2 INTRODUCTION

This is the Environm ental Protection Agency’s (EPA or the Agency ) Final Work Plan (FWP) for the registration review of cyproconazole . This work plan addresses public comments received concerning the Preliminary Work Plan (PWP), which was posted in the cyproconazole registr ation review docket (EPA

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. Cyproconazole is a broad spectrum, systemic, triazole fungicide in the conazole class registered for use on wheat, triticale, soybean, field and seed corn, and peanuts. It currently has one antimicrobial use registered as a composite wood preser vative for structural lumber.

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 whe ther it continues to meet the FI FRA standard for registration. Changes in science, public policy, and pesticide use practices occur over time. The registration review program is intended to make sure that, as the ability to assess risk evolves and as polic ies and practices change, all registered pesticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case.

Informatio n on this program is provided on the Agency’s website

. 1

The FWP begins with any upd ates since the PWP was issued. Next is a summary of substantive

comments received during the public comment period for the PWP concerning anticipated data

needs

, expected risk assessments, or the estimated timeline identified in the PWP

, and a summary of the Agency’s response s to th o se comments

. This section is followed by registration

review planned data needs, risk assessments expected to be conducted , and the projected registration review timeline for cyproconazole

. Lastly, the re is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

The re are no additional updates on cyproconazole since the PWP.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60

- day public comment period on the cyproconazole Preliminary Work Plan , which opened on January 11, 2016 and closed on March 11, 2016 , the Agency received five public

comments. Comments were submitted by Syngenta Crop Protection (Syngenta) , the United States Department of Agriculture (USDA) , the Physici ans Committee for Responsible Medicine (PCRM) , the Center for Biological Diversity (CBD) , and the FIFRA Endangered Species Task Force (FESTF)

. The comments do not address the timeline described in the PWP, but they do address the planned ecological and hum an health risk assessments and data r equirements. In the PWP, EPA also solicited comments on the specific topics of environmental justice , trade irritants

and water quality concerns ; comments were received on the topic of trade irritants only

.

This sectio n does not capture every comment made about the PWP nor all of the Agency’s

responses. Summarized below are public comments that addressed the anticipated registration review data needs, risk assessments, or timeline, or are of a broader regulatory nature. Public

1 https://www.epa.gov/pesticide

- reevaluation3 comments and EPA responses in their entirety are located in the d ocket, EPA

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risk assessment or data needs are in the document Cyproconaz ole: Response to Comments on

EFED and AD Problem Formulation for Registration Review.

Comments submitted by Syngenta in EPA

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1. Comment: Syngenta submitt ed three algal studies (S keletonema costatum, N avicula pelliculosa, and A nabaena flos

- a quae )

, to address data gaps for Guideline 850.4500 Algal

T

oxicity

, and environmental chemistry m ethods for soil and water to address Guideline

850.6100 Environmental C hemistry M ethods

. Syngenta also submitted comments related to study endpoints and E PA models.

Response: The Agency will review the referenced studies during registration review. These data requirements will still be included in the forthcoming Generic Data Call

- In (GDCI), and

S yngenta may cite the submitted data in its 90

- day response to the GDCI. Syngenta’s comments on endpoint and models are addressed in the EFED Response to Comments

document.

2. Comment: In response to questions in the BEAD Chemical Profile, Syngenta believes the

dec line in use of c yproconazole is due to the increased availability of generic triazoles. Syngenta feel s cyproconazole remains a useful tool since it i s effective against Asian soybean rust and performs better in cereals during early timing.

Response: The Agency thanks Syngenta for their comment and will consider this information during registration review.

3. Comment : Syngenta noted that it no longer has any active antimicrobial uses due to recent

cancellations.

Response: The Agency acknowledges that Syngenta no longer has any active antimicrobial products

. There are active antimicrobial products which are owned by other registrants.

Comments submitted by FESTF in EPA

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Comment: The technical registr ant for cyproconazole, as iden tified on the fact sheet in the PWP, is Syngenta, which is a FESTF member and is entitled to rely on FESTF data.

Response: EPA appreciates FESTF’s comments and will consider this information during registration review.

Comments submitted by PCRM in EPA

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Comment: On the a v ian passerine data requirement, PCRM is requesting that the Agency consider selecting representative conazoles with which to generate test data, thereby reducing the number of overall tests conducted. Additionally, PCRM recommends that the4 OECD Test Guideline 223, Avian Acute Oral Toxicity Test be used as the protocol instead of the EPA Guideline 850.2100 in an effort to potentially reduce the number of animals tested.

Respons e: T he Agency supports bridging from representative chemicals to untested

chemicals when appropriate. However, based on the available avian acute oral toxicity studies for several conazoles, a bridging approach is not recommended because the existing

toxi city endpoints vary widely despite similar chemical structures. Therefore, bridging is unlikely to capture the broad range of results possible for the conazole group. With regard to OECD TG 223 as a test protocol, current Agency guidance states that specie s other than bobwhite quail (i.e., passerines) may be used if low background mortality in the laboratory is demonstrated and regurgitation during the study is not observed.

Comments submitted by USDA in EPA

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Comment: USDA stressed the importance of triazole fungicides, including cyproconazole, in provid ing broad protective, curative, and eradicative activities against fungal diseases on broad acre and high value specialty crops

. USDA discussed the importance of triazol e fungicides as part of an effective resistance management strategy

. USDA also noted the importance of avoid ing trade irritants, caused by different domestic tolerance s and

international maximum residue levels (MRLs).

Response: EPA appreciates the USD A’s comments and will consider this information during registration review. The Agency will work to minimize trade irritants by harmonizing

domestic tolerances with international MRLs, to the extent feasible and consistent with

domestic law.

Comments sub mitted by CBD in EPA

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Comment : CBD’s comments focus on the EPA’s duty to consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) on the registration review of cyproconazole in accordance with the Endangered Species Act (ESA). CBD’s

commen ts mention various aspects of the risk assessment process, including use of the best available data to develop endangered species risk assessments, and evaluation of effects on listed species and their designated critical habitat. CBD also expresses conce rn regarding the rigor of the Agency’s preliminary determinations regarding the effects of cyproconazole on listed species and their designated critical habitat

.

Response: EPA has reviewed the comments from CBD on the registration review docket

ope ning for cyproconazole and plans to address many of the concerns raised by CBD as part of the implementation plan for assessing the risks of pesticides to listed species based on the recommendations of the April 2013 National Academy of Sciences (NAS) repo rt. EPA will

add ress concerns specific to cyproconazole in connection with the development of its final registration review decision for cyproconazole.

In November 2013, the EPA, along with the Services and the USDA, released a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. The Interim Approaches were developed jointly by the agencies in response to the NAS report5 recommendations

, and reflect a common approach to risk a ssessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS
report 2 outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments t hat EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA.

The joint Interim Approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presented the joint Interim Appr oaches at the

December 2013 Pesticide Program Dialogue Committee (PPDC) and State

- FIFRA Issues Research and Evaluation Group ( SFIREG) meetings

. The agencies also held stakeholder workshop s in April and October 2014, and in April 2015, allowing additional o pportunities for stakeholders to comment on the Interim Approaches. Additional workshops are planned

to enhance stakeholder involvement. As part of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in connection wi th the development of upcoming r e gistration r eview

decisions. The details of the joint Interim Approaches are contained in the white paper

“ Interim Approaches for National

- Level Pesticide Endangered Specie s Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report” 3

, dated November 1, 2013.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potent ial risks of pesticides to listed species and their designated critical habitat, the EFED and AD Registration Review Problem Formulation for Cyproconazole supporting this FWP does not describe the specific ESA analysis

, includ ing

effects determinations for specific listed species or designated critical habitat , to be conducted during registration review

. In t his problem formulation document

, EPA described

the screening

- level risk assessment to determine the potential effects of cyproconazole on all

taxa of non

- target wildlife and plants , which will assume that listed species and their designated critical habitats may be present in the vicinity of the application of cyproconazole. This screening

- level assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. While the agencies continue to develop a common method for ESA analysis, the planned screening

- level risk ass essment for the registration review of cyproconazole will describe the level of ESA analysis completed for this particular registration review case. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk as sessments for listed species and their designated critical habitats, these methods will be app lied to subsequent analyses for cyproconazole as part of compl eting this registration review.

PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for the conventional uses of cyproconazole only

. The Agency anticipates no exposure for the only existing cyproconazole antimicrobial

2 http://www.nap.edu/catalog.php?record_id=18344

3 http://www.epa.gov/espp/2013/nas.html6 product registered in October 2015; therefore, there are no planned antimicrobial use data needs

at this time. For additi onal detail on data needs, see the EFED and AD Registration Review Problem Formulation for Cyproconazole

, Cyproconazole. Scoping Document in Support of Registration Review for Human Health Assessment and Cyproconazole: Response to Comments

on the EFED Prob lem Formulation for Registration Review

. The planned data needs have not changed from what was included in the PWP

.

Table 1: Planned D ata Needs for the Conventional Uses of Cyproconazole Registration

Review

Guideline

Number 4 Study Title Test

Material Estimated

Timeframe

(Months from receipt of DCI)

850.1350 Mysid chronic toxicity text TGAI 12

850.2100 Avian acute toxicity, passerine species TGAI 12

850.4500 Algal toxicity, freshwater diatom Navicula pelliculosa and marine diatom Skeletonema

costatum TEP 12

850.4550 Cyanobacteria toxicity TEP 12

850.6100 Environmental chemistry methods and associated independent laboratory validation,

water TGAI 12

850.6100 Environmental chemistry methods and associated independent laboratory validation,

soil TGAI 12

850.3040 (Tier 3) Field testing for pollinators 5 TEP 24

Non

- GLN (OECD Test

GLN 237) (Tier 1) Honey bee larvae acute toxicity TGAI 12

Non

- GLN (Tier 1) Honey bee larvae chronic oral toxicity TGAI 12

Non

- GLN (Tier 1) Honey bee adult chronic toxicity TGAI 12

Non

- GLN (Tier 2) Semi

- field testing for pollinators (tunnel or colony feeding studies) 5 TGAI or TEP 24

Non

- GLN (Tier 2) Residues in pollen and nectar/field residue analysis 5 TEP 24

TGAI = technical grade active ingredient; TEP = typical end

- use product

4 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. https://www.regulations.gov/%20

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5 The need for Tier 2/3 pollinator tes ting will be based upon the results of Tier 1 laboratory tests and/or other lines of evidence, and the need for a refined pollinator assessment.7 RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment and ecological and environmental

fate risk assessment for the conventional uses of cyproconazole was completed in 2012 for the use of cyproconazole on peanuts . The antimicrobial human health, environmental fate, and ecological risk assessment for the use of engineered and composite wood products was completed in 2015. Findings and conclusions from these risk assessments are summarized in the EFED and AD Registration Review Problem Formulation for Cyproconazole and Cyproconazole. Scoping Document in Support of Registration Review for Human Health

Assessment

.

D uring registration review, the Agency will conduct a comprehensive ecological risk assessment for all conventional uses of cyproconazole. For human health, EPA will conduct revised dietary, aggregate and occupational risk assessments during registration re view for the conventional uses. If toxicological endpoints or points of departure are revised based on re

- evaluation of existing data, then they will be considered in the new assessments, as well as any changes to the standard operating procedures or defau lt exposure assumptions.

Table 2 below summarizes the planned registration review risk assessments based on the EFED and AD Registration Review Problem Formulation for Cyproconazole and Cyproconazole. Scoping Document in Support of Registration Review fo r Human Health Assessment

. The planned assessments have not changed from what was included in the PWP

. The cyproconazole antimicrobial product registered in October 2015 results in no human or environmental

exposures ; therefore, additional risk assessments are not necessary and the Agency does not plan to update the antimicrobial assessments in the current registration review. Table 2 outlines the planned risk assessments for the conventional uses only.8 Table 2: Pla nned Risk Assessments for the Conventional Uses of Cyproconazole 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

Incidents Will check for updates There are no reported ecological incidents for cyproconazole in the databases consulted; see page 17

of the EFED and AD Registration Review Problem Formulation for Cyproconazole

. Human Health Dietary

Food Yes A revised dietary

- exposure analysis may be conducted to reflect the most recent dietary

- exposure models, revised estimated drinking water concentrations, and/or revised toxicological points of departure. Drinking water Yes The Agency anticipates updating the drinking water

assessment. Cyproconazole parent alone is the r esidue of concern for drinking water, as there are no identified major degradates. Occupational Handlers (mixers, loaders, applicators) Yes Revised occupational handler and post

- application exposure and risk assessments are needed fo r the conventional uses during registration r eview to account for recent changes in exposure assessment assumptions, including body weight, amount treated, and transfer coefficients (TCs). Post

- application Yes

Residential

Handlers No There are no registered products containing cyproconazole at this time that would result in residential exposure. Post

- application No

Other Aggregate Yes A new aggregate risk assessment for cyproconazole may be required during registration r eview to incorporate revised dietary exposure a nalyses and/or toxicological point of departure

. Cumulative No Cyproconazole has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

Tolerances Yes EPA anticipates harmonizing U.S. tolerances and

Code x MRLs, where possible, during registration

r eview.9 Incidents Will check for updates For a discussion of reported human incidents for cyproconazole, see pa ge 11 of the Cyproconazole. Scoping Document in Support of Registration Review for Human Health Assessment and the Cyproconazole: Tier 1 (Scoping) Review of Human Incidents and Epidemiology.

TIMELINE

EPA has created the following estimated timeline for the completion of the cyproconazole registration review in Table 3 below

. Since the PWP was issued, t he projected timeline has been shortened by one year as all of the required data are one year studies, with the exception of Tier

2 /3 pollinator studies. If the Tier 1 pollinator studies trigger the higher

- tiered st udies, th e timeline may be extended

.

Table 3: Registration Review for Cyproconazole

– Projected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period January 2016

- completed

Close Public Comment March 2016

- completed Case Development

Final Work Plan June 2016

- completed

Issue DCI July

- September 2016

Data Submission July

- September 201 7

60

- day Public Comment Period for Draft Risk Assessments 6 January

– March 20 19 Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review

Decision October

– December 20 19

Registration Review Decision and Begin Post

- Decision Follow

- up 202 0 Total (years) 5

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate and ecological

effect s studies for cyproconazole through a D ata C all

- I n Notice , expected to be issued later this

year.

6 The regulations governing registration r eview generally require the Agency to provide a public comment period of

at least 30 calendar days for draft risk assessments; see 40 CFR § 155.53(c). For conventional pesticides, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessment s

.