Citation:

OKINO, M. S., G. CHAPA, K. W. THOMAS, G. L. ROBERTSON, C. B. THOMPSON, A. TSANG, FRED W. POWER, J. B. KNAAK, AND C. C. DARY. USE OF PHARMACOKINETIC MODELS TO ASSESS OCCUPATIONAL AND RESIDENTIAL PESTICIDE EXPOSURE. Presented at International Society for Exposure Analysis Conference, Tucson, AZ, October 30 - November 03, 2005.

Impact/Purpose:

The overall purpose of the Pesticides in Young Children - Border States program is to describe the relationship of health outcomes in children along the United States and Mexico border to repeated pesticide exposures via multiple sources and pathways. The current effort will conduct additional phase II studies and analyze the data to identify and address critical questions about three major areas: (1) the applicability of pesticide biomarkers for use as markers of exposure, (2) the predictive capability of quesionnaires for estimating exposure, and (3) identification of the most appropriate cohorts to be included in the Phase IIIb studies.

Description:

Urinary biomarker measurements were analyzed using a dynamic pharmacokinetic model. The dynamic model provided the structure to link spot urine samples with corresponding exposure and absorbed dose. Data from both occupational and residential studies were analyzed. In the Agricultural Health Study/Pesticide Exposure Study, applicators who sprayed either 2,4-D or chlorpyrifos provided a composite urine sample for the 24-hour period following the day of application and a first-morning void three days following the event. Dermal exposure was assumed to occur over the period spent mixing, loading, and applying the chemical. Following the application event, a subset of participants also provided 24-hour urine samples for 5 consecutive days. The additional urine measurements provided a means to evaluate the dose estimates for the applicators. Some applicators conducted more than one application event during the 5-day urine collection period. For applicators without additional exposure events, the absorbed dose estimates calculated from spot urine samples were within a factor of 2 of the absorbed dose calculated from total urine collection. The scenario uncertainty and the difference compared to total urine collection were higher for applicators with confounding exposure events.

The agreement within a factor of 2 for pesticide applicators without confounding exposure events provided a basis to apply a model-based analysis to residential settings, where spot urine samples were collected. Single spot urine samples were collected in studies of several populations along the U.S.-Mexico border and analyzed for pesticide urinary metabolites. Exposure scenarios were constructed based on questionnaire responses that indicate potential exposure events. Absorbed doses were calculated, and the dose uncertainty was characterized based on quantification of the uncertainty in the modeled exposure scenarios.

Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.

Record Details: