Towards a toxicologically relevant definition of nanomaterials (TO2DENANO)

Introduction and Background: Nanotechnology is one of the fastest growing technologies in the current century and is applied in many aspects of our daily life as Manufactured Nanoparticles (MNPs) or as Manufactured Nanomaterials (MNMs), e.g. in cosmetics and skin care products, clothing, food additives, waste water treatment, specific drug delivery in the body etc. Growing production and use of Manufactured nanomaterials (MNMs) increased the risk of human exposures and raised the global concern over the potential adverse effects of MNMs. In real world applications and in exposure scenarios, MNMs also exist as aggregates and/or agglomerates (AA) of primary particles with one or more external dimensions in the size range of 1 to 100 nm. However, the biological behaviour/toxicity of the AA is not explored in detail. In addition, the current EU definition for the MNM also comprised of AA, but its toxicological relevance is not verified. Such a discrepancy, not only affecting the risk assessment of MNMs but also hamper the application of regulations and the development of guidelines to monitor SNPs in products and goods. Methods: The nano-silica (nSiO2) will be used as a model to evaluate the influence of AA on toxicity and for size distribution, nano-titanium dioxide (nTiO2) will be used. In in vitro studies, MNMs will be exposed to human cell lines such as pulmonary human cell lines (e.g.16 HBE), intestinal cell lines (e.g. Caco2 cells) and macrophages (derived from monocytes THP-1). At the end of exposure, end points such as markers of inflammation (ELISA), oxidative stress (glutathione content) and genotoxicity (comet assay) will be assessed. For in-vivo studies, Swiss albino male mice will be exposed to MNM at different doses and sacrificed at different time points. At the end of exposure, the cells (lung, BAL, blood) will be routinely processed for comet assay to determine the genotoxic potential and, to investigate the other biological end points such as tissue damage, translocation of nanomaterial, markers of inflammation and oxidative stress. Expected outcomes: From the results of in vitro and in vivo studies, the influence of MNM AA and size distribution on toxicity will be compared and analysed. The biological responses due to chronic MNM exposure will also be evaluated. Furthermore, a better understanding of MNM interference at the biological barriers and potential to translocate across these barriers will be established. Subsequently, this project will contribute to build knowledge on the potential risk of MNM for the environment and for human beings, such that a safer use of these materials can be implemented. Building knowledge in this area is one of the prerequisite to safer design and further improvement of the nanotechnologies.Invited lecture, invited by: FPS Public Health, Belgiumstatus: Published onlin