Nanotechnology enters the consumer market more and more. This will unavoidably results in an increased human exposure to manufactured nanomaterials. Monitoring this exposure is problematic because of the lack of defined standardized metrics and protocols. To support this lack, Sciensano aims to support a definition of manufactured nanomaterials (MNM) based on the most toxicologically relevant exposure metrics, and will provide some guidelines for further risk and toxicity analysis. The project specifically focuses on the influence of aggregation/agglomeration and size distribution of manufactured nanomaterials, two important aspects of the current EU definition of MNM, on their toxic activity.
Producers, researchers, and legislators are struggling to assess the impact of aggregation/agglomeration (AA) of MNM on the health risks. Since this aspect is included in the current legal description of MNM, the uncertainties concerning the role of AA are often debated. Unfortunately, sound scientific data on these aspects are lacking. It is generally accepted that for experimental conditions the poly-dispersity of the MNM should be as low as possible (meaning that the size distribution should be as small as possible). An important remark, which is often raised here, is that in ‘real live’ exposure rather happens to poly-disperse MNM and that preparations with a narrow size range are often only used in high tech products. In this research project; we will investigate the aspect of size distribution since it is not clear whether this makes a significant difference in observed biological effects. This issue also represents a challenge for those who measure/analyze the presence of MNM in the environment or samples. To achieve this, nanosilica (nSiO2) is being used as the model for aggregates and nano titanium dioxide (nTiO2) as the model for agglomerates.
By estimating an extensive set of measurands using complementary validated methods, the size and morphological properties of the examined MNM will be characterized in detail. The MNM will be characterized in their pristine state, in the stock dispersion and in the exposure media for in vivo and in vitro assays using state-of-the-art methods including transmission electron microscopy (TEM). In parallel with the TEM experiments, Atomic-Force Microscopy (AFM) measurements will be performed on the different materials in order to characterize their size, size distribution and shape.
Further, in vivo nanotoxicology experiments will be performed to study the influence of NM-dispersions, i.e. AA state and size distribution, on NM uptake by inhalation and ingestion. Also, we will investigate in a structured manner how similar primary MNP (manufactured nanoparticles), with a different state of AA or different size distribution, induce similar and/or different effects in vitro and in vivo.