2 Mesotrione Preliminary Work Pl an – Table of Contents

OVERVIEW ...................................................................................................................... ............. 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY ................................................................... 7

CHEMICAL FACTS ................................................................................................................ ...... 7

USE AND USAGE INFORMATION ............................................................................................ 8

RECENT ACTIONS ................................................................................................................ ....... 9

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 9

TIMELINE ...................................................................................................................... .............. 11

NEXT STEPS .................................................................................................................... ........... 12

Appendix – Additional Areas Considered in the Mesotrione Registration Review ................. 13

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Problem Formulation for the Environmental Fate, Ecologica l Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of the Regi stration Review of

Mesotrione

. I. Maher and M. Wagman. June 3, 2014.

2. Mesotrione

. Human-Health Assessment Scoping Document in Support of Registration

Review. S. Levy, K. Lowe, and M. Perron. June 4, 2014.

3. Mesotrione: Tie r I Review of Hu man I nci dents . E. Evans and S. Recore. February 6, 2014

4. BEAD Chemical Profile (BCP) for Regi stration Review: Mesotrione (122990)

. S. Ratnayake, D. Atwood, S. Smearman. April 9, 2014

5. Mesotrione (122990) Screening Le vel Usage Analysis (SLUA). March 12, 2013

6. EFED Table 1 Report. April 15, 20143 7. HED Master Label Report. April 15, 2014

These and other supporting documents for the meso trione registration re view case may be found in the docket EPA-HQ-OPP-2013-0779 at http://www.regulations.gov

.4 OVERVIEW

The docket for mesotrione is now open, initia ting the first public comment period for this registration review (docket numbe r EPA-HQ-OPP-2013-0779). Mesotrione is a selective herbicide registered for use to control broadleaf weeds in many agricultural and non-agricultural

use sites. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about mesotrione, highlighti ng anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated time line for completing the registration review for

mesotrione.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t mesotrione and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on mesotrione. The Agency encourages all inte rested stakeholders to review the PWP and Appendix and to provide comments and addition al information that will help the Agency’s decision-making process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas iden tified in the PWP and Appendix about which the Agency specifically seeks comments and informa tion. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The PWP begins by listing the anticipated data needs for mesotrione. Next, it discusses the statutory and regulatory author ity for Registration Review. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review time line for mesotrione. Finally, the Appendix to this document

includes identification and discussion of some areas that are considered generally in Registration Review along with some additional chemical case-specific information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data need s for mesotrione. For additional discussion of the anticipated data needs, see the Problem Formulation for the En vironmental Fate, Ecological Risk, Endangered Species, and Drinking Wate r Exposure Assessments in Support of the Registration Review of Mesotrione and Mesotrione. Human-Health Assessment Scoping Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Mesotrione Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Mesotrione

835.4200 Anaerobic soil metabolism 2 TGAI 24 835.4300 Aerobic aquatic metabolism 3 TGAI 24 835.4400 Anaerobic aquatic metabolism 4 TGAI 24

835.6100 Analytical methods with Storage Stability 5 (additional information needed to support previously submitted water monitoring study) TGAI 12

850.1350 Estuarine/Marine Invertebrate Chronic Toxicity Study 6 TGAI 12

850.6100 Analytical method in soil 7 TGAI 12

1 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 Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 An anaerobic soil metabolism study is expected to be requ ired for soils under different pH conditions characteristic

for mesotrione use areas.

3 The study was conducted on two British natural water-sedi ment systems at two pHs. The microbial makeup of the studied system may not be similar to the one in the US. A new study conducted on US natural-water sediment systems in variety of pHs typical in mesotrio ne use areas is expected to be required.

4 The results obtained in this study are essentially the same as those from the two different aerobic aquatic systems. This could suggest that metabolism progresses under suboxic conditions, and may be more influenced by pH than lower oxygen content. An additional study is expected to be required to verify this assumption.

5 This information is needed for the purpose of upgrading an unacceptable Surface Water Monitoring study to supplemental. The surface water samples were stored for up to 18 months before analysis . If upgraded, the available surface water data could be used for qualitative characteriza tion or even used more quan titatively (chronic exposure results) in the risk assessment.

6 Since the mysid was significantly more (~2 orders of magnitude) acutely toxic than the daphnid, chronic data are expected to be required. The results of this study will be used to generate an ACR and be applied to the freshwater invertebrate acute endpoints.

7 Inadequacy was noted of soil extraction methods for aged soil. As a result the extraction and separation of mesotrione and degradates/metabolites were not reliable and quantitatively efficient.6 Table 1: Anticipated Data Needs for the Mesotrione Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

850.6100 Analytical method in water and sediment. 8 TGAI 12

Nonguideline Drinking water treatment methods 9 (additional information needed to support previously submitted water monitoring study) TGAI 8

Anticipated 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 10 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 11 MNBA 12

TGAI = technical grade active ingredient;

8 The methods are expected to be required to support monitoring for mesotrione residues on current and newly submitted environmental fate and ecological effects data.

9 Information on the types of treatment that were used in surface water sa mples from the monitoring study (MRID 47244503) to obtain drinking water are expected to be required. The surface monitoring study had no detections of mesotrione in finished water. The sampling was conducted at the same time and in the same locations as that for untreated water, but there is no information as to the type s of treatment that were used to obtain finished water.

10 MNBA was more acutely toxic than the parent to freshwa ter invertebrates. An acute mysid study with the MNBA degradate is expected to be required.

11 Seedling emergence data are expected to be required fo r MNBA’s effects. The recommended species are the most sensitive ones from the parent mesotrione dataset, onio n (for monocot species), le ttuce and cabbage (for dicot species).7 STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 12

The Agency is implementing the registration revi ew 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 th e FIFRA standard for registration. The regulations governing regi stration review begin at 40 CFR 155.40. 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of mesotrione.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for mesotrione.

Table 2: Chemical Facts for Mesotrione

PC code 122990

Case Number 7256

CAS Number 104206-82-8 Year first registered 2001 Pesticide Type Herbicide

Chemical class Triketone Reregistration Eligibility Decision (RED) Because it was registered after November 1984, mesotrione was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Because it was registered after November 1984, mesotrione was not subject to tolerance reassessment. Cumulative group Not applicable. Mesotr ione has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

12 http://www.epa.gov/oppsrrd1/registration_review/8 40 CFR Citation Tolerances for mesotrione are established in 40 CFR Part 180.571 (a)

Dual-use Mesotrione is registered for conventiona l pesticidal uses only and has no registered antimicr obial or biopesticidal uses. Non-pesticidal uses There are no identifi ed non-pesticidal uses of mesotrione.

Pesticide Re-evaluation Division, Chemical Review Manager Jolene Trujillo trujillo.jolene@epa.gov

703-347-0103 Registration Division, Product Manager Kathryn Montague montague.kathryn@epa.gov

703-305-1243

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for mesotrione. Please see the BEAD Chemical Profile (BCP) for Regist ration Review: Me sotrione (122990) in the registration review

docket for more details.

Table 3: Mesotrione Use and Usage Information

Summary of Use Mesotrione is a selective herbicid e registered for use to control broadleaf weeds in many agricu ltural and non-ag ricultural use

sites.

Use Sites AGRICULTURAL USE SITES: blueberries, caneberries, cranberri es, rhubarb, popcorn, field corn, grass grown for seed, sod, sweet corn, okra, asparagus, millet (pearl and proso), oats, sorghum (grain and sweet), sugarcane, flax, and soybeans.

NON-AGRICULTURAL USE SITES: lawns, ornamental turf (i.e. co mmercial lawn, golf courses, cemeteries, and athletic fields), ornamental flowering plants (cuphea), and recreational areas. Summary of Usage A review of total mesotrione usage data for the last 5 years indicates that the primary us e site is corn, accounting for approximately 98% of both total pounds applied and total acres treated. Field corn represents th e highest percent crop treated in terms of acres grown and acr es treated at 20.2%. Usage data is not

available for mesotrione us e in non-agricultural sites. Formulation Type(s) Granular, water dispersible granules, emulsifiable concentrate, soluble concentrate, so lution-ready to use, pr essurized liquid, and

soluble concentrate/solid Application Method(s) Mesotrione is applied pre- a nd post-emergence through ground or aerial application equipment Technical Registrant(s) Syngenta Crop Protection9 No. of Registrations 27 Section 3 registrations 13 1 Experimental Use Permit 14 Section 24c registrations

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 The Agency currently does not have inform ation regarding total pounds active ingredient applied, percent crop/site treated, application rates: typical and maximum, frequency of application, application intervals, methods of application and target pests for the following registered agricultural sites: okra, oats, and flax. This information may improve future assessments conducted by the Agency related to the use and importance of

mesotrione.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites).

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county.

 Typical application timing (date of first applic ation and application in tervals) – national, state, and county.

 Usage/use information for non-agricultural uses.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed above who supply tech nical mesotrione to the US

market.

RECENT ACTIONS

There are several pending PRIA actions under review for the following proposed new uses: citrus fruit, palm, stone fruit, tree nuts, almond hulls, and mesotrione-tolerant soybeans.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessments for mesotrione were completed in 2009 and 2010 for a new use request. The most recen t ecological and environmental fate risk assessments were completed in 2008 and 2013 for the same purpose. Findings and conclusions

from these risk assessments are summarized in 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 Mesotrione. Human-Health Assessment Scoping Document in Support of Registration Review.

13 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).10 During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of mesotrione. For human health, EPA anticipates th e need to conduct revised dietary, residential, and occupational risk assessments during regist ration review. If toxi cological endpoints or points of departure (PODs) are revised based on the data that are anticipated to be required for registration review, they will be considered in the new assessments, as will any changes to the standard operating procedures or default exposure assumptions.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.

Table 4: Anticipated Risk Assessments for the 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 assess ment. 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 reporte d ecological incidents for mesotrione, see page 23 of the Problem Formulation.

Human Health Dietary Food Y A revised dietary exposur e analysis may be required to reflect the most recent dietary exposure models, potential revised Esti mated Drinking Water Concentrations (EDWCs), and/or changes to the toxicological PODs. Drinking water Y Occupational Handlers (mixers, loaders, applicators) Y During registration revi ew, updated occupational assessments will be conducted to reflect all currently registered uses. In addition, assessments for all uses may be updated if toxicological PODs are revised. Post-application Y

Residential Handlers Y A higher application ra te for handheld equipment was identified during the label review process. This higher rate will need to be assessed. Post-application N

Other11 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.

Cumulative N Mesotrione has not b een identified as a member of a cumulative group that shares a common mechanism of toxicity in mammals. Tolerances N Adequate methods ar e available for enforcement of the currently established tolerances.

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: Tie r I Review of

Hu man I nci dents.

TIMELINE

EPA has created the following estimated timeline for the completion of the Mesotrione registration review in Table 5 below.

Table 5: Projected Mesotrione Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2014- June Close Public Comment 2014- August Case Development

Final Work Plan 2014- November

Issue DCI 2015 Jan.-March

Data Submission 2017 Jan.-March 60-day Public Comment Period for Draft Risk

Assessments 14 2018- July- Sept.

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision 2019- April- June

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

Total (years) 6

14 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.12 NEXT STEPS

After the 60-day public comment period closes , the Agency will review and respond to any comments received in a timely manner and then i ssue a Final Work Plan for the registration

review of Mesotrione.13 Appendix – Additional Areas Considered in the Mesotrione Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, provi ding as much specificity as possible regarding

the nature of the concern.

Water Quality:

Mesotrione is not identified as a cause of impairment for an y water bodies listed as impaired under section 303(d) of the Clean Water Act. 15 In addition, no Tota l Maximum Daily Loads (TMDL) have been developed for Mesotrione. 16 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 17 The Agency invites submission of water quality data for this pesticide. To the extent possible, submi ssions should include the key data

elements noted in the OPP Guidance for Submission of State and Tribal Water Quality Monitoring Data 18 in order to ensure they can be used quantitatively or qualitatively in pesticide

risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to Mesotr ione 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.

ENDANGERED SPECIES:

15 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

16 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

17 http://www.epa.gov/owow/tmdl/

18 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm14 A risk assessment that supports a complete endangered species determination has not been conducted for Mesotrione. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of Mesotrione has “no effect” or “may affect” federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pe sticide’s use “may affect” a listed species or its designated critical habitat, the Agency will c onsult with the U.S. Fish and Wildlife Service

and/or National Marine Fisheries Service (the Se rvices), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the most rece nt registration decisi on for mesotrione, EPA

reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), mesotrione is subject to the endocrine screen ing part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide active ingredient s and 9 inert ingredients. A second list

of chemicals identified for EDSP sc reening was published on June 14, 2013 19 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of know n or likely endocri ne disruptors.

19 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.15 For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening batt ery, please visit our

website. 20

HUMAN STUDIES:

Occupational and Residential

Past mesotrione risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to de termine their dermal and inhalation exposure. Many such studies, involving exposur e to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handl ers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database, and th e 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 c onvincing evidence that the conduct of any of them was either fundamentally unethical or si gnificantly deficient relative to the ethical standards prevailing at the time the research wa s conducted. All applicab le requirements of EPA’s Rule for the Protection of Human Subject s of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barri er to continued reliance on these studies.

20 http://www.epa.gov/endo/