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

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 Ce-141 after intratracheal instillation (IT), gavage, or intravenous (IV) injection of neutron-activated (CeO2)-Ce-141 NPs and (CeCl3)-Ce-141 (ionic Ce-141) 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 (CeO2)-Ce-141 NPs or 0.1 mg kg(-1) (CeCl3)-Ce-141. Sequential analyses of lungs over 28 days showed slow lung clearance of (CeO2)-Ce-141 NPs (half-life = similar to 140 days) and of ionic Ce-141 (half-life = similar to 55 days). However, less than 1% and 6% of instilled Ce-141 was measured in selected extrapulmonary organs in (CeO2)-Ce-141 NPs and ionic Ce-141 groups, respectively. Following gavage (5 mg kg(-1)), nearly 100% of both test materials was excreted in the feces. Since detected Ce-141 activity in tissues could be in nanoparticulate or dissolved form, we also compared the Ce-141 tissue distribution post-IV injection with the IT and gavage data. Both IV-injected ionic (CeCl3)-Ce-141 and (CeO2)-Ce-141 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.