Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vitro: a Systematic Review of the Literature and Meta-analysis.

With the wide use of titanium dioxide nanoparticles (TiO2-NPs), the genotoxicity of TiO2-NPs, which is a factor for safety assessment, has attracted people's attention. However, their genotoxic effects in vitro remain controversial due to inconsistent reports. Therefore, a systematic review was conducted followed by a meta-analysis to reveal whether TiO2-NPs cause genotoxicity in vitro. A total of 59 studies were identified in this review through exhaustive database retrieval and exclusion. Meta-analysis results were presented based on different evaluation methods. The results showed that TiO2-NP exposure considerably increased the percentage of DNA in tail and olive tail moment in comet assay. Gene mutation assay revealed that TiO2-NPs could also induce gene mutation. However, TiO2-NP exposure had no effect on micronucleus (MN) formation in the MN assay. Subgroup analysis showed that normal cells were more vulnerable to toxicity induced by TiO2-NPs. Moreover, mixed form and small particles of TiO2-NPs increased the percentage of DNA in tail. In addition, short-term exposure could detect more DNA damage. The size, coating, duration, and concentration of TiO2-NPs influenced MN formation. This study presented that TiO2-NP exposure could cause genotoxicity in vitro. The physicochemical properties of TiO2-NPs and experimental protocols influence the genotoxic effects in vitro. Comet and gene mutation assays may be more sensitive to the detection of TiO2-NP genotoxic effects.