Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests

The increasing use of titanium dioxide (TiO₂) nanoparticles (NPs) has raised concern about the safety of food additive TiO₂. TiO₂ has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO₂ as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO₂ was limited. In order to investigate the potential genotoxicity of food additive TiO₂, we evaluated the genotoxicity of a commercial food additive TiO₂ (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO₂ neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO₂ does not have genotoxic potential although it contains a fraction of NPs.