However, the final chemical form of this sulfur is unknown; it is most likely to be sulfate, inasmuch as almost all the radioactivity is excreted as sulfate (Yokoyama et al. 1971). No information is available on the sites and rates of oxidation of sulfur dioxide to sulfate within the lungs or peripheral blood. The studies of Gunnison and his colleagues (Gunnison and Palmes 1974, Gunnison and Palmes 1973, Gunnison and Benton 1971) have demonstrated that rabbits exposed to sulfur dioxide develop measurable plasma concentrations of thiosulfonates that persist for days. Humans were found to have comparatively lower blood thiosulfonate concentrations after controlled exposure to sulfur dioxide at 0.3–6.0 ppm (Gunnison and Palmes 1974). Thiosulfonates are formed by the addition of sulfur dioxide across protein disulfide bonds. Although they have been identified thus far only in blood, the formation of lung thiosulfonates could be a mechanism of sulfur dioxide toxicity. The activity of enzymes containing integral disulfide bonds, such as ribonuclease, might be affected by this action of sulfur dioxide. The disruption of disulfide bonds is also believed to be the basis for in vitro potentiation of the red cell membrane effects of the indirect pathway of complement (DeSandre et al. 1970), the complement pathway reportedly responsible for the histamine release that is induced by allergen-reagin and results in asthma attacks (Malley et al. 1973). However, there is no direct evidence to link pulmonary or systemic thiosulfonates with sulfur dioxide toxicity. Furthermore, it should be noted that acetyclysteine, a common aerosol component used in the treatment of bronchitic disorders, is a sulfhydryl compound that is believed to act therapeutically by disrupting disulfide bonds in sputum.

Another potential biochemical mechanism of sulfite toxicity is the formation of free radicals. These reactive chemical species are presumably responsible for a number of the effects of sulfite observed during in vitro incubation with biologic compounds, including reduced pyridine nucleotides, tryptophan, methionine, indol-3-acetic acid, vitamin K, and thiamine (Shih and



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