Toxicological Sciences, Vol 49, 116-123, Copyright © 1999 by Society of Toxicology
F Bahrami, EB Brittebo, A Bergman, C Larsson and I Brandt
Several methylsulfonyl (MeSO2) metabolites formed from chlorinated aromatic
hydrocarbons have been identified in human milk, lung, and body fat, as
well as in the tissues of Baltic grey seals and arctic polar bears. The
tissue localization and nasal toxicity of two methylsulfonyl-substituted
dichlorobenzenes (diCl-MeSO2-B), with the chlorine atoms in the 2,5-, and
2,6- positions, were investigated in female NMRI and C57B1 mice. Using
tape-section autoradiography, animals dosed i.v. with 14C-labeled 2,5-, or
2,6-(diCl-MeSO2-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 (i.p.
injection), whereas 2,5- (diCl-MeSO2-B) induced no signs of toxicity in the
olfactory mucosa at doses as high as 130 mg/kg (i.p. 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 primary site of toxicity and
degeneration of the neuroepithelium may be a secondary 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; i.p. injection), induced no signs of
toxicity in the olfactory mucosa. These and previous results suggest that
2,6- positioned chlorine atoms and an electron withdrawing substituent in
the primary position is an arrangement that predisposes for toxicity in the
olfactory mucosa.
ARTICLES
Localization and comparative toxicity of methylsulfonyl-2,5- and 2,6- dichlorobenzene in the olfactory mucosa of mice
Department of Environmental Toxicology, Uppsala University, Sweden.
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