Bioavailability, distribution and clearance of tracheally instilled, gavaged or injected cerium dioxide nanoparticles and ionic cerium

Abstract

Cerium oxide nanoparticles (NPs) have wide commercial applications. Understanding their fate in the body is fundamental to toxicological evaluations. We compared bioavailability, tissue distribution, clearance and excretion of radioactive ¹⁴¹Ce after intratracheal instillation (IT), gavage, or intravenous (IV) injection of neutron-activated ¹⁴¹CeO₂ NPs and ¹⁴¹CeCl₃ (ionic ¹⁴¹Ce) in Wistar Han rats. First, we evaluated pulmonary responses to IT-instilled CeO₂ NPs and CeCl₃ and observed dose-dependent inflammatory effects. Then, groups of rats were IT-instilled with 1 mg kg⁻¹ of ¹⁴¹CeO₂ NPs or 0.1 mg kg^{−1 141}CeCl₃. Sequential analyses of lungs over 28 days showed slow lung clearance of ¹⁴¹CeO₂ NPs (half-life = ~140 days) and of ionic ¹⁴¹Ce (half-life = ~55 days). However, less than 1% and 6% of instilled ¹⁴¹Ce was measured in selected extrapulmonary organs in ¹⁴¹CeO₂ NPs and ionic ¹⁴¹Ce groups, respectively. Following gavage (5 mg kg⁻¹), nearly 100% of both test materials was excreted in the feces. Since detected ¹⁴¹Ce activity in tissues could be in nanoparticulate or dissolved form, we also compared the ¹⁴¹Ce tissue distribution post-IV injection with the IT and gavage data. Both IV-injected ionic ¹⁴¹CeCl₃ and ¹⁴¹CeO₂ NPs were predominantly retained in the liver, bone and spleen, all organs that typically remove circulating particles. We conclude that nanoceria is slowly cleared from the lungs but has minimal extrapulmonary accumulation. Potential risks from prolonged pulmonary retention need further investigation. Risk from ingested nanoceria is likely far lower due to very low absorption and rapid elimination of ceria not absorbed from the gastrointestinal tract.