Page 1 of 6 **UNITED STA**

**TES ENVIRONMENTA L PROTECTION A** **GENCY WA** **SHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND** 

**P OLLUTION PREVENTION** 

**MEMORANDUM Date:**  November 2 7 , 2012 **SUBJECT:** Triflox ys trobin : Review of Human Incidents **PC Code:** 129112 **DP Barcode:** D 407067 **Decision No.:** 469960 **Registration No.:** NA **Petition No.:** NA **Regulatory Action:** NA **Risk Assessment Type:** NA **Case No.:** NA **TXR No.:** NA **CAS No .:**  141517
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- 7 **MRID No.:** NA **40 CFR:** NA Ver.Apr.08 **FROM:** Shanna Recore, Industrial Hy gienist Toxicology

and Epidemiology Branch Health Effect Division (7509P) and Elizabeth Evans, Environmental Protection Specialist Toxicology

and Epidemiology Branch Health Effect Division (7509P) **THROUGH:** David Miller , Acting Branch Chief

Toxicology

and Epidemiology Branch Health Effects Division (7509P) **TO:** Nancy

Tsaur , Risk Assessor Risk Assessment Branch III Health Effects Division (7509P ) and M oana Appleyard , Chemical Review Manager Risk Management & Implementation Branch V Pesticide Re

- evaluation Division (7508P) Summary and Conclusions Based on the low frequency and severity

of incident cases reported for trifloxystrobin in both IDS and NIOSH SENSOR, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incid ent information and if a concern is triggered, additional analysis will be included in the risk assessment.Page 2 of 6

Detailed Review **I. ACTION REQUESTED**  This review is intended to fulfill our requirement to docket summaries of incident data that were reported to the Agency , as well as to ensure human incident data and the Agricultural Health Study (AHS) are part of the problem formulation phase of registration review. Reports of adverse health effects allegedl y due to a specific pesticide exposure ( i.e. , an “incide nt”) are largel y self

- reported and therefore, generall y speaking, neither exposure to a pesticide or reported s ymptom (or the connection between the two) is validated or otherwise confirmed
. Ty pically , causation cannot be determined based on incident data . However, incident information can be an important source of feedback to the Agency : incidents of severe outcome, or a suggested pattern or trend among less severe incidents , can signal the Agency to further investigate a particular chemical or product. Observational epidemiology studies relate the risk of disease, 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**  Triflox ys trobin is a strobilurin

- class fungicide that controls foliar fungal diseases and soilborne/seedling fungal diseases

. It works b y interrupting mitochondrial respiration in plant

pathogenic fungi, thus inhibiting spore germination and mycelial growth. It is a broad

- spectrum preventative fungicide used for control of many plant diseases in various fruit, nut, vegetable, and field crops, including corn and so ybean. For this evaluation, both OPP Incident Data S ys tem (IDS) and the Centers for Disease Control and Prevention/National In stitute for Occupational Safety and Health (CDC/NI OSH) Sentinel Event Notification Sy stem for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient trifloxy strobin (PC Code 129112 )
. The purpose of the database search is to identify potential patterns i n the frequency and se verity of the health effects attributed to trifloxy strobin exposure. In addition, findings from the AHS were reviewed. The Agricultural Health Study (AHS) is a high qualit y, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. Trifloxy strobin is not included in the AHS, and therefore this study

does not provide information for this report.
**III. RESULTS/DISCUSSI**  **ON a.**  **IDS (Incident Data System)** OPP’s ID S includes reports of alleged human health incidents from various sources, including mandatory

Federal Insecticide, Fungicide and Ro denticide Act (FIFRA) Section 6(a) (2) reports from registrants, other federal and state health and environmental agencies , and individual consumers. Since 1992, OPP has compile d these reports in IDS. IDS contain s reports from across the U.S. and most incidents have all relevant product information recorded. ReportsPage 3 of 6

submitted to the IDS represent anecdotal reports or allegations only , unless otherwise stated in the report. IDS records incidents in one of two modules: Main IDS and Aggregate IDS:

o Main IDS contains incidents resulting in higher severit y outcomes and provides more detail with regard to case specific. This s ys tem stores incident data for death, major and moderate incidents, and it includes information about the location, date and nat

ure of the incident. Main IDS incidents involving only one pesticide are considered to provide more certain information about the potential effects of exposure 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 onl y as counts in what are aggregate summaries
. For the M ain IDS, from January 1, 200 7 to September 13, 2012, there w as 1 incidents reported for single chemical only

in the data

base and 10 additional incidents reported involving more than one chemical. These incidents were classified as moderate severit y . In the single chemical incident, an adult male became ill after blowing into a hose to clear the product causing the product to blow into his face. He went to the emergency room and was admitted. No further information is available (Table 1)
. In A ggregate IDS , from January 1, 200 7 to September 13 , 2012 , there were 20 reported incidents involving trifloxy strobin
.

**b. NIOSH**  **SENSOR** The NIOSH

- led SENSOR

- Pesticides database covers 11 states from 1998
- 2008, although reporting varies from state to state. Cases of pesticide

- related illnesses are ascertained from a variet y of sources, including: reports from local Poison Control Ce nters, state Department of Labor workers’ compensation claims when reported by phy sicians, reports from Stat e Departments of Agriculture, and ph ys ician reports to s tate Departments of Health . Although both occupational and non

- occupational incidents are included in the database, SENSOR

- Pesticides focuses on occupational pesticide incidents, and is of particular value in providing that information. A state SENSOR contact specialist attempts to follow

- up with cases and obtains medical records to verify sy mptoms, circumstances surrounding the exposure, severity , and outcome. Using standardized protocol and case definitions derived from poison center reporting, SENSOR
- Pesticides coordinators at S tate Departments of Health enter the incident interview description provided b y the case , medical report, phy sician into the data s ys tem
. Inorder to be included in the database, all SENSOR

- Pesticides cases, including low severity cases, must have at least two adverse health effects. In S ENSOR
- Pesticides from 199 8 to 2008 , 11 cases , stemming from 10 exposure events, involving triflox ys trobin were identified. Two cases were exposed to a single active ingredientPage 4 of 6

whereas the other 9 invol ve exposure to mul tiple active ingredients. Two cases are moderate in severit y and 9 cases are low severit y. Of the 11 cases, s ix reported respiratory s ymptoms, four reported dermal symptoms, four reported gastrointestinal sy mptoms, and three reported ocular s ymptoms. It is noted that two of reported ocular s ymptoms despite wearing the label

- required ey e protection ; however , both of these cases involved the application of multiple active ingredients. 1 One case narrative states “ P atient was spraying on hop field, wearing full protection: half face respirator, rubber boots, rubber gloves, raingear and goggles. But next day around 11:00 am he experienced ocular sy mptoms. He doesn't know how he got exposed.” The second case narrative states “A 33 y/ o male developed ocular s ymptoms after appl yi ng pesticides and fertilizers in a tank mix. He was wearing eye protection
. ” Both cases were classified as low severity
. Eight of the 11 cases are coded as “ work

- related ” . Of these, seven cases resulted from occupational pe sticide exposure. Specifically , five of these cases are pesticide applicator exposures , one involved a farmworker thinning apples, and one case was coded “ work

- related ” but no further detail provided. One of the two moderate severit y cases involved a sin gle active ingredient. This case occurred in California in 2008 and involved application of Flint Fungicide (EPA reg # 00026400777). This case was spraying Flint Fungicide from a tractor, reported wearing all required PPE, but he blew into a hose to clear it, and the product contacted him. He experienced gastrointestinal sy mptoms and was hospitalized for one day and reported missing at least one day of work. The second moderate severity case occurred in Washington in 2005 and involved a 33 y ear old male applicator who went to a clinic complaining of neurological and gastrointestinal sy mptoms after applying Flint Fungicide. This case, however, was applying Axinphosmethyl 50W in addition to Flint Fungicide.

**c. AHS**  The AHS is a high quality , prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. The AHS includes private and commercial pesticide applicators and their spouses . If there are AHS findings relevant to a particular pesti cide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, if appropriate, full y reviewed in the risk assessment phase of the process
. The AHS includes information on use of 50 different pesticide active ingredients commonly used in agriculture. Triflox ys trobin is not included in the AHS, and therefore this study does not provide information for this report. **IV. CONCLUSION** 

1 In both cases where the applicator reported ocular symptoms despite wearing the label

- required PPE; multiple products w ere implicated. Further investigation identifies an eye protection requirement on labels of the non

triflxoystrobin products. Both of these cases also used pro ducts containing sulfur which do have eye protection requirements on the labels.Page 5 of 6

Based on the low frequency and severity

of incident cases reported for trifloxy strobin in both IDS and NIOSH SENSOR, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered, addit ional analy sis will be included in the risk assessment.Page 6 of 6

Table 1. Main IDS Incident involving Triflox ys trobin as a single chemical **Hum an**  **Incident Chemical: Trifloxystrobin**  **PC Code: 129112 Incident**  **Package Report**  **Incident**

**Date Location**  **Country Reg**  **Number Product** 

**Nam e**  **Exposure**

**Severity Codes**  **Incident Description**
020180
- 00059 5/24/2008 CA US 000264
- 00777 FLINT

FUNGICIDE HC An adult male became ill after blowing into a hose to clear the product causing the product to blow

into his face. He w ent to ER and was admitted. *H C
- Hum an Moderate ( if the person alleged or exhibited symptoms more pronounced, more prolonged or of a more systemic nature than minor symptoms; and involved some form of treatment, even though symptoms were not life threatening and the person returned to his/her pre

- exposure state of health with no additional residual disability)