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In vitro and in vivo experimental data for development and use of pharmacokinetic models for in vitro to in vivo extrapolation of pyrethroid insecticides
HUGHES, M. F., M. P. Chan, J. M. STARR, T. SHAFER, E. J. Scollon, AND M. J. DeVito. In vitro and in vivo experimental data for development and use of pharmacokinetic models for in vitro to in vivo extrapolation of pyrethroid insecticides. Chapter 15, J.B. Knaak, C. Timchalk and Tornero-Velez (ed.), Parameters for Pesticide QSAR and PBPK/PD Models for Human Risk Assessment. American Chemical Society, Washington, DC, , 229-241, (2012).
Pyrethroids are a class of neurotoxic synthetic insecticides. Exposure to pyrethroids can be widespread because of their use in agriculture, medicine, and in residential homes and schools. Our studies are focused on generating in vitro and in vivo data for the development of physiologically-based phannacokinetic models (PBPK) for pyrethroids. Using deltamethrin as a model compound, in vitro metabolic and in vivo tissue time-course data in the rat were determined and used in development of a PBPK model. This model adequately simulated the in vivo blood time course data after intravenous and oral administration of deltamethrin. The model was then used to predict the in vivo administered dose of deltamethrin that would result in blood concentrations equal to in vitro media concentrations of deltamethrin that reduce hippocampal cell firing. The in vitro media concentrations that resulted in a 10 and 50% decrease in cell firing were 10 times lower than the predicted in vivo concentrations, suggesting that the in vitro system does not account for the kinetic differences between the two systems.
The chapter describes data needs for development of a PBPK model for deltamethrin, how the model simulates in vivo deltamethim data, and how it can be used for in vitro to in vivo extrapolation.
Record Details:Record Type: DOCUMENT (BOOK CHAPTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
INTEGRATED SYSTEMS TOXICOLOGY DIVISION