These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.
Toxicology studies of cobalt sulfate heptahydrate (99% pure) were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to a cobalt sulfate heptahydrate aerosol 6 hours per day, 5 days per week, for 16 days or 13 weeks.
In 16-day studies, all rats and mice exposed at the top concentration of 200 mg cobalt sulfate/m3 died (5 animals per group); partial survival was seen in the 50 mg/m3 exposure groups. Degeneration of the olfactory epithelium and necrotizing inflammation occurred in the nose of all rats and mice that died and in animals exposed to 50 mg/m3. Necrotizing inflammation was observed in the larynx and trachea of rats and mice at concentrations as low as 5 mg/m3, and a similar lesion was present in the bronchi at exposure concentrations of 50 mg/m3 or higher. Regenerative and inflammatory lesions, including peribronchial and septal fibrosis in the lung, were found in rats and mice exposed to 50 mg/m3.
In 13-week studies, all rats, all female mice, and all but 2 male mice exposed at the top concentration survived to the end of the studies (target exposure concentrations of 0, 0.3, 1, 3, 10, and 30 mg/m3, 10 animals per group). Rats and mice exposed to 30 mg/m3 lost weight during the first exposure week and then gained weight at the same rate as controls. Lung weights were increased over those of controls in rats exposed at concentrations as low as 1 mg/m3 and in mice exposed to 10 mg/m3 or more. Polycythemia was observed in rats exposed to cobalt sulfate but not in mice. Sperm motility was decreased in mice exposed at 3 mg/m3 or at higher concentrations (lower concentrations were not evaluated), and increased numbers of abnormal sperm were found in mice exposed to 30 mg/m3. Testis and epididymal weights were decreased in mice exposed to 30 mg/m3. Cobalt content in the urine of rats increased with increasing atmospheric cobalt exposure.
Lesions seen in the respiratory tract in 13-week studies in rats and mice included degeneration of the olfactory epithelium, squamous metaplasia of the respiratory epithelium, and inflammation in the nose; inflammation, necrosis, squamous metaplasia, ulcers (rats), and inflammatory polyps (rats) of the larynx; squamous metaplasia of the trachea (mice); and histiocytic infiltrates, bronchiolar regeneration, peribronchiolar and septal fibrosis, and epithelial hyperplasia in the alveoli of the lung. The most sensitive tissue was the larynx, with squamous metaplasia observed in rats and mice at the lowest exposure concentration of 0.3 mg/m3. Thus, a no-observed-adverse-effect level was not reached in these studies.