UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: August 19,2010

SUBJECT: Piperonyl Butoxide (PBO): Review ofHurnan Incidents

PC Code: 067501 Decision No.: NA Petition No.: NA Risk Assessment Type: NA TXRNo.:NA MRID No.: NA DP Barcode: D380374 Registration No.: NA Regulatory Action: NA Case No.: NA CAS No.: 51-03-6 40 CFR:NA

FROM: ShannaRecore, Industrial Hygienist

# J1~~ l'tl
Khin 00, M.D., MPH, Environmental Health

## Scientis~~'
< Ver.Apr.201O

Toxicology and Epidemiology Branch Health Effect Division (7509P)

THROUGH: Mary Manibusan, Branch Chief 

# Va--

Toxicology and Epidemiology Branc Health Effects Division (7509P)

TO: Rebecca Daiss, RiskAssessor Risk Assessment Branch IV Health Effects Division (7509P) and K. St. Clair, CRM Risk Management & Implementation Branch IV Pesticide Re-evaluation Division (7508P)

I. CONCLUSION

Page 1 of3In general, amoderately large number ofincidents have been reported involving piperonyl butoxide (PBO). Although none ofthe incidents involved cases reported for products containing PBO present as a single chemical only, human incident data may warrant further analysis for the risk assessment and/or risk management ofPBO. The Agency will continue to monitorthe incidentinformation and ifa concern is triggered, additional analysis will be included in the risk
assessment.



### II. ACTION REQUESTED

This review is intendedto fulfill our requirementto docket summaries ofincident data that were reported to the Agency, as well as to ensure human incident data, and the Agricultural Health Study are part ofthe problem formulation phase ofregistrationreview. Reports ofadverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are largely self-reported and therefore, generally speaking, neither exposure to apesticide or reported symptom (or the connectionbetween the two) is validated. Typically, causation cannotbe determinedbased on incident data. However, incidentinformation can be an importantfeedback loop to the Agency - incidents ofsevere outcome, or a suggested pattern or trend among less severe incidents can signal the Agency to further investigate aparticular chemical or product. 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.



### III. BACKGROUND

For this evaluation, boththe OPP Incident Data System (IDS) and the Centers for Disease Control and PreventionlNational Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel EventNotification System for Occupational Risk-Pesticides (SENSOR) database were consulted for pesticide incident data on the active ingredient PBO. Additionally, the Agency is looking to include findings from the Agricultural Health Study (AHS), beginning with the problem formulation phase ofregistration review. The purpose ofthe database searches is to identify potential patterns on the extent and severity ofthe health effects attributed to PBO exposure. The 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 compiles these reports in IDS. IDS contain reports from across the U.S. and most incidents have all relevantproductinformationrecorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in the report. The NIOSH SENSOR database covers 12 states from 1998-2006, althoughreporting varies from state to state (the database includes a total of 10,659 cases). Pesticide-related incidents are collected from Department ofLabor workers' compensation claims when reported by physicians, reports from State Departments ofAgriculture, from poison control centers and from State Departments ofHealthbased on reports by physicians suspecting pesticide exposure. Althoughboth occupational and non-occupational incidents are included in the database, SENSORfocuses on occupational pesticide incidents, and is ofparticular value in providing that information. A state SENSOR contact specialist does follow-up with workers and obtains medical records to verify symptoms, circumstances surrounding the exposure, severity, and outcome. Using standardizedprotocol and case definitions, derived from poison center reporting, SENSOR coordinators at State Departments ofHealth enter the incidentinterview description provided by the worker, medical report, physician and patient into the SENSOR data system, accessible to participating states and EPA. The AHS is a high quality, prospective epidemiology study evaluating the link betweenpesticide use and various health outcomes Page 2 of3including cancer. The AHS includes private and commercial pesticide applicators and their spouses. Ifthere are AHS findings relevant to aparticularpesticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, ifappropriate, fully reviewed in the risk assessment phase ofthe process. The AHS includes information on use of50 differentpesticide active ingredients commonly used in agriculture.



### IV. RESULTSIDISCUSSION

IDS records incidents ofgenerally high severity in more detail, in software which we call the main Incident Data System. This system stores incident data for death, major and moderate incidents, and it includes more details aboutthe location, date and nature ofthe incident. The less severe human incidents are reported by registrants as counts we call aggregate summaries and recorded in separate software. For IDS aggregate summaries, from 2000 to May 25, 2010, there are 5542 cases reported for PBO. Because it falls within the categories reported as counts (which includes minor, unknown or no effects), there is no unique reportthat provides details about the incident and single chemical incidents are not distinguished from multiple chemical incidents. For the main IDS, from 2000 to May 25,2010, there are 1227 cases reported for products containing PBO and another active ingredient.

For NIOSH SENSOR from 1998 to 2007, 1168 cases were identified for products that contain both PBO and another active ingredient.

None ofthe incident cases, for IDS or NIOSH SENSOR, were reviewed because none involved

cases reported for products containing PBO present as a single chemical only. Only cases involving the single chemical only are reviewed, as they provide more certain information about the potential effects ofPBO exposure. However, it should be noted that there are no products that contain only PBO because PBO acts as a synergist which enhances the pesticidal properties ofother active ingredients, such as pyrethrins and synthetic pyrethroids. Although PBO is well known to inhibit microsomal enzymes in insects, evidence indicates that PBO does not effectively act as apyrethroid synergistin mammals (EPA 738-R-06-005, June 2006).

Piperonyl butoxide is not included in the AHS, and therefore not considered in this report.

In general, a large number ofincidents have been reported involving PBO; however, PBO is contained in hundreds ofend use products in combination with other active ingredients. Although none ofthe incidents involved cases reported for products containing PBO present as a single chemical only, human incident data may warrant further analysis for the risk assessment and/or risk management ofPBO. The Agency will continue to monitorthe incidentinformation and ifa concern is triggered, additional analysis will be included in the risk assessment.

Page 3 of3