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Pharmacokinetics of a pyrethroid insecticide mixture in the rat
Citation:
Ross, D. G., J. M. STARR, E. SCOLLON, K. M. CROFTON, M. Wolansky, R. Tornero-Velez, M. F. HUGHES, AND M. J. DEVITO. Pharmacokinetics of a pyrethroid insecticide mixture in the rat. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DE, March 06 - 10, 2011.
Impact/Purpose:
The objective of this study was to assess the pharmacokinetics of a pyrethroid mixture.
Description:
Pyrethroid insecticides are used and co-occur in the environment, in residences and day care facilities. Pharmacokinetic models of pyrethroids and assessment of risk from their exposure would be better informed if data are derived from studies using chemical mixtures. The objective of this study was to assess the pharmacokinetics of a pyrethroid mixture. The pyrethroids esfenvalerate (3% of mix), deltamethrin (3%), cyfluthrin (13%), cis-permeethrin (21%), cypermethrin (29%) and trans-permethrin (31%) were administered po in corn oil (1 ml/kg) to adult male long Evans rats. The doses were based on the distribution of pyrethroid residues measured in a nationally representative probability study of child care centers (Tulve et aI., Environ Sci Technol. 2006,40,6269-74). Rats received either a low (11.2 mg/kg) or high (27.4 mg/kg) pyrethroid mixture dose and were sacrificed at 1, 2, 4, 8 or 24 h after dosing. Blood, liver, fat and brain were removed. Tissues were extracted and analyzed for parent chemical by lCIMS/MS. For both doses, the pyrethroid concentrations were highest in fat relative to blood, brain and liver, based on area under the curve from 0 to 24 h (AUCo-24h) and maximal concentration (Cmax) . With dose, the AUCo-24h increased from 4-to 9-fold in blood, 2-to 3-fold in brain, 2-fold in fat and 4-to 6-fold in liver. Cypermethrin and cis-permethrin consistently had the highest AUCo-24h and Cmax in all tissues. trans-Permethrin consistently had lower AUCo-24h and Cmax in all tissues. This suggests that trans-permethrin is metabolized quickly in the rat relative to the other pyrethroids. Determining the pharmacokinetics of a mixture of environmental chemicals such as the pyrethroids is important when assessing the risk to chemicals that have a similar mode of action. (This abstract does not represent US EPA policy.)