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Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur
Citation:
Mwanza, J., D. F. LYKE, R. C. Hertzberg, L. Haber, M. Kohrman-Vincent, R. Li, L. Pan, J. E. SIMMONS, D. MacMillian, D. R. Zehr, A. E. Swank, AND D. W. HERR. Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 33(3):332-346, (2012).
Impact/Purpose:
While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides
Description:
While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the Photic After Discharge (PhAD) of Flash Evoked Potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3 mglkg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg, or repeated treatment with 30 mg/kg, of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Doseresponse models for the acute and repeated exposure data did not differ for plasma or brain ChE activity, or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13 -22%) erythrocyte ChE inhibition than acute exposure. Predicted dose-additive models, based on the acute exposure single-chemical dose-response curves reported previously (Mwanza et al., 2008), were compared to the mixture data. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration. Both treatment paradigms resulted in less than dose-additive responses for brain ChE activity (6 -16%) for the middle range of dosages. Acute treatment with the mixture resulted in greater than dose-additive erythrocyte ChE inhibition (15 -18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16 -22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and showed only small deviations from dose-additivity (brain ChE activity). Erythrocyte ChE activity had larger differences between the acute and repeated treatment paradigms, and showed slightly greater deviations from dose-additivity. Because these treatments resulted in larger dosages than anticipated environmental exposures, concern for non-additive effects in humans is minimized. The small magnitude of the deviations from dose-additivity also suggest that in the absence of repeated exposure data, results from an acute study of readily reversible carbamate toxicity can be used to estimate the response to repeated daily exposures.
