A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced.

In cell culture studies, foetal calf serum (FCS) comprising numerous different proteins is added, which might coat the surface of engineered nanomaterials (ENMs) and thus could profoundly alter their biological activities. In this study, a panel of industrially most relevant metal oxide nanoparticles (NPs) was screened for toxic effects in A549 lung epithelial cells and RAW264.7 macrophages in the presence and absence of FCS. In medium without FCS amorphous SiO₂-NPs were the most cytotoxic NPs and induced a significant pro-inflammatory response in both cell types. An increased anti-oxidative response after exposure to SiO₂-NPs was, however, only observed in RAW264.7 macrophages. Furthermore, pre-coating of SiO₂-NPs with FCS proteins or simply bovine serum albumin abrogated responses in A549 lung epithelial cells. Thus, the protein corona bound to the surface of SiO₂-NPs suppresses their biological effects, an issue which needs to be more carefully considered for in vitro–in vivo extrapolations.