UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460
OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM Date: October28, 2014 SUBJECT: Cyazofamid: Tier I Review ofHuman Incidents

PC Code: 085651 DP Barcode: D423509 Decision No.: 495518 Petition No.: NA RiskAssessment Type: NA TXRNo.:NA MRIDNo.:NA Registration No.: NA Regulatory Action: NA Case No.: NA CAS No.: 120116-88-3 40CFR:NA Ver.Apr.08 FROM: Shanna Recore, Industrial Hygienist**~**

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# D "'A. • Toxicology and Epidemiology Branch**~ ~**  Health Effect Division (7509P)

THROUGH:

TO: and ElizabethEvans, Environmental Protection Specialist Toxicology and Epidemiology Branch Health Effects Division (7509P)

## f}(J/1**~ 1~** **~atf1** David Miller, Acting Branch Chief0Jv JJ Toxicology and Epidemiology Branch Health Effects Division (7509P) Cassi Walls, Risk Assessor Risk Assessment BranchIII Health Effects Division (7509P) and M. Manupella, Chemical Review Manager Risk Management 

### & Implementation Branch 2 Pesticide Re-evaluation Division (7508P) Summary and Conclusions Based onthe low frequency and low severity ofincident cases reported for cyazofamid in both IDS and SENSOR-Pesticides, there does not appearto be a concern at this time thatwould warrant further investigation. The Agency will continue to monitorthe incident information and ifa concern is triggered, additional analysis will be included inthe risk assessment.

Page 1 of4Detailed Review 

### I. ACTIONREQUESTED This review is intended to fulfill ourrequirementto docket summaries ofincident datathatwere reported to the Agency, as well as to ensure human incident data and the Agricultural Health Study (AHS) are part ofthe problem formulation phase ofregistration review. Reports of adverse health effects allegedly due to a specific pesticide exposure 

### (i.e., an "incident") are largely self-reported and therefore, generally speaking, neither exposure to a pesticide or reported symptom (orthe connection betweenthe two) is validated orotherwise confirmed. Typically, causation cannotbe determined based on incident data. However, incident information canbe animportant source offeedback to the Agency: incidents ofsevere outcome, or a suggested pattern ortrend among less severe incidents, can signal the Agency to further investigate a particular chemical orproduct. Observational epidemiology studies relate the risk ofdisease, 

### e.g., cancer, and exposure to an agent such as a pesticide product in the general population or specific sub-groups like pesticide applicators. 

### II. BACKGROUND Cyazofamid is a fungicide whichbelongs to a novel chemical class based onthe cyanoimidazole moiety. Cyazofamid is a broad spectrum fungicide active against oomycete fungi (such as Phytophthora, Plasmopara, Pseudoperonospora, andPythium) and Plasmodiophoromycetes (Plasmodiospora brassicae). It specifically interferes withthe cytochrome bc1 complex (ubiquinol cytochrome 

### c oxidoreductase) in the mitochondrial respiratory chain ofoomycetes fungi. Cyazofamid is used ona variety offood crops including, potatoes, basil, peppers, cucumber, squash, eggplant, tomatoes, broccoli, cabbage, and ornamental plants and turf. Forthis evaluation, both the OPP Incident Data System (IDS) andthe Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel EventNotification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data onthe active ingredient cyazofamid (pc code: 085651). The purpose ofthe database search is to identifypotential patterns inthe frequency and severity of the health effects attributed to cyazofamid exposure. Cyazofamid is not included inthe AHS, and therefore this study does notprovide information for this report. 

### III. RESULTS/DISCUSSION

a. IDS (Incident Data System) OPP's IDS includes reports ofalleged human health incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports from registrants, other federal and state health and environmental agencies, and individual consumers. Since 1992, OPP has compiledthese reports in IDS. IDS contains reports from across the U.S. and most incidents have all relevant product information recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in the report.

Page 2 of4IDS records incidents in one oftwo modules: Main IDS and Aggregate IDS:

o MainIDS contains incidents resulting inhigher severity outcomes and provides more detail with regard to case specifics. This system stores incident data for death, major and moderate incidents, and it includes information aboutthe location, date and nature ofthe incident. Main IDS incidents involving only one active ingredient (as opposedto pesticide products with multiple active ingredients) are considered to provide more certain information aboutthe potential effects ofexposure from the pesticide.

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, orno effects outcomes). These are reported by registrants only as counts inwhat are aggregate summaries. Forthe Main IDS, from January 1, 2009 to August 12, 2014, there were 0 incidents reported involving cyazofamid. In Aggregate IDS, from January 1, 2009 to August 12,2014, there were 2 incidents reported involving cyazofamid. These incidents were classified as minor severity. Overall, there are few incidents involving cyazofamidreported to IDS. 

### b. SENSOR-Pesticides The SENSOR-Pesticides database covers 11 states from 1998-2010, although reporting varies from state to state. Cases ofpesticide-related illnesses are ascertained from a variety ofsources, including: reports from local Poison Control Centers, state Department ofLabor workers' compensation claims when reported byphysicians, reports from State Departments of Agriculture, and physician reports to state Departments ofHealth. Althoughboth occupational and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on occupational pesticide incidents, and is ofparticular value inproviding that information. The state coordinator at each ofthe 11 respective state Departments ofHealth conducts case followup activities such as obtaining medical records to verify symptoms and severity. Using standardized protocol and case definitions derived from poison center reporting, the state SENSOR-Pesticide coordinator enters the incident information into the state-based system which is sent to NIOSH annually to be aggregated. A query ofSENSOR-Pesticides from 1998-2010 identifies no cases involving cyazofamid (pc code 085651).



### c. Agricultural Health Study (AHS) The AHS is a high quality, prospective epidemiology study eyaluating the linkbetweenpesticide use and various health outcomes including cancer. The AHS includes private and commercial pesticide applicators and their spouses. Ifthere are AHS findings relevant to a particular pesticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase oftheprocess and, ifappropriate, fully reviewed inthe risk assessmentphase ofthe process. The AHS includes information onuse of80 differentpesticide Page 3 of4active ingredients commonly used in agriculture. Cyazofamid is not included in the AHS, and therefore this study does notprovide infonnation for this report. 

### IV. CONCLUSION Based onthe low frequency and low severity ofincident cases reported for cyazofamid in both IDS and SENSOR-Pesticides, there does not appearto be a concern at this time thatwould warrant further investigation. TheAgency will continue to monitor the incident infonnation and ifa concern is triggered, additional analysis will be included inthe risk assessment.

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