Abstract
PP-29-117 Background/Aims: Surveys in the United States have repeatedly demonstrated the presence and co-occurrence of various pyrethroid pesticides in residences and daycare facilities. Since pyrethroids co-occur and have similar modes of action, pharmacokinetic models will be better informed if data are derived from studies using chemical mixtures. The objective of this research was to develop and apply methods with sufficient sensitivity to determine tissue clearance profiles for a mixture of pyrethroids. Methods: The pyrethroids selected for the mixture (cis- and trans-permethrin, cyfluthrin, cypermethrin, deltamethrin, and esfenvalerate) and their relative proportions in the dosing solution were based on the distribution of pyrethroid residues measured in a nationally representative probability study of 168 child care centers. The pyrethroids were administered orally in a corn oil vehicle to adult male Long-Evans rats. Animals received either a high or low concentration dose and were sacrificed at 1, 2, 4, 8, or 24 hours after dosing. Tissue concentrations in brain, subcutaneous fat, liver, and whole blood were determined. Two replicates of each sample were analyzed to evaluate method reproducibility. Results: There was little variability associated with the replicate tissue results compared with results from different animals at the same dose and time point. The limit of quantitation for all pesticides in all tissues was less than 3 ηg/g and this sensitivity allowed the determination of elimination rate constants for all pyrethroids in blood and brain except the low dose esfenvalerate. Elimination rate constants were also calculated for cis-permethrin, cypermethrin, deltamethrin, and esfenvalerate in liver. The half-life of all pyrethroids in blood, liver, and brain was less than 6 hours while the fat functioned effectively as a storage compartment. Conclusion: The use of empirically based chemical mixtures to determine clearance estimates is feasible and may provide an effective way to relate laboratory kinetic data to human exposure.
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