Localization and comparative toxicity of methylsulfonyl-2,5-and 2,6-dichlorobenzene in the olfactory mucosa of mice

Several methylsulfonyl (MeSO2) metabolites formed from chlorinated aromatic hydrocarbons have been identified in human milk, lung, and body fat, as we ll as in the tissues of Baltic grey seals and arctic polar bears. The tissu e localization and nasal toxicity of two methylsulfonyl-substituted dichlor obenzenes (diCl-MeSO2-B), with the chlorine atoms in the 2,5-, and 2,6- pos itions, were investigated in female NMRI and C57B1 mice. Using tape-section autoradiography, animals dosed iv with C-14-labeled 2,5-, or 2,6-(diCl-MeS O2-B) showed a preferential uptake of radioactivity in the olfactory mucosa and the tracheobronchial epithelium. Histopathology showed that 2,6-(diCl- MeSO2-B) is a potent toxicant that induces necrosis in the olfactory mucosa following a single dose as low as 4 mg/kg (ip injection), whereas 2,5-(diC l-MeSO2-B) induced no signs of toxicity in the olfactory mucosa at doses as high as 130 mg/kg (ip injection). Necrosis of the Bowman's glands was the first sign of 2,6-(diCl-MeSO2-B)-induced toxicity followed by degeneration of the neuroepithelium, which implies that the Bowman's gland may be the pr imary site of toxicity and degeneration of the neuroepithelium may be a sec ondary effect. Administration of the parent compounds, 1,3-dichlorobenzene and 1,4-dichlorobenzene, or the chlorinated analog 1,2,3-trichlorobenzene ( 85, 85, and 105 mg/kg, respectively; ip injection), induced no signs of tox icity in the olfactory mucosa, These and previous results suggest that 2,6- positioned chlorine atoms and an electron withdrawing substituent in the pr imary position is an arrangement that predisposes for toxicity in the olfac tory mucosa.