Safety assessment of cerium oxide nanoparticles: combined repeated-dose toxicity with reproductive/developmental toxicity screening and biodistribution in rats

Abstract

Cerium oxide nanoparticles (CeO₂ NPs) are widely used in various commercial applications because of their characteristic properties. People can be easily exposed to CeO₂ NPs in real life, but the safety assessment of CeO₂ NPs has not been fully investigated. Therefore, in this study, we conducted a combined repeated-dose and reproductive/developmental toxicity screening study (OECD testing guideline 422) to investigate the potential hazards on human health, including reproductive/developmental functions, after repeated daily CeO₂ NPs oral gavage administration to both males and females. In addition, tissues from parental animals and their pups were collected to analyze the internal accumulation of cerium. CeO₂ NPs were orally administered to Sprague-Dawley rats at doses of 0, 100, 300 and 1000 mg/kg during their pre-mating, mating, gestation and early lactation periods. In the general systemic and reproductive/developmental examinations, no marked toxicities were observed in any in-life and terminal observation parameters in this study. In the biodistribution analysis, cerium was not detected in either parental or pup tissues (blood, liver, lungs and kidneys). Repeated oral exposure of CeO₂ NPs did not induce marked toxicities affecting general systemic and reproductive/developmental functions up to the dose level of 1000 mg/kg and the CeO₂ NPs were not systemically absorbed in parental animals or their pups. This result could be used in risk assessment for humans, and additional toxicity studies with CeO₂ NPs will be necessary considering various physicochemical properties and exposure probabilities of these nanoparticles.

Keywords:

• Cerium oxide nanoparticles
• nanotoxicity
• safety assessment
• biodistribution

Acknowledgments

The authors especially thank the technical staff of the developmental and reproductive toxicology research group at KIT for their technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Institute of Environmental Research [Grant No. NIER-SP2013-141].