Physiologically Based Pharmacokinetic and Pharmacodynamic (PBPK/PD) Model for Interpreting Dermal Dose and Disposition of Organophosphorus Insecticides. C. C. Dary, J. B. Knaak, F. W. Power, E. J. Furtaw, and J. N. Blancato, US Environmental Protection Agency, NV, SUNY, Buffalo
Physiologically-based pharmacokinetic/ pharmacodynamic (PBPK/PD) models are particularly suited for interpretation of cumulative risk via the dermal route for which aggregate exposure must be assessed for chemicals having a common mechanism of toxicity. To this end, a quantitative structure-activity relationship (QSAR) database was compiled containing physicochemical descriptors and percutaneous absorption, pharmacokinetic, and metabolic parameter estimates, for 31 organophosphorus (OP)insecticides. The molecular descriptors were obtained using molecular modeling software (HyperChem® ChemPlus™, Accord/Excel 2001©, Accelrys Inc.,and QSARis™). Percutaneous absorption and metabolic parameter estimates were obtained from the published literature. Results indicate that QSAR techniques can provide reasonable estimates of metabolic and skin absorption parameter values for individual OP insecticides and mixtures for use in cumulative risk assessment. This approach holds great promise for advancing our understanding of a dynamic source-to-exposure-to-dose process involving aggregate exposure of infants and children to a broad range of OP insecticides with differing chemical structures.
The U.S. EPA Office of Research and Development funded this research. The abstract was reviewed and approved. The oral presentation has not been reviewed. Mention of trade names or commercial products does not constitute endorsement.
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