Integrative comparison of cadmium and iron oxide as yellow pigment in terms of cellular stress and genotoxicity in vitro and in vivo

Backgrounds: Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Considering the toxicity of cadmium, yellow iron oxide has been suggested as a substitute due to its cost-effectiveness. However, cellular and molecular safety information of yellow iron oxide is not fully understood. Methods: Metal-mediated cellular stress indicated by metallothionein 1 expression were measured by western blotting and qRT-PCR in cadmium- or iron oxide-treated HepG2 cells. Genotoxicity were detected using comet assay and micronuclei assay in HepG2 cells and rat liver tissue. Observed toxicological effects were quantified and scored on a scale bar for integrated analysis. Results: Yellow iron oxide showed significantly low metallothionein 1 expression and genotoxicity in all results. This result indicates high potential of iron oxide as an alternative to cadmium. Conclusion: We demonstrated the comparative toxicity of the cadmium and yellow iron oxide in terms of stress-responsive biomarker expression and genotoxicity in HepG2 cells and rat liver tissue. Our study with the integrated strategy suggests usefulness of the yellow iron oxide as a substitute material in cadmium-containing products and reports useful tool to comprehensively assess the toxicity of suspected toxicants or newly developed materials.