Cobalt molybdate

Endpoint summary

Description of key information

Read-across data
LOAEC (rat): 0.114 mg Co2+/m³ 
LOAEC (mouse): 0.114 mg Co2+/m³

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

0.114 mg/m³

Study duration:

subchronic

Species:

other: rats and mice

Additional information

There are no data available on repeated dose toxicity for cobalt molybdenum oxide. However, there are reliable data for soluble cobalt and molybdenum substances considered suitable for read-across using the analogue approach. For identifying hazardous properties of cobalt molybdenum oxide, the existing forms of cobalt molybdenum oxide at very acidic and physiological pH conditions are relevant for risk assessment of human health effects. Cobalt molybdenum oxide is a metal-organic salt, which is highly water soluble (~ 508 mg/L) and nearly completely dissociates in aqueous solutions. As it is expected that cobalt molybdenum oxide is capable of forming ions at very acidic and physiological pH conditions, cobalt cations and molybdate anions will be present and completely bioavailable, same as for other soluble cobalt and molybdenum compounds.Due to the existing cobalt and molybdate ions, data from other soluble cobalt and molybdenum substances are used in the derivation of toxicological endpoints for cobalt molybdenum oxide. For further details refer to the analogue justification.

 

Cobalt substances

In a 13-week inhalation study, groups of mice and rats were exposed to cobalt(II)sulfate heptahydrate aerosols at concentrations of 0.3, 1, 3, 10 and 30 mg/m³ (calculated as anhydrous salt and equivalent to 0.114, 0.38, 1.14, 3.8 and 11.4 mg Co2+/m³, respectively) for 6 hours/day and 5 days/week (Bucher, 1991). All rats, all female mice, and all but 2 male mice exposed at the top concentration survived to the end of the studies (10 animals per group). Rats and mice exposed to 11.4 mg Co2+/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 0.114 mg Co2+/m³ and in mice exposed to 3.8 mg Co2+/m³ or more. Polycythemia was observed in rats exposed to the test substance but not in mice. Cobalt content in the urine of rats increased with increasing atmospheric cobalt exposure. Both in rats and mice, lesions seen in the respiratory tract 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 0.114 mg Co2+/m³. Thus, no NOAEC could be determined, neither in rats nor in mice.

 

Molybdenum substances

After an extensive literature/data search and evaluation program on animal and human repeated dose toxicity data of molybdenum substances conducted by the Molybdenum Consortium and the International Molybdenum Association, only the inhalation toxicity experiments conducted with molybdenum trioxide in the context of the NTP (1997) toxicology and carcinogenesis studies in rats and mice are considered to be sufficiently robust and reliable for regulatory risk assessment. All other references evaluated in this process lacked relevance because of severe shortcomings in the applied methodology and/or quality of reporting/documentation, thereby rendering them unsuitable for regulatory purposes (reference evaluation report: Tabular quality and reliability assessment report – Human and animal repeated dose toxicity data on molybdenum substances, EBRC unpublished report February 2010, EBRC Hannover, Germany)

Inhalation: Groups of 10 male and 10 female F344/N rats and mice were exposed to molybdenum trioxide by inhalation at concentrations of 1, 3, 10, 30, or 100 mg/m³ for 6.5 h/d, 5 d/week, for 13 weeks (NTP, 1997). All rats and mice survived to the end of the study. The final mean body weights of exposed animals were similar to those of the control groups. No clinical findings related to molybdenum trioxide exposure were observed. There were no significant chemical-related differences in absolute or relative organ weights or sperm counts or motility for both species. In mice there were significant increases in liver copper concentrations in female mice exposed to 30 mg/m³ and in male and female mice exposed to 100 mg/m³ compared to those of the control groups. In rats no significant increases in liver copper concentration were determined. No chemical-related lesions were observed in rats and mice.

Dermal: Toxic effects of molybdenum substances after repeated exposure via the dermal route are not considered to be of any relevance or concern: molybdenum substances, for which studies are available, are virtually non-toxic upon acute exposure via the dermal route, and are of very low general systemic toxicity. Further, the dermal absorption of molybdate anions has been shown to be low to negligible.

Justification for classification or non-classification

Although the respiratory tract was damaged in rats and mice, soluble cobalt substances will not be classified in repeated dose toxicity since also carcinogenic effects in the respiratory tract were observed in a 2-year inhalation study (NTP, 1998, see carcinogenicity). Therefore, cobalt molybdenum oxide is classified as carcinogenic (DSD: Carcinogenicity category 2; R49; CLP: Carcinogenicity category 1B; H350). According to CLP, there should be no double classification for the same effect, thus no classification for repeated dose toxicity.

Based on an analogue approach, the available data on repeated dose toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.