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Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (ASiO2 NM)

Affiliation
EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
Brandão, Fátima;
Affiliation
EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
Costa, Carla;
Affiliation
EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
Bessa, Maria João;
Affiliation
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (Narilis), University of Namur, Namur, Belgium
Dumortier, Elise;
Affiliation
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (Narilis), University of Namur, Namur, Belgium
Debacq-Chainiaux, Florence;
Affiliation
StratiCELL Laboratories, Research and Development, Les Isnes, Belgium
Hubaux, Roland;
Affiliation
StratiCELL Laboratories, Research and Development, Les Isnes, Belgium
Salmon, Michel;
Affiliation
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (Narilis), University of Namur, Namur, Belgium
Laloy, Julie;
Affiliation
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Stan, Miruna S.;
Affiliation
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Hermenean, Anca;
Affiliation
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Gharbia, Sami;
Affiliation
Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
Dinischiotu, Anca;
Affiliation
Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
Bannuscher, Anne;
Affiliation
Institute of Energy and Environmental Technology (IUTA) e.V., Duisburg, Germany
Hellack, Bryan;
ORCID
0000-0002-5288-7876
Affiliation
Bundesinstitut für Risikobewertung (BfR), Abteilung 7 - Chemikalien- und Produktsicherheit, Fachgruppe 76 - Faser-und Nanotoxikologie
Haase, Andrea;
Affiliation
EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
Fraga, Sónia;
Affiliation
EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
Teixeira, João Paulo

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.

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