EURO-NanoTox is an internationally visible, national contact point in the field of nanotoxicology that will cover all aspects of the human toxicology of nano-structured materials. EURO-NanoTox is comprised of partner institutes based at different sites and is thus a “virtual center”. It is coordinated by the BioNanoNet Forschungsgesellschaft mbH.

The EURO-NanoTox testing portfolio

As described in the Euro-NanoTox strategic position paper, an Austrian platform for standardized in-vitro and in-vivo testing will be established. EURO-NanoTox will serve as an entry portal for researchers and industrial partners who seek critical toxicological data for nano-structured materials and want to develop research projects in this field.

The portfolio of EURO-NanoTox will be structured in the following way:

1. Formulation of testing strategies for nanostructured materials

  • Preparation of reviews concerning various classes or non-cited material based on the current literature
  • Formulation of testing strategies for the stepwise determination of human toxicology of nanostructured materials

2. Sample pre-evaluation

  • Physico-chemical characterization of nano-structured materials
  • Endotoxin testing of samples (Limulus amoebocyte lysate assay)

3. in-vitro testing

  • Cytotoxicity (viability, membrane integrity, proliferation, apoptosis, mitochondrial membrane potential, oxidative stress)

    Effect on route of entry cells (cell line used for screening in brackets)
    - Pulmonary delivery (A549)
    - Skin (HaCaT)
    - Nasal (16HBE14o)
    - Oral (CaCo-2)
    - Endothelium (EAhy 926)
    - Implants (L929 fibroblasts)

    Effect on specific organs
    - Liver (Tib-73, HepG2)
    - Kidney (HK-2, MDCK)
  • Hemocompatibility (hemolysis, prothrombin fragment 1+2, platelet activation, leukocyte activation, complement activation)
  • Immunotoxicology (activation of PBMC, cytokine release, lymphocyte proliferation, macrophage function)
  • Genotoxicology (micronucleus test)
  • Degradation of nano-structured materials
    - in buffer
    - in the presence of proteolytic enzymes
    - in blood
  • Effect on metabolism (Vivid Assay)

4. ex-vivo testing

  • Cytochrome P450 studies

5. in-vivo testing

In-vivo testing will be performed using only mice since a significantly smaller amount of nano-structure material will be needed than with rats. This is advantageous since the preparation of standardized nano-structured materials is expensive and often a limiting factor.

  • Systemic toxicology will be based on cytotoxicology and hemotoxicology data
    - Acute toxicology
    - Short term toxicology (≤ 1 month)
    - Chronic toxicology (≥ 12 month)
  • Immunotoxicology (performed on wild type mice for a 6 week period)
    - Humoral and cell-mediated immunological response (IgA/IgG isotyping, Th1/Th2 and CD4/CD8 typing)
    - Histopathology, primarily of organs involved in local and systemic antigen defence
  • Genotoxicology/Mutagenicity
    - P 53 mouse model
    - Mouse models sensitive to oxidative stress
  • Degradation of nano-structured materials
    - Investigation by mass spectroscopy in blood and/or specific organs
  • Effect on metabolism and clearing
    - Investigation by mass spectroscopy in blood and/or specific organs