TARGET SITE BIOACTIVATION OF THE NEUROTOXIC ORGANOPHOSPHORUS INSECTICIDE PARATHION IN PARTIALLY HEPATECTOMIZED RATS

Target organ bioactivation of phosphorothionate insecticides to their potent anticholinesterase oxon metabolites (for example, parathion to paraoxon) may be extremely important in toxicity because liver and blood provide so much potential protection by a variety of mechanisms, such as the aliesterases which serve as alternate phosphorylation sites. To determine whether the brain can produce sufficient oxon in vivo to contribute to toxicity, male rats were partially hepatectomized and injected i.v. with 1.5 mg/kg parathion. After 30 minutes, brain AChE was inhibited 68% whereas liver and plasma aliesterases were unaffected. Because aliesterases are far more sensitive to paraoxon inhibition than is brain AChE, these results indicate that neither the liver nor extra-hepatic tissues were contributing oxon into the blood stream. Thus target site activation of parathion occurred in vivo at sufficient levels to contribute substantially to toxicity.