Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds

• Published in: Toxicology (Amsterdam) 2015-07, Vol.333, p.195-205
• Main Authors: Behl, Mamta, Stout, Matthew D, Herbert, Ronald A, Dill, Jeffrey A, Baker, Gregory L, Hayden, Barry K, Roycroft, Joseph H, Bucher, John R, Hooth, Michelle J
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms - chemically induced; Adrenal Gland Neoplasms - pathology; Adrenal Medulla - drug effects; Adrenal Medulla - pathology; Animals; Cancer; Carcinogenicity; Carcinogenicity Tests; Carcinogens; Cobalt; Cobalt - chemistry; Cobalt - toxicity; Emergency; Exposure; Female; Hematologic Neoplasms - chemically induced; Hematologic Neoplasms - pathology; Inhalation; Inhalation Exposure; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Male; Mice; Mutagenicity Tests; Pancreatic Neoplasms - chemically induced; Pancreatic Neoplasms - pathology; Rats; Rats, Inbred F344; Respiratory System - drug effects; Respiratory System - pathology; Risk Assessment; Salmonella; Salmonella - drug effects; Salmonella - genetics; Solubility; Species Specificity; Testis - drug effects; Testis - pathology; Time Factors; Toxicity; Toxicity Tests, Chronic
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2015.04.008

Abstract Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure.