Hierarchical stress response following exposure to increasing concentration of AEROSIL® 200 fumed amorphous silica NPs. A549 cells (n = 3) were exposed for 24 h to increasing concentrations of fumed silica AEROSIL® 200 NPs (0.1, 1.0, 1.5, 3.0 and 6.0 μg/cm2). Between 1.0 and 1.5 μg/cm2, the silica NPs activated Rho signaling pathways and clathrin-mediated endocytosis. From 3.0 μg/cm2, proinflammatory effectors were activated and the “coagulation system pathway” was triggered. Beyond 6.0 μg/cm2, the pathways of “xenobiotic metabolism” and “acute phase response” were activated. The vertical scale represents the percentage of dead cells, as determined by ATP assays, in relation to the tested doses of silica NPs. These data exemplify the paradigm of dose dependent toxic events developed by Meng et al. . This figure is freely adapted from their scheme with permission from Meng et al. , American Chemical Society, although the quantitative data and pathways are those obtained in experiments described in the current article.