The most important inferences from the Ekaterinburg nanotoxicology team’s animal experiments assessing adverse health effects of metallic and metal oxide nanoparticles

During 2009–2017 we have studied nanoparticles of elemental silver or gold and of iron, copper, nickel, manganese, lead, zinc, aluminium and titanium oxides (Me-NPs) using, in most cases, a single low-dose intratracheal instillation 24 h before the bronchoalveolar lavage to obtain a fluid for cytological and biochemical assessment and, in all cases, repeated intraperitoneal injections in non-lethal doses to induce subchronic intoxications assessed by a lot of toxicodynamic and toxicokinetic features. We have also studied the same effects for a number of relevant combinations of these Me-NPs and have revealed some important patterns of their combined toxicity. Besides, we have carried out long-term inhalation experiments with Fe2O3, NiO and amorphous SiO2 nano-aerosols. We have demonstrated that Me-NPs are much more noxious as compared with their fine micrometric counterparts although the physiological mechanisms of their elimination from the lungs proved to be highly active. Even if water-insoluble, Me-NPs are significantly solubilized in some biological milieus in vitro and in vivo, which may explain some important peculiarities of their toxicity. At the same time, the in situ cytotoxicity, organ-systemic toxicity and in vivo genotoxicity of Me-NPs strongly depends on specific mechanisms characteristic of a particular metal. For some of the Me-NPs studied, we have proposed standards of presumably safe concentrations in workplace air. Along with this, we have proved that the adverse effects of Me-NPs could be significantly alleviated by background or preliminary administration of adequately composed combinations of some bioprotectors. Keywords: Metallic nanoparticles, Toxicity, Genotoxicity, Combined nano-impacts, Permissible exposure levels, Bioprotectio