# Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials
###### Abstract  
Surface-modified nano-SiO2 is a common additive in many products. However, the safety of nano-SiO2 products under various modifications is still unclear. In this study, we investigated the genotoxicity and acute pulmonary toxicity of nano-SiO2 with or without modification. The samples used in this study included: sample A (SA, 55.16 nm, 411.3 mg/mL), modified sample A (mSA, 82.29 nm, 37.7 mg/mL), sample B (SB, 22 nm, 358.0 mg/mL), and modified sample B (mSB, 86.64 nm, 37.7 mg/mL). In the genotoxicity study, we conducted an Ames test, chromosomal aberration test (CA), and a micronucleus (MN) test. The SA, mSA, and mSB groups showed negative results in all these genotoxicity tests. Only SB showed a weakly positive reaction in these assays, but the genotoxicity could be reversed after S9 metabolism or modification. In the acute pulmonary toxicity test, the rats were given an intratracheal instillation (IT) (0.5 mL/kg) of diluted samples and sacrificed after 1 or 14 days. The mortality rate, number of leukocytes and cytokines of TNF-\(\alpha\) in the bronchoalveolar lavage fluid (BALF), and the pathology in the lungs were determined. The results revealed that mSA posed acute toxicity in rats. After modification, the pulmonary toxicity was increased in mSA but decreased in mSB on Day 1, and no significant difference was observed on Day 14. In conclusion, there was no observed genotoxicity in either SA or SB, while mSA posed acute inhalation toxicity to rats that decreased in mSB after modification. This indicates that the decrease in pH level in SA and decrease in the solid content in SB are considered after the trifluroosilane surface-modified amorphous nano-silica.  
naporticle modification; genotoxicity; pulmonary toxicity; silica +
Footnote †: journal: Applied Sciences  
clearance ability of the lungs, the term \"particle overload\" is used to characterize these conditions. The hallmark of the particle-overloaded lung is an impairment of alveolar macrophage (AM)-mediated lung clearance which has been demonstrated in all species tested so far, and eventually leads to the accumulation of excessive lung burdens [6]. When particle overload occurs, it may induce many biological hazards that have been mentioned in previous studies, such as carcinogenesis [7], genotoxicity [8], and pulmonary toxicity [9].  
The toxicity of nano-silica in the lungs may vary according to different particle sizes and crystalline form [10]. Nano-silicas with smaller sizes induce more reactive oxygen species (ROS) in the lung [11; 12]. The ROS may interfere with cell function by interacting with macrophages and alveolar cells and induce DNA or protein damage [13; 14]. Therefore, nanomaterials may induce genotoxicity through direct or indirect pathways [15; 16; 17; 18; 19; 20; 21]. In recent research, surface modification of nano-silica has been developed. Surface modification may improve the dispersion [22], surface activity, and compatibility with other materials of nano-powder. Therefore, modification may produce new physical, chemical, and mechanical properties and functions in the applications of nanomaterials. In previous research, when compared to unmodified nonporous silica nanoparticles, amine modification of nonporous silica nanoparticles reduced murine lung inflammation and improved the overall biocompatibility of the nanomaterial [23].  
In this study, we focused on the evaluation of the toxicity and biocompatibility of trifluorosilane surface-modified amorphous nano-silica. To evaluate the changes of toxicity before and after the nano-silica modification, we conducted genotoxicity and rat pulmonary toxicity tests.