Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials

First steps towards an intelligent testing strategy

Lucian Farcal, Fernando Torres Andón, Luisana Di Cristo, Bianca Maria Rotoli, Ovidio Bussolati, Enrico Bergamaschi, Agnieszka Mech, Nanna B. Hartmann, Kirsten Rasmussen, Juan Riego-Sintes, Jessica Ponti, Agnieszka Kinsner-Ovaskainen, François Rossi, Agnes Oomen, Peter Bos, Rui Chen, Ru Bai, Chunying Chen, Louise Rocks, Norma Fulton & 10 others Bryony Ross, Gary Hutchison, Lang Tran, Sarah Mues, Rainer Ossig, Jürgen Schnekenburger, Luisa Campagnolo, Lucia Vecchione, Antonio Pietroiusti, Bengt Fadeel

Research output: Contribution to journalArticle

69 Citations (Scopus)

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.

Original languageEnglish
Article numbere0127174
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - May 21 2015

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nanomaterials
Nanostructures
toxicity testing
Nanostructured materials
Oxides
oxides
Toxicity
Testing
testing
In Vitro Techniques
toxicity
Assays
Risk assessment
Chemical properties
risk assessment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials : First steps towards an intelligent testing strategy. / Farcal, Lucian; Andón, Fernando Torres; Di Cristo, Luisana; Rotoli, Bianca Maria; Bussolati, Ovidio; Bergamaschi, Enrico; Mech, Agnieszka; Hartmann, Nanna B.; Rasmussen, Kirsten; Riego-Sintes, Juan; Ponti, Jessica; Kinsner-Ovaskainen, Agnieszka; Rossi, François; Oomen, Agnes; Bos, Peter; Chen, Rui; Bai, Ru; Chen, Chunying; Rocks, Louise; Fulton, Norma; Ross, Bryony; Hutchison, Gary; Tran, Lang; Mues, Sarah; Ossig, Rainer; Schnekenburger, Jürgen; Campagnolo, Luisa; Vecchione, Lucia; Pietroiusti, Antonio; Fadeel, Bengt.

In: PLoS One, Vol. 10, No. 5, e0127174, 21.05.2015.

Research output: Contribution to journalArticle

Farcal, L, Andón, FT, Di Cristo, L, Rotoli, BM, Bussolati, O, Bergamaschi, E, Mech, A, Hartmann, NB, Rasmussen, K, Riego-Sintes, J, Ponti, J, Kinsner-Ovaskainen, A, Rossi, F, Oomen, A, Bos, P, Chen, R, Bai, R, Chen, C, Rocks, L, Fulton, N, Ross, B, Hutchison, G, Tran, L, Mues, S, Ossig, R, Schnekenburger, J, Campagnolo, L, Vecchione, L, Pietroiusti, A & Fadeel, B 2015, 'Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: First steps towards an intelligent testing strategy', PLoS One, vol. 10, no. 5, e0127174. https://doi.org/10.1371/journal.pone.0127174
Farcal, Lucian ; Andón, Fernando Torres ; Di Cristo, Luisana ; Rotoli, Bianca Maria ; Bussolati, Ovidio ; Bergamaschi, Enrico ; Mech, Agnieszka ; Hartmann, Nanna B. ; Rasmussen, Kirsten ; Riego-Sintes, Juan ; Ponti, Jessica ; Kinsner-Ovaskainen, Agnieszka ; Rossi, François ; Oomen, Agnes ; Bos, Peter ; Chen, Rui ; Bai, Ru ; Chen, Chunying ; Rocks, Louise ; Fulton, Norma ; Ross, Bryony ; Hutchison, Gary ; Tran, Lang ; Mues, Sarah ; Ossig, Rainer ; Schnekenburger, Jürgen ; Campagnolo, Luisa ; Vecchione, Lucia ; Pietroiusti, Antonio ; Fadeel, Bengt. / Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials : First steps towards an intelligent testing strategy. In: PLoS One. 2015 ; Vol. 10, No. 5.
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AU - Bussolati, Ovidio

AU - Bergamaschi, Enrico

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AU - Ross, Bryony

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AU - Mues, Sarah

AU - Ossig, Rainer

AU - Schnekenburger, Jürgen

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