**6. Conclusions**

This review is a critical update of the current knowledge on underlying toxicological, molecular, and cellular mechanisms induced by exposure to Al2O3 NPs on the lungs. Human and animal studies point out that inhalation of Al2O3 particles can induce aluminosis, local respiratory symptoms (cough, shortness of breath), and pro-inflammatory response and may trigger long-term pulmonary fibrosis. Not enough cohort studies and clinical studies on healthy volunteers are performed to better understand these mechanisms and to establish clear exposure–response relationships. In studies with animals or cells, physico-chemistry of Al2O3 particles has to be extensively analyzed and published in order to improve the understanding of related biological effects. Inhalation exposures are closer to realistic environmental exposures, and long-term animal studies are necessary to determine whether pro-inflammatory reactions may reverse or turn into fatal diseases such as pulmonary fibrosis. Three-dimensional co-culture models may also allow studying these underlying pro-inflammatory and cytotoxic mechanisms for several weeks of exposure, as it was recently performed [64,65]. Consequently, in order to improve the analysis of pro-inflammatory and pro-fibrogenic effects, a combination of long-term animal studies by inhalation exposures and the use of dedicated 3D co-culture models is needed.

**Author Contributions:** Writing—original draft preparation, S.D. and A.B.; writing—review and editing, S.D. and S.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Informed Consent Statement:** Not applicable.

**Acknowledgments:** Authors kindly acknowledge Marco Valente for proofreading the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.
