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The administration of tungsten to rats maintained on a low molybdenum diet resulted in a doseand time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC L.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHS03 per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats.The survival time of rats exposed to SO2 at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO2. At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO2, death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO2. Respiratory death probably results from the toxicity of gaseous SO2 before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO2.Animals exposed to SO2 (1) or given parenteral bisulfite (2) excrete 80-90% of the sulfur as sulfate in the urine. It has also been shown with rats that 70-95% of the radioactivity of ingested [35S ]sulfite is absorbed through the intestines and voided within 24 hr with no detectable sulfite in the urine (3). Sulfite oxidase (EC 1.8.3.1) an enzyme capable of oxidizing sulfite to sulfate, has been purified from animal livers and characterized as a molybdoprotein (4-7). Presumably the normal function of this enzyme is the oxidation of endogenous sulfite arising from the degradation of sulfur amino acids. The only evidence for the essentiality of sulfite oxidase is the report of the complete deficiency of the enzyme in a child who excreted no sulfate in his urine and who suffered from severe neurologic defects (8, 9).Recently we have been able to produce deficiencies of sulfite oxidase and xanthine oxidase (EC 1.2.3.2) the two major molybdoproteins of rat liver, by maintaining animals on a low molybdenum diet and treating them with tungsten, which has been shown to be a competitive antagonist of molybdenum utilization in animal systems (10)(11)(12). Using these rats deficient in sulfite oxidase, we have been able to demonstrate that this enzyme is involved in the oxidative metabolism of SO2 and bisulfite which results in the detoxification of these compounds. MATERIALS AND METHODSMale CD outbred rats weighing about 150 g were obtained from Charles River, Wilmington, Mass. Animals were housed in plastic cages, and food and water were freely available. The temperatur...

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