We demonstrate for 24
metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (E(c)) levels with the cellular redox potential (-4.12 to -4.84 eV) was strongly correlated to the ability of
Co(3)O(4), Cr(2)O(3), Ni(2)O(3), Mn(2)O(3), and
CoO nanoparticles to induce
oxygen radicals, oxidative stress, and
inflammation. This outcome is premised on permissible electron transfers from the
biological redox couples that maintain the cellular redox equilibrium to the conduction band of the
semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic
inflammation and
cytokine responses in the lungs of C57 BL/6 mice.
Co(3)O(4), Ni(2)O(3), Mn(2)O(3), and
CoO nanoparticles could also oxidize
cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute
pulmonary inflammation that is not predicted by E(c) levels, the adverse
biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. These results demonstrate that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on
semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials.