Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot?

Abstract

No detailed information on in vivo biokinetics of CeO₂ nanoparticles (NPs) following chronic low-dose inhalation is available. The CeO₂ burden for lung, lung-associated lymph nodes, and major non-pulmonary organs, blood, and feces, was determined in a chronic whole-body inhalation study in female Wistar rats undertaken according to OECD TG453 (6 h per day for 5 days per week for a 104 weeks with the following concentrations: 0, 0.1, 0.3, 1.0, and 3.0 mg/m³, animals were sacrificed after 3, 12, 24 months). Different spectroscopy methods (ICP-MS, ion-beam-microscopy) were used for the quantification of organ burden and for visualization of NP distribution patterns in tissues. After 24 months of exposure, the highest CeO₂ lung burden (4.41 mg per lung) was associated with the highest aerosol concentration and was proportionally lower for the other groups in a dose-dependent manner. Imaging techniques confirmed the presence of CeO₂ agglomerates of different size categories within lung tissue with a non-homogenous distribution. For the highest exposure group, after 24 months in total 1.2% of the dose retained in the lung was found in the organs and tissues analyzed in this study, excluding lymph nodes and skeleton. The CeO₂ burden per tissue decreased from lungs > lymph nodes > hard bone > liver > bone marrow. For two dosage groups, the liver organ burden showed a low accumulation rate. Here, the liver can be regarded as depot, whereas kidneys, the skeleton, and bone marrow seem to be dumps due to steadily increasing NP burden over time.

Keywords:

• Nanoparticle
• cerium dioxide
• inhalation toxicity
• chronic
• low-dose

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

The authors express their gratitude for this financial support by the European Commission. The authors acknowledge the service of J. Schoon, G. Duda, and S. Geißler (Julius Wolff Institute and Berlin-Brandenburg Center for Regenerative Therapies, both Charité, Berlin, Germany) who provided cryosections of the bone samples. The authors also thank S. Stumpp (Julius Wolff Institute) and Thomas Fischer, Katrin Maul and Philipp Reichardt (all at BfR) for their unremitting excellent technical assistance.

Disclosure statement

The authors declare no potential conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

The work reported here has been undertaken as part of the EU FP7 project ‘NANoREG’ [Grant Agreement number 310584].