Date of Award:

5-1980

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Animal, Dairy, and Veterinary Sciences

Department name when degree awarded

Toxicology

Committee Chair(s)

Joseph C. Street

Committee

Joseph C. Street

Abstract

A computer simulation model of blood cholinesterase inhibition in rats resulting from a single oral or dermal dose of parathion was developed and tested. The model consists of a set of non-linear differential equations describing the absorption, distribution and metabolism of parathion and the kinetics of inhibition and reactivation of erythrocyte and plasma cholinesterase. The equations are numerically integrated to produce the time-course of each of the cholinesterase activities of the blood. The model was tested for validity by a comparison of the activities predicted by the model to values determined experimentally in male rats. The model successfully simulated plasma cholinesterase activity after a four milligram per kilogram oral dose, and total blood cholinesterase activity after a one milligram per kilogram oral dose. Erythrocyte cholinesterase activity was closely predicted for the first three hours after a four milligram per kilogram oral dose, but inhibition was overestimated during the next two hours. Agreement between model output and observed erythrocyte cholinesterase activity was good for the first twenty four hours after initiation of a fifteen milligram per kilogram dermal dose, but the rate of activity regeneration was overestimated. Es-timated erythrocyte cholinesterase inhibition is sensitive to changes in the values of parameters controlling liver paraoxon metabolism and the phosphorylation reaction between paraoxon and the enzyme, but in general, the model is not sensitive to small perturbations of parameter values. The model has potential for interpreting human exposures to parathion and for investigating the relationships between various parameters and blood cholinesterase inhibition.

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