title: Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 2: intratracheal instillation and intravenous injection.
abstract: Synthetic amorphous silica nanomaterials (SAS) are extensively used in food and tire industries. In many industrial processes, SAS may become aerosolized and lead to occupational exposure of workers through inhalation in particular. However, little is known about the in vivo genotoxicity of these particulate materials. To gain insight into the toxicological properties of four SAS (NM-200, NM-201, NM-202, and NM-203), rats are treated with three consecutive intratracheal instillations of 3, 6, or 12 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection (cumulative doses of 9, 18, and 36 mg/kg). Deoxyribonucleic acid (DNA) damage was assessed using erythrocyte micronucleus test and the standard and Fpg-modified comet assays on cells from bronchoalveolar lavage fluid (BALF), lung, blood, spleen, liver, bone marrow, and kidney. Although all of the SAS caused increased dose-dependent changes in lung inflammation as demonstrated by BALF neutrophilia, they did not induce any significant DNA damage. As the amount of SAS reaching the blood stream and subsequently the internal organs is probably to be low following intratracheal instillation, an additional experiment was performed with NM-203. Rats received three consecutive intravenous injections of 5, 10, or 20 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection. Despite the hepatotoxicity, thrombocytopenia, and even animal death induced by this nanomaterial, no significant increase in DNA damage or micronucleus frequency was observed in SAS-exposed animals. It was concluded that under experimental conditions, SAS induced obvious toxic effects but did cause any genotoxicity following intratracheal instillation and intravenous injection.
authors.affiliation: INRS, Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, 54519, Vandoeuvre les Nancy Cedex, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Guichard
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Maire
authors.forename: Sylvie
authors.initials: S
authors.lastname: Sébillaud
authors.forename: Caroline
authors.initials: C
authors.lastname: Fontana
authors.forename: Cristina
authors.initials: C
authors.lastname: Langlais
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Micillino
authors.forename: Christian
authors.initials: C
authors.lastname: Darne
authors.forename: Joanna
authors.initials: J
authors.lastname: Roszak
authors.forename: Maciej
authors.initials: M
authors.lastname: Stępnik
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Binet
authors.forename: Laurent
authors.initials: L
authors.lastname: Gaté
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000097:blood; D015162:Micronucleus Tests; D009153:Mutagens / Q000009:adverse effects; D053758:Nanoparticles / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D012822:Silicon Dioxide / Q000009:adverse effects* / Q000138:chemical synthesis; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D009153:Mutagens; D008315:Malondialdehyde; D012822:Silicon Dioxide
keywords: in vivo comet assay; mammalian erythrocyte micronucleus assay; nanoparticle; synthetic amorphous silica