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Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat
Citation:
SCOLLON, E., J. M. STARR, M. F. HUGHES, K. M. CROFTON, M. WOLANSKY, AND M. J. DEVITO. Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 290(1):1-6, (2012).
Impact/Purpose:
This manuscript examined the relationship between blood and brain concentration of the pyrethroid bifenthrin with motor activity in rats. With increased concentration of bifenthrin in these tissues, motor activity in the rats decreased. Correlation was higher with brain concentration.
Description:
Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household products. Due to the phase-out oforganophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain pyrethroid concentrations are predictive of neurotoxic effects. Adult male rats received acute oral bifenthrin dissolved in com oil vehicle. Exposures for the 4 and 7-h testing time points were 0, 0.1, 1, 2, 4, 6, 8, 12, 16 mg/kg and 0, 0.05,0.5, 1,3,4.5,6,9 mg/kg, respectively (n=4-8/group). Motor activity was measured in figure 8 mazes for 1 hr at 4-and 7-hr post exposure. Whole blood and brain were collected immediately following motor activity assays. Bifenthrin was vortex extracted from tissue using 20:80 acetone:hexane, cleaned with silica solid phase extraction cartridges, and analyzed using LC/MS/MS. Limits of quantitation were 100 pg/ml and 150 pg/g for blood and brain. Bifenthrin exposure decreased motor activity in a dose dependent manner. Doses of 3 mg/kg or higher decreased motor activity 20% to 70% of vehicle control levels in both the 4-and 7-hr groups. Motor activity was fit to administered dose, brain and blood bifenthrin concentrations using a Hill model. Whole blood and motor activity fits were different between groups. ED50 and slope factor for the 4-(85 and 3.1) and 7-h (41 and 0.5) groups were estimated. Motor activity and brain concentration fits were not different between groups, and therefore the data were combined. Estimates for ED50 and slope factor were 278 ng/g and 1.6, respectively. These data suggest that blood or brain concentrations can be used as a dose metric to estimate effects on motor function.
