Translocation of intranasal (i.n.) instillation of different-sized cerium dioxide (CeO2) particles: potential adverse effects in mice

Cerium oxide (CeO2), one of many engineered nanomaterials (ENMs), is composed primarily of metal oxides, such as cerium oxide (CeO2). CeO2-containing materials are widely used as a polishing agent for glass mirrors, plate glass, television tubes, ophthalmic lenses, and precision optics. The widespread use of this nanomaterial (NM) resulted in increased environmental contamination levels and consequent human exposure. However, the influence of Ce on humans remains to be determined. The aim of this study was to expose female ICR mice to varying nanoparticle sizes of 35 nm, 300 nm as well as a mixture of 1-5 µM CeO2 particles through intranasal (i.n.) instillation at 40 mg/kg dose on day 1, 3 and 5, and the experiment terminated on day 7. Histopathology findings demonstrated that hydropic degeneration was prominently associated with hemorrhage in renal cortex and medulla in all CeO2-administered groups. In liver of CeO2-exposed mice, hydropic degeneration was also prominent. Serum chemistries also indicated signs of renal and hepatic lesion as evidenced by significantly decreased serum levels of total bilirubin (TBIL) and total phosphate (TP) and activity of alkaline phosphatase (ALP). ICP-MS analysis group demonstrated that Ce levels were not significantly higher in liver and kidneys of mice exposed to 35 nm CeO2. An increase in Ce content was observed in hepatic and renal tissues of mice exposed to 300 nm or 1–5 µM CeO2. The levels of Ce were similar in these two groups suggesting a threshold level of Ce was attained regardless of NP size. Data thus demonstrated that i.n. instillation of different-sized CeO2 particles translocated to liver and kidney and that size difference of CeO2 particles did not exert significant in the observed histopathology responses.