Inhalation toxicity and carcinogenicity studies of cobalt sulfate

Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at in jection sites in animals, and reports have suggested that exposure to cobal t-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been perf ormed with a soluble cobalt salt using a route relevant to occupational exp osures. Groups of 50 male and 50 female F344/N rats and B6C3F(1) mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m(3) cobalt sulfate h exahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rat s, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar infl ammation, and interstitial fibrosis were observed in the lung in all expose d groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m(3) male r ats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveo lar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The in cidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m 3 female rats were increased. Nonneoplastic lesions of the respiratory trac t were less severe in mice than in rats. In mice, alveolar/bronchiolar neop lasms in 3.0 mg/m3 males and females were greater than those in the control s, and lung tumors occurred with significantly positive trends. Male mice h ad liver lesions consistent with a Helicobacter hepaticus infection. Incide nces of liver hemangiosarcomas were increased in exposed groups of male mic e; however, because of the infection, no conclusion could be reached concer ning an association between liver hemangiosarcomas and cobalt sulfate. In s ummary, exposure to cobalt sulfate by inhalation resulted in increased inci dence of alveolar/bronchiolar neoplasms and a spectrum of inflammatory, fib rotic, and proliferative lesions in the respiratory tracts of male and fema le rats and mice. Adrenal pheochromocytomas were increased in female rats, and possibly in male rats.