Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy

• DOI: 10.1371/journal.pone.0127174
• Publication Date: 2015-05-21T17:55:02Z
• Authors: Lucian Farcal; Fernando Torres A...; Luisana Di Cristo; Bianca Maria Rotoli; Ovidio Bussolati; Enrico Bergamaschi; Agnieszka Mech; Nanna B. Hartmann; Kirsten Rasmussen; Juan Riego-Sintes; Jessica Ponti; Agnieszka Kinsner...; François Rossi; Agnes Oomen; Peter Bos; Rui Chen; Ru Bai; Chunying Chen; Louise Rocks; Norma Fulton; Bryony Ross; Gary Hutchison; Lang Tran; Sarah Mues; Rainer Ossig; Jürgen Schnekenbu...; Luisa Campagnolo; Lucia Vecchione; Antonio Pietroiusti; Bengt Fadeel
• Keywords: Nanomaterials; Nanotoxicology; In vitro toxicology; Reproductive toxicity

Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with objective to identify evaluate vitro test methods toxicity order facilitate development an intelligent testing strategy (ITS). Six representative oxide NMs provided by EC-JRC Repository were tested nine laboratories. evaluated 12 cellular models representing 6 different target organs/systems (immune system, respiratory gastrointestinal reproductive organs, kidney embryonic tissues). conducted using 10 assays cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion oxidative stress. Thorough characterization all Commercially relevant properties selected: two TiO2 surface chemistry - hydrophilic (NM-103) hydrophobic (NM-104), forms ZnO uncoated (NM-110) coated triethoxycapryl silane (NM-111) SiO2 produced manufacturing techniques precipitated (NM-200) pyrogenic (NM-203). Cell specific effects observed; macrophages most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 21 days) significantly affected barrier integrity presence ZnO, but not SiO2, while stem (EST) classified as potentially 'weak-embryotoxic' 'non-embryotoxic'. A hazard ranking could be established (ZnO NM-110 > NM-111 NM-203 NM-200 NM-104 NM-103). This case tissues, which displayed higher compared SiO2. Importantly, methodology applied cell- NM-specific responses, a low variability observed between assays. Overall, this approach, based on battery systems assays, complemented exhaustive NMs, deployed ITS suitable also provides rich source data modeling NM effects.