National Toxicology Program

TOX-5
Toxicity Studies of Cobalt Sulfate Heptahydrate in F344/N Rats and B6C3F₁ Mice (Inhalation Studies) (CAS No. 10026-24-1)

Toxicology studies of cobalt sulfate heptahydrate (99% pure) were conductedby exposing groups of F344/N rats and B6C3F₁ mice of each sex to a cobaltsulfate heptahydrate aerosol 6 hours per day, 5 days per week, for 16 daysor 13 weeks.

In 16-day studies, all rats and mice exposed at the top concentration of200 mg cobalt sulfate/m3 died (5 animals per group); partial survival wasseen in the 50 mg/m³ exposure groups. Degeneration of the olfactoryepithelium and necrotizing inflammation occurred in the nose of all ratsand mice that died and in animals exposed to 50 mg/m³. Necrotizinginflammation was observed in the larynx and trachea of rats and mice atconcentrations as low as 5 mg/m³, and a similar lesion was present in thebronchi at exposure concentrations of 50 mg/m³ or higher. Regenerative andinflammatory lesions, including peribronchial and septal fibrosis in thelung, 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 miceexposed at the top concentration survived to the end of the studies (targetexposure concentrations of 0, 0.3, 1, 3, 10, and 30 mg/m³, 10 animals pergroup). Rats and mice exposed to 30 mg/m³ lost weight during the firstexposure week and then gained weight at the same rate as controls. Lungweights were increased over those of controls in rats exposed atconcentrations 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 inmice. Sperm motility was decreased in mice exposed at 3 mg/m³ or at higherconcentrations (lower concentrations were not evaluated), and increasednumbers of abnormal sperm were found in mice exposed to 30 mg/m³. Testisand epididymal weights were decreased in mice exposed to 30 mg/m³. Cobaltcontent in the urine of rats increased with increasing atmospheric cobaltexposure.

Lesions seen in the respiratory tract in 13-week studies in rats and miceincluded degeneration of the olfactory epithelium, squamous metaplasia ofthe 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); andhistiocytic infiltrates, bronchiolar regeneration, peribronchiolar andseptal fibrosis, and epithelial hyperplasia in the alveoli of the lung.The most sensitive tissue was the larynx, with squamous metaplasia observedin rats and mice at the lowest exposure concentration of 0.3 mg/m³. Thus, ano-observed-adverse-effect level was not reached in these studies.

Report Date: January 1991

(NOTE: These studies were supported in part by funds from the Comprehensive EnvironmentalResponse, 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.)

Growth & Survival Curves for NTP 13-Week Toxicity Studies

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