Epithelial binding of 1,1,2,2-tetrachloroethane in the respiratory and upper alimentary tract

The bioactivation and binding of 14C-labelled 1,1,2,2-tetrachloroethane (TCE) in the tissues of C57B1 mice were studied. As shown by autoradiography with heated and organic solvent-extracted tissue sections of i.v. injected mice, a high and selective localization of bound metabolites occurred in the nasal olfactory mucosa, preferentially in the Bowman's glands. High levels of bound metabolites were also present in epithelia of the trachea, bronchi and bronchioli and in the squamous epithelia of the oral cavity, tongue and esophagus. An epithelial binding was observed in tissue slices incubated with 14C-TCE. Incubation of 14C-TCE with homogenates of the olfactory mucosa and liver showed that the olfactory mucosa had a higher ability to activate 14C-TCE into products that become irreversibly bound to protein. Addition of metyrapone, glutathione or sodium dithionite to the incubations decreased the level of irreversible binding, suggesting that the activation of TCE to reactive products is mediated via an oxidative cytochrome P-450 dependent process in the olfactory mucosa.