2



### Topramezone Preliminary Work Plan

– Table of Contents

OVERVIEW

................................ ................................ ................................ ................................ ... 3

ANTICIPATED DATA NEEDS

................................ ................................ ................................ .... 4

STATU TORY AND REGULATORY AUTHORITY

................................ ................................ ... 5

CHEMICAL FACTS

................................ ................................ ................................ ...................... 5

USE AND USAGE INFORMATION

................................ ................................ ............................ 6

R ECENT ACTIONS

................................ ................................ ................................ ....................... 8

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

................................ 8

TIMELINE

................................ ................................ ................................ ................................ .... 10

NEXT STEPS

................................ ................................ ................................ ............................... 11

Appendix

– Addi tional Areas Considered in the Topramezone Registration Review

............. 12

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments to be Conducted for the Registration Review for Topramezone

. August 26, 2015

2. Topramezone. Human

- Health Assessment Scoping Document in Support of Registration

Review. July 10, 2015

3. Topramezone: Tier I Review of Human Incidents. July 30, 2015

4. BEAD Chemical Profile for Registration Review: Topramezone. March 9, 2015

5. Topramezone Screening Level Usage Analysis. December 4, 2014

These and other supporting documents for the topramezone registration review case may be

found in the docket EPA

- HQ

- OPP

- 2015

- 0127 at http://www.regulations.gov

.3

OVERVIEW

The docket for topramezone is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2015

- 0127 )

. This case includes the following active ingredient : topramezone. Topramezone is a broad

- spectrum systemic herbicide registered for use to control broadleaf and certain grass weeds. The mode of action in plants is inhibition of

the 4

- hydroxyphenylpyruvate dioxygenase ( HPPD ) enzyme

. Topramezone is currently registered for use on corn, non

- cropped areas, residential and non

- residential turf grass, and aquatic use sites. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about topramezone , highlighting 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 timeline for completing the registration

review for topramezone

.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about topramezone and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on

topramezone . The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additiona l 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 identified in the PWP and Appendix about which the Agency specifically seeks comme nts and information. Interested stakeholders could include:

environmental non

- profit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, residential, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for topramezone

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides chemical facts, use and usage information, r ecent actions, the anticipated risk assessments, and a projected registration review timeline for topramezone

. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally in R egistration R eview along with some additional chemical case

- specific

information.4

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for topramezone . For additional discussion of the anticipated data needs, see the Problem Formulation for the Ecolog ical Risk and Drinking Water Exposure Assessments to be Conducted for the Registration Review for Topramezone

, August 26, 2015 and Topramezone. Human

- Health Assessment Scoping Document in Support of Registration Review, July 10, 2015

Table 1: Anticipated Data Needs for the Topramezone Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated D ata Needs for the Parent Topramezone

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.2300 Avian reproduction study (mallard) TGAI 24

850.3040 Field testing for pollinators (Tier 3) 2 TEP 24

850.4500 Algal toxicity study TEP 12

850.6100 Environmental chemistry methods/independent

laboratory validations in soil, water 3 TGAI 12

Non

guideline (OECD TG237) Acute oral toxicity to larval honey bees (Tier 1) TGAI 12

Non

guideline Chronic oral toxicity to adult honey bees (Tier 1) TGAI 12

Non

guideline Chronic oral toxicity to larval honey bees (Tier 1) TGAI 12

Non

guideline Semi

- field testing for pollinators (tunnel or

colony feeding studies) (Tier 2) 2 TEP 12

Non

guideline Field trial of residues in pollen and nectar (Tier

2) 2 TEP 12

TGAI = technical grade active ingredient; TEP = typical end

- use product ;

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 A vailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

2 Study may be waived depending on results of Tier 1 pollinator studies.

3 ECM/ILV needed for soil. Only the ILV is needed for water.5

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 States (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Age ncy), based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability

to assess risk e volves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable 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 program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website

. 4

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 F IFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40

. T he 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 respondin g to comments and data received in the docket during this initial comment period, the Agency will develop a F inal W ork P lan (FWP) and anticipated schedule for the registration review of topramezone

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for topramezone

.

Table 2: Chemical Facts for Topramezone

PC code 123009

Case Number 7268

CAS Number 210631

- 68

- 8

Year first registered 2005 Pesticide Type Herbicide

Chemical class n/a

R eregistration Eligibility Decision (R E D) Because it was registered after November 1984, topramezone was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Because it was registered after 1996, topramezone was not subject to tolerance reassessment.

Cumulative group Topramezone belongs to a group of chemicals that inhibit the HPPD enzyme.

4 http://www.epa.gov/oppsrrd1/registration_review/6 Table 2: Chemical Facts for Topramezone

40 CFR Citation Tolerances for topramezone are established in 40 CFR §180.612.

Dual

- use Topramezone is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses.

Non

- pesticidal uses HPPD inhibitors are used to treat genetic diseases of tyrosine

catabolism.

Pesticide Re

- evaluation Division, Chemical

Revi ew Manager Jose Gayoso, gayoso.jose@epa.gov , (703) 347

- 8652

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 topramezone

. Please see the BEAD Chemical Profile for Registration Review: Topramezone. March 9, 2015 in the registration

review docket for more details

.

Table 3: Topramezone Use and Usage Information

Summary of Use Broad spectrum, systemic pre

- and post

- emergence herbicide used to control broadleaf weeds and grasses by inhibition of the HPPD

enzyme and block age of the pathway of phenylquinone biosynthesis in plants

. Use Sites Residential turf grass, golf courses, sod farms, non

- crop ornamentals, rights

- of

- way, tree plantations, aquatic vegetation,

and other non

- crop areas, as well as for application to corn (field, pop, seed, and sweet). Summary of Usage From 2006

- 2013, an annual average of approximately 19,000 lbs of active ingredient (a.i.) were applied. In the same timeframe, approximately 1.3 million acres of field and sweet corn were treated with topramezone. The average application rate was 0.01 lbs a.i. per acre. Approximately 93% of the total pounds of topramezone applied was to field corn but the percent crop treated (the ratio of base acres treated to crop acres grown) for field corn was <2.5%, whereas the percent crop treated for sweet corn was 15%.

No national level topramezone usage data were found on nonagricultural sites. Formulation Type(s) Suspension (flowable) and emulsifiable concentrates. Application Method(s) Products can be applied by ground, aerial, and hand held spray equipment. Technical Registr ant (s) Amvac, BASF7 Table 3: Topramezone Use and Usage Information

No. of Registrations 7 Section 3 products 5

Restricted Use No

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

 For some terrestrial uses, the number of applications of topramezone that can be applied per calendar year or the maximum annual application rate for a given use is not explicitly stated on many of the current labels.

 The following uncer tainties exist regarding aquatic uses of topramezone:

o There is no defined maximum duration of maintaining some concentration of topramezone in the water body. The current label language is vague and states to

‘retreat the water to maintain a sufficient con centration for a minimum of 60 days or until satisfactory weed control is achieved.

o No maximum depth is stated on the label. It is possible the water bodies may become stratified; therefore, the concentration of topramezone based on total volume may result in a much higher concentration in a given layer if thorough mixing is not observed.

o The label indicates a maximum rate of 62 fl oz/acre

- ft (1.35 lb a.i./acre

- ft). This would suggest a potential for periods of time where concentrations may temporarily exc eed the target concentration during an application (i.e., > 0.05 mg a.i./L) upon initial and subsequent applications of topramezone until dilution (i.e., achieving the desired concentration).

o The treatment of flowing water is dependent on flow rate and len gth of time that the application occurs. The label doesn’t provide information on minimum or maximum flow rates that can be treated. Potential Concentration Spikes: The maximum concentration permitted for the direct in

- water uses (single or multiple applic ations) per year, per season, or per treatment period should also be clarified in the current label (Oasis® aquatic herbicide, EPA Re g. No. 7969

- 339 ).

 C onfirmation of the following label information : sites of application ; formulations ; application methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; and geographic limitations on use

.

 U se distribution ( e.g. , acreage and geographical distribution of relevant use site s)

.

 M edian and 90 th percentile reported use rates (lbs ai/ A ) from usage data

– national, state, and county

.

 Typical a pplication timing (date of first application and application intervals)

– national, state, and county

.

 Usage/use information for non

- agricultural uses

.

 Typical application interval (days)

.

 S tate or local use restrictions

.

5 Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website ( http://oaspub.epa.gov/pestlabl/ppls.home ).8

 F oreign technical registrants not listed above who supply technical topramezone to the

US market

.

RECENT ACTIONS

On September 10, 2013 , a new use of topramezone was registered for direct applications to various aquatic sites.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for topramezone was completed in

2013 for a new us e on non

- crop aquatic sites. T he most recent ecological and environmental fate risk assessment was completed in 2013 for the same purpose . Findings and conclusions from

these risk assessments are summarized in the Problem Formulation for the Ecological R isk and Drinking Water Exposure Assessments to be Conducted for the Registration Review for Topramezone, August 26, 2015 and Topramezone. Human

- Health Assessment Scoping Document in Support of Registration Review, July 10, 2015.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of

topramezone. For human health, EPA anticipates the need to conduct revised occupational

handler and post

- application risk assessment s during registration review

. If toxicological endpoints or points of departure are revised based on the data that are anticipated to be required for registration review

, they will be considered in the new assessment s
, as w ell as any changes to

the standard operating procedures or default exposure assumptions.

T able 4 below summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document

.9

Table 4: Anticipated Risk Assessments for the Topramezone 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 Both topramezone and environmental transformation products are considered the stressors of concern. EFED will use a total toxic residue (TTR) approach, which is based on the assumption that the transformation products are of equal toxicity to the assessed organisms tested with the parent compound.

The TTRs are defined as t opramezone, M670H05, M670H01, and M670H10 for all taxa except plants. For plants, M670H05 is excluded.

Incidents Will check for updates For a discussion of reported ecological incidents for

topramezone , see page 24 of the Problem

Formulation.

Human Health Dietary

Food N A new dietary exposure assessment is not anticipated to be needed during Registration Review unless there are significant increases to the drinking water exposure estimates and/or there are updates to the toxicity endpoints or safety factors. Drinking water N A new dietary exposure assessment is not anticipated to be needed during Registration Review unless there are significant increases to the drinking water exposure estimates and/or there are updates to the toxicity endpoints or safety factors. Occupational Handlers (m ixer s, loader s, applicators ) Y Updated occupational handler exposure assessments will be conducted during Registration Review for

topramezone use on corn ; all other exposure scenarios

will be re

- evaluated if there are changes in the toxicity endpoints or safety factors.

Post

- application Y Updated occupational post

- application exposure assessments will be conducted during Registration Review for topramezone use on corn ; all other exposure scenarios will be re

- evaluated if there are changes in the toxicity endpoints or safety factors.

Residential

Handlers N New residential handler exposure and risk assessments are not anticipated to be needed during Registration Review unless there are updates to the toxicity endpoints or safety factors.10

Post

- application N New post

- application residential exposure and risk assessments are not anticipated to be needed during Registration Review unless there are updates to the toxicity endpoints or safety factors. Further, the Agency will examine the need for a volatilization assessment, as well as evaluate the potential

top ramezone exposure from spray drift during Registration Review.

Other Aggregate N N ew aggregate assessments are not anticipated to be needed during Registration Review, unless there are changes in uses, procedures, drinking water exposure estimates, toxicity endpoints, and/or safety factors.

Cumulative N ? The Agency has sought additional information from registrants regarding the mode of action/adverse outcome pathway (MOA/AOP) for HPPD inhibiting chemicals. Submitted data are currently under review

and will be used to evaluate the need for a cumulative assessment as part of Registration Review.

Tolerances N

Incidents Will check for updates For a discussion of reported human incidents for

topramezone see page 9 of the Scoping Document and

the Topramezone: Tier I Review of Human Incidents. July 30, 2015

TIMELINE

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

.

Table 5: Projected Topramezone Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period September 2015

Close Public Comment November 2015 Case Development

Final Work Plan February 201 6

Issue DCI April

– June 2016

Data Submission April

– June 2018

6 0

- day Public Comment Period for Draft Risk

Assessments 6 Oct.

– Dec. 2019

6 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, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessment s

.11 Table 5: Projected Topramezone Registration Review Timeline

Activities Estimated Date Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision July

- Sept. 2020

Registration Review Decision and Begin Post

- Decisi on Follow

- up 2021

Total (years) 6

NEXT STEPS

After the 6 0

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

review of topramezone.12



### Appendix

– Additional Areas Considered in the Topramezone Registration

Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference t o sou rces of additional information c ould be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum r esidue limits (MRL s ) 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 market s, providing as much specificity as possible regarding

the nature of the concern

.

Water Quality:

Topramezone is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act

. 7 In addition, no Total Maximum Daily Loads (TMDL) have been developed for torpramezone

. 8 More information on impaired water bodies and TMDLs can be found at the Agency’s website

. 9 The Agency invites submission of water quality data for this pesticide. T o the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 10 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Aquatic benchmarks have been established for topramezone and are available online. 11 Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks if applicable.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involve ment of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks infor mation on any groups or segments of the

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

8 http://iaspub. epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

11 http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm13

population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to topramezone compared to the general population. Please comment if you are aware of a ny sub

- populations that may have atypical, unusually high exposure compared to the general population.

ENDANGERED SPECIES :

A risk assessment that supports a complete endangered species determination has not been

conducted for topramezone. The ecological risk assessment planned during registration review

will allow t he Agency to determine whether use of topramezone has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical

habitats. Whe n 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.

END OCRINE DISRUPTOR SCREENING PROGRAM :

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 assess ments 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 weigh ts, 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 effect s in different taxonomic groups. As part of its most recent registration decision for topramezone EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as requ ired by FFDCA section 408(p),

topramezone is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

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

det erminations. 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 ingred ients. A second list14

of chemicals identified for EDSP screening was published on June 14, 2013 12 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of known or l ikely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our

website. 13

HUMAN STUDIES :

Occupation al and Residential

Past topramezone risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA ha s reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical

sta ndards prevailing at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these st udies.

12 Se e http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

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