Differences in the toxicity of cerium dioxide nanomaterials after inhalation can be explained by lung deposition, animal species and nanoforms

Abstract

Considerable differences in pulmonary responses have been observed in animals exposed to cerium dioxide nanoparticles via inhalation. These differences in pulmonary toxicity might be explained by differences in lung deposition, species susceptibility or physicochemical characteristics of the tested cerium dioxide nanoforms (i.e. same chemical substance, different size, shape, surface area or surface chemistry). In order to distinguish the relative importance of these different influencing factors, we performed a detailed analysis of the data from several inhalation studies with different exposure durations, species and nanoforms, namely published data on NM211 and NM212 (JRC repository), NanoAmor (commercially available) and our published and unpublished data on PROM (industry provided). Data were analyzed by comparing the observed pulmonary responses at similar external and internal dose levels. Our analyses confirm that rats are more sensitive to developing pulmonary inflammation compared to mice. The observed differences in responses do not result purely from differences in the delivered and retained doses (expressed in particle mass as well as surface area). In addition, the different nanoforms assessed showed differences in toxic potency likely due to differences in their physicochemical parameters. Primary particle and aggregate/agglomerate size distributions have a substantial impact on the deposited dose and consequently on the pulmonary response. However, in our evaluation size could not fully explain the difference observed in the analyzed studies indicating that the pulmonary response also depends on other physicochemical characteristics of the particles. It remains to be determined to what extent these findings can be generalized to other poorly soluble nanomaterials.

KEYWORDS:

• Cerium dioxide
• nanomaterial
• species differences
• nanoform
• inhalation
• toxicity
• lung deposition

Acknowledgments

The authors would like to thank Dr Wendel Wohlleben and Kai Werle for the reactivity analysis using the Ferric Reduction Ability of Serum assay.

Disclosure statement

The contents of this paper do not necessarily reflect the views and polices of the RIVM or those of the Netherlands Ministry of Infrastructures and Water Management. The authors have no conflict of interest to disclose. Lan Ma-Hock, Jana Keller, Karin Küttler, Volker Strauss and Robert Landsiedel are employees of BASF SE, a chemical company producing and marketing nanomaterials (but not the test materials of the present study, which were selected based on purely scientific considerations).