Nanoscale CeO₂ is increasingly used for industrial and commercial applications, including catalysis, UV-shielding and as an additive in various nanocomposites. Because of its increasing potential for consumer and occupational exposures, a comprehensive toxicological characterisation of this nanomaterial is needed. Preliminary results from intratracheal instillation studies in rats point to cytotoxicity and inflammation, though these studies may not accurately use realistic nanoscale exposure profiles. By contrast, published in vitro cellular studies have reported limited toxicological outcomes for the case of nano-ceria. Here, the authors present an integrative study evaluating the toxicity of nanoscale CeO₂ both in vitro, using the A549 lung epithelial cell line, and in vivo using an intact rat model. Realistic nano-ceria exposure atmospheres were generated using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES), and rats were exposed via inhalation. Finally, the use of a nanothin amorphous SiO₂ encapsulation coating as a means of mitigating CeO₂ toxicity was assessed. Results from the inhalation experiments show lung injury and inflammation with increased PMN and LDH levels in the bronchoalveolar lavage fluid of the CeO₂-exposed rats. Moreover, exposure to SiO₂-coated CeO₂ did not induce any pulmonary toxicity to the animals, representing clear evidence for the safe by design SiO₂-encapsualtion concept.