Fig. 13. Untargeted metabolomic analysis was used to reveal the effect of exposure of two different doses (12.5 and 25 μg mL⁻¹) of ZnO, SiO₂, TiO₂, and CeO₂ NPs on the metabolism of human bronchial epithelial cells (BEAS-2B). (a) Schematic diagram of the study workflow. (b) Hierarchical cellular stress responses based on metabolomics and functional assays. The cells were maintained in the healthy state at the tier 1 stage. At an intermediate level of cellular stress (tier 2), the exposure to SiO₂, TiO₂, and CeO₂ NPs altered several metabolic pathways and induced inflammation. At a high level of cellular stress (tier 3), ZnO NPs significantly affected toxicity and DNA damage related metabolic pathways. Only a short list of significantly altered pathways is presented due to the limited space. Adapted with permission from ref. 217 Copyright 2019, the American Chemical Society.