Abstract: Abstract: Objective To compare and evaluate the pulmonary toxic potential of metal oxide nanoparticles (NPs), including copper oxide, ferric oxide, titanium oxide and silica in C57/BL6 mice. Methods C57/BL6 mice were exposed to metal oxide NPs via intra-tracheal instillation. Mice survival rate, lung wet-dry ratio and the expression level of cytokines in mice BAL fluid were evaluated. Results All mice died within 24 h after administration of high dose copper oxide NPs, while no mice was found dead when the same dose of the other metal oxide NPs were administered. Mice exposed to copper oxide also had significantly higher lung wet-dry ratio and higher interleukin-6 expression level in BAL fluid compared to control group. The administration of the other metal oxides did not result in significant increase of lung wet-dry ratio or elevation of IL-6 in BAL fluid compared to control group. Conclusion Copper oxide NPs demonstrated high lethality in C57/BL6, and can cause pulmonary edema, resulting in acute lung injury. In comparison, the other metal oxide NPs have much lower toxic potential and have little pulmonary injury effect in mice at the doses we used. High expression of IL-6 may play an important role in copper oxide NP-induced acute lung injury.

Key words: Copper oxide, metal oxides, nanomaterials, acute lung injury