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BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE
Citation:
SCOLLON, E., J. M. STARR, M. F. HUGHES, K. M. CROFTON, M. J. WOLANSKY, AND M. J. DEVITO. BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmacokinetic research to better characterize exposure and risk. This work tested the hypothesis that blood and brain pyrethroid concentrations are predicitive of neurotoxic effects. Adult male rats received acute oral bifenthrin in corn oil vehicle. Exposures for the 4 and 7 hr 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 or 8/group). Motor activity was measured in figure 8 mazes for 1 hr at 4- and 7-hr post exposure. Whole blood and brain tissue were collected immediately following behavioral testing. Tissues were vortex extracted in hexane, eluted through 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. Combining the 4- and 7-hour groups, the relationship between whole blood or brain bifenthrin concentrations and motor activity were described using a Hill model. Model fits to the blood data (R2=0.68, p<0.0001) estimated ED50 of 323 ng/ml tissue with a slope factor of 1.4. Model fits to the brain concentration data (R2=0.69, p<0.0001) estimated the ED50 of 219 ng/g with a slope factor of 2.3. These data suggest that blood or brain concentrations can be used as a dose metric to estimate effects on motor function, and that this relationship is independent of time of exposure. (This abstract does not represent EPA policy).