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: Shanna Recore, 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, Risk Assessor

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

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In general, a moderately 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 monitor the

incident information and if a concern is triggered, additional analysis will be included in the risk

assessment.

II. ACTION REQUESTED

This review is intended to fulfill our requirement to 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 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 between the two) is validated. Typically, causation cannot be determined based on

incident data. However, incident information can be an important feedback loop to the Agency -

incidents ofsevere 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.

III. BACKGROUND

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease

Control and PreventionlNational Institute for Occupational Safety and Health (CDC/NIOSH)

Sentinel Event Notification 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 of alleged 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 relevant product information recorded. 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, although reporting

varies from state to state (the database includes a total of 10,659 cases). Pesticide-related

incidents are collected from Department of Labor workers' compensation claims when reported

by physicians, reports from State Departments ofAgriculture, from poison control centers and

from State Departments of Health based on reports by physicians suspecting pesticide exposure.

Although both occupational and non-occupational incidents are included in the database,

SENSOR focuses on occupational pesticide incidents, and is of particular 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 standardized protocol and case definitions, derived from poison center

reporting, SENSOR coordinators at State Departments of Health enter the incident interview

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 between pesticide use and various health outcomes

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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 of

the process and, if appropriate, fully reviewed in the risk assessment phase ofthe process. The

AHS includes information on use of 50 different pesticide active ingredients commonly used in

agriculture.

IV. RESULTSIDISCUSSION

IDS records incidents of generally 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 about the 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 report that 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

of other 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 a pyrethroid synergist in 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 of end 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 monitor the incident information

and if a concern is triggered, additional analysis will be included in the risk assessment.

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