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.

In vitro cell transformation induced by synthetic amorphous silica nanoparticles

“…Interestingly, the same batches of SAS were evaluated for their toxicological effect in previous in vivo or in vitro studies. All four SAS were able to cause lung inflammation in rats by intratracheal instillation, but did not induce any DNA damage, neither in the lung nor in other secondary organs [11]. Similarly, none of them induced DNA damage in different tissues of rats exposed by gavage.…”

“…Data on the genotoxic properties of SAS, mostly assessed by the comet assay for detecting DNA damage or by the micronucleus assay for chromosomal damage, are however less clear. Generally, positive responses in genotoxicity assays are reported more frequently in vitro [5][6][7][8][9] than in vivo [10][11][12]. However, in vitro results remain quite variable and depend on the physical and chemical characteristics of the SAS and the cell type used.…”

Macrophages participate in local and systemic inflammation induced by amorphous silica nanoparticles through intratracheal instillation

“…Previous studies have reported the same phenomenon in vivo or in vitro. [10][11][12][13][14][15] The mitochondria were observed to be more susceptible than other organelles. In the heart and liver of the SiNP-treated group, more secondary lysosomes were observed than in the control group.…”

“…Hepatotoxicity following intravenous injections of SiNPs has been observed, as expected, because the liver is the primary organ for toxin biotransformation. [13][14][15] Li et al 16 found that acute oral administration of mesoporous SiNPs led to renal damage. Further, the intraperitoneal treatment of amorphous SiNPs probably induced inflammation and DNA damage in the lung, heart, liver, kidney, and brain.…”

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

“…In contrast, amorphous SiO 2 nanoparticles caused no morphologic change in Balb/3T3 cells and result in no genetic toxicity, as separately revealed by the Cell Transformation Test and the MN assay (Uboldi et al, 2012). Guichard et al discovered that no significance of DNA injury caused by artificial amorphous SiO 2 nanoparticle as evaluated applying the red blood cell MN test and the normative and Fpg-reformed SCEG on cells derived from broncho-alveolar lavage fluid (BALF), the lungs, sanguis, splenic organ, hepar, keest, and kidneys in rats treated with intratracheal instillations at 3, 24 and 48 h (Guichard et al, 2015). No obvious augment in DNA injury was noted in several tissues (sanguis, splenic organ from femur, hepar, keest, kidney, duodenum, and colon) of amorphous SiO 2 nanoparticles -exposed rats following oral exposure for 3 d using the alkaline and Fpg-reformed comet assays (Tarantini et al, 2015).…”