Comprehensive Evaluation of the Genotoxic Potential of Food Additive Titanium Dioxide in Human Intestinal Cell Systems

Titanium dioxide (TiO₂), widely recognized as a whitening food additive, has been extensively employed in food products such as confectionery, sauces, and coffee creamers. The potential genotoxicity of TiO₂ has recently raised increasing concern, especially after the European Union prohibited its use as a food additive due to genotoxicity risks. The contradictory outcomes of in vitro and in vivo studies emphasize the necessity for more rigorous and systematic evaluation. In this study, we assessed the potential genotoxicity of food-grade TiO₂ in human intestinal cell lines and intestinal barrier models. Three distinct genotoxicity assays were conducted: the comet assay (DNA tail formation), chromosomal aberration analysis, and the micronucleus assay. The results revealed that TiO₂ exposure led to DNA damage primarily associated with oxidative stress in various intestinal cell systems at actual intake levels, regardless of metabolic activation; however, it did not trigger chromosomal aberrations or micronucleus formation. Thus, TiO₂ appears to cause in vitro genotoxic damage at the DNA level, but not at macroscopic endpoints, such as chromosomal aberrations or micronucleus formation. Further in-depth in vivo study is required to definitively determine the potential genotoxicity of TiO₂ in the food industry.