2 

### Uniconazole-P Preliminary Work Plan – Table of Contents

OVERVIEW ...................................................................................................................... ............. 3

ANTICIPATED DATA NEEDS .................................................................................................... 3

STATUTORY AND REGULATORY AUTHORITY ................................................................... 5

CHEMICAL FACTS ................................................................................................................ ...... 6
USE AND USAGE INFORMATION ............................................................................................ 6

RECENT ACTIONS ................................................................................................................ ....... 7

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 8

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

NEXT STEPS .................................................................................................................... ........... 11 Appendix – Additional Areas Considered in the Uniconazole-P Registration Review ................ 12

References:

This Preliminary Work Plan summarizes the En vironmental Protection Ag ency’s current position based on the following documents:

1. Problem Formulation for th e Ecological Risk and Drinking Water Exposure Assessments to be Conducted for the Registration Review of Uniconazole and Uniconazole-P . James K. Wolf, Frank Farruggi a, and Rosanna Louie-Juzwiak. December 15, 2015.

2. Uniconazole-P. Human Health Assessment Sc oping Document in Support of Registration

Review. Jaime D’Agostino, Zaida Figueroa, and William Drew. December 15, 2015.

3. Uniconazole: Tier I (Scoping) Review of Human Incidents and Epidemiology . Shana Recore. September 1, 2015.

4. BEAD Chemical Profile (BCP) for Regi stration Review: Uniconazole (128676). Leonard Yourman, Don Atwood, and Andrew Lee. December 22, 2015.

5. EFED Table 1 Report. Ingredient: Uniconazole (128976). April 8, 2015.

6. HED Master Label Report. Ingredient: Uniconazole (128976). April 8, 2015.

These and other supporting documents for the unic onazole-P registration review case may be found in the docket EPA-HQ-OPP-2015-0729 at http://www.regulations.gov

.3 OVERVIEW

The docket for uniconazole-P is now open, initiating the first public comment period for this registration review (docket number EPA-HQ-O PP-2015-0729). Uniconazole is a plant growth regulator. The resolved S-isomer, identified as unic onazole-P, is the active pesticidal ingredient and is the active ingredie nt in registered end-use products. Unic onazole-P is registered for use in greenhouses on ornamental plants and fruiting vege tables (Crop Group 8) transplants, including eggplant, groundcherry, pepino, pepper, tomatillo, and tomato. The product is specified for use in commercial greenhouses, lathhouses, and shad ehouses as a foliar spray, bulb dip, or grounddirected applications using handheld equipment. There are no uniconazo le registrations. This Preliminary Work Plan (PWP) document explai ns what EPA’s Office of Pesticide Programs knows about uniconazole-P, highlight ing anticipated data and asse ssment needs, identifying the types of information that would be especially useful to the Agen cy in conducting the review, and providing an anticipated timeline for completi ng the registration review for uniconazole-P.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t uniconazole-P 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 uniconazole-P. 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 a ddition 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 inform ation. 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 Preliminary Work Plan begins by listing the anticipated data needs for uniconazole-P. Next, it discusses the statutory and re gulatory authority for Registrati on Review. Then the document provides chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration revi ew timeline for uniconazole-P. Finally, the Appendix to this document includes identifica tion and discussion of some areas that are considered generally in Registra tion Review along with some a dditional chemical case-specific

information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data n eeds for uniconazole-P. Pr oposed label language

would limit shadehouse and lathhouse applications to soil drench ; if approved, the vegetative vigor toxicity study (GL. 850. 4150) would not be needed. For additional discussion of the anticipated data needs, see the Problem Formulation for the Ec ological Risk and Drinking Water Exposure Assessments to be Conducted for th e Registration Review of Uniconazole and
Uniconazole-P and Uniconazole-P. Human Health Assess ment Scoping Document in Support of Registration Review

.4 Table 1: Anticipated Data Needs for th e Uniconazole-P Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

850.4400 Aquatic plant growth: Tier II vascular plants TGAI 12
850.4500 Aquatic Plant Growth: Tier II Algal Toxicity TGAI 12

850.4550 Aquatic Plant Growth: Tier II Cyanobacteria Toxicity TGAI 12

850.3020 Honey bee acute contact toxicity TGAI 12

NonGuideline Study (Tier I) Honey bee adult acute oral toxicity TGAI 12

NonGuideline Study (Tier I) Honey bee larvae acute oral toxicity TGAI 12

NonGuideline Study (Tier I) Honeybee adult chronic oral toxicity TGAI 12

NonGuideline Study (Tier I) Honey bee larvae chronic oral toxicity TGAI 12

850.3030 Honey bee toxicity of residues on foliage TGAI 12

NonGuideline Study (Tier II) Semi-field testing for pollinators (tunnel or colony feeding studies) TEP 24

NonGuideline Study (Tier II) Field trial of residues in pollen and nectar TEP 24

850.3040 (Tier III) Field testing for pollinators TEP 24

850.4100 Terrestrial plant toxicity: Tier II seedling

emergence TEP 12

850.4150 Terrestrial plant toxicity: Tier II vegetative vigor TEP 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 Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-00285 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 re view program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard 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. 2

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 registra tion 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 registrati on 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 uniconazole-P.

2 http://www2.epa.gov/pesticide-reevaluation6 CHEMICAL FACTS

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

Table 2: Chemical Facts for Uniconazole-P

PC code 138976 (The uniconazole PC Code is 128976.)

Case Number 7007 CAS Number 83657-17-4 (T he uniconazole CAS Number is 83657-22-1.) Year first registered 1984 Pesticide Type Plant Growth Regulator

Chemical class Triazole Reregistration Eligibility Decision (RED) No RED was completed for uniconazole-P.

Tolerance Reassessment Eligibility Decision (TRED) Not applicable.

Cumulative group Not applicable. Uniconazo le-P has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for uniconazole-P are established in 180.643. Dual-use Uniconazole-P is registered for conventional pesticidal uses only and has no registered antimicr obial or biopesticidal uses Non-pesticidal uses There are no identifi ed non-pesticidal us es of uniconazole-P.

Pesticide Re-evaluation Division, Chemical Review Manager Susan Bartow, bartow.susan@epa.gov, 703-603-0065

Registration Division, Product Manager Tony Kish, kish.tony@epa.gov, 703-308-9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage info rmation for uniconazole-P. Please see the BEAD Chemical Profile (BCP) for Regist ration Review: Uniconazole (128676) in the registration

review docket for more details.

Table 3: Uniconazole-P Use and Usage Information

Summary of Use Uniconazole is a plant gr owth regulator. The resolved S-isomer, identified as uniconazole-P, is th e active pesticidal ingredient and is the active ingredient in registered end-use products. Uniconazole-P reduces plant height by reducing internode elongation through inhibition of gibberellin biosynthesis. Use Sites Uniconazole-P is registered for use in greenhouses on ornamental plants and fruiting vegetables (Crop Group 8) transplants, including eggplant, groundcherry, pepino, pepper, tomatillo, and7 Table 3: Uniconazole-P Use and Usage Information

tomato. The product is specified for use in commercial greenhouses, glasshouses, lathhous es, and shadehouses (where plants are grown in containers). Dire ct application to dirt floors or to plants/pots in direct contact with dirt floors of greenhouses,

lathhouses or shade stru ctures is prohibited. Summary of Usage EPA does not have current usage data for uniconazole-P. Formulation Type(s) Emulsifiab le and soluble concentrates. Application Method(s) Products can be appl ied by foliar spray, dr ench, bulb or cutting dip, and as a pre-plant application to the soil surface. Technical Registrant(s) Valent U.S.A. Corporation; Fine Agrochemicals, Ltd No. of Registrations 4 section 3 products 3 and 1 section 24c product.

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.

 Updated information on the use of uniconazole -P to indicate its role in nursery and transplant management.

 The relative importance of uniconazole-P (i n comparison with alternatives, such as paclobutrazol) to assess benefits or impacts to growers of uniconazole-P.

 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 distribution 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 uniconazole-P to the
US market.

RECENT ACTIONS

There are no recent actions for uniconazole-P.

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

(http://oaspub.epa.gov/pestlabl/ppls.home).8 ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health ri sk assessment for uniconazole-P was completed on March 31, 2008 in preparation for a new us e request on Fruiting Vegetables Crop Group 8 (Except Cucurbits). The most recent ecological and environmental fate risk assessment was completed on April 10, 2008 in support of the proposed addition of shadehouse and lathhouse uses to the Sumagic product label. Findings a nd conclusions from these risk assessments are

summarized in the Problem Formulation for the Ecologi cal Risk and Drinking Water Exposure Assessments to be Conducted for the Regist ration Review of Uniconazole and Uniconazole-P and
Uniconazole-P. Human Health Assessment Sc oping Document in Support of Registration

Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for outdoor uses of uniconazole-P. For human health, EPA anticipat es the need to conduct revised dietary and occupational risk assessments during registration review. If toxicologica l endpoints or points of departure are revised based on the data that are an ticipated to be required for registration review, they will be considered in the new assessments, as well as 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.9 Table 4: Anticipated Risk Asse ssments for the Uniconazole-P 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 Yes In support of registration review, an exposure and risk

assessment for outdoor uses will be conducted for the parent uniconazole-P. An updated drinking water assessment (DWA) is anticipated to be needed

Incidents Will check for updates For a discussion of reporte d ecological incidents for uniconazole-P, see page 9 of the Problem

Formulation.

Human Health Dietary Food Yes The Agency will conduct a new dietary risk assessment to incorporate a new acute endpoint and point of departure for th e general U.S. population.

The assessment will include revised estimated drinking water concentr ations (EDWCs), if applicable, as well as updated consumption information and the latest version of the dietary

model. Drinking water Yes The agency will conduct a new drinking water assessment for uniconazole-P, to account for new modeling techniques introduc ed since the previous risk assessment. The new drinking water assessment

will include the current residues of concern (uniconazole-P, its R-enantiomer and the Z-isomer). Occupational Handlers (mixers, loaders, applicators) Yes The Agency will reevaluate the occupational handler assessment for uniconazole-P to address updates to exposure policies, includ ing updates to default exposure data used for handler scenarios and assumptions for body weights. Post-application Yes Updated post-application (dermal) exposure assessments may be required in Registration Reviewbased upon revisions to the Agency’s scenariospecific surrogate exposure data and assumptions for body weights. Any changes related to toxicological POD will also be incorporat ed. The Agency may alsorevisit the need for a quantitative occupational postapplication (inhalation) exposure assessment.
Residential

Handlers No There are no residentia l uses currently registered for uniconazole-P; therefore, a quantitative residential exposure/risk assessment is not necessary.10 Post-application No Exposure from drif t is not expected, but the Agency may consider whether a volat ilization risk assessment will be needed for uniconazole-P during registration

review.

Other Aggregate Yes Evaluates the combined risk from dietary and residential exposures. Cumulative No There is currently no evidence to indicate that conazoles share common mechanisms of toxicity, and the Agency is not following a cumulative risk approach based on a common mechanism of toxicity

for the conazoles. Tolerances Yes The tolerance expr ession for uniconazole in 40CFR §180.643[a] should be revised to state, “Tolerances

are established for residues of the fungicide/plant growth regulator unico nazole-P, including its metabolites and degradates, in or on the commodities listed in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only uniconazole-P [( E )-( S )-1-(4- chlorophenyl)-4,4-dimethyl-2-(1 H -1,2,4-triazol-1- yl)pent-1-en-3-ol], its R -enantiomer and its Z

isomer.”

Incidents Will check for updates There were no reported human incidents for uniconazole-P, see page 10 of the Scoping Document

and Uniconazole: Tier I (Sc oping) 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.

 Clarification of the test material (e.g., unic onazole-P) in the environmental fate studies.

 The soil texture (i.e., particle size distri bution) and cation exch ange capacity (CEC) information submitted by the registrant (M RID 40573602) in order to compare Japanese

soils to United States soils is not sufficient. Other factors such as parent material is equally important, for which there was no information submitted, may influence the sorption observed in these two soils. The units of measurement and what was included in the exchangeable acidity would be informative (it is assumed to be meq Fe+3 + Al+3/100 g). Specific information would include soil mi neralogy (i.e., clay), soil parent material (i.e., volcanic), drainage class, and climat e conditions (temperature and precipitation) would be informative to relate the Japanese soils used for the aerobic soil metabolism study and the soil sorption partition coefficients to U.S. soils.

 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).11 TIMELINE

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

Table 5: Projected Uniconazole- P Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2015 December Close Public Comment 2016 February Case Development Final Work Plan 2016 May Issue DCI 2016 July - September Data Submission 2018 July - September 60-day Public Comment Period for Draft Risk

Assessments 4 2020 January - March

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

Registration Review Decisi on and Begin Post-Decision 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 i ssue a Final Work Plan for the registration

review of uniconazole-P.

4 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 

### Appendix – Additional Areas Considered in the Uniconazole-P 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:

Uniconazole-P is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 5 In addition, no Total Maximum Daily Loads (TMDL) have been developed for uniconazole-P. 6 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 7 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 8 in order to ensure they can be us ed 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 unicon azole-P 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.

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

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

group_name=PESTICIDES

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

8 http://www2.epa.gov/pesticide-reevaluation/opp-guidance- submission-state-and-tribal-water-quality-monitoringdata13 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for uniconazole-P. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of uniconazole-P 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 pes ticide’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 most recen t registration decision for uniconazole-P, 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), uniconazole-P is subject to the endocrine screening part of th e 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 scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 9 and includes some pesticides

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

chemicals.14 scheduled for registration review and chemicals found in water

. Neither of these lists should be

construed as a list of known or likely endocrine disruptors.

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. 10

HUMAN STUDIES:

Occupational

Past uniconazole-P risk assessments rely in pa rt on data from studies in which adult human subjects were intentionally exposed to a pest icide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pestic ide 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 prev ailing 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 studies.

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