title: Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats.
abstract: Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29mg/kg) compared to λ-cyhalothrin (2.65mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects.
authors: Toxicity Assessment Division, National Health Effects and Environmental Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA. Electronic address: Moser.ginger@epa.gov.
authors: Virginia C
authors: VC
authors: Moser
authors: FMC Corporation, 701 Princeton South Corporate Center, Ewing, NJ, USA.
authors: Zhiwei
authors: Z
authors: Liu
authors: Health Effects Division, Office of Pesticide Programs, Office of Chemical Safety and Pollution Prevention, US Environmental Protection Agency, Washington, DC, USA.
authors: Christopher
authors: C
authors: Schlosser
authors: FMC Corporation, 701 Princeton South Corporate Center, Ewing, NJ, USA.
authors: Terri L
authors: TL
authors: Spanogle
authors: FMC Corporation, 701 Princeton South Corporate Center, Ewing, NJ, USA.
authors: Appavu
authors: A
authors: Chandrasekaran
authors: Toxicity Assessment Division, National Health Effects and Environmental Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA.
authors: Katherine L
authors: KL
authors: McDaniel
mesh_terms: D000818:Animals; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D009570:Nitriles; D011722:Pyrethrins; C037304:cyhalothrin
keywords: Cyhalothrin; Motor activity; Neurotoxicity; Pyrethroids; Toxicokinetics