Michael Bushell

Cerium oxide nanoparticles are promising materials as novel nanoscale therapeutics and are commonly used materials in industrial processes. Most cytotoxicity studies on cerium oxide nanoparticles are made from in-lab prepared materials making comparison between studies challenging, especially when performed on unique cell lines under non-standard conditions. Using commercially available nanoparticles we show that particle stability/agglomeration may be critical in determining the cytotoxicity in some cell lines, while in other cell lines, larger sized primary particles are linked to higher cytotoxicity, contrasting what has been reported in the literature for smaller cerium nanoparticles. To accelerate the development of cerium oxide enabled commercial processes and biomedical innovations, a clearer understanding of the interactions between cerium oxide nanoparticles and cells is needed to better understand their fate in and impact on biological systems.

Nickel oxide (NiO) nanoparticles from several manufacturers with different reported sizes and surface coatings were characterized prior to assessing their cellular toxicity. The physical characterization of these particles revealed that sizes often varied from those reported by the supplier, and that particles were heavily agglomerated when dispersed in water, resulting in a smaller surface area and larger hydrodynamic diameter upon dispersion. Cytotoxicity testing of these materials showed differences between samples; however, correlation of these differences with the physical properties of the materials was not conclusive. Generally, particles with higher surface area and smaller hydrodynamic diameter were more cytotoxic. While all samples produced an increase in reactive oxygen species (ROS), there was no correlation between the magnitude of the increase in ROS and the difference in cytotoxicity between different materials.

Physical chemical characterization of nanomaterials is critical to assessing quality control during production, evaluating the impact of material properties on human health and the environment, and developing regulatory frameworks for their use. We have investigated a set of 29 nanomaterials from four metal oxide families (aluminum, copper, titanium and zinc) with a focus on the measurands that are important for the basic characterization of dry nanomaterials and the determination of the dose metrics for nanotoxicology. These include crystalline phase and crystallite size, measured by powder X-ray diffraction, particle shape and size distributions from transmission electron microscopy, and specific surface area, measured by gas adsorption. The results are compared to the nominal data provided by the manufacturer, where available. While the crystalline phase data are generally reliable, data on minor components that may impact toxicity is often lacking. The crystal and particle size data highlight the issues in obtaining size measurements of materials with broad size distributions and significant levels of aggregation, and indicate that reliance on nominal values provided by the manufacturer is frequently inadequate for toxicological studies aimed at identifying differences between nanoforms. The data will be used for the development of models and strategies for grouping and read-across to support regulatory human health and environmental assessments of metal oxide nanomaterials.