Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase‐deficient rats

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Abstract
We report on the distribution, metabolism, and toxicity of sulfite in the respiratory tract and other tissues of rats exposed to endogenously generated sulfite or to inhaled sulfur dioxide (SO 2 ). Graded sulfite oxidase deficiency was induced in several groups of rats by manipulating their tungsten to molybdenum intake ratio. Endogenously generated sulfite and S‐sulfonate compounds (a class of sulfite metabolite) accumulated in the respiratory tract tissues and in the plasma of these rats in inverse proportion to hepatic sulfite oxidase activity. In contrast to this systemic mode of exposure, sulfite exposure of normal, sulfite oxidase‐competent rats via inhaled SO 2 (10 and 30 ppm) was restricted to the airways. Minor pathological changes consisting of epithelial hyperplasia, mucoid degeneration, and desquamation of epithelium were observed only in the tracheas and bronchi of the rats inhaling SO 2 , even though the concentration of sulfite plus S‐sulfonates in the tracheas and bronchi of these rats was considerably lower than that in the endogenously exposed rats. We attribute this histological damage to hydrogen ions stemming from inhaled SO 2 , not to the sulfite/ bisulfite ions that are also a product of inhaled SO 2 . In addition to the lungs and trachea, all other tissues examined, except the testes, appeared to be refractory to high concentrations of endogenously generated sulfite. The testes of grossly sulfite oxidase‐deficient rats were severely atrophied and devoid of spermatogenic cells.