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

MEMORANDUM Date: February 20, 2013 SUBJECT: Captan: ReviewofHumanIncidents
PC Code: 081301 DP Barcode: D409190 Decision No.: 474467 Petition No.: NA RiskAssessment Type: NA TXRNo.:NA MRIDNo,:NA Registration No.: NA Regulatory Action: NA Case No.: NA CAS No.: 133-06-2 40CFR:NA Ver.Apr.08 FROM: Shanna Recore, Industrial Hygienist 

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# 1**$:!~­** Toxicology and Epidemiology Branch Health Effects Division (7509P) TO: Thurston Morton, Risk Assessor Risk Assessment Branch IV Health Effects Division (7509P) and Christina Scheltema, Chemical Review Manager Risk Management & Implementation Branch 3 Pesticide Re-evaluation Division (7508P) Summary and Conclusions Based on the lowfrequency and severity ofincident cases reported for captan inboth IDS and NIOSH SENSOR-Pesticides, there does not appearto be a concern atthis time that would warrant further investigation. The Agency will continue to monitor the incident information and ifa concern is triggered, additional analysis will be included intherisk assessment.

Page 1 of6The Agricultural Health Study (AHS) is also a potential source ofinformation associated with human health effects associated with certainpesticides. Captan is included in the AHS, and therefore this study does provide information for this report.

Detailed Review 

### I. ACTION REQUESTED This review is intended to fulfill ourrequirementto docket summaries ofincident datathat were 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 (or the connection betweenthe two) is validated or otherwise confirmed. Typically, causation cannotbe determined based onincident data. However, incident information canbe an important source offeedback to the Agency: incidents ofsevere outcome, or a suggested pattern ortrend among less severe incidents, can signal the Agencyto 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 Captan is a fungicide used to control diseases onorchard crops, seed treatments, ornamentals, lawns andturf, and is also used as an in-canpreservative in adhesives and paint. Formulations include dust, emulsifiable concentrate, flowable concentrate, water dispersible granules, wettable powder, and a variety ofothers. 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 captan (PC Code: 081301). The purpose ofthe database search is to identifypotential patterns inthe frequency and severity of the health effects attributed to captan exposure. In addition, findings from the AHS were reviewed. The Agricultural Health Study (AHS) is a high quality, prospective epidemiology study evaluating the linkbetween pesticide use and various health outcomes including cancer. Captan is included inthe AHS and provides information for this report.


### III. RESULTS/DISCUSSION a. IDS (IncidentData System) OPP'sIDS includes reports ofalleged humanhealth incidents from various sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports Page 2 of6from registrants, other federal and state health and environmental agencies, and individual consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from across the U.S. and most incidents have all relevantproductinformation recorded. Reports submitted to the IDS represent anecdotal reports or- allegations only, unless otherwise stated in the report. IDS records incidents in one oftwo modules: Main IDS and Aggregate IDS:

o Main IDS contains incidents resulting in higher severity outcomes and provides more detailwith regard to case specifics. This system stores incidentdata for death, major and moderate incidents, and it includes information about the location, date and nature ofthe incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide products with multiple active ingredients) are consideredto provide more certain information about the potential effects ofexposure from the pesticide.

o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcomes). These are reported by registrants only as counts in what are aggregate summaries. For the Main IDS, from January 1, 2007 to December 11, 2012, there were 6 incidents reported for single chemical only in the database. There were 4 additional incidents reported involving more than one chemical. All ofthese incidents were classified as moderate severity. Overall, there are few incidents involving captanreported to IDS. In Aggregate IDS, from January 1, 2007 to December 11, 2012, there were 16 reported incidents involving captan. 

### b. NIOSH SENSOR The NIOSH SENSORdatabase covers 11 states from 1998-2009, 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 whenreported by physicians, reports from State Departments of Agriculture, and physicianreports to state Departments ofHealth. Although both occupational and non-occupational incidents are included inthe database, SENSOR focuses onoccupational pesticide incidents, and is ofparticular value inproviding that information. A state SENSOR contact specialist attempts to follow-up with cases and obtains medical records to verify symptoms, circumstances surrounding the exposure, severity, and outcome. Using standardized protocol and case definitions derived from poison center reporting, SENSORcoordinators at State Departments ofHealth enterthe incident interview descriptionprovided by the case, medical report, physician and patient into the SENSOR data system. The SENSORdata system is accessible to participating states and EPA. A query ofSENSOR-Pesticides 1998-2009 identifies 36 cases stemming from 33 events. Ofthe 36 cases, 9 involvedthe single active ingredient Captan and 27 involved multiple active
Page 3 of6ingredients. One case was high in severity, 8 cases were moderate in severity, and 27 were low

_ in severity. The high severity case occurred inNew York in 1998; the case was spraying a tree inhis yard (with Dragon Fruit Tree Spray and Al-Joe'sBonide A Complete Tree Fruit Spray) and was exposed. The case was admittedto ICU for nervous system (and other) symptoms and was treated with pralidoxime and atropine. Each ofthe 8 moderate severity cases reported symptoms involving the nervous system. A breakdown ofsymptoms reported for all cases is provided.

SENSOR-Pesticides 1998-2009: Reported Health Effects for Captan Cases* Dermal 10 Ocular 9 Respiratory 14 Gastrointestinal 18 Renal 1 Nervous System 22 Cardiovascular 6 Misc. 9 * Cases may report multiple health effects



### c. Agricultural Health Study (AHS) The AHS is a high quality, prospective epidemiology study evaluating the link betweenpesticide 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 inthe problem formulationlscoping phase ofthe process and, ifappropriate, fully reviewed inthe risk assessmentphase ofthe process. The AHS includes information onuse of50 differentpesticide active ingredients commonly used in agriculture. Greenburg et al. (2008) evaluated captan exposure in relation to cancer outcomes within the Agricultural Health Study (AHS) and did not observe an association with any cancer site tested (only anatomical cancer sites for which at least 15 exposed cases were included in this study). In this analysis, authors evaluatedprostate, lung, colon, colorectal and all blood cancers combined among 4383 participants who reported using captan intheir lifetime, and among 2912 new cases ofcancer determined inthe cohort. Among this total group of48, 986 AHS participants, authors did not identify any statistically significant, elevatedrisks ofany cancer in relationto captan use. Similarly, 

### in separate AHS studies ofspecific anatomical cancer sites (prostate, lung, breast, colorectal, pancreatic and cutaneous melanoma) in association 

### with use ofpesticides, including captan, authors did notreport elevated risks ofthese cancers with captan use. Engel et al. (2005) reported slightly elevated risks ofbreast cancer among female spouses ofAHS pesticide applicators who reported use ofcaptan, but these analyses were based upon small number of captan exposed cases, and should be interpreted with caution. In others areas ofAHS research,
Page 4 of6industrial hygienists performed several studies evaluating the validity ofthe AHS method of exposure assessment as applied to fungicide applicators. As a result, several changes to the AHS exposure metric for fungicide users were made (Hines et al, 2007, 2008, and 2011). The new AHS exposure algorithm is reflective ofthese modifications for fungicide uses, but was not utilized inthese earlier studies ofcaptan and cancer (Greenburg et al. 2008 and Engel et al. 2005). This may, inpart, explain the lack ofan association with captan, ifan associationtruly exists. AHS researchers planto update these initial captan analyses using additional pesticide (including captan) exposure information collected since the time ofenrollment, as well as the updated AHS exposure metric. As these newer analyses are completed, EPAwill continue to reviewthe literature regarding evidence ofthe carcinogenicpotential ofcaptan inthe AHS cohort. 

### IV. CONCLUSION Based onthe lowfrequency and severity ofincident cases reported for captan in both IDS and NIOSH SENSOR-Pesticides, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitorthe incident information and ifa concern is triggered, additional analysis will be included inthe risk assessment. In addition, EPAwill continue to reviewthe literature regarding evidence ofthe carcinogenic potential of captan inthe AHS cohort.

Articles Reviewed: 1: Hines CJ, Deddens JA, Coble J, Kamel F, AlavanjaMC. Determinants ofcaptan air and dermal exposures among orchard pesticide applicators inthe Agricultural Health Study. Ann Occup Hyg. 2011 Jul;55(6):620-33. doi: 10.1093/annhyg/mer008. Epub 2011 Mar 22. PubMedPMID: 21427168; PubMed Central PMCID: PMC3131503.

2: Greenburg DL, Rusiecki J, Koutros S, Dosemeci M, Patel R, Hines CJ, HoppinJA, Alavanja MC. Cancer incidence among pesticide applicators exposedto captan in the Agricultural Health Study. Cancer Causes Control. 2008 Dec;19(10):1401-7. doi: 10.1007/s10552-008-9187-9. Epub 2008 Jun 28. PubMedPMID: 18587656.

3: Hines CJ, Deddens JA, Jaycox LB, Andrews RN, Striley CA, Alavanja MC. Captan exposure and evaluation ofa pesticide exposure algorithm among orchard pesticide applicators inthe Agricultural Health Study. Ann Occup Hyg. 2008 Apr;52(3):153-66. doi: 10.1093/annhyg/menOOl. Epub 2008 Mar 6. PubMed PMID: 18326518.

4: Hines CJ, Deddens JA, Coble J, Alavanja MC. Fungicide applicationpractices andpersonal protective equipmentuse among orchard farmers inthe agricultural health study. J Agric SafHealth. 2007 Apr;13(2):205-23. PubMed PMID: 17555208.
Page 5 of65: Engel LS, Hill DA, HoppinJA, Lubin JH, Lynch CF, Pierce J, Samanic C, Sandler DP, BlairA, AlavanjaMC. Pesticide use and breast cancerrisk among farmers' wives inthe agricultural health study. Am J Epidemiol. 2005 Jan 15;161(2):121-35. PubMed PMID: 15632262.

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