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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-HQ-OPP-2015-0128 at http://www.regulations.gov.
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OVERVIEW

The docket for cyazofamid is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2015-0128). This case includes the active 

ingredient cyazofamid. Cyazofamid is a selective fungicide with products registered 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) document 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 information 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 stakeholders 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 identified in the PWP and Appendix about which the 

Agency specifically seeks comments and information. Interested stakeholders could include: 

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, 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 Review. 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 discussion 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. 
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Table 1: Anticipated Data Needs for the Cyazofamid Registration Review

Guideline 

Number1 Study Title1

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

Nonguideline Chronic oral toxicity to adult honey bees TGAI 12

Nonguideline Chronic oral toxicity to larval honey bees TGAI 12

NonguidelineSemi-field testing for pollinators (tunnel or 

colony feeding studies) TEP 12

Nonguideline Field trial of residues in pollen and nectar TEP 12

NonguidelineWhole 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 ReceivedUnder 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 Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 The study listed in this section was previously 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.
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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 pesticides 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 Agency 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 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. The regulations governing registration 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 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/registration_review/
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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 biopesticidal 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, kish.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 food 

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 concentrate

Application Method(s) Products can be applied by ground, aerial, chemigation, and hand 

held spray equipment.

Technical Registrant(s) ISK Biosciences Corp.
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Table 3: Cyazofamid Use and Usage Information

No. of Registrations 3 Section 3 products4

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 methods 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 adopting 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 90th 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.

 Typical 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 purpose. 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).
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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 occupational 

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 aggregate 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 assessments based on the 

EFED Problem Formulation and HED Scoping Document.
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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 dietary 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 occupational handler risk assessment is 

anticipated during registration review to account for 

recent changes in exposure assessment assumptions, 

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 body 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 need for a volatilization 

assessment, as well as evaluate the potential 

cyazofamid exposure from spray drift during 

Registration Review.

Other
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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.

 Water quality monitoring data (see Appendix for further details).
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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 

Assessments5

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-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 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 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.
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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 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, 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 be found at the Agency’s website.8 The Agency invites submission of water 

quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process9in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental 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 potential 

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

7http://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/

9 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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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 species (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 National 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 studies 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, including 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 

chronic 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 assessment 

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 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 other such endocrine effects as the Administrator 

may designate.” The EDSP employs 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 

systems. 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 must 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 identified for EDSP screening was published on June 14, 201310 and includes some 

 

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

chemicals.
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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 pesticide 

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 multi-pesticide generic 

exposure databases, and has found no clear and convincing evidence that the conduct of any of 

them was either fundamentally unethical or significantly deficient relative to the ethical 

standards prevailing at the time the research was conducted. All 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/