Characterization of Nanoparticle Batch-To-Batch Variability

Sonja Mülhopt, Silvia Diabaté, Marco Dilger, Christel Adelhelm, Christopher Anderlohr, Thomas Bergfeldt, Johan Gómez de la Torre, Yunhong Jiang, Eugenia Valsami-Jones, Dominique Langevin, Iseult Lynch, Eugene Mahon, Inge Nelissen, Jordi Piella, Victor Puntes, Sikha Ray, Reinhard Schneider, Terry Wilkins, Carsten Weiss, Hanns-Rudolf Paur

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.