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USE OF PHARMACOKINETIC MODELING TO DESIGN STUDIES FOR PATHWAY-SPECIFIC EXPOSURE MODEL EVALUATION
Citation:
Hu, Y., G G. Akland, E. D. Pellizzari, M Berry, AND L J. Melnyk. USE OF PHARMACOKINETIC MODELING TO DESIGN STUDIES FOR PATHWAY-SPECIFIC EXPOSURE MODEL EVALUATION. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 112(17):1697-1703, (2004).
Impact/Purpose:
The purpose of this research is to reduce uncertainties in exposure assessments of young children by improving EPA's ability to measure exposures in the context of aggregate and cumulative exposure assessments. The general objective of this research is to support FQPA children's exposure assessment efforts by improving procedures and reducing uncertainty in measurements for dietary exposure of young children, a critically needed area for improved risk assessment. Specifically, this research will evaluate a protocol and companion model for measuring or otherwise assessing the combined dietary intake of a young child as influenced by pesticides, or other environmental contaminants, which contaminate their foods during the eating process (indirect ingestion exposure). This research will continue to develop the important factors which are needed to characterize excess intake of pesticides by young children. Specifically, the research will measure pesticide surface transfer efficiencies for food contacts with surfaces and eating activity patterns of young children that define the frequency of contacts with contaminated surfaces. A series of reports/products are anticipated by the end of FY05.
Description:
Validating an exposure pathway model is difficult because the biomarker, which is often used to evaluate the model prediction, is an integrated measure for exposures from all the exposure routes/pathways. The purpose of this paper is to demonstrate a method to use pharmacokenetic modeling and computer simulation to guide the design of field studies to validate pathway models. The children's dietary intake model was discussed in detail as an example. Three important aspects were identified for a successful design to evaluate the children's dietary intake model: (1) longitudinal design of the study with alternating exposure status for the route/pathway of interest; (2) short biological half-life of the selected chemical; and (3) surface loading of selected chemical at sufficient levels. Exposure from other pathways, such as inhalation and non-dietary ingestion exposure, would not mask the dietary exposure under normal circumstances. This study proposed and demonstrated the use of a pharmacokinetic model in the design of a study to evaluate a path-specific exposure model, which has not been explored previously.