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DOSE-DEPENDENT DISTRIBUTION AND ELIMINATION OF CIS- AND TRANS-PERMETHRIN IN THE RAT
Citation:
SCOLLON, E., J. M. STARR, M. F. HUGHES, R. TORNERO-VELEZ, H. M. WHEELER, D. G. ROSS, AND M. J. DEVITO. DOSE-DEPENDENT DISTRIBUTION AND ELIMINATION OF CIS- AND TRANS-PERMETHRIN IN THE RAT. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
This work tested the hypothesis that the disposition of permethrin into blood, brain, liver and fat compartments in the rat is dose-dependent.
Description:
Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, use of pyrethroids has increased. The potential for increased human exposure to pyrethroids has prompted pharmacokinetic research to better characterize exposure and risk. This work tested the hypothesis that the disposition of permethrin into blood, brain, liver and fat compartments in the rat is dose-dependent. Adult male Long Evans rats were orally gavaged with permethrin (40:60 cis:trans) in corn oil at 1 ml/kg. Dose-tissue concentration relationships were assessed by dosing rats with 1, 3, 10, 30 or 100 mg/kg and sacrificing at 2 hr (n=4 rats/dose). Tissues were removed, extracted and analyzed by HPLC/MS/MS for parent isomer. Increasing doses resulted in increasing tissue concentrations. Blood and brain concentrations were not different. Permethrin tissue concentrations over time in blood, brain, fat and liver were also assessed. Rats were dosed with 1 or 10 mg/kg and sacrificed at 1, 2, 3, 4, 6, 12, 24, 36 or 48 hr (n=4 rats/time point). Permethrin concentrations were greater in rats dosed with 10 mg/kg than 1 mg/kg in all tissues. Elimination patterns were similar for both isomers. However, area under the curve (AUC) was greater for cis- relative to trans-permethrin in all tissues. Relative rankings of AUC in each of the tissues were fat>blood>brain>liver. AUCs were 10-fold greater in the 10 mg/kg than 1 mg/kg rats for blood, fat and liver. However, trans-permethrin concentrations in the brain were not different between the dose levels (p>0.05). This work demonstrates permethrin tissue concentration is dose-dependent. However, brain trans-permethrin was independent of dose in this study. Furthermore, the fat and liver compartments contained the highest and lowest permethrin concentrations, respectively. (This abstract does not represent EPA policy).