Respiratory toxicity of amorphous silica nanoparticles: a review

Silica nanoparticles exert detrimental effects on the respiratory system, regardless of the exposure route. The adverse outcome pathway framework has been recently developed in toxicological research to characterize the pathways that lead to harmful outcomes. Here, we review the adverse effects of amorphous silica nanoparticles on respiratory health with focus on underlying mechanisms and influencing factors, using the adverse outcome pathway framework for the first time. We found that the increase in reactive oxygen species levels induces oxidative stress and leads to mitochondrial dysfunction. Molecular changes further lead to cellular alterations such as epithelial injury, macrophage, and fibroblast activation. Respiratory cellular damage further induces inflammation and fibrosis in the lungs and airways.