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 (TiO 2 -NPs), the genotoxicity of TiO 2 -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 TiO 2 -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 TiO 2 -NP exposure considerably increased the percentage of DNA in tail and olive tail moment in comet assay. Gene mutation assay revealed that TiO 2 -NPs could also induce gene mutation. However, TiO 2 -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 TiO 2 -NPs. Moreover, mixed form and small particles of TiO 2 -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 TiO 2 -NPs influenced MN formation. This study presented that TiO 2 -NP exposure could cause genotoxicity in vitro. The physicochemical properties of TiO 2 -NPs and experimental protocols influence the genotoxic effects in vitro. Comet and gene mutation assays may be more sensitive to the detection of TiO 2 -NP genotoxic effects.