Abstract
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 the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry – hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO – uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques – precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially ‘weak-embryotoxic’ and ZnO and SiO2 NMs as ‘non-embryotoxic’. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2. Importantly, the in vitro methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.
Highlights
Due to their unique physico-chemical properties, nanomaterials (NMs) are commonly used in various applications in the industrial, electrical, pharmaceutical and biomedical fields [1] and are included in several consumer products such as cosmetics and food, or specially designed for imaging and drug delivery applications
Detailed descriptions of the physico-chemical properties of the NMs used in this study, as well as, the methods and SOPs used for their characterization can be found in recent JRC reports [21,22,23]
This is confirmed by Gas Chromatography—Mass Spectrometry (GC-MS) analysis which for both NMs identified the presence of different silanes
Summary
Due to their unique physico-chemical properties, nanomaterials (NMs) are commonly used in various applications in the industrial, electrical, pharmaceutical and biomedical fields [1] and are included in several consumer products such as cosmetics and food, or specially designed for imaging and drug delivery applications. In an ITS, data from i) in vivo, ii) in vitro tests, iii) in silico models and iv) physico-chemical properties are integrated as efficiently as possible with regard to costs, the number of experimental animals and time in order to reach a conclusion on potential risks in a specific exposure scenario [7]. In this aim, in vitro tests are especially relevant in an early phase of an ITS for screening purposes and for steering decisions for the choice of subsequent steps. In vitro tests can be used both for identification of potential, relevant toxicity endpoints as well as providing insight in the biokinetics of a specific NM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
