Grant Agreement no. 032731. 6^th FP related to toxicological issues and safety risk identification in novel materials for nanopharmaceutical applications. – closed in 2009

The present proposal aims at the development of innovative multidisciplinary sets of tests and indicators for toxicological profiling of nanoparticles (NPs) as well as unravelling the correlation between the physicochemical characteristics of NPs and their toxic potential on various organs of the human body. For a comprehensive understanding of the complex data to be obtained on toxicology of NPs, based on in-vitro and ex-vivo studies, we will employ conventional toxicology combined with the methodologies of toxicogenomics, metabonomics, Knowledge Discovery from Data (KDD) and Data Mining (DM). This research program is focused towards understanding the relation of size and surface chemistry on the deposition, uptake, translocation, and toxicity of a few selected industrially important NPs as well as novel synthesized NPs, whose size and surface chemistry will be methodically modified. Since it was shown that the penetration of NPs into the human body proceeds principally through inhalation or orally, whereas penetration through healthy skin is restricted, we have chosen lung and intestine as the primary interacting tissues/organs with NPs, while liver, kidney and the immunological system have been selected to be the secondary major sites of interaction, following the penetration of NPs into the blood circulation. The interaction of the NPs with these different target organs will be studied by making use of alternative methods to animal experimentation by employing in-vitro cell systems as well as ex-vivo studies based on precision-cut slices of lung, liver and kidney. The present proposal addresses the needs of the European society for assessing the risk of occupational and general population exposure to industrially manufactured NPs. It will generate new knowledge on potential health risk or the absence of it, providing objective arguments for recommendations and regulations.