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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 mesotrione. This work plan addresses public comments received 

concerning the Preliminary Work Plan (PWP), which was posted in the mesotrione registration 

review docket (EPA-HQ-OPP-2013-0779). Mesotrione is a pre and post-emergence selective 

herbicide registered for the control of broadleaf weeds in many agricultural and non-agricultural 

use sites.

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.1

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 mesotrione. Lastly, there is a discussion of next steps. 

UPDATES SINCE THE PWP WAS ISSUED 

As part of the problem formulation for the ecological risk and drinking water exposure 

assessments for mesotrione (PC Code 122990; D417229), a review of the available 

ecotoxicological data was performed. While the classification for many of the submitted studies 

did not change after review (still deemed Acceptable), the classification for a number of aquatic 

toxicity studies did change. Although these studies were reclassified, the Agency does not expect 

to require additional data to upgrade the studies at this time. Please see the Reclassification of 6 

Mesotrione Aquatic Ecotoxicology Studies document for further detail. 

The Agency recently finalized guidance on assessing risks to pollinators.2

 In keeping with the 

guidance, the Agency now expects to require, as appropriate, data that will enable an evaluation 

of the risks to different life stages of pollinators (i.e., adults and larvae). For mesotrione, the 

Agency expects to require the following data that were not included in the Preliminary Work 

Plan: acute and chronic oral toxicity to larval honey bees and chronic oral toxicity to adult honey 

bees. 

SUMMARY OF COMMENTS AND AGENCY RESPONSES 

 

1

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

2 http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance
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During the 60-day public comment period on the mesotrione Preliminary Work Plan, which 

opened on June 25, 2014 and closed on August 25, 2014, the Agency received three public 

comments. Comments were submitted by Syngenta Crop Protection, FESTF- FIFRA 

Endangered Species Task Force, and The Center for Biological Diversity. 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, 

however EPA only received comments on trade irritants. 

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-2013-0779. Summarized public comments and Agency responses related to the 

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

Submitted to the Mesotrione Registration Review Docket (Docket ID: EPA-HQ-OPP-2013-

0779). 

Comments submitted by Syngenta Crop Protection LLC in EPA-HQ-OPP-2013-0779-0012 

Comment: In reference to Table 1 of the Preliminary Work Plan, Syngenta Crop Protection 

provided data that had not been submitted to the Agency previously, additional information to 

support the various data submissions, and data waiver requests. 

Response: EPA will review all of the recently submitted data, supporting rationales, and waiver 

requests to determine if the data and/or supporting rationale satisfy the anticipated data 

requirements and can be used in the registration review risk assessment. 

Comment: Trade irritants: We have evaluated the mesotrione MRLs established in top export 

markets for cranberries, blueberries, caneberries, corn, sorghum, millet, oats, asparagus and 

soybean and have compiled this information in Appendix 1 to this document. Mesotrione is 

currently being reviewed for the establishment of Codex MRLs and we believe that Codex MRLs 

will be established in 2015. 

Response: EPA will work to harmonize these MRL’s during registration review. 

Comments submitted by FESTF- FIFRA Endangered Species Task Force in EPA-HQOPP-2013-0779-0011 

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 mesotrione uses. 

Response: The Agency is aware of the data developed by FESTF for mesotrione and when 

appropriate will use that data to fulfill data requirements. 
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Comments submitted by The Center for Biological Diversity’s (CBD) in EPA-HQ-OPP2013-0779-0010. 

Comment: The Center for Biological Diversity’s (CBD) comments focus on the EPA’s 

independent duty under the Endangered Species Act (ESA) to consult with the U.S. Fish and 

Wildlife Service and the National Marine Fisheries Service (the Services) on the registration 

review of mesotrione. 

Response: EPA plans to address the concerns raised by CBD as part of the implementation plan 

for assessing the risks of pesticides to listed species, which will be based on the 

recommendations of the April 2013 National Academy of Sciences (NAS) report. EPA will 

address concerns specific to mesotrione in connection with the development of its registration 

review decision. 

At this time, EPA has not fully developed its risk assessment process for listed species. In 

November 2013, the EPA, along with the Services and the U.S. Department of Agriculture, 

released a summary of their joint Interim Approaches for assessing risks to listed species from 

pesticides. The Interim Approaches were developed jointly by the Agencies in response to the 

NAS recommendations and reflect a common approach to risk assessment shared by the 

Agencies as a way of addressing scientific differences between the EPA and the Services. 

The NAS report, available at http://www.nap.edu/catalog.php?record_id=18344, outlines 

recommendations on specific scientific and technical issues related to the development of 

pesticide risk assessments that EPA and the Services must conduct in connection with their 

obligations under the ESA and FIFRA. The joint Interim Approaches were released prior to a 

stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint 

Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and 

State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings, allowing additional 

opportunities for stakeholders to comment on the Interim Approaches. As part of a phased, 

iterative process for developing the Interim Approaches, the Agencies will also consider public 

comments on the Interim Approaches in connection with the development of upcoming 

Registration Review decisions. The details of the joint Interim Approaches are contained in the 

white paper “Interim Approaches for National-Level Pesticide Endangered Species Act 

Assessments Based on the Recommendations of the National Academy of Sciences April 2013 

Report,” dated November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html. 

 
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PLANNED DATA NEEDS 

Table 1 below summarizes the planned data needs for mesotrione based on the Problem 

Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking 

Water Exposure Assessments in Support of the Registration Review of Mesotrione, and Response 

to Comments documents. The planned data needs have not changed from what was included in 

the PWP. 

Table 1: Planned Data Needs for the Mesotrione Registration Review 

Guideline 

Number3 Study Title3 Test Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

Data Needs for the Parent Mesotrione

835.4200 Anaerobic soil metabolism TGAI 24 

835.4300 Aerobic aquatic metabolism TGAI 24 

835.4400 Anaerobic aquatic metabolism TGAI 24 

 850.1350 Estuarine/Marine Invertebrate Chronic 

Toxicity Study 

TGAI 12 

850.6100 

Analytical method in soil and independent 

laboratory validation TGAI 12 

Analytical method in water and sediment. 

and independent laboratory validation TGAI 12 

Analytical methods with Storage Stability 

(additional information needed to support 

previously submitted surface water 

monitoring study MRID 47244503) 

TGAI 12 

Nonguideline 

Drinking water treatment methods (additional 

information needed to support MRID 

47578301 and previously submitted surface 

water monitoring study MRID 47244503) 

TGAI 8 

Nonguideline 

Pollinator Acute Oral Toxicity – honey bee 

larvae4 TGAI 12 

 

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 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 4

 Draft protocol for the chronic oral toxicity study with honeybee larval should be submitted to EPA for review prior 

to initiation. EPA has not developed a guideline for these studies, but that the OECD is currently working on 

guidance for a 21-day larval toxicity study that can provide both acute and chronic oral toxicity data for bee 

larvae. When the guidance is finalized, EPA will indicate whether it may be used to satisfy a requirement for both 

acute and chronic oral toxicity data for honey bee larvae. Registrants may elect to submit a separate acute (single 

dose) larval toxicity study following the OECD guideline TG237, for acute: http://www.oecdilibrary.org/environment/test-no-237-honey-bee-apis-mellifera-larval-toxicity-test-single-exposure_9789264203723-

en and for repeat dose: 
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Table 1: Planned Data Needs for the Mesotrione Registration Review 

Guideline 

Number3 Study Title3 Test Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

Nonguideline 

Pollinator Chronic Oral Toxicity – honey bee 

larvae4 TGAI 24 

Nonguideline 

Pollinator Chronic Oral Toxicity – honey bee 

adult5 TGAI 24 

Data Needs for the Degradates

835.4100 Aerobic soil metabolism MBNA 24 

835.4300 Aerobic aquatic metabolism MBNA 24 

850.1035 Estuarine/Marine invertebrate acute toxicity MNBA 12 

850.6100 

Analytical method in soil MNBA & 

AMBA 12 

Analytical method in water and sediment. MNBA & 

AMBA 12 

850.4100 Terrestrial Plant Seedling Emergence Tier II 

Study MNBA 12 

TGAI = technical grade active ingredient; TEP = typical end-use product; MNBA=4-

(methylsulfony1)-2-nitrobenzoic acid; AMBA=2-amino-4-(methylsulfonyl) benzoic acid 

 

 

http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf 5

 Draft protocol for the chronic study with adult honeybee should be submitted to EPA for review prior to initiation. 

OECD is developing study guidance for assessing the chronic (10-day) oral toxicity to the honey bee. Discussion of 

the study design elements for the 10-day adult toxicity test can be found in Appendix O of the European Food Safety 

Authority (EFSA) guidance document: EFSA. Guidance on the risk assessment of plant protection products on bees 

(Apis mellifera, Bombus spp. and solitary bees. EFSA Journal 2013;11(7):3295, 266 pp. 

doi:10.2903/j.efsa.2013.3295. Available online: www.efsa.europa.eu/efsajournal or at:

http://www.efsa.europa.eu/en/efsajournal/doc/3295.pdf
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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 mesotrione. For human health, EPA 

will conduct revised dietary, residential, and occupational risk assessments during registration 

review. If toxicological endpoints or points of departure are revised based on the data that are 

required for registration review and/or current policy, they will be considered in the new 

assessments, as well as any changes to the standard operating procedures or default exposure 

assumptions. 

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. 
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Table 2: Planned Risk Assessments for Mesotrione 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 

Y The stressors of concern are mesotrione and 

mesotrione’s major degradates, MNBA and AMBA. 

A total toxic residues (TTR) approach will be used 

for the ecological risk assessment. The drinking water 

assessments conducted to support future human 

health risk assessments of mesotrione will incorporate 

modeling of the parent only in surface and 

groundwater. See page 26 of the Problem 

Formulation for more detail. 

Incidents Will check for 

updates 

For a discussion of reported ecological incidents for 

mesotrione, see page 23 of the Problem Formulation. 

Human Health 

Dietary 

Food Y A revised dietary exposure analysis may be required 

to reflect the most recent dietary exposure models, 

potential revised Estimated Drinking Water 

Concentrations (EDWCs), and/or changes to the 

toxicological PODs. 

Drinking water Y 

Occupational 

Handlers (mixers, loaders, 

applicators) 

Y Revised occupational handler assessments will be 

necessary to reflect maximum application rates. In 

addition, assessments for all uses may be updated if 

toxicological PODs are revised. 

Post-application Y Revised occupational post-application assessments 

will be necessary to reflect all currently registered 

uses (including SLN registrations). In addition, 

assessments for all uses may be updated if 

toxicological PODs are revised. 

Residential 

Handlers Y A higher application rate for handheld equipment was 

identified during the label review process. This 

higher rate will need to be assessed. In addition, 

assessments for all uses may be updated if 

toxicological PODs are revised. 

Post-application Y May be updated if toxicological PODs are revised. 

Other 

Aggregate Y New aggregate risk assessment may be required 

during registration review to incorporate revised 

dietary exposure analyses, revised residential 

exposure assessments, and/or changes to the 

toxicological PODs. 
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Cumulative N Mesotrione has not been identified as a member of a 

cumulative group that shares a common mechanism 

of toxicity in mammals. 

Tolerances Y Adequate methods are available for enforcement of 

the currently established tolerances. EPA will work to 

harmonize tolerances and MRLs during registration 

review. 

Incidents Will check for 

updates 

For a discussion of reported human incidents for 

mesotrione, see pages 10 and 11 of the Scoping 

Document and the Mesotrione: Tier I Review of 

Human Incidents.

TIMELINE

EPA has created the following estimated timeline for the completion of the mesotrione 

registration review in Table 3 below. The projected timeline has not changed since the PWP. 

Table 3: Registration Review for Mesotrione – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period June 2014 – Completed 

Close Public Comment August 2014 – Completed 

Case Development 

Final Work Plan Dec. 2014 - Completed 

Issue DCI 2015: Jan.- March 

Data Submission 2017: Jan.- March 

60-day Public Comment Period for Draft Risk Assessments6[1] 2018: July – Sept. 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration Review 

Decision 

2019: April - June 

Registration Review Decision and Begin Post-Decision Follow-up 2020 

Total (years) 6 

NEXT STEPS 

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

effects studies for mesotrione through a Data Call-In Notice, expected to be issued in January –

March of 2015. 

 

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 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.