Tricobalt dicitrate

Carcinogenicity

Description of key information

No NOAECs were identified neither for rats nor for mice.
LOAEC (local, rat): 0.37 mg/m3 (Tricobalt dicitrate; recalculated value)
LOAEC (local, mouse): 0.37 mg/m3 (Tricobalt dicitrate; recalculated value)

Justification for classification or non-classification

There are no data available on carcinogenicity of Tricobalt dicitrate. However, there are reliable data available for the structurally related compound cobalt(II)sulfate heptahydrate. Thus, read-across was conducted based on the structural analogue.

DSD: Carcinogenicity category 2; R49

CLP: Carcinogenicity category 1B

Additional information

There are no data available on carcinogenicity of Tricobalt dicitrate. However, there are reliable data available for the structurally related compound cobalt(II)sulfate heptahydrate. Thus, read-across was conducted based on the structural analogue.

Groups of mice and rats were exposed to cobalt(II)sulfate heptahydrate aerosols by inhalation at concentrations of 0, 0.3, 1 and 3 mg/m3 (calculated as anhydrous salt; equivalent to 0.5, 1.6 and 4.8 mg/m3 cobalt hydrogencitrate) 6 hours/day, 5 days/week, for 105 weeks (NTP, 1998).

Mean body weights were increased in all treated female mice and decreased only in the high-dose male mice. Survival was not adversely affected by treatment. The incidences of benign and malignant alveolar/bronchiolar neoplasms were increased in a concentration-dependent manner in male and female mice.

Males: 11/50, 14/50, 19/50, and 28/50 for 0, 0.3, 1, and 3 mg/m3, respectively.

Females: 4/50, 7/50, 13/50, and 18/50 for 0, 0.3, 1 and 3 mg/m3, respectively.

In rats, mean body weights and survival were unaffected by treatment. Female animals exhibited a concentration-related increase in the incidence of benign and malignant alveolar/bronchiolar neoplasms and of benign and malignant pheochromocytomas of the adrenal medulla. The incidences of benign and malignant alveolar/bronchiolar neoplasms were 0/50, 3/49, 15/50 and 15/50 for 0, 0.3, 1 and 3 mg/m3, respectively and of benign and malignant pheochromocytomas were 2/48, 1/49, 4/50, and 10/48 for 0, 0.3, 1, and 3 mg/m3, respectively.

In males, increased incidence of benign and malignant alveolar/bronchiolar neoplasms was observed, but only a marginally increased incidence of pheochromocytomas of the adrenal medulla. The incidences of benign and malignant alveolar/bronchiolar neoplasms were 1/50, 4/50, 4/48, and 7/50 for 0, 0.3, 1, and 3 mg/m3, respectively and of begnin and malignant pheochromocytomas were 15/50, 19/50, 25/49, and 20/50 for 0, 0.3, 1, 3 mg/m3, respectivley.

Although many of the alveolar/bronchiolar lesions were morphologically similar to those that arise spontaneously, the lesions in rats, unlike those in mice, were predominantly fibrotic, squamous or mixtures of alveolar/bronchiolar epithelium and squamous or fibrous components. Squamous metaplasia of alveolar/bronchiolar epithelium, which is a common response to pulmonary injury, was observed in number of rats.

The marginally increased incidence of pheochromocytomas in males was considered an uncertain finding because it occurred only in the 1 mg/m3 group and was not supported by increased incidence or severity of hyperplasia. Marginal increases in adrenal medullary tumors may have been exposure related.

In summary, cobalt(II)sulfate heptahydrate was found to be carcinogenic in mice and rats when administered by inhalation. There was clear evidence of carcinogenicity in male mice, female mice and female rats, based on increased incidences of lung tumors. In addition, female rats had an increase incidence of pheochromocytoma of the adrenal medulla. Some evidence of carcinogenicity in male rats was observed, based on increased incidences of lung tumors at the highest exposure level. No NOAECs were identified, neither for rats nor for mice. The local LOAECs were determined to be 0.3 mg/m3 (equivalent to 0.37 mg/m3 Tricobalt dicitrate) for mice and rats.