Evaluation of Toxicity Ranking for Metal Oxide Nanoparticles via an in Vitro Dosimetry Model

It has been argued that in vitro toxicity testing of engineered nanoparticles (NPs) should consider delivered dose (i.e., NP mass settled per suspension volume) rather than relying exclusively on administered dose (initial NP mass concentration). Delivered dose calculations require quantification of NP sedimentation in tissue cell culture media, taking into consideration fundamental suspension properties. In this article, we calculate delivered dose using a first-principles “particles in a box” sedimentation model, which accounts for the particle size distribution, fractal dimension, and permeability of agglomerated NPs. The sedimentation model was evaluated against external and our own experimental sedimentation data for metal oxide NPs. We then utilized the model to construct delivered dose–response analysis for a library of metal oxide NPs (previously used for hazard ranking and prediction making) in different cell culture media. Hierarchical hazard ranking of the seven (out of 24) toxic metal oxide NP...