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### Metconazole Preliminary Work Plan – Table of Conten ts

OVERVIEW ..........................................

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

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

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

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

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

CHEMICAL FACTS ....................................

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

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

................................................... ................ 7

RECENT ACTIONS ....................................

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

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIE W ................................ 8

TIMELINE ..........................................

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

NEXT STEPS ........................................

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

Appendix – Additional Areas Considered in the Metco nazole Registration Review ................... 12

References:

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

1. Metconazole: Preliminary Problem Formulation for t he Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposu re Assessments in Support of the Registration Review. He Zhong, Ph.D., and Michael Lowit, Ph.D. December 10, 2015.

2. Metconazole. Human Health Scoping Document in Supp ort of Registration Review . Barry O’Keefe, Nancy Dodd, and Myron Ottley. November 24 , 2015.

3. Metconazole: Revised Tier I (Scoping) Review of Hu man Incidents and Epidemiology

. Elizabeth Evans and Shanna Recore. September 15, 2 015.

4. BEAD Chemical Profile (BCP) for Registration Review : Metconazole (125619). Tara Chandgoyal, Ph.D., Don Atwood, Ph.D., and Stephen S mearman. December 14, 2015.

5. Metconazole (125619) Screening Level Usage Analysis (SLUA) . May 8, 2015.3

6. Environmental Fate and Effects Division Label Data Report: Metconazole PC Code

125619. March 18, 2015.

7. Health Effects Division Master Label Report Spreads heet: Metconazole PC Code 125619. March 18, 2015.

These and other supporting documents for the metcon azole registration review case may be found in the docket EPA-HQ-OPP-2015-0013 at http://www.regulations.gov

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OVERVIEW

The docket for metconazole is now open, initiating the first public comment period for this registration review (docket number EPA-HQ-OPP-2015- 0013). Metconazole is a demethylation inhibiting (DMI) fungicide registered for agricultu ral uses including bushberries, tree nuts, almonds, potatoes, sweet potatoes, corn, sugar beet s, small grains, sugarcane, canola, cotton, peanuts, soybeans, sunflowers and dry beans. Metco nazole is also registered for residential use on ornamentals and on golf course turf. This Preli minary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about metconazole, highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providi ng an anticipated timeline for completing the registration review for metconazole.

The registration review process was designed to inc lude a public participation component to solicit input from interested stakeholders. The Ag ency intends, by sharing this information in the docket, to inform the public of what it knows about metconazole and what types of new data or other information would be helpful for the Agency t o receive as it moves toward a decision on metconazole. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional inf ormation that will help the Agency’s decision-making process for this chemical. In addi tion 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 stakeholders could include: environmental non-profit or interest groups; pestic ide 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 the ant icipated data needs for metconazole. Next, it discusses the statutory and regulatory authority fo r Registration Review. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review ti meline for metconazole. Finally, the Appendix

to this document includes identification and discus sion of some areas that are considered generally in Registration Review along with some ad ditional chemical case-specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for metconazole. For additional discussion of the anticipated data needs, see the Metconazole: Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Spe cies, and Drinking Water Exposure Assessments in Support of the Registration Review and Metconazole. Human Health Scoping Document in Support of Registration Review

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Table 1: Anticipated Data Needs for the Metconazol e Registration Review

Guideline

Number 1 Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for Metconazole

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.3040 Full field testing for pollinators (Tier III) TEP 24

850.6100 Environmental Chemistry Method/Independent

Laboratory Validation water TGAI 12

870.3465 90-day inhalation (rat) TGAI 24

Nonguideline Adult honeybee chronic oral toxicity (Tier I) TGAI 12

Nonguideline Larval honeybee acute oral toxicity (Tier I) TGAI 1 2

Nonguideline Larval honeybee chronic oral toxicity (Tier I) TGAI 12

Nonguideline Residues in Pollen and Nectar (Tier II) TEP 24

Nonguideline Chronic toxicity to benthic invertebrates (whole

sediment; 3 test species: freshwater Midge ( Chironomus dilutes ); freshwater amphipod ( Hyalella azteca ); and estuarine amphipod ( Leptocheirus plumulosus ) TGAI 24

Nonguideline Semi-field testing for pollinators (tunnel and

feeding studies (Tier II) TEP 24

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

STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mand ated 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 Agency) , based on scientific data showing that they will not cause unreasonable risks to human hea lth or the environment when used as directed on product labeling. The registration review progr am is intended to make sure that, as the ability to assess risk evolves and as policies and practice s change, all registered pesticides continue to meet the statutory standard of no unreasonable adve rse effects to human health or the environment. Changes in science, public policy, an d pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make

1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Eff ects Tests – including renumbering and other designations or c hanges for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availabilit y” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA-H Q-OPPT-2009-0154-00286

sure that as change occurs, products in the marketp lace can be used safely. Information on this program is provided on EPA’s website. 2

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 co ntinues to meet the FIFRA standard for registration. The regulations governing registrati on 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 t he pesticide and what additional risk analyses

and data or information it believes are needed to m ake a registration review decision. After reviewing and responding to comments and data recei ved in the docket during this initial comment period, the Agency will develop a Final Wor k Plan (FWP) and anticipated schedule for the registration review of metconazole.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts fo r metconazole.

Table 2: Chemical Facts for Metconazole

PC code 125619

Case Number 7049

CAS Number 125116-23-6 Year first registered 2007 Pesticide Type Fungicide

Chemical class Triazole Reregistration Eligibility Decision (RED) Metconazole was registered after November 1984; the refore, it was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Metconazole was registered after November 1984; the refore, it was not subject to tolerance reassessment. Cumulative group No cumulative risk assessment is r equired at this time since the Agency has not made a determination regarding a com mon mode of action.

40 CFR Citation Tolerances for metconazole are esta blished in 40 CFR §

180.617. Dual-use Conventional pesticide uses only. Non-pesticidal uses No non-pesticidal uses.

Pesticide Re-evaluation Division, Chemical Review Manager Jordan Page, page.jordan@epa.gov 703.347.0467

Registration Division, Product Manager Hope Johnson; johnson.hope@epa.gov , 703.305.5410

2 http://www2.epa.gov/pesticide-reevaluation7

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information fo r metconazole. Please see the BEAD Chemical Profile (BCP) for Registration Review: Me tconazole (125619) in the registration

review docket for more details.

Table 3: Metconazole Use and Usage Information

Summary of Use Metconazole is a broad-spectrum tria zole fungicide active ingredient that works systemically by preventing sp ore formation and inhibiting mycelial growth. Metconazole acts p rimarily as an inhibitor of ergosterol biosynthesis, thereby inter fering with synthesis of fungal cell membranes and providing sy stemic seed and seedling protection.

Use Sites Use sites for metconazole are bushberries (including blueberries and cranberries), tree nuts, almonds, stone fruits, tuberous and corm vegetables (including potatoes and sweet potat oes), corn (field, pop, seed, and sweet), sugar beets, barley, oats, rye, wheat, triticale, sugarcane, canola, cotton, peanuts, soyb eans, sunflowers and dry beans and peas. Metconazole is also registe red for residential use on ornamentals and golf course turf

. Summary of Usage Average usage (2010-2013) was appr oximately 210,000 pounds of active ingredient applied annually on approximat ely 5,440,000

acres. Formulation Type(s) Emulsifiable concentrate, flowa ble concentrate, soluble concentrate, water dispersible granule, ready-to-us e Application Method(s) Applications can be made with ground, aerial, airblast, chemigation, hand held, or seed treatment equipment

. Technical Registrant(s) Kureha Corporation No. of Registrations 14 Section 3 products 3 , 3 24(c)s

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.

• Certain metconazole labels are unclear with respect to application parameters such as maximum number of applications and minimum applicat ion interval (see Metconazole: Preliminary Problem Formulation for the Environment al Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Ass essments in Support of the Registration Review , Table 1). Without further information, EPA expec ts to use conservative assumptions to approximate these param eters in order to conduct a quantitative risk assessment. However, the Agency will work with registrants to clarify information on metconazole product labels.

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

• Maximum annual application rates per acre (maximum lb ai/A/year) for labels that refer only to per-crop or per-season rates.

• Use/Usage information for metconazole as an agricul tural seed treatment including use distribution (e.g., acreage and geographical distri bution).

• Usage/use information for non-agricultural uses.

• Foreign technical registrants not listed above who supply technical metconazole to the

US market.

RECENT ACTIONS

Tolerances for stone fruit, tree nut, pea and bean (except for soybean), rapeseed and sunflower subgroups were established in May 2015.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIE W

The most recent human health risk assessment for me tconazole was completed in 2014 for certain new uses and crop groupings. The most recen t ecological and environmental fate risk assessment was completed in 2014 for the same purpo se. Findings and conclusions from these

risk assessments are summarized in the Metconazole: Preliminary Problem Formulation for t he Environmental Fate, Ecological Risk, Endangered Spe cies, and Drinking Water Exposure Assessments in Support of the Registration Review

.

During registration review, the Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of metconazole. For human health, EPA anticipates the need to conduct revised residential and occupational risk assessments during registration r eview if toxicological endpoints or points of departure are revised based on the data that are an ticipated to be required for registration review. Changes to the standard operating procedures or def ault exposure assumptions could also trigger the need for revised assessments. An updated dieta ry assessment for common triazole degradates/metabolites may also be needed.

Table 4 below summarizes the anticipated registrati on review risk assessments based on the EFED Problem Formulation and HED Scoping Document.9

Table 4: Anticipated Risk Assessments for the Metc onazole 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 Agency will conduct a comprehensive ecological risk assessment including an endangered species assessment during registration review.

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

for metconazole, see page 21 of the Problem

Formulation.

Human Health Dietary Food N New dietary exposure assessment is not anticipated to be needed during registration

review. Drinking water Y A new drinking water assessment fo r metconazole may be needed during registration

review.

Metconazole may be considered in an updated drinking water assessment for the triazole degradates common to members of this

chemical class

. Occupational Handlers (mixers, loaders, applicators) Y A new occupational handler and postapplication assessment will be needed for registration review if the inhalation toxicity data anticipated to be required for registration review result in establishment of a new endpoint and point of departure for inhalation exposures. Post-application Y

Residential Handlers Y A new residential handler assessment may be needed if data anticipated to be required during registration review result in a new endpoint and point of departure for inhalation exposures. Post-application Y The need for spray drift and vol atilization assessments will be determined during registration review.

Other Aggregate 4 N May be needed if changes to endpoints and points of departure for inhalation exposure result in changes to the residential risk

assessment.10

Cumulative N There is currently no evidence to indi cate that

members of this chemical class share a common mechanism of toxicity, and EPA is not following a cumulative risk approach based on a common mechanism of toxicity.

Tolerances N There is no harmonization issue with C odex and

Canadian

MRLs are the same as U.S. tolerances.

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

metconazole, see page 9 of the Scoping

Document and Metconazole: Revised Tier I (Scoping) Review of Human Incidents and Epidemiology

.

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

• Ecological incidents not already reported to the Ag ency.

• Water quality monitoring data (see Appendix for fur ther details).

TIMELINE

EPA has created the following estimated timeline fo r the completion of the metconazole registration review in Table 5 below.

4 Additionally, a dietary assessment for the triazol e degradates common to members of this chemical cla ss may be

needed.11 Table 5: Projected Metconazole Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period Decemb er 2015 Close Public Comment February 2016 Case Development

Final Work Plan May 2016

Issue DCI July-September 2016 Data Submission July-September 2018 60-day Public Comment Period for Draft Risk

Assessments 5 January-March 2020

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision October-December 2020

Registration Review Decision and Begin Post-Decisio n Follow-up 2021

Total (years) 6

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 issue a Final Work Plan for the registration

review of metconazole.

5 The regulations governing Registration Review gene rally require the Agency to provide a public commen t period of at least 30 calendar days for draft risk assessm ents; see 40 CFR Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public co mment period generally for draft risk assessments.12



### Appendix – Additional Areas Considered in the Metco nazole Registration

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interes t to the Agency where your comments, data submissions, or reference to sources of additional information could 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 t oward 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 o f MRLs or disparities between U.S. tolerances and MRLs in key export markets, providin g as much specificity as possible regarding

the nature of the concern.

Water Quality:

Metconazole is not identified as a cause of impairm ent for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 6 In addition, no Total Maximum Daily Loads (TMDL) have been developed for metconazole. 7 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 8 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to th e quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impa ired Water Body and Other Water Quality Data in OPP’s Registration Review Ris k Assessment and Management Process 9 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fai r treatment and meaningful involvement 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 info rmation on any groups or segments of the population who, as a result of their location, cult ural practices, or other factors, may have atypical, unusually high exposure to metconazole co mpared to the general population. Please comment if you are aware of any sub-populations tha t may have atypical, unusually high exposure compared to the general population.

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation_ cy.cause_detail_303d?p_cause_group_id=885

7 http://iaspub.epa.gov/tmdl_waters10/attains_nation. tmdl_pollutant_detail?p_pollutant_group_id=885&p_po llutant_ group_name=PESTICIDES

8 http://www.epa.gov/tmdl/

9 http://www2.epa.gov/pesticide-reevaluation/opp-guid ance-submission-state-and-tribal-water-quality-moni toringdata13

ENDANGERED SPECIES:

A risk assessment that supports a complete endanger ed species determination has not been conducted for metconazole. The ecological risk ass essment planned during registration review will allow the Agency to determine whether use of m etconazole has “no effect” or “may affect” federally listed threatened or endangered species ( listed species) or their designated critical habitats. When an assessment concludes that a pest icide’s use “may affect” a listed species or its designated critical habitat, the Agency will consul t with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Servi ces), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews numerou s studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinog enicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. The se studies include endpoints which may be susceptible to endocrine influence, including effec ts on endocrine target organ histopathology, organ weights, 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 a nd reproductive effects in different taxonomic groups. As part of its most recent regis tration decision for metconazole, EPA

reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. Howev er, as required by FFDCA section 408(p), metconazole is subject to the endocrine screening p art of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether cer tain 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 oth er such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered appr oach to making the 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 estrogen, a ndrogen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screenin g and are found to have the potential to interact with E, A, or T hormonal systems will proc eed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests a re necessary based on the available data. Tier 2 testing is designed to identify any adverse endocri ne-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 ord ers/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingre dients and 9 inert ingredients. 10 A second list of chemicals identified for EDSP screening was publ ished on June 14, 2013 11 and includes some

10 http://www2.epa.gov/endocrine-disruption/overview- first-list-chemicals-tier-1-screening-under-endocri nedisruptor

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

chemicals.14

pesticides scheduled for registration review and ch emicals found in water

. Metconazole does not appear on either list. Neither of these lists shou ld be construed as a list of known or likely 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 th e Tier 1 screening battery, please visit our

website. 12

HUMAN STUDIES:

Occupational and Residential

Past metconazole risk assessments rely in part on d ata 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 Handler Exposure Task Force (AHETF) da tabase, the Agricultural Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these m ulti-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 standards prevailing at the time the research was conducted. All applicabl e requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Pa rt 26) have been satisfied, and there is no regulatory barrier to continued reliance on these s tudies.

12 http://www2.epa.gov/endocrine-disruption