ICONS – Integrated Testing Strategy for mechanistic assessment of the respiratory toxicity of functionalized multiwalled carbon nanotubes (MWCNT)
The ERA-NET SIINN project ICONS, coordinated by the University of Leuven (B), will be performed in cooperation with the partners University of Babes-Bolyai (RO), University of North Carolina (USA), and Fraunhofer ITEM (D).
ICONS will use a variety of relevant in vitro and in vivo toxicity tests to better understand the mechanistic basis of multi-walled carbon nanotubes (MWCNT) toxicity and the physico-chemical parameters that result in toxic effects.
The strategy will be developed with regard to MWCNT modification, namely surface functionalisation, with a focus on investigating two critical health risks of MWCNT (pulmonary fibrosis and genotoxicity). Selected multi-walled carbon nanotubes with different types and degrees of functionalisation, all derived from the same MWCNT batch (Nanocyl NC7000), will be studied under four main aspects with the same experimental strategy:
- Detailed characterisation of physico-chemical properties of pristine and functionalised multi-walled carbon nanotubes
- Testing with a broad range of in-vitro assays, enabling comparison of samples with regards to their ability to induce pro-fibrogenic or genotoxic responses and drawing of mechanistic conclusions
- In vivo study using oro-pharyngeal aspiration in two species (rat and mouse) to identify relevant and meaningful MWCNT candidates.
- A 28-day in vivo inhalation study in rats for validation regarding comparability of in vitro vs. in vivo, hazard and dose-response characterisation.
In addition, biopersistence analysis will be carried out, as this is a very important factor of chronic inhalation toxicity. This analysis will be performed in parallel with the oro-pharyngeal aspiration and the inhalation study to enable identification of similarities and allow derivation of a correlation between these bioassays.
Investigation of functionalised multi-walled carbon nanotubes in artificial body fluids over a defined period of time will provide insights into the stability and structural changes on the surfaces of multi-walled carbon nanotubes in such media. These data will be correlated with the biopersistence and toxicity data.
Overall, ICONS will bring together complementary methods and scientific expertise that will substantially advance mechanistic know-how and safety testing of nanomaterials.
Prof. Dr. Dominique Lison, Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université catholique de Louvain, Louvain-La-Neuve (BE)
Louvain Centre for Toxicology and Applied Pharmacology (LTAP),
Université catholique de Louvain, Louvain-La-Neuve, Belgien (BE)
University Babes-Bolyai, Cluj-Napoca (RO)
Fraunhofer-Institute for Toxicology and Experimental Medicine (ITEM), Hannover (DE))
North Carolina State University, Raleigh, NC (USA)