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PLoS One. 2015 May 21;10(5):e0127174. doi: 10.1371/journal.pone.0127174. eCollection 2015.

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

Author information

1
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
2
Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
3
Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
4
Nanobiosciences Unit, Institute for Health and Consumer Protection, European Commission-Joint Research Centre, Ispra, Italy.
5
Nanobiosciences Unit, Institute for Health and Consumer Protection, European Commission-Joint Research Centre, Ispra, Italy; Technical University of Denmark, Kongens Lyngby, Denmark.
6
National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
7
Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing, P. R. China.
8
Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland.
9
Centre for Nano Safety, Edinburgh Napier University, Edinburgh, United Kingdom.
10
Centre for Nano Safety, Edinburgh Napier University, Edinburgh, United Kingdom; Institute of Occupational Medicine, Edinburgh, United Kingdom.
11
Institute of Occupational Medicine, Edinburgh, United Kingdom.
12
Biomedizinisches Technologiezentrum, Westfälische Wilhelms-Universität, Münster, Germany.
13
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

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.

PMID:
25996496
PMCID:
PMC4440714
DOI:
10.1371/journal.pone.0127174
[Indexed for MEDLINE]
Free PMC Article

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