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INTRODUCTION

This is the Environmental 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 

registration review docket (EPA-HQ-OPP-2015-0462). 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 preservative 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 whether it continues to meet the FIFRA 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 policies 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. 

Information on this program is provided on the Agency’s website.

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The FWP begins with any updates 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 responses to those 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, there is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

There 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 Physicians 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 human health risk assessments and data requirements. 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 section 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-reevaluation
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comments and EPA responses in their entirety are located in the docket, EPA-HQ-OPP-2015-

0462. Summarized public comments and Agency responses related to the anticipated ecological

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

EFED and AD Problem Formulation for Registration Review.

Comments submitted by Syngenta in EPA-HQ-OPP-2015-0462-0010.

1. Comment: Syngenta submitted three algal studies (Skeletonema costatum, Navicula 

pelliculosa, and Anabaena flos-aquae), to address data gaps for Guideline 850.4500 Algal 

Toxicity, and environmental chemistry methods for soil and water to address Guideline

850.6100 Environmental Chemistry Methods. Syngenta also submitted comments related to 

study endpoints and EPA 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 

Syngenta 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 

decline in use of cyproconazole is due to the increased availability of generic triazoles. 

Syngenta feels cyproconazole remains a useful tool since it is 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-HQ-OPP-2015-0462-0014

Comment: The technical registrant for cyproconazole, as identified 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-HQ-OPP-2015-0462-0013.

Comment: On the avian 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 the 
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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.

Response: The 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 

toxicity 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 species 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-HQ-OPP-2015-0462-0011.

Comment: USDA stressed the importance of triazole fungicides, including cyproconazole, in

providing broad protective, curative, and eradicative activities against fungal diseases on 

broad acre and high value specialty crops. USDA discussed the importance of triazole 

fungicides as part of an effective resistance management strategy. USDA also noted the 

importance of avoiding trade irritants, caused by different domestic tolerances and 

international maximum residue levels (MRLs). 

Response: EPA appreciates the USDA’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 submitted by CBD in EPA-HQ-OPP-2015-0462-0012

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 

comments 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 concern 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 

opening 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) report. EPA will 

address 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 report 
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recommendations, and reflect a common approach to risk assessment shared by the agencies 

as a way of addressing scientific differences between the EPA and the Services. The NAS 

report2 outlines recommendations on specific scientific and technical issues related to the 

development of pesticide risk assessments that 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 Approaches at the 

December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues 

Research and Evaluation Group (SFIREG) meetings. The agencies also held stakeholder 

workshops in April and October 2014, and in April 2015, allowing additional opportunities 

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 with the development of upcoming registration review 

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

“Interim Approaches for National-Level Pesticide Endangered Species 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 potential 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, including

effects determinations for specific listed species or designated critical habitat, to be 

conducted during registration review. In this 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 assessment 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 assessments for listed species and their 

designated critical habitats, these methods will be applied to subsequent analyses for 

cyproconazole as part of completing 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.html
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product registered in October 2015; therefore, there are no planned antimicrobial use data needs 

at this time. For additional 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 Problem Formulation for Registration Review. The planned data needs have not 

changed from what was included in the PWP.

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

Review

Guideline 

Number4 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 pollinators5 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 analysis5 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 Availability” 77 FR 38282, June 27, 2012. 

https://www.regulations.gov/%20-%20!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 5 The need for Tier 2/3 pollinator testing 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.
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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.

During 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 review 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 default 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 for 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.
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Table 2: Planned 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 residue

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 for the 

conventional uses during registration review 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 review to 

incorporate revised dietary exposure analyses 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 

Codex MRLs, where possible, during registration 

review.
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Incidents Will check 

for updates

For a discussion of reported human incidents for 

cyproconazole, see page 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, the 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 studies, the 

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 2017

60-day Public Comment Period for Draft Risk Assessments6 January – March 2019

Registration Review Decision

60-day Public Comment Period for Proposed Registration Review 

Decision

October – December 2019

Registration Review Decision and Begin Post-Decision Follow-up 2020

Total (years) 5

NEXT STEPS

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

effects studies for cyproconazole through a Data Call-In Notice, expected to be issued later this 

year.

 6 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 §155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.