title: Relative potencies for acute effects of pyrethroids on motor function in rats.
abstract: The prevalence of pyrethroids in insecticide formulations has increased in the last decade. A common mode-of-action has been proposed for pyrethroids based on in vitro studies, which includes alterations in sodium channel dynamics in nervous system tissues, consequent disturbance of membrane polarization, and abnormal discharge in targeted neurons. The objective of this work was to characterize individual dose-response curves for in vivo motor function and calculate relative potencies for eleven commonly used pyrethroids. Acute oral dose-response functions were determined in adult male Long Evans rats for five Type I (bifenthrin, S-bioallethrin, permethrin, resmethrin, tefluthrin), five Type II (beta-cyfluthrin, lambda-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate) and one mixed Type I/II (fenpropathrin) pyrethroids (n = 8-18 per dose; 6-11 dose levels per chemical, vehicle = corn oil, at 1 ml/kg). Motor function was measured using figure-8 mazes. Animals were tested for 1 h during the period of peak effects. All pyrethroids, regardless of structural class, produced dose-dependent decreases in motor activity. Relative potencies were calculated based on the computed ED30s. Deltamethrin, with an ED30 of 2.51 mg/kg, was chosen as the index chemical. Relative potency ratios ranged from 0.009 (resmethrin) to 2.092 (esfenvalerate). Additional work with environmentally-based mixtures is needed to test the hypothesis of dose-additivity of pyrethroids.
authors.affiliation: National Research Council, Research Triangle Park, North Carolina 27711, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wolansky
authors.forename: C
authors.initials: C
authors.lastname: Gennings
authors.forename: K M
authors.initials: KM
authors.lastname: Crofton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D011722:Pyrethrins / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute
chemical_list: D007306:Insecticides; D011722:Pyrethrins