nanOxiMet

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nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects

Toxicological studies indicate that the specific surface area (SSA) and the oxidative potential (OP) of particles are highly promising metrics to predict the toxic potency of nanomaterials.

Thus the main objective of the nanOxiMet project was to evaluate a possible grouping of nanomaterials (NM) based on: (1) in- depth analysis of the physical chemical characteristics, especially their oxidative potential detected by different approaches and specific surface area and (2) evaluation of their potential toxic response in cells. Sixteen nanomaterials (e.g. TiO2, CeO2, Cu, Ni etc.) in suspension (deionized water and cell culture media) were investigated.

For the intrinsic characterisation not all methods were found to be useful or applicable. However, the electron paramagnetic resonance spectroscopy (EPR) appeared to be the most appropriate intrinsic oxidative potential analysis method. The BET method and dynamic light scattering are recommended for specific surface area determination and calculation, respectively.

However, only few moderate associations between specific surface area and toxicological endpoints were identified. For oxidative potential and specific surface area-adjusted oxidative potential, several associations with toxicological effects were found. EPR approaches were most strongly associated with endpoints related to cellular oxidative stress, but alternative oxidative potential methods also revealed complementary associations. This emphasises the need to use a set of oxidative potential methods that at least enables detection of potential Fenton-like reactivity and electron transfer.

The toxicological investigations yielded problems concerning the reliable detection of specific effects, further highlighting the importance of identifying assay artefacts. Cell-based oxidative potential analyses using fluorescence and EPR spectroscopy turned out to be most feasible. Good correlations were found between intrinsic and cell-based oxidative potential assays, but concurrent evaluation of both aspects is important to include all nanomaterials. Cellular effects could be ranked according to the 3-tiered oxidative stress paradigm. This was achieved for all 16 nanomaterials and hence verified its applicability to grouping approaches.

Schematic and statistical grouping revealed that oxidative potential analyses of nanomaterials are highly useful and applicable to existing grouping schemes. Oxidative potential and oxidative potential per specific surface area were identified as promising metrics in toxicological testing and grouping of nanomaterials. The nanOxiMet project approach is applicable to novel types of nanomaterials as well as materials for which detailed (in vivo) toxicity data are already available. This will result in (further) validation of oxidative potential and oxidative potential /specific surface area as metrics in nanomaterials grouping.

  • Standard Operation Procedures (SOPs) and nanomaterials datasheets are available via the publication area.

Grant Number: ERA-Net SIINN - FKZ 03X0128
Duration: 01.06.2013 - 30.05.2016

Project Lead

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PD Dr. Thomas Kuhlbusch, Institute of Energy and Environmental Technology e.V. (IUTA)

Project Partners

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Institute of Energy and Environmental Technology e.V. (IUTA), Duisburg (DE)
Leibniz Institut für Umweltmedizinische Forschung (IUF) Logo
Leibniz Research Institute for Environmental Medicine (IUF) gGmbH, Duesseldorf (DE)
Universität Duisburg-Essen (UDE) Logo
Science Support Centre (SSC), University Duisburg-Essen (UDE), Essen (DE)
University Paris Diderot (UDP) Logo
Unit of Functional and Adaptive Biology (BFA), University Paris Diderot (UDP), Paris (FR)

Publications

  • nanOxiMet (2016) "Nanoparticle suspension preparation by cup horn sonication V1.1" [PDF, 205 KB]
  • nanOxiMet (2016) "Procedure for solubility testing of NM suspensions V1.0" [PDF, 157 KB]
  • nanOxiMet (2016) "Size distribution analysis by spray characterisation V1.0" [PDF, 355 KB]
  • nanOxiMet (2016) "Particle size and zeta potential analysis via DLS/ELS V1.1" [PDF, 166 KB]
  • nanOxiMet (2016) "Scanning Electron Microscopy (SEM) Analysis of Nanoparticle Samples V1.0" [PDF, 176 KB]
  • nanOxiMet (2016) "NMR spectroscopy analysis for specific surface area determination V1.0" [PDF, 173 KB]
  • nanOxiMet (2016) "Specific surface area analysis by BET theory V1.0" [PDF, 159 KB]
  • nanOxiMet (2016) "UV/VIS and optical band gap identification of NM suspensions V1.0" [PDF, 187 KB]
  • nanOxiMet (2016) "pH and Redox Potential Analysis V1.0" [PDF, 120 KB]
  • nanOxiMet (2015) "Cellular DCF-DA assay V1.0" [PDF, 330 KB]
  • nanOxiMet (2014) "EPR spectroscopy analysis using the spin probe CPH V1.0" [PDF, 181 KB]
  • nanOxiMet (2014) "EPR spectroscopy analysis using the spin trap DMPO for OH• detection V1.0" [PDF, 184 KB]
  • nanOxiMet (2014) "Cellular viability - WST-1 assay Protocol for adherent cells V2.0" [PDF, 191 KB]
  • nanOxiMet (2015) "Cellular viability - WST-1 assay in NR8383 macrophages V1.0" [PDF, 245 KB]

List of nanOxiMet Materials [PDF, 95 KB]    

2016

  • Aragao-Santiago L., L.C. Bui, A. Evola, S. Boland, A. Baeza-Squiban (2016). The oxidative potential of nanomaterials as a predictive indicator of their toxicity. European Society of Toxicology In Vitro (ESTIV) 2016 International Conference, 14-17 October 2016, Juan-les-Pins, France. [Poster]
  • Boland S. (2016). In vitro models of the human bronchial epithelium to study the toxicity of nanomaterials. Seminary at UMR-S 1139 INSERM/University of Paris Descartes, Paris, France. [Oral]
  • Hellack B., Aragao-Santiago L, Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Kolling J, Albrecht C, Schins RPF, Kuhlbusch TAJ (2016). Oxidantien-Bildungspotential als Maß für die Gruppierung von Nanomaterialien und Voraussage von gesundheitlichen Auswirkungen auf den Menschen. 2. NanoCare Clustertreffen, 03-04 May 2016, Frankfurt /M., Germany. [Oral]
  • Aragao-Santiago L., Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Albrecht C, Schins RPF (2016). The three tiers of oxidative stress response – Results of the nanOxiMet project. nanOxiMet workshop, 2. May 2016, Frankfurt /M., Germany. [Oral]
  • Hellack B, Kuhlbusch TAJ, Aragao-Santiago L, Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Kolling J, Albrecht C, Schins RPF (2016). Characterisation of NM – Results of the nanOxiMet project. nanOxiMet workshop, 2. May 2016, Frankfurt /M., Germany. [Oral]
  • Kuhlbusch TAJ, Aragao-Santiago L, Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Kolling J, Albrecht C, Schins RPF, Hellack B (2016). Oxidant Generating Capacity as a metric for grouping of nanomaterials – Results of the nanOxiMet project. nanOxiMet workshop, 2. May 2016, Frankfurt /M., Germany. [Oral]
  • Schins RPF, Kolling J, Neumeyer-Sickinger A, Albrecht C (2016). Oxidant generation properties and oxidative stress – Results of the nanOxiMet project. nanOxiMet workshop, 2. May 2016, Frankfurt /M., Germany. [Oral]
 

2015

  • Boland S, Santiago-Aragao L, Baeza-Squiban A, Neumeyer-Sickinger A, Albrecht C, Schins RPF, Hellack B, Kuhlbusch TAJ (2015). Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects: the nanOxiMet project. CompNanoTox 04-06 Nov 2015, Malaga, Spain. [Oral]
  • Hellack B., L.A. Santiago, S. Boland, A. Baeza-Squiban, A. Neumeyer-Sickinger, C. Albrecht, R.P.F. Schins, T.A.J. Kuhlbusch (2015). Surface area detection of nanomaterials for exposure and toxicological assessments. European Aerosol Conference, September 6–11, 2015, Milan, Italy. [Poster]
  • Hellack B, Aragao-Santiago L, Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Albrecht C, Schins RPF, Kuhlbusch TAJ (2015). Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. EuroNanoForum SIINN-ERANET Workshop, 10-12 Juni 2015, Riga, Latvia. [Oral]
  • Neumeyer-Sickinger A., C. Albrecht, J. Werner, R. Wedekind, B. Hellack, TAJ Kuhlbusch, R.P.F. Schins (2015). Nanopartikel-induzierte Toxizität, Entzündung und oxidativer Stress in Lungenzelllinien: Ergebnisse aus dem nanOxiMet Projekt. 1. Clustermeeting NanoCare, 19-20 May 2015, Frankfurt /M., Germany. [Poster]
  • Hellack B, Aragao-Santiago L, Boland S, Baeza-Squiban A, Neumeyer-Sickinger A, Albrecht C, Schins RPF, Kuhlbusch TAJ (2015). Oxidantien-Bildungspotential als Maß für die Gruppierung von Nanomaterialien und Voraussage von gesundheitlichen Auswirkungen auf den Menschen. 1. Clustermeeting NanoCare, 19-20 May 2015, Frankfurt /M., Germany. [Oral]
  • Neumeyer-Sickinger A., C. Albrecht, J. Werner, R. Wedekind, B. Hellack, T.A.J. Kuhlbusch, R.P.F. Schins (2015). Screening of the toxicity, oxidant generating and inflammogenic properties of sixteen types of nanoparticles. 81st Annual Congress of the DGPT 2015, Kiel, Germany. [Poster]
  • Aragao-Santiago L., L.C. Bui, J. Dairou, S. Boland. A. Baeza-Squiban (2015). Characterization of the oxidative potential of nanomaterials. Journée scientifique de l'Université Paris Diderot: L'environnement, parlons-en!, 2015, Paris, France. [Poster]
  • Baeza-Squiban A (2015). Evaluation du potentiel oxydant des nano matériaux pour prédire leur toxicité. Journées « Formation Ingénieurs Citoyens en Nano-microtechnologies », Lyon, France. [Oral]
  • Baeza-Squiban, A. (2015). Nanoparticle et stress oxydant. Ecole scientifique de GIENS (Groupe Interdisciplinaire pour l'étude des Effets environnementaux des NanotechnologieS), Luzarches, France. [Oral]
  • Boland S (2015). Atout et limites des tests in vitro pour évaluer la toxicité des nanoparticules. Séminaire du comité de direction et collège d'experts de Francopa, 2015, Paris, France. [Oral]
 

2014

  • Aragao-Santiago L, Bui LC, Dairou J, Boland S, Baeza-Squiban A (2014). Characterization of the oxidative potential of nanomaterials. The Fourth International Conference NANOSAFE 2014, Nov 2014, Grenoble, France. [Oral]
  • Kuhlbusch TAJ, Hellack B, Albrecht C, Schins RPF, Neumeyer A, Boland S, Baeza-Squiban A, Aragao-Santiago L(2014). NanOxiMet - Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. MODENA COST action work group meeting, 10-11 October 2014, Syracuse, Italy. [Oral]
  • Aragao-Santiago L, Boland S, Baeza-Squiban A (2014). Characterization of the oxidative potential of nanomaterials. Nanosafety Forum for Young Scientists, 8-9 October 2014, Syracuse, Italy. [Oral]
  • Boland S. (2014). Mechanisms of pulmonary toxicity induced by nanomaterials. Third workshop on the risk management of engineered nanomaterials, 22. August 2014, Tsukuba, Japan. [Oral]
  • Boland S., A. Baeza-Squiban, L. Aragao-Santiago (2014). Characterization of the oxidative potential of nanomaterials. International antioxidant congress, June 12–13 2014, Paris, France. [Poster]
  • Aragao-Santiago L., L.C. Bui, J. Dairou, S. Boland, A. Baeza-Squiban (2014). Characterization of the oxidative potential of nanomaterials. ESTIV2014, June 10-13, 2014, Egmond aan Zee, Netherlands. [Poster]
  • Aragao-Santiago L., L.C. Bui, J. Dairou, S. Boland, A. Baeza-Squiban (2014). Characterization of the oxidant potential of nanomaterials. NANOTOX 2014, 7th International Nanotoxicology Congress, April 23–26, 2014, Antalya, Turkey. [Poster]
  • Boland S., A. Baeza-Squiban, L. Aragao-Santiago (2014). Caractérisation du potentiel oxydant des nanoparticules. Congress of the Association for research in toxicology (Association pour la recherche en toxicologie – ARET), Paris, France. [Poster]
 

2013

  • Kuhlbusch T.A.J., B. Hellack, C. Asbach, L. Aragao-Santiago, S. Boland, A. Baeza‐Squiban, A. Neumeyer, C. Albrecht, R.P.F. Schins (2013). nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. NanoSafety 2013, 20-22 November 2013, Saarbrücken, Germany. [Poster]
  • Kuhlbusch T.A.J., B. Hellack, C. Asbach, L. Aragao-Santiago, S. Boland, A. Baeza‐Squiban, A. Neumeyer, C. Albrecht, R.P.F. Schins (2013). nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. 6th International Symposium on Nanotechnology, Occupational and Environmental Health, 28-31 October 2013, Nagoya, Japan. [Poster]
  • Kuhlbusch TAJ, Hellack B, Boland S, Baeza-Squiban A, Albrecht C und Schins R. (2013). Oxidantien-Bildungspotential als Maß für die Gruppierung von Nanomaterialien und Voraussage von gesundheitlichen Auswirkungen auf den Menschen. IUTA-Seminar, 25 Juli 2013, Duisburg, Germany. [Oral]
  • Kuhlbusch T.A.J., B. Hellack, S. Boland, A. Baeza‐Squiban, C. Albrecht, R.P.F. Schins (2013). nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. EuroNanoForum 2013, Dublin Ireland. [Poster]
  • Hellack B., S. Boland, A. Baeza‐Squiban, C. Albrecht, R.P.F. Schins, T.A.J. Kuhlbusch (2013). nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects. IPTC 2013. [Poster]
 
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