Hydrochemical reactivity. The reactivity of materials is considered key information and one of the key drivers for the observed increased toxicities of MNM as compared to bulk materials as well as ultrafine air-pollution particles. However, the term particle reactivity is not specifically defined and it cannot be considered as one parameter alone (Xxxxxx, Xxxxxx et al. 2014). In this work, the hydrochemical reactivity of MNM are considered to include the causticity (acid-base-reactivity) and oxidative-reductive activity as well as dissolution, transformation and interactions between particles and medium constituents in specific test item preparation and exposure mediums. Moreover, determination of these reactivity end-points in intracellular/ intraorganism compartments is also of critical importance as discussed above. Even-though the mentioned reactivity end-points are not fundamentally new, there are no standardized methods or protocols established in toxicology to measure and determine them for application in exposure characterization and hazard assessment. The lack of harmonized standard methods is an obstacle for establishment of potential causal relationships between the different reactivity phenomena and toxicological effects. However, as can be anticipated from chemical modeling, the solubility and reactivity of (at least some) materials are very sensitive to variations in the test conditions. For example, it has been demonstrated that the solubility of ZnO and speciation of dissolved Zn varies with the composition of the mediums, but also with the CO2 concentrations in the test atmosphere (Xxxxx, Galceran et al. 2012, Xx, Xxx et al. 2013, Xxxx, Xxxx et al. 2016). Consequently, to understand the true (or the most likely fate) of a test material in a specific test system; or in a cell or an organism; it is essential to study the reactivity in the specific mediums of interest and under the exact conditions of the test or exposure. Therefore, a generic in situ measurement methods are needed that can be used to detect and quantify the relevant reactivity parameters real-time at the specific exposure conditions. If successful, such methodologies can serve as a future high-throughput screening methods. At this point in time, the particle reactivity is usually only considered to be the surface reactivity and ability of the test materials to produce reactive oxygen species, such as superoxide and hydroxyl radicals (e.g., Xxx et al., 2006;(Xxx, Xxxxxxxxx et al. 2006, Arts, Xxxxx et ...
