Additionally, the committee noted that the available data did not provide convincing evidence of genotoxicity for titanium dioxide as a food additive, but recognized the limitations in current methodologies with respect to the testing of poorly soluble particulate materials. Although there were uncertainties in the genotoxicity data, the experts took into account the fact that the additive was not carcinogenic in adequately conducted two-year studies in mice and rats at doses of up to 7,500 mg/kg BW per day for mice, and 2,500 mg/kg BW per day for rats, the highest doses tested. There was also no evidence of reproductive or developmental toxicity in studies in rats at doses up to 1,000 mg/kg BW per day, the highest doses tested.  

Health advocates urge US regulators to ban common food coloring additive, by Tom Perkins, The Guardian, June 2, 2023

For research published in Archives of Toxicology in 2020, scientists fed one group of mice a solution containing titanium dioxide for one month, and compared it to those that did not receive the additive. They found “the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed” in the titanium dioxide group when compared with the control group. The tests also revealed that the titanium dioxide exposure could cause locomotor dysfunction, or mobility issues “by elevating the excitement of enteric neurons, which might spread to the brain via gut-brain communication by vagal pathway.” The researchers concluded: “These findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.”