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Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats
Citation:
Moser, Ginger, Z. Liu, C. Schlosser, T. Spanogle, A. Chandrasekaran, AND Kathy Mcdaniel. Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 313:97-103, (2016).
Impact/Purpose:
This manuscript presents dose-response data for decreased locomotor activity and increased incidence of salivation following acute administration of lambda- and gamma-cyhalothrin in rats. In the same subjects, brain and plasma levels were determined for each isomer. Administered dose correlated well with tissue concentrations, which furthermore showed good correlations with activity changes and salivation. Gamma-cyhalothrin, an enriched isomer, was about two-fold more potent than lambda-cyhalothrin, which contains about 43% of the gamma isomer. Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of neurobehavioral effects. These data are important to the EPA OPP to inform their risk assessment deliberations.
Description:
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 1.5 h 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 (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/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 was 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 are a good predictor of behavioral effects.
