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Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure, part 2: Intratracheal instillation and intravenous injection
Author(s) -
Guichard Yves,
Maire MarieAline,
Sébillaud Sylvie,
Fontana Caroline,
Langlais Cristina,
Micillino JeanClaude,
Darne Christian,
Roszak Joanna,
Stępnik Maciej,
Fessard Valérie,
Binet Stéphane,
Gaté Laurent
Publication year - 2015
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21928
Subject(s) - micronucleus test , genotoxicity , bronchoalveolar lavage , comet assay , neutrophilia , dna damage , pharmacology , inhalation exposure , intratracheal instillation , spleen , in vivo , lung , micronucleus , toxicity , chemistry , toxicology , inhalation , medicine , immunology , biology , anesthesia , dna , biochemistry , microbiology and biotechnology
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. Environ. Mol. Mutagen. 56:228–244, 2015. © 2014 Wiley Periodicals, Inc.