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Pharmacokinetic Evaluation of Permethrin Enantiomers in Rat Tissues
Citation:
SEY, Y. M., R. A. HARRISON, E. M. ULRICH, AND M. J. DEVITO. Pharmacokinetic Evaluation of Permethrin Enantiomers in Rat Tissues. Presented at 2009 Annual Society of Toxicology meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
Pyrethroids are neurotoxic insecticides that are used in agricultural, residential, and public health activities. The ubiquitous exposures to pyrethroids require understanding of the risk posed to human and ecological health. Since identification of the active toxicophore is essential for improved risk analysis, understanding the active stereoisomer is not only important but remains largely unresolved.
Description:
Pyrethroids are neurotoxic insecticides that are used in agricultural, residential, and public health activities. The ubiquitous exposures to pyrethroids require understanding of the risk posed to human and ecological health. Since identification of the active toxicophore is essential for improved risk analysis, understanding the active stereoisomer is not only important but remains largely unresolved. While evaluation of the exposure, toxicity and disposition of pyrethroid isomers has been examined at the diastereoisomer level, information at the enantiomer level is limited. Thus, this study aimed to develop a LC/MS method to identify and quantitate all four permethrin stereoisomers in rat tissues for improved risk analysis. Adult male Long Evans rats were exposed to a single dose of permethrin (40:60% cis:trans) orally at 10 mg/kg or intravenously (IV, jugular vein) at 5 mg/kg body weight. Serial blood samples were collected over 24 hrs. Permethrin isomers were extracted from samples, cleaned by solid phase extraction, dried, and reconstituted before analysis by LC/MS. Stereoisomer separation was achieved on a Chiralcel-OJ stationary phase with 98:2 hexane:ethanol mobile phase at 0.8 ml/min. Detection of selected ions was by atmospheric pressure chemical ionization mass spectrometry in the positive mode. For both blood and brain, the limit of quantitation was between 50-150 pg/µl per permethrin enantiomer. Matrix based calibration curves were linear for each enantiomer over a range of 50-5000 pg/µl with regression coefficient exceeding 0.99. Initial findings indicate that the IV and oral area under the plasma concentration time curve (AUC) for the cis- isomers was greater than the trans-, indicating slower degradation/elimination of cis-permethrin. However, there was no difference in the AUC among the cis- and trans-enantiomers. These studies suggest that the pharmacokinetics of the permethrin diastereomers are different but at the enantiomeric level, the pharmacokinetics are similar. (This abstract does not reflect EPA policy).