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CEFIC-LRI N1 project: Genotoxicity of a synthetic amorphous silica (SAS) in rats

: Knebel, Jan

The Toxicologist 53 (2014), Nr.1, S.158, PS 601
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <53, 2014, Phoenix/Ariz.>
Fraunhofer ITEM ()

There is a debate about direct genotoxic potential of nanoparticles. Due to their high specific surface area, nanostructured materials are of special interest. Thus, genotoxicity was one focus in the expanded toxicity testing of NM-200. This test item is a synthetic amorphous, precipitated silica available at the EU JRC nanomaterials repository. As part of a subacute 14-day inhalation test in Wistar rats (strain: Crl:WU) with aerosol concentrations of 1, 5 and 25 mg/m3, a micronucleus test in vivo and a comet assay ex vivo with alveolar macrophages were conducted. Inhaled NM-200 did not significantly enhance the micronucleus frequency in polychromatic bone marrow erythrocytes of both male and female rats, i.e. was not clastogenic/aneugenic in this cell type. In the in vivo comet assay, particularly after the 14-days recovery period, a slight, concentration-dependent increase in DNA-damage was noted in BAL cells from NM-200 treated male rats, as compared to the negative controls, but there was no significant induction of oxidative DNAdamage. Nevertheless, a slight significant increase of 8-OH-dG positive nuclei was observed in lung epithelial cells by immunohistochemistry in all treatment groups at day 1 and day 14 postexposure. In a parallel in vitro comet assay with primary rat alveolar macrophages no significant clastogenic potential or potential to induce oxidative DNA-base lesions (8-OH-dG) was obvious, irrespective of cytotoxicity in the highest NM-200 concentration. In a chromosomal aberration test (OECD 473) NM-200 treated cultures demonstrated low aberration frequencies in the range of historic negative controls. Hence, the conclusion was 'unclassified' for structural chromosomal aberrations. Finally, NM-200 did not significantly increase mutant frequencies up to the limit concentration of 5000 g/ml in a mouse lymphoma assay (OECD 476) and thus exhibited no substance-specific mutagenic potential. Overall conclusion: For NM-200 there is no evidence for systemic or local genotoxic activity if applied to lungs of animals.