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RELATIVE POTENCIES FOR ACUTE EFFECTS OF PYRETHROIDS ON MOTOR FUNCTION IN RATS.
Citation:
Wolansky, M. J., M J. DeVito, C. Gennings, W. H. Carter, R. A. Carchman, AND K M. Crofton. RELATIVE POTENCIES FOR ACUTE EFFECTS OF PYRETHROIDS ON MOTOR FUNCTION IN RATS. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
A proposed common mode-of-action for pyrethroid insecticides, includes alterations in sodium channel dynamics in nervous system tissues, consequent disturbance of neuronal membrane polarization, abnormal discharge in targeted neurons, and changes in nervous system function. The present work provides in vivo functional data for use in the cumulative risk assessment of pyrethroids. This work characterized dose-response curves and calculated relative potencies for motor dysfunction produced by 11 commonly used pyrethroids. Five Type I (bifenthrin, s-bioallethrin, permethrin, resmethrin, tefluthrin) and six Type II compounds (beta-cyfluthrin, lambda-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin) were tested in adult male Long Evans rats. Acute oral dose-response curves for motor function were characterized for each chemical [n=7-12 per dose, 6-8 dose levels per chemical, 1 ml/kg corn oil vehicle]. Motor function was measured using figure-8 mazes. Animals were tested for one hr during the period of peak effects (between 1 and 4 hour after dosing, as determined in pilot studies). All pyrethroids, regardless of structural class, produced dosage-dependent decreases in motor activity. Individual chemical ED30s were calculated using a 'flexible single-chemicals-required' method of analysis applicable to chemicals with differing maximum-effect asymptotes (Gennings et al., 2004). Relative potencies were calculated based as the ratio of each chemical's ED30 to the ED30 of the index chemical, deltamethrin (ED30 ~3 mg/kg). Preliminary data analyses revealed ED30s that ranged from 1.4 to 210 mg/kg and estimations of the relative potency ratios for the pyrethroids ranged from 0.5 to 70. These data suggest a common toxicity endpoint for effects on general motor function in rats that can be used for assessing cumulative risk. Future work will test the ability of this common endpoint to predict additivity of pyrethroid mixtures. (This is abstract does not necessarily reflect USEPA policy)