Comparison of the Toxicity of Naphthalene and Naphthalene-1,2-Dihydrodiol (DIOL)

Abstract

Naphthalene metabolism and toxicity have been extensively investigated and these data indicate that the lung and eye toxicity are mediated by reactive intermediates. The elegant studies conducted in Buckpitt’s laboratory implicate a 1,2-epoxide as one reactive intermediate which is extensively conjugated with glutathione (Buckpitt et al., 1987). Data from this laboratory also suggest that the liver may form a precursor metabolite or reactive metabolite which is transported to the lung (Buckpitt and Warren, 1983). Studies of the ocular effects of naphthalene suggest that the well known liver metabolite, naphthalene-1,2-ihydrodiol (DIOL), may be transported to the eye where it is oxidized to the catechol metabolite, 1,2-dihydroxynaphthalene (VanHeyningen and Pirie, 1967). The catechol is easily oxidized non-enzymatically presumably to potentially reactive quinones and semiquinones. A more recent report also suggests the involvement of quinones in the ocular toxicity of naphthalene (Wells et al., 1989) and an in vitro study indicates that multiple quinone-derived metabolites are formed from D1OL when its oxidation is catalyzed by hepatic dihydrodiol dehydrogenase (Smithgall et al., 1988). Naphthalene is extensively metabolized and at least two epoxides as well as the the catechol/quinone metabolites are potentially reactive, toxic metabolites (Horning et al., 1980).