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

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. 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. 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. 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.