In vivo-induced size transformation of cerium oxide nanoparticles in both lung and liver does not affect long-term hepatic accumulation following pulmonary exposure

<div><p>Recent findings show that cerium oxide (CeO₂) nanoparticles may undergo <i>in vivo</i>-induced size transformation with the formation of smaller particles that could result in a higher translocation following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO₂). Therefore, we compared liver deposition of CeO₂ and TiO₂ nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 μg of NPs in female C57BL/6 mice. Mice exposed to 162 μg CeO₂ or TiO₂ nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO₂ nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO₂ nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO₂ nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO₂ and TiO₂ nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO₂ nanoparticles indicate <i>in vivo</i> processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.</p></div

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Additional file 2: of Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

Hepatic Saa1 mRNA expression level following intratracheal instillation, intravenous injection and oral gavage of 162 μg of TiO2, CeO2 or CB NPs 1, 28 and 180 days post-exposure. (DOCX 15 kb