Toxicological Sciences, Vol 49, 56-67, Copyright © 1999 by Society of Toxicology
JR Bucher, JR Hailey, JR Roycroft, JK Haseman, RC Sills, SL Grumbein, PW Mellick and BJ Chou
Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial
and agricultural uses. Several cobalt compounds have induced sarcomas at
injection sites in animals, and reports have suggested that exposure to
cobalt-containing materials may cause lung cancer in humans. The present
studies were done because no adequate rodent carcinogenicity studies had
been performed with a soluble cobalt salt using a route relevant to
occupational exposures. Groups of 50 male and 50 female F344/N rats and
B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3
cobalt sulfate hexahydrate, 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 rats, proteinosis, alveolar epithelial metaplasia,
granulomatous alveolar inflammation, and interstitial fibrosis were
observed in the lung in all exposed groups. Nonneoplastic lesions of the
nose and larynx were also attributed to exposure to all concentrations of
cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or
3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased
over those in the control groups. Lung tumors occurred with significant
positive trends in both sexes. The incidences of adrenal pheochromocytoma
in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased.
Nonneoplastic lesions of the respiratory tract were less severe in mice
than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males
and females were greater than those in the controls, and lung tumors
occurred with significantly positive trends. Male mice had liver lesions
consistent with a Helicobacter hepaticus infection. Incidences of liver
hemangiosarcomas were increased in exposed groups of male mice; however,
because of the infection, no conclusion could be reached concerning an
association between liver hemangiosarcomas and cobalt sulfate. In summary,
exposure to cobalt sulfate by inhalation resulted in increased incidence of
alveolar/bronchiolar neoplasms and a spectrum of inflammatory, fibrotic,
and proliferative lesions in the respiratory tracts of male and female rats
and mice. Adrenal pheochromocytomas were increased in female rats, and
possibly in male rats.
ARTICLES
Inhalation toxicity and carcinogenicity studies of cobalt sulfate
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. bucher@niehs.nih.gov
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