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INTRODUCTION

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

the registration review of mesosulfuron-methyl. This work plan addresses public comments 

received concerning the Preliminary Work Plan (PWP), which was posted in the mesosulfuronmethyl registration review docket (EPA-HQ-OPP-2012-0833). Mesosulfuron-methyl is an

herbicide in the sulfonylurea family and is registered for use as a post-emergence treatment to 

control annual grasses and broadleaf weeds, especially wild oat (Avena fatua) and wild mustard 

(Synapis arvensis), in triticale and wheat (winter, spring, and durum).

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. Changes in science, public policy, and pesticide use practices 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 the statutory standard. 

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

Information on this program is provided on the Agency’s website.

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The FWP begins with any updates since the PWP was issued. Next is a summary of substantive 

comments received during the public comment period for the PWP concerning anticipated data 

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a 

summary of the Agency’s responses to those comments. This section is followed by registration 

review planned data needs, risk assessments expected to be conducted, and the projected

registration review timeline for mesosulfuron-methyl. Lastly, there is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

The Agency previously requested evidence that weathered and aged residues are efficiently 

extracted by the enforcement procedure (possibly using radioactive samples from the livestock 

metabolism studies); however, HED has now determined that this requirement can be waived 

because the extraction solvents in the goat and hen metabolism studies and in the enforcement 

method are similar. 

The Agency, based on a weight of evidence approach, concludes that immunotoxicity studies

are not required as this time for bensulfuron-methyl, chlorsulfuron, ethametsulfuron,

flazasulfuron, foramsulfuron, halosulfuron-methyl, mesosulfuron-methyl, metsulfuron-methyl,

orthosulfamuron, primisulfuron-methyl, prosulfuron, sulfometuron-methyl, sulfosulfuron,

triasulfuron, and triflusulfuron-methyl.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the mesosulfuron-methyl Preliminary Work Plan, 

which opened on June 26, 2013 and closed on August 26, 2013, the Agency received 2 public 

comments. Comments were submitted by Bayer Crop Science and the FIFRA Endangered 

 

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http://www.epa.gov/oppsrrd1/registration_review/
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Species Task Force (FESTF). The comments do not address the timeline described in the PWP, 

but they do address the planned ecological and human health risk assessments and data

requirements. In the PWP, EPA also solicited comments on the specific topics of environmental 

justice, water quality concerns, and trade irritants, but no comments or information were received 

on those issues.

This section does not capture every comment made about the PWP nor all of the Agency’s 

responses. Summarized below are public comments that resulted in changes to the anticipated

registration review data needs, risk assessments, or timeline, or are of a broader regulatory 

nature. Public comments and EPA responses in their entirety are located in the docket, EPAHQ-OPP-2012-0833. Summarized public comments and Agency responses related to the 

anticipated ecological risk assessment or data needs are in the Response to Public Comments on 

the Mesosulfuron-methyl Registration-Review Problem Formulation.

Comments submitted by FIFRA Endangered Species Task Force (FESTF) in EPA-HQOPP-2012-0833-0009.

1. Comment: The Preliminary Work Plan notes that an endangered species determination has 

not yet been completed. In response to the Agency’s endangered species data requirements, 

data developed by FESTF will address species proximity to Mesosulfuron-methyl uses. 

Response: The Agency is aware of the data developed by FESTF for Mesosulfuron-methyl 

and when appropriate will use that data to fulfill data requirements. 

Comments submitted by Bayer Crop Science in EPA-HQ-OPP-2012-0833-0010.

2. Comment: There are no unknown major metabolites in the submitted study. All metabolites 

were identified and described in the reports MRIDs 45386430 and 45386431. The structures of 

the metabolites are reported. BCS also synthesized these metabolites. Metabolite Unknown A 

(coded as BCS-CV14885) was synthesized and shown not to have any herbicidal activity 

(Rosinger, C., 1999; MRID 45386331).Similarly Unknown D (coded as BCS-CO60720) was 

synthesized and tested with Lemna and green algae and found to be non-toxic. Therefore, based 

on the structural elucidation of these metabolites, the submitted report (Steinfuhrer and Zumdick, 

2000; MRID 45386430) should fulfill the requirements and repeat of the study is not warranted.

Response: Two major degradates (unknown A and unknown D) were thought to be unidentified 

at the time of the problem formulation. BCS indicated that structures (coded BCS-CV14885 and 

BCS-CO60720) were proposed in the aerobic aquatic metabolism study (MRID 45386430). 

EFED acknowledges these structures.

Data needs were reassessed given this new information and EFED has revised its 

recommendations on the value of data on toxicity to certain aquatic organisms (see below). 

EFED does not have any toxicity data for BCS-CV14885 or BCS-CO60720 (BCS incorrectly 

indicates that MRID 45386331 contains information about herbicidal activity of these 

degradates). BCS-CV14885 and BCS-CO60720 are SU bridge-intact degradates; therefore, 

toxicity to terrestrial and aquatic plants will be assumed the same as that of mesosulfuron-methyl

in the absence of data and a TTR approach will be used to estimate EECs. Following the same 
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assessment procedures in the problem formulation, it was determined that BCS-CV14885 and 

BCS-CO60720 toxicity studies with fish, aquatic invertebrates, aquatic non-vascular plants, 

birds, and mammals are unlikely to change risk conclusions. However, the lack of BCSCV14885 and BCS-CO60720 toxicity information for aquatic vascular plants could impact risk 

conclusions (see pg 22 of problem formulation). 

In addition, a recent DER review found that the available ECM/ILV water studies (MRID 

46451701 and 46451702) did not include the major degradates of mesosulfuron-methyl in 

aquatic environments (USEPA, 2013). 

The following studies are recommended in addition to those indicated in the problem 

formulation:

Aquatic plant growth (850.4400) - vascular plant (BCS-CV14885 and BCS-CO60720)

ECM/ILV (water) (850.6100) - to include the major degradates observed in aquatic 

environments (AE F160459, AE F160460, AE F140584, AE F147447, AE F092944, 

BCS-CV14885 (benzoic acid with guanidine), and BCS-CO60720 (methyl ester of 

benzoic acid with guanidine))

The following study is no longer recommended:

Aerobic Aquatic Metabolism (835.4300)

Modifications are made for the following study recommended in the problem formulation:

ECM/ILV (soil) (850.6100) - to include the major degradates observed in soil

environments (AE F154851, AE F099095, and AE F092944). Minor degradate observed 

in the soil environment are not recommended.
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PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for mesosulfuron-methyl based on the 

Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological 

Risk, Endangered Species, and Drinking Water Exposure Assessments for Mesosulfuron-methyl,

Mesosulfuron-methyl. and Response to Public Comments on the Mesosulfuron-methyl 

Registration-Review Problem Formulation. The table has been updated since the PWP to reflect 

public comments which resulted in changes to the data needs. 

Table 1: Planned Data Needs for the Mesosulfuron-methyl Registration Review

Guideline 

Number2 Study Title2

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

835.6200 Aquatic Field Dissipation TGAI 24

850.4400 Aquatic plant growth (vascular plants)

BCS-CV14885 

BCS-CO60720

AE F154851

AE F140584

12

850.4500 Aquatic plant growth (freshwater green alga) TGAI 12

850.6100

Environmental chemistry methods and associated independent 

laboratory validation. (Water) 

AE F160459

AE F160460

AE F140584

AE F147447

AE F092944

BCS-CV14885 

BCS-CO60720 

12

Environmental chemistry methods and associated independent 

laboratory validation. (Soil)

AE F154851

AE F099095

AE F092944

12

870.7800 Immunotoxicity3 TGAI 12

Non-guideline

(Special 

Study)

Non-Target Plant Reproductive Toxicity4 TEP 24

TGAI = technical grade active ingredient; TEP = typical end-use product;

 

2 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028

3 Based on the weight of evidence approach (WOE) determined in part by review of previously submitted data for 

other sulfonyl urea herbicides, the Agency has determined that generation of new Immunotoxicity studies for each 

sulfonyl urea herbicide is unnecessary. The previously submitted data provide sufficient information for EPA to 

characterize potential impacts of the sulfonyl urea herbicides on Immunotoxicity. Therefore, to satisfy this 

anticipated data requirement, registrants may wish to consider citing these existing data in response to the DCI that 

the Agency expects to issue.

4 Based in part on a review of previously submitted data for another sulfonyl urea herbicide, the Agency has 

determined that generation of new non-guideline plant reproduction studies for each sulfonyl urea herbicide is 

unnecessary. The previously submitted data provide sufficient information for EPA to characterize potential 

impacts of the sulfonyl urea herbicides on plant reproduction. Therefore, to satisfy this anticipated data requirement, 

registrants may wish to consider citing these existing data in response to the DCI that the Agency expects to issue.
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RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the Agency will conduct a comprehensive ecological risk assessment, 

including an endangered species assessment, for all uses of mesosulfuron-methyl. For human 

health, EPA will evaluate whether the existing dietary and occupational risk assessments will 

need to be updated during registration review. If toxicological endpoints or points of departure 

are revised, they will be considered in the new assessments, as well as any changes to the

standard operating procedures, default exposure assumptions, and estimated drinking water 

concentrations.

Table 2 below summarizes the planned registration review risk assessments based on the EFED 

Problem Formulation and HED Scoping Document and the planned assessments have not 

changed from what was included in the PWP.

Table 2: Planned Risk Assessments for the Mesosulfuron-methyl Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Yes 

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

mesosulfuron-methyl, see page 19 of the Problem 

Formulation.

Human Health

Dietary

Food Yes

Drinking water Yes If drinking water residues of concern or estimated 

residue levels in drinking water are revised, a new 

drinking water assessment may be needed.

Occupational

Handlers (mixers, loaders, 

applicators)

Yes A revised up-to-date occupational handler 

assessment may be needed during Registration 

Review to account for changes to the Agency’s 

Occupational and Residential Exposure policies. 

Post-application No There is no dermal endpoint for mesosulfuronmethyl.

Residential

Handlers No There are no residential uses of mesosulfuronmethyl. 
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Table 2: Planned Risk Assessments for the Mesosulfuron-methyl Registration Review

Post-application No There are no residential uses of mesosulfuronmethyl, so a conventional residential post-application 

assessment will not be conducted during Registration 

Review; however, the Agency will examine the need 

for a spray drift and volatilization assessment for 

mesosulfuron-methyl during Registration Review.

Other

Aggregate Yes An aggregate assessment that evaluates the combined 

risk from dietary and residential exposures will be 

conducted if drinking water residues of concern or 

estimated residue levels in drinking water are revised 

and a new drinking water assessment is undertaken, or 

if an assessment is conducted for exposures from spray 

drift or volatilization.

Cumulative No Mesosulfuron-methyl has not been identified as a 

member of a cumulative group that shares a common 

mechanism of toxicity in mammalian species.

Tolerances No Tolerances will not be reassessed, but the tolerance 

expression for mesosulfuron-methyl will be revised. 

See page 8 of the Scoping Document.

Incidents Will check for 

updates

For a discussion of reported human incidents for 

mesosulfuron-methyl, see page 8 of the Scoping 

Document and Mesosulfuron-methyl: Review of 

Human Incidents.
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TIMELINE

EPA has created the following estimated timeline for the completion of the mesosulfuron-methyl

registration review in Table 3 below. The projected timeline has changed since the PWP. 

Table 3: Registration Review for Mesosulfuron-methyl – Projected Registration Review 

Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period June 2013 – Completed

Close Public Comment August 2013 –

Completed

Case Development

Final Work Plan November 2013 –

Completed

Issue DCI 2014 January-March

Data Submission 2016 January-March

60-day Public Comment Period for Draft Risk Assessments5 2018 July-September

Registration Review Decision

60-day Public Comment Period for Proposed Registration Review 

Decision

2018 January – March

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

Total (years) 6

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate and ecological 

effects studies for mesosulfuron-methyl through a Data Call-In Notice, expected to be issued in 

January-March of 2014. 

 

5 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.