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Key value for chemical safety assessment

Additional information

Iron(II,III) oxide 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 abberations (V79 Chinese hamster cells). The results were negative in all 3 in vitro tests. In the chromosome abberation test it is mentioned by the authors that the particles were phagocytosed; however, mutagenic effects were not observed.

Iron(III) oxide 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 Fe2O3. The result was negative.

The coverage of the present endpoint mainly depends on the 3 tests performed with Fe3O4 particles. These studies are considered sufficient to cover the endpoint for genetic toxicity for all iron oxides (see read-across statement attached in overall summary of IUCLID Chapter 7). Due to 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 abberation test but still, no mutagenic response was exerted. Based on the read-across statement 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 Fe3O4 cover adequately this endpoint and are summarized as key studies. Two publications available in the public domain examined the mutagenicity of Fe2O3 particles and were added as supporting studies. No mutagenic response was exhibited in all in vitro studies with both substances. Additional information is provided by an in vivo study performed with Fe2O3 particles intraracheally 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.