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Toxicokinetics of the pyrethroid insecticide bifenthrin in blood and brain of the rat
Citation:
ROSS, D., J. M. STARR, B. C. EDWARDS, J. Hutchinson, M. J. DeVito, AND M. F. HUGHES. Toxicokinetics of the pyrethroid insecticide bifenthrin in blood and brain of the rat. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
This abstract describes toxicokinetics of the pyrethroid insecticide bifenthrinin blood and brain of the rat. Concentration of bifenthrinin in blood increased proportionately with dose, based on area under the curve data. In brain, there was a disproportionate increase in the concentration of bifenthrin with dose.
Description:
Bifenthrin is a pyrethroid insecticide and human exposure to it can occur by oral, pulmonary and dermal routes. Pyrethroids are neurotoxic agents and it is generally believed that the parent pyrethroid is the toxic entity. The objective of this study was to assess the toxicokinetics of blfenthrlnin blood and brain of the rat. Adult male long Evans rats were administered bifenthrin by oral gavage in corn oil (1 ml/kg) at dose of 0.3 or 3 mg/kg, Animals were sacrificed from 0.25 to 48 h after dosing and blood and brain were removed. Tissues were extracted and analyzed for bifenthrin by HPlC/MS/MS. For 0.3 mg/kg bifenthrin in blood, the maximal concentration (Cmax) was 86.1 ng/ml, the time of maximal concentration (Tmax) was 1 h and the area under the curve from 0 to 48 h (AUCo-48h) was 208.5 ng-h/ml. For 3 mg/kg bifenthrin in blood, the Cmax was 946.5 ng/ml, the Tmax was 1 h and the AUCo-48h was 2118.6 ng-h/ml. For 0.3 mg/kg bifenthrin in brain, the Cmax was 11.9 ng/g, the Tmax was 2 h and the AUCo-48h was 78.4 ng-h/g. For 3 mg/kg bifenthrin in brain, the Cmax was 142.8 ng/g, the Tmax was 6 h and the AUCo48h was 2729.8 ng-h/g. There was a proportional increase in blood bifenthrin AUCo-48h with dose. However, there was a disproportionate increase in brain bifenthrin AUCo-48h with dose. This suggests that there may be either greater uptake or decreased clearance of bifenthrin in brain, which may explain the dose-dependent neurotoxic response of this insecticide in the rat. (This abstract does not represent USEPA policy.)