Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study.

Version 1 : Received: 20 May 2021 / Approved: 21 May 2021 / Online: 21 May 2021 (13:17:36 CEST)

A peer-reviewed article of this Preprint also exists.

García-Salvador, A.; Katsumiti, A.; Rojas, E.; Aristimuño, C.; Betanzos, M.; Martínez-Moro, M.; Moya, S.E.; Goñi-de-Cerio, F. A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study. Nanomaterials 2021, 11, 1577. García-Salvador, A.; Katsumiti, A.; Rojas, E.; Aristimuño, C.; Betanzos, M.; Martínez-Moro, M.; Moya, S.E.; Goñi-de-Cerio, F. A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study. Nanomaterials 2021, 11, 1577.

Abstract

Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, toxicological effects of these ENMs should be further studied. Acute and subchronic toxicity of CeO2-NPs were assessed. First an in vitro multi-dose short-term (24h) toxicological assessment was performed in three different cell lines: A549 and Calu3, representing the lung tissue, and 3T3 as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well stablished reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air-Liquid Interface (ALI), to study long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENM, highlighting the need of subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in the organism.

Keywords

Cerium oxide NPs; acute and subchronic toxicity; in vitro; pulmonary and interstitial cell lines; human airway epithelial model; air-liquid interface; aerosolized NPs.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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