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A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application
Citation:
Tornero-Velez, R., J. Davis, E. Scollon, J. Starr, M. Goldsmith, R. Setzer, J. Xue, V. Zartarian, M. DeVito, AND M. Hughes. A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 130(1):33-47, (2012).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL′s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
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 (PBPK) models of deltamethrin 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 10 mg/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 (SHEDS) 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.
URLs/Downloads:
A Pharmacokinetic Model of cis- and trans- Permethrin Disposition in Rats and Humans With Aggregate Exposure Application (PDF, NA pp, 161 KB, about PDF)Toxicological Sciences
