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

MEMORANDUM
Date: October 23, 2014 SUBJECT: Spiromesifen: Tier I Review ofHuman Incidents

PC Code: 024875 DP Barcode: D422439 Decision No.: 494564 Petition No.: NA Registration No.: NA Regulatory Action: NA CaseNo.: NA RiskAssessment Type: NA TXRNo.:NA MRIDNo.:NA CAS No.: 283594-90-1 40CFR:NA

FROM: Elizabeth Evans, Environmental Protection Specialist Toxicology and Epidemiology Branch Health Effects Division (7509P) and Shanna Recore, Industrial Hygienist Toxicology and Epidemiology Branch Health Effect Division (7509P)

THROUGH: David Miller, ActingBranch Chief

# t{);J!.,ifv•l/ Toxicology and Epidemiology Branch Health Effects Division (7509P) 

### TO: Sarah Levy, RiskAssessor Risk Assessment Branch V Health Effects Division (7509P) and Julia Stokes, Chemical Review Manager Risk Management & Implementation Branch 2 Pesticide Re-evaluation Division (7508P) Summary and Conclusions Ver.Apr.08

Based onthe low frequency and low severity ofcases involving spiromesifenreported inboth IDS and SENSOR-Pesticides, there does not appearto 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.
Page 1of5Detailed Review 

### I. ACTION REQUESTED This review is intended to fulfill ourrequirementto docket summaries ofincident data that 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 exposureto a pesticide or reported symptom (orthe connectionbetweenthe two) is validated orotherwise confirmed. Typically, causation cannotbe determined based onincident data. However, incident informationcanbe animportant 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 productinthe general population or specific sub-groups like pesticide applicators. 

### II. BACKGROUND Spiromesifenbelongs to the keto-enols class ofpesticides. The keto-enols are derivatives of tetronic acid (spirocyclic tetronic acids) and are reported to act through inhibition oflipid biosynthesis. This active ingredient works on all developmental stages ofmites. However, mite juvenile stages are more susceptible than adults. The active ingredient is also effective against whitefly nymphs and pupal stages. Forthis evaluation, boththe OPP Incident Data System (IDS) and the 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 ingredientcarboxin (pc code: 024875). The purpose ofthe database search is to identifypotential patterns inthe frequency and severity of the health effects attributed to carboxin exposure. Spiromesifenis not included inthe AHS, and therefore this study does notprovide information for this report. 

### III. RESULTS/DISCUSSION

a. IDS (IncidentData System) OPP's IDS includes reports ofalleged humanhealth 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 relevantproductinformationrec<?rded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in the report.

Page 2 of5IDS records incidents in one oftwo modules: Main IDS and Aggregate IDS:

o Main IDS 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 opposed to pesticide products with multiple active ingredients) are consideredto 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 in what are aggregate summaries.
For the Main IDS, from January 1, 2009 to August 12, 2014, there were 3 incidents reported for the single chemical only in the database. These incidents were classified as moderate severity. These casesreported gastrointestinal, dermal, respiratory, ocular, and neurological (headache) symptoms. More details regarding these incidents can be found in Appendix 1. There was 1 additional incident reported involving more than one chemical.
In Aggregate IDS, from January 1, 2009 to August 12, 2014, there were 2 incidents reported involving spiromesifen inthe database. These incidents were classified as minor severity. Overall, there are few incidents involving spiromesifenreported 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 physicianreports to state Departments ofHealth. Although both occupational and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on occupational pesticide incidents, and is ofparticular value in providing that information. The state coordinator at each ofthe 11 respective state Departments ofHealthconducts case followup activities such as obtaining medical records to verify symptoms and severity. Using standardized protocol and case definitions derived from poison centerreporting, the state SENSOR-Pesticide coordinatorenters the incident information into the state-based system which is sentto NIOSH annually to be aggregated.
A query ofSENSOR-Pesticides from 1998-2010 identifies two cases involving spiromesifen (pc code 024875); both cases involved a single active ingredient and will analyzed for this memo. Both cases were lowin severity. Both cases were work-related and involved agricultural spray drift. One case involved a civil engineer who inhaled the pesticide that was being sprayed while he was surveying. This case experienced gastrointestinal symptoms. The second case involved a mechanic who was drifted upon by an aerial application while fixing/welding a waterpump in a potato circle. The following day he soughtmedical care. This case experienced respiratory symptoms as well as a headache.
Page 3 of5

### c. Agricultural Health Study (AHS) The AHS is a high quality, prospective epidemiology study evaluating the linkbetweenpesticide use and various health outcomes including cancer. The AHS includes private and commercial pesticide applicators and their spouses. Ifthere are AHS findings relevantto a particular pesticide going through registration review, the Agency will ensure they are consideredinthe problem formulation/scoping phase oftheprocess and, ifappropriate, fully reviewed inthe risk assessmentphase ofthe process. The AHS includes informationonuse of80 differentpesticide active ingredients commonlyused in agriculture. Spiromesifenis not included inthe AHS, and therefore this study does notprovide information for this report. 

### IV. CONCLUSION Based onthe lowfrequency and low severity ofcases involving spiromesifenreported inboth IDS and SENSOR-Pesticides, there does not appearto be a concern atthis 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 4 of5Appendix 1

Human Incidents 

### I Chemical: Spiromesifen 

### I PC Code: 024875 ' 

### - - ..

.... .. ,. Uoao Incident Package Incident Report Date Location Reg Number Product Name Severity IncidentDescription A 28 year old male was spraying the diluted productyesterday, when some ofit splashed back into his eye. He developed redness inthe eye, and removed and discarded his contacts. The next day, he was evaluated by MD, who diagnosed him 020611- GAINESVILLE, OBERON4SC with a chemicalbum and prescribed 00002 2/4/2009 FL 000264-00850 INSECTICIDE/MITICIDE Moderate ointment. A 40 year oldmale usedthe product at work. He did not wearPPE when using the product. He came home from work and took a shower. Then he had dinner and two cocktails. About 6 hours later, he got out of bed and urinated around the bedroom and then collapsed on the floor. He also experienced vomiting and a rash on the 021485- OBERON2SC back ofhis neck. On follow-up two day 00001 1/1/2009 SALEM, OR 000264-00719 INSECTICIDE/MITICIDE Moderate later, he had not seen a MD and was fine. A 44 year old male was sprayed by a crop duster. Afterhis exposure, he was able to briefly wash up at an outdoor irrigation well but full skin and clothing decontamination took place some hours later. Thateveninghe beganto develop a rash/dermal eruption and felt nauseated. Two days later he also experienced blurred vision, vomiting, diarrhea, respiratory 023302- PANHANDLE, OBERON4SC irritation, coughing, headache, and 00001 7/31/2011 TX 000264-00850 INSECTICIDE/MI'I]<:IDg_, Moderate elevated blood pressure.



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