You are here:
RELATIONSHIPS BETWEEN TISSUE LEVELS OF CARBARYL, A PROTOTYPICAL CARBAMATE PESTICIDE, AND CHOLINESTERASE INHIBITION IN LONG EVANS RATS.
Citation:
HERR, D. W., J. GRAFF, R. S. MARSHALL, AND S. J. PADILLA. RELATIONSHIPS BETWEEN TISSUE LEVELS OF CARBARYL, A PROTOTYPICAL CARBAMATE PESTICIDE, AND CHOLINESTERASE INHIBITION IN LONG EVANS RATS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
As part of an effort to link pharmacokinetics with biochemical and physiological endpoints, the relationships between cholinesterase (ChE) activity and tissue levels of a prototypical N-methyl carbamate pesticide were examined. In a dose-response study, carbaryl (0, 3, 7.5, 15, 30, 50 mg/kg) was administered (po) acutely to adult, male, Long Evans rats in a corn oil vehicle. Subjects were sacrificed 40 min after treatment. Plasma and brain levels of carbaryl were analyzed using HPLC. In a time-course study, carbaryl (30 mg/kg) was administered, and the animals sacrificed 0.5, 1, 2, 4, 6, or 24 h later. Plasma levels of carbaryl were quantified using HPLC. In both studies, erythrocyte (RBC) and brain ChE activity were quantified using a radiometric assay. In the dose-response study, significant inhibition of ChE activity was observed starting at 15 (RBC) and 7.5 (brain) mg/kg. At 40 min, carbaryl was detected in plasma and brain tissues at all doses. Significant dose-related correlations were observed between plasma carbaryl levels and RBC ChE activity, and between brain carbaryl levels and brain ChE activity. Additionally, a good correlation between plasma and brain levels of carbaryl at 40 min was shown. The time-course study showed maximal inhibition of RBC ChE at 0.5 h, returning to control levels by 2 h. Carbaryl could be detected in plasma up to 4 h after dosing. A significant correlation between plasma carbaryl and RBC ChE inhibition existed. These studies show that tissue dosimetry can explain some variability in biological responses (such as ChE inhibition) between individual subjects produced by a N-methyl carbamate pesticide. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.