Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5859674 | Toxicology | 2010 | 12 Pages |
Abstract
Carbaryl is a N-methylcarbamate pesticide and, like others in this class, is a reversible inhibitor of cholinesterase (ChE) enzymes. Although studied for many years, there is a surprising lack of information relating tissue levels of carbaryl with ChE activity in the same animals. The present studies were undertaken to describe the dose-response relationship about 40Â min (approximate time of maximal ChE inhibition) after oral treatment in adult, post-natal day (PND) 17, and PND11 rats. Additionally, the time-course of plasma ChE activity and carbaryl levels in adult rats was determined after a 30Â mg/kg dosage of carbaryl. The time-course study found that carbaryl levels could be detected in plasma 1Â h after dosing, but rapidly decreased below the level of quantitation by the 2Â h time point. In the dose-response studies, treatment-related increases in plasma and brain carbaryl levels were observed 40Â min after dosing. Plasma levels of carbaryl increased linearly, while brain levels appeared to asymptote after 75Â mg/kg carbaryl. Plasma and brain levels of carbaryl appeared to be linearly related with a slope close to 1 after various dosages (range: 1-75Â mg/kg) of carbaryl at the 40Â min time point. Finally, the dose-related relationship between tissue levels of carbaryl and ChE activity was described using a first order exponential decay function with an asymptote. The parameters of this function did not appear to differ between adult, PND17, or PND11 rats. This indicates that age-related differences in brain ChE inhibition by carbaryl are unlikely to be the result of greater tissue levels of the pesticide in PND11 animals. These are the first studies to report the relationship between brain and plasma tissue levels of carbaryl and ChE activity on an individual animal basis. The results of these experiments will be useful to extend physiologically-based pharmacokinetic models for carbaryl and their application in risk assessment.
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Authors
David W. Herr, Jean-Claude Mwanza, Danielle F. Lyke, Jaimie E. Graff, Virginia C. Moser, Stephanie Padilla,