24 Safe-by-Design Guidance for Multicomponent Nanostructured Materials (MCNM): Heavy Metals Containing Perovskites

Abstract Industry develops increasingly complex and advanced materials while incorporating the Safe-by-Design (SbD) concept into the R&D goals. Within HARMLESS (EU H2020), we use concepts of similarity for the risk screening during the SbD iterations. We rely predominantly on Novel Approach Methodologies (NAMs) due to ethical reasons, speed and parallel testing of several SbD versions. In general, aerosolization of nanostructured materials leading to inhalation of respirable fraction is considered one of the most important routes of exposure. Depending on the physicochemical properties of the materials, MCNM may either dissolve or persist within the lung. We selected in chimico NAMs (i.e., biodissolution in lung simulant fluids and surface reactivity assay) to understand how the properties of six different perovskites, intended to be used in the automotive catalysis sector, are connected to inhalation hazard endpoints. They all share a common concern: Co and Ni (heavy metals) in the structure. We found that the composition and surface properties play an important role in determining the particles fate upon inhalation, influencing metals bioavailability and the induced oxidative damage. At pH 7.5 and 4.5 simulant fluids, both relevant for pulmonary clearance, dissolution depended minimally on the noble metal doping but rather on the %weight of heavy metal in the structure. Furthermore, high surface reactivity was observed for all perovskites. Interestingly, the induced oxidative damage was correlating with the Ni %weight, surface thickness and Ni oxidation state. The results allowed us to rank different SbD versions against benchmarks, providing Safe-by-Design guidance on multicomponent, heavy metals-containing perovskites.