Assessment of Combined and Comparative Toxicity of Zinc Oxide and Copper Oxide Nanoparticles in the In Vivo Experiment

Abstract

Introduction: Apart from the targeted production of many metal and oxide nanomaterials with desired properties (so- called engineered nanoparticles) and their wide and diverse use in engineering, science, and medicine, even more important potential health risks to human health may be associated with some old technologies. Non-engineered metal oxide nanoparticles (MeO-NPs) generated spontaneously during arc welding, production of steel and non-ferrous metals, pollute the workplace and ambient air along with submicron particles (> 100 nm) of the same metal oxides. The most important sources of by-production of zinc oxide nanoparticles include primary smelting or re-smelting of brass, an alloy of copper and zinc of various proportions (sometimes with a much lower amount of lead, tin, and other metals). The rationale of the study of the comparative and combined toxicity of zinc oxide nanoparticles (ZnO-NPs) and copper oxide nanoparticles (CuO-NPs) is their simultaneous presence in aerosol emissions from brass metallurgy. The objective of our study was to estimate the comparative and combined toxicity of ZnO-NPs and CuO-NPs. Methods: Stable suspensions of MeO-NPs obtained by laser ablation of 99.99 % pure zinc and copper under a layer of deionized water, were injected intraperitoneally 18 times during 6 weeks to outbred male rats separately (in equal mass doses) or in combination for a comparative assessment and analysis of the type of the combined exposure to the studied nanoparticles for a large number of signs (including DNA fragmentation). Results: We established that, judging by some direct and indirect evidence, the subchronic effect of ZnO-NPs on the body was more detrimental than that of CuO-NPs. The mathematical description of the results using the response surface method showed that, similar to other previously studied binary toxic combinations, the response of the body to the combined exposure to CuO and ZnO nanoparticles was characterized by a complex interaction of various types of combined toxicity, depending on the effect it was evaluated for, the levels of the effect and doses. When analyzing the type of the combined effect of ZnO-NPs and CuO-NPs, we observed both the antagonism and additivity according to some indicators of the state of the body, which makes us evaluate their combined exposure as dangerous.