Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM)

This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials.Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.This work was funded by the Portuguese Foundation for Science and Technology (FCT) through ERA-NET SIINN project NanoToxClass (SIINN/0001/2013). FB and MJB are recipients of FCT PhD scholarships (SFRH/BD/101060/2014 and SFRH/BD/12046/2016). Thanks are due to FCT/MCTES for the financial support through national funds to EPIUnit (UIDB/04750/2020). J. Laloy performed STIS at the University of Namur with funding provided by BfR (grant agreement number 1329-561). F. Debacq-Chainiaux is a research associate at FRS-FNRS (National Funds for Scientific Research, Belgium).info:eu-repo/semantics/publishedVersio