Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro

Title:Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro

Volume: 15 Issue: 18

Author(s): Angela Ivask, Tiina Titma, Meeri Visnapuu, Heiki Vija, Aleksandr Kakinen, Mariliis Sihtmae, Suman Pokhrel, Lutz Madler, Margit Heinlaan, Vambola Kisand, Ruth Shimmo and Anne Kahru

Affiliation:

Keywords: In vitro toxicity, Metals, QSAR, Reactive oxygen species, Risk assessment, Safe by design, Solubilization.

Abstract: The knowledge on potential harmful effects of metallic nanomaterials lags behind their increased use in consumer products and therefore, the safety data on various nanomaterials applicable for risk assessment are urgently needed. In this study, 11 metal oxide nanoparticles (MeOx NPs) prepared using flame pyrolysis method were analyzed for their toxicity against human alveolar epithelial cells A549, human epithelial colorectal cells Caco2 and murine fibroblast cell line Balb/c 3T3. The cell lines were exposed for 24 h to suspensions of 3-100 μg/mL MeOx NPs and cellular viability was evaluated using. Neutral Red Uptake (NRU) assay. In parallel to NPs, toxicity of soluble salts of respective metals was analyzed, to reveal the possible cellular effects of metal ions shedding from the NPs. The potency of MeOx to produce reactive oxygen species was evaluated in the cell-free assay. The used three cell lines showed comparable toxicity responses to NPs and their metal ion counterparts in the current test setting. Six MeOx NPs (Al₂O₃, Fe₃O₄, MgO, SiO₂, TiO₂, WO₃) did not show toxic effects below 100 µg/mL. For five MeOx NPs, the averaged 24 h IC50 values for the three mammalian cell lines were 16.4 µg/mL for CuO, 22.4 µg/mL for ZnO, 57.3 µg/mL for Sb₂O₃, 132.3 µg/mL for Mn₃O₄ and 129 µg/mL for Co₃O₄. Comparison of the dissolution level of MeOx and the toxicity of soluble salts allowed to conclude that the toxicity of CuO, ZnO and Sb₂O₃ NPs was driven by release of metal ions. The toxic effects of Mn₃O₄ and Co₃O₄ could be attributed to the ROS-inducing ability of these NPs. All the NPs were internalized by the cells according to light microscopy studies but also proven by TEM, and internalization of Co₃O₄ NPs seemed to be most prominent in this aspect. In conclusion, this work provides valuable toxicological data for a library of 11 MeOx NPs. Combining the knowledge on toxic or non-toxic nature of nanomaterials may be used for safe-by-design approach.

Cite this article as:

Ivask Angela, Titma Tiina, Visnapuu Meeri, Vija Heiki, Kakinen Aleksandr, Sihtmae Mariliis, Pokhrel Suman, Madler Lutz, Heinlaan Margit, Kisand Vambola, Shimmo Ruth and Kahru Anne, Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro, Current Topics in Medicinal Chemistry 2015; 15 (18) . https://dx.doi.org/10.2174/1568026615666150506150109