title: Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.
abstract: Biomonitoring of pyrethroid exposure is largely conducted but human toxicokinetics has not been fully documented. This is essential for a proper interpretation of biomonitoring data. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers have been documented and compared with previously available kinetic data following permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of cypermethrin acutely. The same volunteers were exposed to permethrin earlier. Blood samples were taken over 72 h after treatment and complete timed urine voids were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3-phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and permethrin, were quantified. Blood and urinary time courses of all three metabolites were similar following cypermethrin and permethrin exposure. Plasma levels of metabolites reached peak values on average ≈ 5-7 h post-dosing; the elimination phase showed mean apparent half-lives (t½ ) for trans-DCCA, cis-DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing. Corresponding mean values obtained from urinary rate time courses were peak values at ≈ 9 h post-dosing and apparent elimination t½ of 6.3, 6.4 and 6.4 h for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data confirm that the kinetics of cypermethrin is similar to that of permethrin in humans and that their common biomarkers of exposure may be used for an overall assessment of exposure.
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, PO Box 6128, Main Station, Montreal, Quebec, Canada, H3C 3J7.
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, PO Box 6128, Main Station, Montreal, Quebec, Canada, H3C 3J7.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coté
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, PO Box 6128, Main Station, Montreal, Quebec, Canada, H3C 3J7.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouchard
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007306:Insecticides / Q000097:blood / Q000652:urine; D008297:Male; D026023:Permethrin / Q000097:blood / Q000652:urine; D011722:Pyrethrins / Q000097:blood / Q000652:urine; D066007:Toxicokinetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007306:Insecticides; D011722:Pyrethrins; C017160:cypermethrin; D026023:Permethrin
keywords: 3-PBA; DCCA; Exposure biomarkers; cypermethrin; oral exposure; permethrin; pyrethroids