Tricobalt dicitrate

Endpoint summary

Additional information

There are no data available on genetic toxicity of Tricobalt dicitrate. However, there are reliable data available for structurally related cobalt compounds. Thus, read-across was conducted based on structural analogues.

In vitro

Soluble cobalt salts were found to be generally nonmutagenic in Salmonella typhimurium strains when compounds with a valence state of II were tested (Zeiger et al., 1992; Ogawa et al., 1986; Tso and Fung, 1981). However, Ogawa et al. (1986) could show that when the Ames test was performed with 9-aminoacridine in the presence of varying concentrations of cobalt(II)chloride, a remarkable increase in the mutagenic activity was observed in TA1537 and TA2637. Furthermore cobalt(II)chloride could induce mutation when combined with 4 -aminoquinoline, harman or norharman, which were not themselves mutagenic in the strains TA1537 or TA2637.

In mouse bone marrow cells, micronucleus formation was not significantly altered by treatment with cobalt(II)chloride hexahydrate in the presence or absence of S9 mix (Suzuki et al., 1993). However, no positive control substance was used to validate this assay.

In vivo

30 hours following single intraperitoneal injection of cobalt(II)chloride hexahydrate in mice, a dose-dependent increase in micronucleus formation was seen at 69.7 and 38.7 mg/kg bw, but not at 19.4 mg/kg bw Tricobalt dicitrate (recalculated values, equivalent to 25, 50 and 90 mg/kg bw cobalt(II)chloride hexahydrate) (Suzuki et al., 1993).

Reference:

Tso, WW and Fung, WP, 1981, Mutagenicity of metallic cations. Toxicology Letters, 8: 195 -200

Short description of key information:
In vitro: Negative results in the Ames test and in the micronucleus assay. However, cobalt(II)chloride was identified as comutagen in the Ames test.
In vivo: Positive result in the micronucleus assay.

Endpoint Conclusion:

Justification for classification or non-classification

There are no data available on genetic toxicity of Tricobalt dicitrate. However, there are reliable data available for structurally related cobalt compounds. Thus, read-across was conducted based on structural analogues.

If there are positive results in at least one valid in vivo mutagenicity test using intraperitoneal application, or from at least one valid in vivo genotoxicity test using intraperitoneal application plus supportive in vitro data, classification is warranted. In this case all in vitro tests were negative. It cannot be ruled out that a positive test result in intraperitoneal studies in rodents only may be relevant to humans. But because of the absorption of cobalt salts after orally intake, Tricobalt dicitrate has to be classified.

DSD: Mutagenicity Category 3, R68

CLP: Mutagenicity Category 2