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Key value for chemical safety assessment

Additional information

Iron(II,III) oxide (Fe3O4) was tested adequately for gene mutations in bacteria (Salmonella/microsome test) and in mammalian cells for gene mutations (V79/HPRT test, Chinese hamster lung cells) and chromosome aberrations (V79 Chinese hamster cells). The results were negative in all 3in vitrotests. In the chromosome aberration test it is mentioned by the authors that the particles were phagocytosed; however, mutagenic effects were not observed.

Iron(III) oxide (Fe2O3) was also tested for gene mutations in bacteria, and based on the results it was deemed as non-mutagenic. Iron(III) oxide's mutagenicity was also examined in vivo with the Comet assay. DNA single strand breaks were measured in four types of cells (alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes) of rats after endotracheal administration of a single dose (3.75 mg/kg bw) of iron(III) oxide (Fe2O3). The result was negative.

The coverage of the present endpoint mainly depends on the 3 tests performed with iron(II,III) oxide (Fe3O4) particles. These studies are considered sufficient to cover the endpoint for genetic toxicity for all iron oxides. Owing to the lack of solubility of iron oxides, genetic toxicity is not expected, unless the particles are phagocytosed by the cells. This can be ruled out in the case of bacterial assays (Ames test), since phagocytosis does not occur. Regarding the mammalian cell mutagenicity, Fe3O4 particles were indeed observed within the cell in the chromosome aberration test but still, no mutagenic response was exerted. The aforementioned result can also be expected when other iron oxide particles are tested. Particle size is a determinative factor; large iron oxide particles, produced by abrasive techniques, will not enter the mammalian cell and thus, genetic toxicity testing is not really relevant.

It can be concluded that iron oxide particles are not mutagenic and no classification and labelling regarding genotoxicity is required.

Short description of key information:
Three in vitro studies with iron(II,III) oxide (Fe3O4) cover adequately this endpoint and are summarized as key studies. Two publications available in the public domain examined the mutagenicity of iron(III) oxide (Fe2O3) particles and were added as supporting studies. No mutagenic response was exhibited in any in vitro study with either substance. Additional information is provided by an in vivo study performed with Fe2O3 particles intratracheally instilled in rats. No DNA breaks were measured in 4 cell types tested. Based on these results iron oxides are considered non-mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification and labelling required based on the discussion above.