2 

### Ametryn Preliminary Work Plan – Table of Contents

Overview 3

Anticipated Data Needs 4

Statutory and Regulatory Authority 5

Ametryn Facts 5

Use and Usage Information 6

Recent Actions 7

Anticipated Risk Assessments for Registration Review 7

Timeline 9

Next Steps 10

Appendix – Additional Areas Considered in the Ametryn Registration Review 11

References:

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

1. Preliminary Problem Formula tion for Environmental Fate , Ecological Risk, Endangered Species, and Human Health Drinking Wate r Exposure Assessments for Ametryn. A. Sayer. May 14, 2013.

2. Ametryn. Human Health Risk Scoping Do cument in Support of Registration Review . K. Lowe. May 9, 2013.

3. Ametryn: Review of Human Incident Reports . S. Recore. January 31, 2013.

4. BEAD Ametryn Profile for Re gistration Review: Ametryn. S. Ratnayake. March 30, 2012.

5. Ametryn Screening Level Usage Analysis . January 12, 2012.

6. PRD Label Data Report: Food/Feed & N on-Food/Non-Feed Uses Considered in Registration Review Work Planning . November 14, 2012.

These and other supporting documents for the amet ryn registration review case may be found in the docket EPA-HQ-OPP-2013-0249 at http://www.regulations.gov

.3 OVERVIEW

The docket for ametryn is now open, initiati ng the first public comment period for this registration review (docket num ber EPA-HQ-OPP-2013-0249). Ametr yn is a triazine herbicide

used for selective control of broadleaf and grassy weeds in corn, pineapple, and sugarcane

. There are no non-agricultural or residential uses registered. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pes ticide Programs knows about ametryn, highlighting anticipated data and assessment needs, identify ing 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 ametryn.

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 ametryn and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on ametryn. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional inform ation that will help the Agency’s decisionmaking process for ametryn. 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 comments and information. Interested stakeholde rs 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 Preliminary Work Plan begins by listing th e anticipated data need s for ametryn. Next, it discusses the statutory and regul atory authority for Registration Review. Then the document provides ametryn facts, use and usage inform ation, recent actions, the anticipated risk assessments, and a projected registration review timeline for ametryn. Finally, the Appendix to

this document includes identification and discussion of some areas that ar e considered generally in Registration Review along with some a dditional ametryn case-specific information.4 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipa ted data needs for ametryn. For additional discussion of the anticipated data needs, see the: Preliminary Problem Formula tion for Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Ametryn and Ametryn: Human Health Risk Scoping Document in Support of Registration

Review

.

Table 1: Anticipated Data Needs for the Ametryn Registration Review

Guideline

Number 1,2 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

835.2240 Photodegradation in water TGAI 12

835.4100 Aerobic soil metabolism TGAI 24
835.4300 Aerobic aquatic metabolism TGAI 24
850.4500 Algal toxicity TEP 12
850.4550 Cyanobacteria toxicity TEP 12
870.3465 90-day inhalation 3 TGAI 24
870.7800 Immunotoxicity 4 TGAI 12
TGAI = technical grade active ingredie nt; 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 Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 Page 31 of the Problem Formulation incorrectly indicates environmental chemistry me thods (ECM) and associated independent laboratory validation (ILV) for water (Guideline 850.6100) are needed for ametryn. Acceptable ECM and ILVs for soil, sediment, and wate r have been submitted for ametryn, and therefore, EPA does not anticipate requiring Guideline 850.6100.

3 A 28-day inhalation toxicity study will be sufficient. Ther efore, the study duration can be reduced from 90 days to 28 days.

4 Recently, OPP published the findings of its retrospective analysis of immunotoxicity studies submitted to the Agency, concluding that none of the studies included in th e analysis resulted in a Poin t of Departure (POD) that is lower than the PODs selected from other available guideline toxicology studies ( http://www.epa.gov/pesticides/regulati ng/immunotoxicity-ret ro-analysis.pdf ). EPA will consider requests for waivers for this study, particularly in light of the retr ospective analysis. A weight-of-evidence rationale will be

considered relative to the chemical’s t oxicological profile, primary target organ system(s) and mode of toxic action, and any immuno-related data available from structurally-related compounds.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 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. 1

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) a nd 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 ametryn.

AMETRYN FACTS

Table 2 provides a summary of the cu rrent regulatory status for ametryn.

Table 2: Ametryn Facts

PC code 080801

Case Number 7036

CAS Number 834-12-8 Year first registered 1964 Pesticide Type Herbicide Ametryn class Triazine Reregistration Eligibility Decision (RED) September 2005

1 http://www.epa.gov/oppsrrd1/registration_review/6 Table 2: Ametryn Facts

Cumulative group Not applicable. Ametryn has not been identified as a member of a cumulative group that shares a common mechanism of toxicity. Ametryn was not included in the 2006 triazine cumulative risk assessment that included the pesticide active ingredients atrazine, simazine, propazine, and the metabolites desethyl-s-atrazine (DEA), desisopropyl-s-atrazine (DIA), a nd diaminochlorotriazine (DACT),

because it does not share the sa me toxicity profile as these

chlorotriazines. 40 CFR Citation Tolerances for ametryn are established in 40 CFR §180.258(a). Dual-use Ametryn is registered for c onventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses. Non-pesticidal uses There are no identi fied non-pesticidal uses of ametryn.

Pesticide Re-evaluation Division, Ametryn Review Manager Molly Clayton clayton.molly@epa.gov

703-603-0522 Registration Division, Product Manager Kable Bo Davis davis.kable@epa.gov

703-306-0415

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for ametryn. Please see the memo BEAD Ametryn Profile for Registration Review: Ametryn in the registration review docket for more

details.

Table 3: Ametryn Use and Usage Information

Summary of Use Ametryn is a triazine herbicide used for selective control of broadleaf and grassy weeds in corn, pineapple, and sugarcane

. There are no non-agricultural or residential uses registered. Ametryn can be applied as pre-emergence and as a post-emergence directed spray. Use Sites Pineapple, sugarcan e, and corn (f ield and pop) Summary of Usage Based on private market usage data from 2000-2010, usage averaged approximately 200,000 pounds active ingredient (a.i.) for 350,000 acres treated. Formulation Type(s) Ametryn is formulated as water dispersible granules. Application Method(s) It can be applied by conventional ground sprayers. Aerial application is allowed in Florida for sugarcane only. Technical Registrant(s) S yngenta Crop Protection, LLC No. of Registrations Two Section 3 products 2

Restricted Use No

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

(http://oaspub.epa.gov/pestlabl/ppls.home).7 Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of particul ar interest to EPA, are described below.

 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 te chnical ametryn to the US

market.

RECENT ACTIONS

In November 2012, EPA approved a 24c Special Local Need (SLN) registration for use of ametryn on pineapple in Hawaii. While ametry n is already approved for use nation-wide on pineapple, the SLN includes different use directions for pineapples in Hawaii, such as modified spray drift language.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for ametryn was completed in 2005 in preparation for the RED. The most r ecent ecological and environmental fate risk assessment was completed in 2005 for the same purpose. Findings and conclusions from these

risk assessments are summarized in the Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Ametryn and Ametryn: Human Health Risk Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an endangere d species assessment, for all uses of ametryn. For human health, EPA anticipates the need to conduct revised dietary an d occupational risk assessments during registration review. If toxico logical endpoints or po ints of departure are revised, they will be considered in the new assess ments, as well as any changes to the standard operating procedures or defa ult exposure assumptions.

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

EFED Problem Formulation and HED Scoping Document.8 Table 4: Anticipated Risk Assessments for the Ametryn 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 It is anticipated that the parent ametryn will be

considered the stressor of concern for the terrestrial exposure assessment. For the aquatic exposure assessment, in the absence of data on the toxicity of degradates NOA 428383 and NOA 423271, it is anticipated that these degradates and the parent ametryn will be considered the stressors of concern using the total toxic resi due (TTR) approach. For additional information, see page 25 of the Problem

Formulation.

Incidents Will check for updates No ecological incidents re ported for ametryn; see page 24 of the Problem Formulation.

Human Health Dietary Food Y EPA anticipates updating the dietary assessment during registration review to take into account any new toxicity or exposure data, changes to safety factors, or changes in standard risk assessment operating procedures. Drinking water N Occupational Handlers (mixers, loaders, applicators) Y EPA anticipates updating th e occupational assessment during registration review to take into account any new toxicity or exposure data, changes to safety factors, or changes in standard risk assessment operating procedures. Post-application Y

Residential Handlers N Ametryn is not regi stered for residential use, registered uses are not anticipated to result in residential exposure, and ther efore, a residential risk assessment is not anticipated to be required. Post-application N

Other Aggregate Y Evaluates the combined risk from dietary and residential exposures. Since there are no residential uses, EPA anticipates that the aggregate assessment will be updated to take into account any changes to dietary risk estimates only. Cumulative N Ametryn has not been identified as a member of a cumulative group that shares a common mechanism of toxicity. See page 6 of this document for

additional details.9 Table 4: Anticipated Risk Assessments for the Ametryn Registration Review

Tolerances Y Tolerances for am etryn are established under 40 CFR §180.258. EPA anticipates updating the residue

definition for the tolerance expression for ametryn in accordance with current policy on tolerance

definitions.

Incidents Will check for updates For a discussion of reported human incidents for ametryn, see page 10 of the Scoping Document and

the Ametryn: Review of Human Incident Reports

.

Guidance for Commenters: Additional ecological information requested for this registration review, and of particular interest to EPA, is described below.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).

TIMELINE

EPA has created the following estimated timeline for the completion of the ametryn registration

review in Table 5 below.

Table 5: Projected Ametryn Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2013 – June Close Public Comment 2013 – August Case Development

Final Work Plan 2013 – November Issue DCI 2014 July - September Data Submission 2016 July - September 60-day Public Comment Period for Draft Risk

Assessments 3 2018 January – March

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision 2018 July – September

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

Total (years) 6

3 The regulations governing Registration Review require the Agency to provide a public comment period of at least

30 calendar days for draft risk assessments; see 40 CFR Pa rt 155.53(c). The Agency pl ans to provide a 60 calendar day public comment period for draft risk assessm ents as a general standard of practice.10 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 ametryn.11 

### Appendix – Additional Areas Considered in the Ametryn 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:

Ametryn is not identified as a cau se of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 4 In addition, no Total Maximum Daily Loads (TMDL) have been developed for ametryn. 5 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 6 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should c onform to the quality standards in Appendix

A of the OPP Standard Operating Procedure: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Re view Risk Assessment and Management Process 7 in order to ensure they can be us ed quantitatively or qua litatively 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 amet ryn 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.

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

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for ametryn. The ecological risk asse ssment planned during registration review will allow the Agency to determine whether use of am etryn has “no effect” or “may affect” federally listed threatened or endangered species (listed sp ecies) or their designate d critical habitats. When an assessment concludes that a pesticid e’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 its reregistration decision for ametryn, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), ametryn is subject to the endocrine screening part of the Endocrine Disruptor Screenin g 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 ingredients and 9 inert ingredients. Ametryn is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for ametryn. For further information on the status of the EDSP, the policie s and procedures, the lis t of 67 chemicals, future lists, the test guidelines and the Tier 1 screeni ng battery, please visit our website. 8

8 http://www.epa.gov/endo/13 HUMAN STUDIES:

Occupational

Past ametryn risk assessments rely in part on da ta 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 Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Databa se. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databa ses, 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 standards prevai ling at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subj ects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on

these studies.