Human health no-effect levels of TiO2 nanoparticles as a function of their primary size

As engineered nanomaterials are increasingly introduced on the market into a broad range of commodities or nanoproducts, there is a need for operational, reliable tool, enabling to consistently assess the risks and impacts associated with the releases of nanoparticles. The lack of a developed metric that accurately represents their toxic effects while capturing the influence of the most relevant physicochemical properties is one of the major impediments. Here, we investigate the relationships between the toxic responses of nano-sized and micro-sized particles in in vivo toxicological studies and their physicochemical properties. Our results for TiO2 particles indicate statistically significant associations between the primary particle size and their toxicity responses for combined inhalation and ingestion exposure routes, although the numerical values should be considered with care due to the inability to encompass influences from other relevant physicochemical properties like surface coatings. These findings allow for expressing mass-based adverse effect levels as a continuous function of the primary size of particles. This meaningful, exploratory metric can thus be used for screening purposes and pave the way for reaching adaptive, robust risk assessments of nanomaterials, e.g. for setting up consistent threshold levels, as well as consistent life cycle assessments of nanoproducts. We provide examples of such applications.