Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)

Abstract

Boris A Katsnelson,1 Larisa I Privalova,1 Marina P Sutunkova,1 Vladimir B Gurvich,1 Nadezhda V Loginova,1 Ilzira A Minigalieva,1 Ekaterina P Kireyeva,1 Vladimir Y Shur,2 Ekaterina V Shishkina,2 Ya B Beikin,3 Oleg H Makeyev,4 Irene E Valamina4 1The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, Russia; 2The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia; 3The City Clinical Diagnostics Centre, Ekaterinburg, Russia; 4The Ural State Medical University, Ekaterinburg, Russia Abstract: The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 µm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently conservative approach of decreasing approximately tenfold the exposure limits officially established for respective micro-scale industrial aerosols. It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity of metallic NPs could be markedly attenuated. Therefore we believe that, along with decreasing NP-exposures, enhancing organisms’ resistance to their adverse action with the help of such bioprotectors can prove an efficient auxiliary tool of health risk management in occupations connected with them. Keywords: nanoparticles, metals, metal oxides, toxicity