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THE DEVELOPMENT OF PHARMACOKINETIC PARAMETERS FOR PREDICTING THE EFFECTS OF PESTICIDES
Impact/Purpose:
EPA's Office of Pesticide Programs (OPP) has identified research to improve use of biological data, including pharmacokinetic data, in risk assessments as one of its highest priorities. The objective of this research is to develop and improve physiologically based pharmacokinetic parameters for predicting the effects of pyrethroid pesticides. Efforts will help characterize exposure-dose relationships, and results can be applied by OPP to identify and prioritize risks associated with pesticide exposures, thereby reducing uncertainty in risk assessment under the Food Quality Protection Act (FQPA). Through the use of intermittent exposures, an additional contribution of this research will be in the area of cumulative risk.
Description:
This research involves the development and improvement of pharmacokinetic data for predicting the effects of exposure to pyrethroid pesticides. Pharmacokinetics address the exposure-dose relationship in an organism, and resulting data are useful for making extrapolations between responses observed in animals and humans. We are developing an experimental database of pharmacokinetic parameters for pyrethroid pesticides following oral and dermal exposures in rodents. Neurotoxicological endpoints of such exposures are being evaluated. Our neurotoxicological results will be integrated with the pharmacokinetic data in order to conduct pharmacodynamic modeling of dose-response relationships. Ultimately, we will use these models to study interactions of binary mixtures and intermittent exposures to pyrethroid pesticides. Our research will help identify key parameters for pharmacokinetic and pharmacodynamic models for interspecies extrapolation, they will provide information on the use of pharmacokinetic data in risk assessments, and they will assist in characterizing cumulative risks.