title: A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application.
abstract: Permethrin is a broad-spectrum pyrethroid insecticide and among the most widely used insecticides in homes and crops. Managing the risks for pesticides such as permethrin depends on the ability to consider diverse exposure scenarios and their relative risks. Physiologically based pharmacokinetic models of delta methrin disposition were modified to describe permethrin kinetics in the rat and human. Unlike formulated deltamethrin which consists of a single stereoisomer, permethrin is formulated as a blend of cis- and trans-diastereomers. We assessed time courses for cis-permethrin and trans-permethrin in several tissues (brain, blood, liver, and fat) in the rat following oral administration of 1 and 10mg/kg permethrin (cis/trans: 40/60). Accurate simulation of permethrin in the rat suggests that a generic model structure is promising for modeling pyrethroids. Human in vitro data and appropriate anatomical information were used to develop a provisional model of permethrin disposition with structures for managing oral, dermal, and inhalation routes of exposure. The human permethrin model was used to evaluate dietary and residential exposures in the U.S. population as estimated by EPA's Stochastic Human Exposure and Dose Simulation model. Simulated cis- and trans-DCCA, metabolites of permethrin, were  consistent with measured values in the National Health and Nutrition Examination Survey, indicating that the model holds promise for assessing population exposures and quantifying dose metrics.
authors.affiliation: NERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA. tornero-velez.rogelio@epa.gov
authors.forename: Rogelio
authors.initials: R
authors.lastname: Tornero-Velez
authors.forename: Jimena
authors.initials: J
authors.lastname: Davis
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Scollon
authors.forename: James M
authors.initials: JM
authors.lastname: Starr
authors.forename: R Woodrow
authors.initials: RW
authors.lastname: Setzer
authors.forename: Michael-Rock
authors.initials: MR
authors.lastname: Goldsmith
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chang
authors.forename: Jianping
authors.initials: J
authors.lastname: Xue
authors.forename: Valerie
authors.initials: V
authors.lastname: Zartarian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: DeVito
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
mesh_terms: D000818:Animals; D004032:Diet; D004333:Drug Administration Routes; D004781:Environmental Exposure; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007536:Isomerism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D026023:Permethrin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow; D018570:Risk Assessment; D014018:Tissue Distribution
chemical_list: D007306:Insecticides; D026023:Permethrin