Toxicokinetics of permethrin biomarkers of exposure in orally exposed volunteers

•The time courses of key biomarkers of permethrin exposure were assessed in volunteers.•Permethrin and its metabolites were rapidly cleared from the body.•Time profiles of trans-DCCA, cis-DCCA and 3-PBA concentrations evolved in parallel.•Elimination rate time courses of metabolites in plasma and urine also evolved in parallel.•A steady-state equilibrium should be reached within 3 days of a repeated exposure. Permethrin is a widely used pyrethroid insecticide for which the toxicokinetics of exposure biomarkers in humans is not fully documented. The time courses of key biomarkers of permethrin exposure were thus assessed in accessible biological matrices of orally exposed volunteers. Six volunteers ingested 0.1mg/kg body weight of permethrin (60:40 trans/cis). Blood samples were withdrawn at fixed periods over 72h following ingestion and complete timed-urine voids were collected over 84h post-dosing. Cis-and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acids (cis-and trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were quantified in samples. In plasma, peak concentrations of cis-DCCA, trans-DCCA and 3-PBA were reached about ≈7h post-dosing, and elimination appeared monophasic with a mean apparent elimination half-life (t½) of 6.2, 7.1 and 6.5h, respectively. In urine, elimination rate time courses of cis-DCCA, trans-DCCA and 3-PBA evolved in parallel with plasma, with respective mean apparent elimination t½ of 4.5, 5.4 and 5.7h. Over the 84h period post-treatment, 43–46% of administered molar dose were excreted in urine as trans-DCCA (molar % of trans-permethrin) and 3-PBA. Results show similarities in the different metabolite profiles and a rapid equilibrium between urine and plasma levels; data should help interpret the significance of biological measurements and optimal sampling strategies.