Molecular Modelling Analysis of the Metabolism of Chloroform
Chloroform is still widely used as a solvent in industrial processes and formed as a by-product during chlorination of water intended for human consumption and paper bleaching. The main public health concern from chloroform exposure lies in its carcinogenic potential as it has been found to induce liver cancer in mice and renal tumours in male rats. It is believed that chloroform-induced toxicity is due to its cytochrome P450-mediated bioactivation to reactive metabolites. The compound can be metabolized by two different pathways, one of which follows oxidative dechlorination leading to the formation of phosgene and the other follows a reductive pathway leading to the formation of a reactive free radical. Molecular modelling analyses provide support to the idea that some of the metabolites of chloroform are more toxic than the parent compound. The metabolite phosgene is found to have electron-deficient regions on its molecular surface so that it can react with cellular glutathione, thus compromising the antioxidant status of the cell.
Cited References Fulltext