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2



### Cyazofamid Preliminary Work Plan

– Table of Contents

OVERVIEW

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

ANTICIPATED DATA NEEDS

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

STATUTORY AND REGULATORY AUTHORITY

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

CHEMICAL FACTS

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

USE AND USAGE INFORMATION

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

RECENT ACTIONS

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

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

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

TIMELINE

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

NEXT STEPS

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

Appendix

– Additional Areas Considered in the Cyazofamid Registration Review

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

References:

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

1. Problem Formulation for Registration Review of Cyazofamid . Environmental Fate and

Effects Division. March 16, 2015

2. Cyazofamid. Human Health Assessment Scoping Document in Support of Registration

Review. Health Effects Division. November 21, 2014

3. Cyazofamid. Tier I Review of Human Incidents. Health Effects Division. October 28, 2014

4. BEAD Chemical Profile for Registration Review: Cyazofamid. Biological and Economic Analysis Division. February 2, 2015

5. Cyazofamid Screening Level Usage Analysis (SLUA). Biological and Economic Analysis

Division. May 22, 2014

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

in the docket EPA

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3 OVERVIEW

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

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- 0128). This case includes the active ingredient cyazofamid. Cyazofamid is a selective fungicide with products re gistered for use on a variety of food crops, ornamentals, and turf to control fungal pathogens such as Downy mildew and Pythium. Products containing cyazofamid are registered for both agricultural and residential

uses. The Preliminary Work Plan (PWP) docu ment explains what EPA's Office of Pesticide Programs knows about cyazofamid, 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 cyazofamid.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this infor mation in the docket, to inform the public of what it knows about cyazofamid and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on cyazofamid. The Agency encourages all interested stake holders to review the PWP and Appendix and to provide comments and additional 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 identi fied in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include:

environmental non

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

The Preliminary Work Plan begins by listing the anticipated data needs for cyazofamid. Next, it discusses the statutory and regulatory authority for Registration Revie w. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review timeline for cyazofamid. Finally, the Appendix

to this document includes identification and dis cussion of some areas that are considered generally in Registration Review along with some additional chemical case

- specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for cyazofamid. For additional discussion of the anticipated data needs, see the Problem Formulation for Registration Review of Cyazofamid

and Cyazofamid. Human Health Assessment Scoping Document in Support of Registration

Review.Docket Number EPA

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4 Table 1: Anticipated Data Needs for the Cyazofamid Registration R eview

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Cyazofamid

850.1075 Acute toxicity estuarine and marine organisms TGAI 12

850.1300 Freshwater invertebrate life cycle TGAI 12

850.1350 Estuarine/marine invertebrate life cycle TGAI 12

850.1400 Estuarine/marine fish early life stage TGAI 12

850.3040 Field testing for pollinators TEP 24

850.4550 Toxicity to cyanobacteria TEP, TGAI 12

850.6100 Environmental chemistry methods/independent

laboratory validations in soil, sediment, and water TGAI 12

OECD

TG237 Acute oral toxicity to larval honey bees TGAI 12

Non

guideline Chronic oral toxicity to adult honey bees TGAI 12

Non

guideline Chronic oral toxicity to larval honey bees TGAI 12

Non

guideline Semi

- field testing for pollinators (tunnel or

colony feeding studies) TEP 12

Non

guideline Field trial of residues in pollen and nectar TEP 12

Non

guideline Whole sediment chronic toxicity invertebrates

( Chironomid, Leptocheirus, and Hyalella ) TGAI 24

Anticipated Data Needs for Degradates

850.1300 Freshwater invertebrate life cycle CTCA 12

850.1400 Freshwater fish early life stage CTCA 12

850.2100 Avian oral toxicity (passerine species) CCIM 12

Outstanding Data Requirements from Conditional Registration(s) 2

860.1380 Storage Stability TGAI Received

Under review.
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

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2 The study listed in this section was previou sly required as a condition of registration in November 2004 and is under review. This study will not be included in the anticipated Registration Review DCI because it is already required as a condition of registration.Docket Number EPA

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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 Agency), 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 evolves and as policies and practices change, all registered pes ticides 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 Agenc y periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided on EPA’s website. 3

The Agency is implementing the registration review program pursuant to Se ction 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 FIFRA standard for registration. The regulations governing registration r eview 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 wh at 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 docket during this initial

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of cyazofamid.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Cyazofamid

PC code 085651

Case Number 7056

CAS Number 120116

- 88

- 3 Year first registered 2004 Pesticide Type Fungicide

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

Tolerance Reassessment Eligibility Decision (TRED) Because it was registered after 1996, cyazofamid was not subject

to tolerance reassessment.

3 http://www.epa.gov/oppsrrd1/regis tration_review/Docket Number EPA

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6 Table 2: Chemical Facts for Cyazofamid

Cumulative group Not applicable. Cyazofamid has not been identified as a member

of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for cyazofamid are established in 40 CFR §180.601.

Dual

- use Cyazofamid is registered for conventional pesticidal uses only and has no registered antimicrobial or biop esticidal uses.

Non

- pesticidal uses There are no identified non

- pesticidal uses of cyazofamid.

Pesticide Re

- evaluation Division, Chemical Review Manager Jose Gayoso, Gayoso.jose@epa.gov, (703) 347

- 8652

Registration Division, Product Manager Tony Kish, k ish.tony@epa.gov, (703) 308

- 9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for cyazofamid. Please see the BEAD Chemical Profile for Registration Review: Cyazofamid in the registration review docket for more

details.

Table 3: Cyazofamid Use and Usage Information

Summary of Use Cyazofamid is a selective fungicide registered for use to control a variety of pests, such as Downy mildew and Pythium.

Use Sites Cyazofamid is currently registered for use on a variety of foo d

crops , including potatoes, basil, peppers, cucumber, squash, eggplant, tomatoes, broccoli, and cabbage.

Cyazofamid is also registered for use on ornamentals and turf.

These include residential uses. Summary of Usage The major agricultural use of cyazofamid is on cucurbits and carrots, both in terms of pounds of active ingredient (A.I.) applied and average percent crop treated. In the reporting period from

2004

- 2012, the annual average of cyazofamid that was applied on cucumbers and carrots was 3, 000 lbs. for both.

For the years 2006

- 2012, cyazofamid annual usage averaged 6,000 pounds of A.I. treating an annual average of 82,000 acres, and an overall average application rate of 0.073 pounds A. I. per

acre. Formulation Type(s) Emulsifiable concent rate Application Method(s) Products can be applied by ground, aerial, chemigation, and hand held spray equipment. Technical Registrant(s) ISK Biosciences Corp.Docket Number EPA

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Table 3: Cyazofamid Use and Usage Information

No. of Registrations 3 Section 3 products 4

Restricted Use No

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

 Confirmation of the following label information: sites of application; formulations; application metho ds and equipment; maximum application rates; frequency of application, application intervals, and maximum number of applications per season; and geographic limitations on use.

 Site/crop specific information on the target pests, damage, economic thresholds, best time to treat, as well as alternatives to cyazofamid.

 Site/crop specific information on the formulation, application method, application rates, frequency of application, and timing of applications.

 Site/crop specific information on barriers of adopti ng chemical and non

- chemical alternatives to cyazofamid (e.g. price, efficacy, application methods, use restrictions, etc.).

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

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

– national, state, and county.

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

– national, state, and county.

 Usage/use information for non

- agricultural uses.

 Typica l application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed above who supply technical cyazofamid to the US

market.

RECENT ACTIONS

There are no recent actions for cyazofamid.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent human health risk assessment for cyazofamid was completed on June 28, 2012 for a request to add several new uses. The most recent ecological and environmental fate risk assessment was completed in 2012 for the same pur pose. Findings and conclusions from these

risk assessments are summarized in the Problem Formulation for Registration Review of Cyazofamid and Cyazofamid. Human Health Assessment Scoping Document in Support of Registration Review.

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

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8 During registration review, the Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of cyazofamid. For human health, EPA anticipates the need to conduct revised occupa tional handler and post

- application exposure and risk assessments during registration review to account for recent changes in exposure assessment assumptions, including body weight, amount treated, and transfer coefficients. New dietary exposure and aggre gate risk assessments are not anticipated during Registration Review, unless there are significant increases to the drinking water exposure estimates that need to be incorporated.

Table 4 below summarizes the anticipated registration review risk assessm ents based on the

EFED Problem Formul ation and HED Scoping Document.Docket Number EPA

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9 Table 4: Anticipated Risk Assessments for the Cyazofamid 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 assessment will consider risk from the parent compound as well as cyazofamid degradates.

Incidents Will check for updates No incidents have been reported to the Agency. For a

discussion of reported ecological incidents for cyazofamid, see page 19 of the Problem Formulation.

Human Health Dietary

Food N A revised d ietary exposure risk assessment is not anticipated during Registration Review, unless there are significant increases to the drinking water exposure estimates that need to be incorporated. Drinking water Y A new drinking water assessment may be necessary following review of requested fate and transport data and to incorporate updated models. Occupational Handlers (mixers, loaders, applicators) Y A revised occup ational handler risk assessment is anticipated during registration review to account for recent changes in exposure assessme nt assu mptions, including body weight and amount treated.

Post

- application Y A revised occupational post

- application risk assessment is anticipated during registration review to account for recent changes in exposure assessment assumptions, including bod y weight and transfer

coefficients.

Residential

Handlers N Because residential uses have been assessed with the most recent SOPs and maximum application rates, a

revised residential handler assessment is not anticipated during Registration Review.

Post

- application N Because residential uses have been assessed with the most recent SOPs and maximum application rates, a revised residential post

- application assessment is not anticipated during Registration Review. However, the Agency will examine the ne ed for a volatilization assessment, as well as evaluate the potential cyazofamid exposure from spray drift during Registration Review.

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10 Aggregate N Evaluates the combined risk from dietary and residential exposures.

A new aggregate assessment is not anticipated during Registration Review, unless changes in uses, procedures, or drinking water exposure estimates

occur. Cumulative N Cyazofamid is not a member of a cumulative group and no cumulative risk assessment is planned

. Tolerances N

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

cyazofamid, see page 8 of the Scoping Document and

the Cyazofamid. Tier I Review of Human Incidents.

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 already reported to the Agency.

 W ater quality monitoring data (see Appendix for further details).Docket Number EPA

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11 TIMELINE

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

Table 5: Projected Cyazofamid Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period 2015

– March

Close Public Comment 2015

– May Case Development

Final Work Plan 2015

– August

Issue DCI 2015 Oct.

– Dec.

Data Submission 2017 Oct.

– Dec.

60

- day Public Comment Period for Draft Risk

Assessments 5 2019 April

- June

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision 2020 Jan.

- March

Registration Review Decision and Begin Post

- Decis ion

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 cyazofamid.

5 The regulations governing Registration Review generally require the Agency to provide a public c omment 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.Docket Number EPA

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12 

### Appendix

– Additional Areas Considered in the Cyazofamid Registration

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest 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 toward facilitating irritant res olution. 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, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

Cyazofamid is not identified as a cause of impairment 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 cyazofamid. 7 More information on impaired water bodies and

TMDLs can b e 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 the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired

Wat er Body and Other Water Quality Data in OPP’s Registration Review Risk 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 envir onmental justice, the fair 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 pot ential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to cyazofamid 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.

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_pollut

ant_ group_name=PESTICIDES

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

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13 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for cyazofamid. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of cyazofamid has “no effect” or “may affect” federally listed threatened or endangered s pecies (listed species) or their designated critical habitats. When 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 Nat ional Marine Fisheries Service (the Services), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studi es include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, incl uding effects 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

chroni c studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for cyazofamid, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assess ment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), cyazofamid is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether ce rtain 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 em ploys a two

- tiered approach 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, androgen, or thyroid (E, A, or T) hormonal

s ystems. 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 mus t 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 ingredients. A second list

of chemicals identif

ied for EDSP screening was published on June 14, 2013 10 and includes some

10 See http://www.regulations.gov/#!documentDetail;D=EPA

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chemicals.Docket Number EPA

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14 pesticides 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 EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our

website. 11

HUMAN STUDIES:

Occupational and Residential

Past cyazofamid 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 p esticide 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 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 wa s 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.

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