.” The EDSP employs a two

- tiered approach to making the

statu torily 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 te sts 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 secti on 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. Bensulfur on 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 D ocket 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 Decision8 Open Public Comment Period for Proposed Registration Review

D ecision 2018

– Oct.

– Dec.

Cl ose Public C omment P eriod 2019

– Jan.

– March Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2019 Total ( years ) 8

Summary of Comments and Agency Responses

The bensulfuron methyl registration review docket was open for a 6 0

- day com ment period beginning on September 30, 2011

. During the comment period, a comment w as 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 i f 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 us ing TG223 may be class ified

as acceptable if it is scientifically valid, is conducted using the LD 50 - slope test or limit dose

test guidelines (the LD 50 - only test is not adequate for fulfilling data requirements), and meets all of the following criteria:

• The study is condu cted 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 submit ting 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 LD 50 - 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 LD 50 , 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.9 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
evaluat ion 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 a bsorption 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 esti mate dermal absorption. An in

- vi vo 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 me thyl 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 t o specifically assess neurotoxicity parameters and histopathology or to assess

f unctions 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 dev eloped
for bensulfuron methyl registration review. Additionally, t he Agency is currently working on a retrospective analysis to determine whether or not the immunotoxicity study will be required and the decision may affect b ensulfuron methyl registration r eview.

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

Env ironmental 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, 2 011.

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 Me thods and ILV for Water) TGAI 24

850.2100 Avian Acute Oral Toxicity 1 TGAI 12

850.2300 Avian Reproduction 2 TGAI 24

850.4100 Seedling Emergence

, Tier II 2, 3 TEP, degradate 4 12

850.4150 Vegetative Vigor, Tier II 2, 3 TEP, 12

850.4400 Aquatic Plant Toxic ity T est using Lemna spp. Tier II 2,3 TEP, degradate 4 12

850.5400 Algal Toxicity, Tier II 2, 3 TGAI Degradate 4 12

870.3200 21/28

- Day Dermal Toxicity TGAI 24

870. 4200 Carcinogenicity Study (rats only) TGAI 48

870.6200 Neurotoxicity Screening Battery (Ac ute and Subchronic) TGAI 24

870.7800 Immunotoxicity TGAI 12

NON

- GDLN Special Study for Non

- target Plant Reproductive Toxicity 1 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 wo uld 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 (deg radates occurring at 10% or greater than the parent) found.