Project

nanOxiMet

nanOxiMet – Oxidant generating capacity as a metric to allow grouping of nanomaterials and prediction of human health effects

Toxicological studies indicate that the specific surface area (SSA) and the oxidative potential (OP) of particles are highly promising metrics to predict the toxic potency of nanomaterials.

Thus the main objective of the nanOxiMet project was to evaluate a possible grouping of nanomaterials (NM) based on: (1) in- depth analysis of the physical chemical characteristics, especially their oxidative potential detected by different approaches and specific surface area and (2) evaluation of their potential toxic response in cells. Sixteen nanomaterials (e.g. TiO₂, CeO₂, Cu, Ni etc.) in suspension (deionized water and cell culture media) were investigated.

For the intrinsic characterisation not all methods were found to be useful or applicable. However, the electron paramagnetic resonance spectroscopy (EPR) appeared to be the most appropriate intrinsic oxidative potential analysis method. The BET method and dynamic light scattering are recommended for specific surface area determination and calculation, respectively.

However, only few moderate associations between specific surface area and toxicological endpoints were identified. For oxidative potential and specific surface area-adjusted oxidative potential, several associations with toxicological effects were found. EPR approaches were most strongly associated with endpoints related to cellular oxidative stress, but alternative oxidative potential methods also revealed complementary associations. This emphasises the need to use a set of oxidative potential methods that at least enables detection of potential Fenton-like reactivity and electron transfer.

The toxicological investigations yielded problems concerning the reliable detection of specific effects, further highlighting the importance of identifying assay artefacts. Cell-based oxidative potential analyses using fluorescence and EPR spectroscopy turned out to be most feasible. Good correlations were found between intrinsic and cell-based oxidative potential assays, but concurrent evaluation of both aspects is important to include all nanomaterials. Cellular effects could be ranked according to the 3-tiered oxidative stress paradigm. This was achieved for all 16 nanomaterials and hence verified its applicability to grouping approaches.

Schematic and statistical grouping revealed that oxidative potential analyses of nanomaterials are highly useful and applicable to existing grouping schemes. Oxidative potential and oxidative potential per specific surface area were identified as promising metrics in toxicological testing and grouping of nanomaterials. The nanOxiMet project approach is applicable to novel types of nanomaterials as well as materials for which detailed (in vivo) toxicity data are already available. This will result in (further) validation of oxidative potential and oxidative potential /specific surface area as metrics in nanomaterials grouping.

• Standard Operation Procedures (SOPs) and nanomaterials datasheets are available via the publication area.