Grouping of Poorly Soluble Low (Cyto)Toxic Particles: Example with 15 Selected Nanoparticles and A549 Human Lung...

Poorly soluble, low (cyto)toxic particles (PSLTs) are often regarded as one group, but it is important that these particles can be further differentiated based on their bioactivity. Currently, there are no biological endpoint based groupings for inhaled nanoparticles (NPs) that would allow us to subgroup PSLTs based on their mode of action. The aim of this study was to group NPs based on their cytotoxicity and by using the in vitro response of the endo-lysosomal system as a biological endpoint. The endo-lysosomal system is a main cellular loading site for NPs. An impaired endo-lysosomal system in alveolar type II cells may have serious adverse effects on the maintenance of pulmonary surfactant homeostasis. The 15 different NPs were tested with human lung adenocarcinoma (A549) cells. The highly soluble NPs were most cytotoxic. With respect to PSLTs, only three NPs increased the cellular load of acid and phospholipid rich organelles indicating particle biopersistence. All the rest PSLTs could be regarded as low hazardous. The presented in vitro test system could serve as a fast screening tool to group particles according to their ability to interfere with lung surfactant metabolism. We discuss the applicability of the suggested test system for bringing together substances with similar modes-of-action on lung epithelium. In addition, we discuss this approach as a benchmark test for the comparative assessment of biopersistence of PSLTs.