Physico-chemical determinants of toxicity : a rational approach towards safer nanostructured materials.

Nanomaterials are engineered structures with dimensions of 100 nm or less, which achieve unique mechanical, optical, electrical and magnetic properties. Although these materials are already widely used in different applications, ranging from cosmetics and tires to medical applications, concerns about their effects on human health, in occupational settings and possibly for the consumer and the general population at large, are raised. A number of research reports have pointed towards their harmful effects on different target organs, which include the respiratory tract, the brain, the cardio-vascular system, the skin and the liver. Understanding how nanomaterials exert toxic effects and identifying physico-chemical determinants of nanomaterials toxicity are the main issues that will be investigated in collaboration with three other research groups (UCL-TOXI, KULeuven-LUNG and KULeuven-COK).

A single model material, i.e. silicon-based nanoparticles (SNP), will be used to assess genotoxicity and apoptosis in epithelial, endothelial and mesothelial cells by a reverse combinatorial approach. These in vitro data together with the in vitro data from the other research groups, concerning the production of inflammatory mediators by macrophages and platelet aggregation and coagulation, will be used to develop a paradigm for SNP toxicity that will be critically tested in vivo in two species (rat and mouse) with contrasting sensitivity. Additionally, the cellular and molecular mechanisms underlying the response to SNP toxicity will be investigated, focusing on interactions with the cytoskeletal proteins, induction of aneuploidy, effects on the DNA repair capacity and on cellular trafficking.