Neodecanoic acid, zinc salt, basic

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with zinc neodecanoate basic is available, thus the genetic toxicity will be addressed with existing data on the individual assessment entities zinc and neodecanoate.

Zinc neodecanoate basic is not expected to be genotoxic, since the two assessment entities zinc and neodecanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Zinc

Several in vitro studies and two in vivo studies are available on the genotoxicity of zinc oxide. Data on other zinc compounds have also to be taken into account, as the basic assumption is made that after intake all zinc compounds (including metallic zinc) are changed (at least in part) to the ionic species and that it is this zinc cation that is the determining factor for the biological activities of the zinc compounds.

The genotoxicity of soluble and slightly soluble zinc compounds have been extensively investigated in a wide range of in vitro and in vivo studies. The in vitro investigations included non-mammalian and mammalian test systems covering the endpoints of gene mutation, chromosomal aberrations, sister chromatide exchange, unscheduled DNA synthesis (UDS), as well as cell transformation. Available in vivo genotoxicity assays included the micronucleus test and chromosomal aberration test.

The investigated zinc compounds did not increase the mutation frequencies in bacterial systems. Zinc oxide was consistently negative in the Ames test. There was some evidence that zinc oxide induced in the absence of metabolic activation the formation of mutation colonies. Several reviewers noted, however, that these mutations were observed at cytotoxic concentrations and that the analysis did not distinguish between big and small colonies which could be caused by gene mutation or chromosomal aberrations (Thompson et al.,1989, WHO, 2001; EU RAR, 2004; MAK, 2009).

Conflicting information was further found when zinc compounds were examined for their potential to induce chromosomal aberrations or sister chromatide exchange in mammalian cell systems or when evaluated in the cell transformation assay. Positive as well as negative results were obtained in these cell systems with either soluble or slightly soluble zinc compounds. In those studies where, chromosomal aberrations or sister chromatide exchange has been observed, these were generally considered to be weak and occurred only at high, often cytotoxic concentrations. Moreover, these positive in vitro findings have also to be seen in context of the impact that changes in zinc levels can have on cell system processes that are controlled by a strict metal homeostasis. A change of this metal homeostasis due to increased zinc levels, may lead to a binding of zinc to amino acids like cystein and therefore to an inhibition of certain enzymes. This can lead to interactions with the energy metabolism, signal transmission and apoptotic processes which can lead to the observed clastogenic or aneugenic effects in in vitro systems (EU RAR, 2004; MAK, 2009).

In addition to above mentioned in vitro investigations, zinc compounds have also been studied in in vivo studies including the micronucleus test and chromosomal aberration test. The zinc compounds were negative in both assays.

 

The German MAK committee reviewed the existing in vivo evidence and concluded that particularly those studies indicating clastogenic effects involved a lot of methodological uncertainties which do not allow overruling those in vivo studies which did not provide any evidence for chromosomal aberrations in vivo. Moreover, the Dutch rapporteur of EU risk assessment of zinc compounds under the EU existing substance legislation considered the positive in vitro findings for chromosomal aberration and SCE assays to be overruled by the overall weight of evidence of negative in vivo tests for this endpoint (EU RAR, 2004).

 

Neodecanoate

Neodecanoic acid is not mutagenic in vitro in bacterial mutation assays (with and without metabolic activation) and was not clastogenic in a cytogenetic assay. Although a test on in vitro gene mutation in mammalian cells is not provided, the bacterial reverse mutation test covering the same endpoint did not show any sign of mutagenic potential with an without metabolic activation. This data suggests that neodecanoic acid is not genotoxic in vitro and likely not genotoxic in vivo.

No classification for genetic toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

Zinc neodecanoate basic

Zinc neodecanoate basic is not expected to be genotoxic, since the two assessment entities zinc and neodecanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. Further testing is not required. Thus, zinc neodecanoate basic is not to be classified according to regulation (EC) 1272/2008 as genetic toxicant. For further information on the toxicity of the individual assessment entities, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Zinc neodecanoate basic is not expected to be genotoxic, since the two assessment entities zinc and neodecanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity. Thus, zinc neodecanoate basic is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments as genetic toxicant.