Tissue Distribution and Covalent Binding of [14C]1,1-Dichloroethylene in Mice: In vivo and in vitro Studies
1,1-Dicholorethylene (DCE), a widely used compound in the manufacture of plastics, has been shown to be toxic to kidney, liver and lung in laboratory animals1–5, and to exhibit some mutagenic and carcinogenic potential6–8. Its toxicity has been suggested to result from covalent binding of reactive metabolites to cellular macromolecules3,9,10; these metabolites are nprm jly detoxified by conjugation with reduced glutathione (GSH)11–16. However the exact mechanisms of its expressed toxicity and its application to man are not understood. Species differences among animals in toxicity of DCE are thought to be due to the relative amount of bioactivated and covalently bound DCE produced in each species We present in this paper the in vivo tissue distribution and covalent binding as well as the in vitro metabolism and covalent binding of DCE in the mouse, the species Wight to be most suscep-tible to its toxicity9,10, with particular reference to the kidney, liver and lung.
KeywordsLiver Microsome Vinylidene Chloride Subcellular Fraction Covalent Binding Reactive Metabolite
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