ICONS was launched in January of 2016 and creates a complementary and interdisciplinary collaboration between four laboratories in Romania, Belgium, Germany and the USA to integrate transnational expertise in the toxicology of multi-walled carbon nanotubes (MWCNT). ICONS will apply a structured range of relevant in vitro and in vivo toxicity assays to better understand toxicity mechanisms and determinants. The strategy is developed for a single type of MWCNT variation, i.e. surface functionalization, by addressing critical health effects of MWCNT (i.e. lung fibrosis and genotoxicity). Selected MWCNT with varying types and degrees of functionalization, all derived from the same MWCNT batch (Nanocyl NC7000) are under investigation.
The integrated experimental strategy includes four main steps:
(1) extensive characterisation of physico-chemical properties of pristine and functionalized MWCNT,
(2) testing them in a broad panel of in vitro assays, which will enable to compare samples for their capacity to generate a pro-fibrogenic or genotoxic response and to derive mechanistic conclusions,
(3) in vivo studies using oro-pharyngeal administration in two species (rats and mice) to identify relevant and meaningful MWCNT candidates for,
(4) a 28 days in vivo inhalation study in rats, which will serve for validation with respect to in vivo relevance, hazard and dose-response characterisation.
In addition, biopersistence, which is a very important determinant of chronic respiratory toxicity, is under investigation using oropharyngeal and inhalation studies to identify similarities and to derive a relation between these bioassays. Investigation of the functionalized MWCNT in artificial body fluids over time will provide information on the stability and structural/surfaces changes of the MWCNT in such media. These data will be related to biopersistence and toxicity data.
Overall, ICONS is aimed at integrating a complementary set of technical skills and scientific competences among investigators that will significantly advance mechanistic knowledge, nanomaterials safety testing and provide a high impact model for investigating physico-chemical determinants of their toxicity for advancing the safe implementation of nanotechnology.