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In vitro and in vivo experimental data for pyrethroid pharmacokinetic models: the case of bifenthrin
Citation:
HUGHES, M. F., J. M. STARR, E. SCOLLON, AND M. DeVito. In vitro and in vivo experimental data for pyrethroid pharmacokinetic models: the case of bifenthrin. Presented at American Chemical Society 242nd National Meeting, Denver, CO, August 28 - September 01, 2011.
Impact/Purpose:
Our studies are focused on generating in vitro and in vivo data for the development of pharmacokinetic models for pyrethroids. Using bifenthrin as a model compound, the rat and human hepatic intrinsic clearance are 224 and 20 ml/min/kg bw, respectively.
Description:
Pyrethroids are a class of neurotoxic synthetic pesticides. Exposure to pyrethroids has increased due to declining use of other classes of pesticides. Our studies are focused on generating in vitro and in vivo data for the development of pharmacokinetic models for pyrethroids. Using bifenthrin as a model compound, the rat and human hepatic intrinsic clearance are 224 and 20 ml/min/kg bw, respectively. Oxidative in vitro metabolism of bifenthrin predominates over hydrolysis. Peak bifenthrin blood and brain concentrations after oral administration (0.3 and 3 mg/kg) in the rat occur at 1 and 4-6 hr, respectively. The momentary bifenthrin brain concentration correlates with the neurotoxic effect in the rat independent of time. This type of data can be used for development of animal models with extrapolation to human models leading to decreased uncertainties in the risk assessment of the pyrethroids. (This abstract does not necessarily represent USEPA or NIH policy.)