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Content archived on 2024-05-29

Cellular interaction and Toxicology with engineered Nanoparticles

Final Report Summary - CELLNANOTOX (Cellular interaction and toxicology with engineered nanoparticles)

The CELLNANOTOX project aimed to develop innovative multidisciplinary sets of tests and indicators for toxicological profiling of Nanoparticles (NPs), as well as to unravel the correlation between the physicochemical characteristics of NPs and their toxic potential on various organs of the human body.

The studies carried out within the CELLNANOTOC project addressed the needs of the European society for assessing the risk of occupational and general population exposure to industrially manufactured NPs. The initiative focussed 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 of novel synthesised NPs, whose size and surface chemistry was methodically modified. The project was expected to generate new knowledge on potential health risk or the absence of it, providing objective arguments for recommendations and regulations.

For a comprehensive understanding of the complex data to be obtained on toxicology of NPs based on in vitro and ex vivo studies, conventional toxicology combined with the methodologies of toxicogenomics, metabonomics, Knowledge discovery from data (KDD) and Data mining (DM) was employed. Since the penetration of NPs into the human body proceeded principally through inhalation or orally, whereas penetration through healthy skin was restricted, lung and intestine were chosen as the primary interacting tissues and organs with NPs, while liver, kidney and the immunological system were selected to be the secondary major sites of interaction, following the penetration of NPs into the blood circulation. The interaction of NPs with these different target organs was studied through 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 various cellular systems showed somewhat different susceptibility towards the exposure to NPs, though the overall trend of the toxicological response was similar. The toxicological response depended on the cellular model as well as on the duration of exposure to NPs. Longer exposure time resulted in higher toxicity than a short one. Large part of the observed toxicity could be attributed to the effect of ions which leached from the NPs into the extracellular millie. One of the consequences of being exposed to NPs was an oxidative stress imposed on the cells and an inflammatory response of the cells to NPs. It was finally verified, by using different methods, that NPs were able to internalise different cells.