Bismuth tris(2-ethylhexanoate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with bismuth tris (2-ethylhexanoate) is available, thus the genetic toxicity will be addressed with existing data on the individual moieties bismuth and 2-ethylhexanoate.

Bismuth tris (2-ethylhexanoate) is not expected to be genotoxic, since the two moieties bismuth and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells, in vitro clastogenicity and for the assessment entity 2 -ethylhexanoate in an in vivo clastogenicity assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Bismuth

Publications are available in which soluble bismuth salts were tested. Colloidal bismuth subcitrate was tested to induce sister chromatid exchanges or chromosome aberrations and bismuth subsalicylate and bismuth nitrate were both tested to induce gene mutation in bacterial cells. There is no indication for genotoxic/mutagenic effects of either colloidal bismuth subcitrate, bismuth subsalicylate or bismuth nitrate in these available publications.

 

In addition, in an available guideline study with the soluble bismuth hydroxide nitrate oxide the gene mutation potential was determined in the hprt locus of L5178Y mouse lymphoma cells. The study included treatments up to the maximum practicable concentration, 140 µg/mL (limited by solubility in the primary vehicle), in two independent experiments in the absence and presence of a rat liver metabolic activation system (S9).

Results show that bismuth hydroxide nitrate oxide does not induce gene mutation in mouse lymphoma cells.

Due to the fact, that soluble bismuth compounds are not mutagenic, it can be considered that bismuth metal as a poorly soluble substance (resulting in a lower bioavailability) is not mutagenic or genotoxic and should not be classified as such.

2-ethylhexanoic acid

in vitro

2-ethylhexanoic acid was negative in the bacterial Ames test with S. typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 and E. coli WP2 uvr A (Jung et al., 1982; Zeiger et al., 1988; Warren et al., 1982), as well as in a HPRT locus assay with mammalian CHO cells (Schulz et al., 2007). In cultured human lymphocytes, 2-ethylhexanoic acid induced a minimal increase in frequency of sister-chromatid exchanges (below 1.5 fold increase at concentrations of the test substance of 0.63 to 2.5 mM; Sipi et al., 1992), which is not considered significant.

in vivo

In an in vivo micronucleus assay with mice, 2-ethylhexanoic acid was administered by gavage up to the maximum tolerated oral dose of 1600 mg/kg/day. No bone marrow toxicity was observed, nor did the test substance induce any bone marrow micronuclei (Holstrom et al., 1994).

Bismuth tris (2-ethylhexanoate)

Bismuth tris (2-ethylhexanoate) is not expected to be genotoxic, since the two moieties bismuth and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells, in vitro clastogenicity and for the assessment entity 2 -ethylhexanoate in an in vivo clastogenicity assay. Further testing is not required. Thus, bismuth tris (2-ethylhexanoate) is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Bismuth tris (2-ethylhexanoate) is not expected to be genotoxic, since the two moieties bismuth and 2-ethylhexanoic acid have not shown gene mutation potential in bacteria and mammalian cells, in vitro clastogenicity and for the assessment entity 2 -ethylhexanoate in an in vivo clastogenicity assay. Thus, bismuth tris (2-ethylhexanoate) is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant.