title: Toxicokinetics of permethrin biomarkers of exposure in orally exposed volunteers.
abstract: 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 0.1 mg/kg body weight of permethrin (60:40 trans/cis). Blood samples were withdrawn at fixed periods over 72 h following ingestion and complete timed-urine voids were collected over 84 h post-dosing.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 ≈7 h post-dosing, and elimination appeared monophasic with a mean apparent elimination half-life (t½) of 6.2, 7.1 and 6.5 h, 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 5.7 h. Over the 84 h 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.
authors.affiliation: Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and University of Montreal Public Health Research Institute (IRSPUM), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Mylène
authors.initials: M
authors.lastname: Ratelle
authors.affiliation: Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and University of Montreal Public Health Research Institute (IRSPUM), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Côté
authors.affiliation: Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management, and University of Montreal Public Health Research Institute (IRSPUM), University of Montreal, Roger-Gaudry Building, U424, P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada. Electronic address: michele.bouchard@umontreal.ca.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouchard
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001565:Benzoates / Q000097:blood / Q000652:urine; D015415:Biomarkers; D001711:Biotransformation; D006207:Half-Life; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D026023:Permethrin / Q000493:pharmacokinetics* / Q000633:toxicity*; D055815:Young Adult
chemical_list: D001565:Benzoates; D015415:Biomarkers; D007306:Insecticides; C063165:1-deaza-2-chloro-N(6)-cyclopentyladenosine; D026023:Permethrin; C017618:3-phenoxybenzoic acid; D000241:Adenosine
keywords: 3-PBA; DCCA; Exposure biomarkers; Oral exposure; Permethrin; Pyrethroids