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Key value for chemical safety assessment

Additional information

Two different in vitro studies were performed to evaluate the mutagenicity of barium hexaferrite. In Salmonella and E.coli the substance did not shown mutagenic activity, while some positive results were observed in vitro micronucleus test performed on V79 and CHO cell lines. During the preliminary citotoxicity test (performed in order to evaluate the most suitable concentrations of test substance for both CHO and V79 cells), an unexpected, marked citotoxicity was observed in CHO cells not exposed to the substance but treated with metabolic activator S9. For this reason, CHO cells were tested with the substance only in absence of S9 activation, while V79 cells were exposed to barium hexaferrite both with and without S9. Positive results were observed at the highest concentration levels tested for both CHO and V79 cells; in V79 cells the mutagen activity was observed only in presence of metabolic system. Overall, the results are unclear. The citotoxicity due to S9 in CHO cells and the different results observed in the two cell lines would make desirable a verification by means of an in vivo test, as it is foreseen by the Regulation EC 1907/2006. However, toxicokinetics evidences do not support the adsorption (after oral administration) and the subsequently reaching of the target tissue by the substance, making non reliable the validated in vivo mutagenicity tests. Indeed, B.11 (In Vivo Mammalian Bone Marrow Chromosome Aberration Test) and B.12 (In Vivo Mammalian Erythrocyte Micronucleus Test) sections of the Regulation CE 440/2008 reports that: "If there is evidence that the test substance, or a reactive metabolite, will not reach the target tissue, it is not appropriate to use this test".

In light of above issue, no further test was performed.


Short description of key information:
In vitro studies gave conflicting results. The Ames test was negative in all tested strains without and with metabolic activation, regardless the concentration tested. In vitro micronucleus test in V79 and CHO cells showed some mutagenic activity at the highest dose levels tested. In vivo testing was considered scientifically unjustified. Because the toxicokinetics evidences show that barium hexaferrite is not able to reach target organs.

Endpoint Conclusion:

Justification for classification or non-classification

Even if the mutagenic potential of the substance, assessed in in vitro studies, remains uncertain, the toxicokinetics evidences show that the barium hexaferrite is not able to reach the specific target (the germ cells). Therefore, according to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, the substance should not be classified as mutagen to germ cells.