Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 2: intratracheal instillation and intravenous injection.

Nanosized synthetic amorphous silicas (SAS) have been extensively used in food and tire industries. During industrial processes, they might be aerosolized leading to occupational exposure of workers mainly through inhalation. However, a few is known about the in vivo genotoxicity of these nanomaterials. In order to gain insight on their toxicological properties, 4 different SAS (NM 200, NM 201, NM 202 and NM 203) were administered to rats by intratracheal instillation 48, 24 and 3 hours prior to tissue collection. DNA damage was assessed using the erythrocyte micronucleus test, alkaline and Fpg-modified comet assay on cells isolated from bronchoalveolar lavage (BAL), lung, blood, spleen, liver, bone marrow and kidney. Methylmethane sulfonate and N-ethyl-N-nitrosourea were used as positive controls. Although all SAS induced a dose-dependent increase of lung inflammatory response demonstrated by an elevation of BAL neutrophilic granulocytes, none of them induced any genotoxicity since no increase of DNA damage in all tissues investigated and micronucleus frequency in bone marrow erythrocytes were detected. Since the amount of SAS reaching the blood stream and the internal organs is likely to be low following intratracheal instillation, an additional genotoxicity experiment was performed following a 3 day-repeated intravenous injection of NM 203. Despite the toxicity of this SAS inducing death, hepatotoxicity and thrombocytopenia, no significant increase of DNA damage and micronucleus frequency was observed in SAS-exposed animals. In our experimental conditions, after intratracheal instillation or intravenous injection, SAS induced obvious toxic effects but did not show any genotoxicity.