Cerium Oxide Nanoparticles are More Toxic than Equimolar Bulk Cerium Oxide in Caenorhabditis elegans

Engineered cerium oxide nanoparticles (CeO₂ NPs) are widely used in biomedical and engineering manufacturing industries. Previous research has shown the ability of CeO₂ NPs to act as a redox catalyst, suggesting potential to both induce and alleviate oxidative stress in organisms. In this study, Caenorhabditis elegans and zebrafish (Danio rerio) were dosed with commercially available CeO₂ NPs. Non-nano cerium oxide powder (CeO₂) was used as a positive control for cerium toxicity. CeO₂ NPs suspended in standard United States Environmental Protection Agency reconstituted moderately hard water, used to culture the C. elegans, quickly formed large polydisperse aggregates. Dosing solutions were renewed daily for 3 days. Exposure of wild-type nematodes resulted in dose-dependent growth inhibition detected for all 3 days (p < 0.0001). Non-nano CeO₂ also caused significant growth inhibition (p < 0.0001), but the scale of inhibition was less at equivalent mass exposures compared with CeO₂ NP exposure. Some metal and oxidative stress-sensitive mutant nematode strains showed mildly altered growth relative to the wild-type when dosed with 5 mg/L CeO₂ NPs on days 2 and 3, thus providing weak evidence for a role for oxidative stress or metal sensitivity in CeO₂ NP toxicity. Zebrafish microinjected with CeO₂ NPs or CeO₂ did not exhibit increased gross developmental defects compared with controls. Hyperspectral imaging showed that CeO₂ NPs were ingested but not detectable inside the cells of C. elegans. Growth inhibition observed in C. elegans may be explained at least in part by a non-specific inhibition of feeding caused by CeO₂ NPs aggregating around bacterial food and/or inside the gut tract.