Dissolution behavior of metal oxide nanomaterials in cell culture medium versus distilled water

Solubility is a key criterion used in the hazard assessment of metal oxide–engineered nanomaterials (ENMs). The present study investigated solubility of CuO, NiO, and TiO 2 ENMs compared with their bulk analogues in two aqueous media: water and Dulbecco’s modified Eagle’s medium (DMEM). Particle size distributions were characterized using dynamic light scattering (DLS) and tunable resistive pulse sensing (TRPS). After centrifugal separation, the dissolved metal fraction was quantified using inductively coupled plasma optical emission spectroscopy (ICP-OES). Overall, solubility of the metal oxides decreased in the order CuO ≥ NiO > TiO 2 in both media, with each ENM displaying higher solubility than its bulk analogue. However, the metal oxide ENMs responded differently to the two aqueous media, when comparing their solubility using a low initial concentration (10 mg/L) versus a high initial concentration (100 mg/L). In DMEM, both nano-CuO and nano-NiO displayed increased solubility at the higher initial concentration by 3.8-fold and 1.4-fold, respectively. In water, this trend was reversed, with both nano-CuO and nano-NiO displaying increased solubility at the lower initial concentration by 3.3-fold and 1.2-fold, respectively. Interestingly, solubility trends displayed by nano-TiO 2 were the opposite of those displayed by nano-CuO and nano-NiO. In DMEM, nano-TiO 2 displayed decreased solubility at the higher initial concentration (0.3-fold), whereas in water, nano-TiO 2 displayed increased solubility at the higher initial concentration (5.5-fold). These results show the importance of evaluating the solubility of ENMs in biologically relevant fluids at concentrations that correspond to toxicity assays, for the purposes of read-across and grouping ENMs.