Dose-dependent toxicokinetics of permethrin in rats: A comparative analysis of four exposure levels

Pyrethroid metabolites are used as biomarkers of human exposure but the influence of exposure levels on their toxicokinetics remains unclear. We examined the effect of administered dose on the toxicokinetics of permethrin metabolites. Sprague-Dawley rats were administered single gavage doses of permethrin (trans/cis 60:40) at 0.004, 0.04, 0.4 and 4 mg/kg bw. Serial blood, urine and fecal samples were collected. Trans- and cis-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acids (trans/cis-DCCA), 3-phenoxybenzoic acid (3-PBA), and 4-hydroxy-3-phenoxybenzoic acid (4-OH3PBA) were quantified. A clear effect of dose on metabolite profiles in blood was observed: appearance rate increased with doses, while terminal elimination half-life and mean residence time decreased. In urine, the predominant elimination route, fraction of metabolites recovered declined significantly at 0.4 and 4 mg/kg bw, whereas minor fecal excretion pathway was unaffected by dose. These findings show that permethrin dose governs both rates and extent of metabolite disposition, with key implications for exposure reconstruction from biomonitoring data.