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Titanium dioxide is the most widely used whitening pigment in the world and has been linked to adverse health effects, particularly genotoxicity and intestinal inflammation. It is applied as food coloring and a whitening agent to a wide variety of foods, including chewing gum, cakes, candies, breads and ice cream. 

The production of ROS was studied on white blood cells as a model to screen the effect on eukaryotic cells after being exposed to samples and solar simulated irradiation (according to the level of penetration under the skin). For that purpose, the leukocytes were separated from anticoagulated fresh blood using the Ficoll-Hypaque reactive in a well-known technique [33]. Then, 50 μL of suspensions of P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL), vitaminB2@P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL) and vitamin B2 (0.2 mg/mL and 0.02 mg/mL) were prepared and mixed with 50 μL of white blood cells suspension. A solution of 3% H₂O₂ was used as positive control and PBS as negative control. Then, the samples were irradiated using the LED panel for 3 and 6 h to simulate the light penetration into the skin. Also, a set of samples was kept in the dark as control. Finally, the ROS were detected through the colorimetric assay employing the nitroblue tetrazolium salt (NBT salt) and the absorbance at 650 nm was measured. The experiment was reproduced twice; the standard deviation was calculated and p-value < 0.05 were considered significant.

if you compare the levels—which went as high as 50,000 milligrams/killigrams per day— to what humans are actually exposed to, we're talking orders of magnitude. It was a huge amount, Norbert Kaminski, PhD, a professor of pharmacology & toxicology and director of the Center for Research on Ingredient Safety at Michigan State University told Health.

For a review published in 2023 in the journal Environmental Pollution, researchers examined E171 as a possible factor promoting obesity-related metabolic disorders. Because gut microbiota play an important role in immune function maintenance and development, and because titanium dioxide as a food additive has been shown to alter gut microbiota, researchers wanted to review “the dysregulations along the gut microbiota-immune system axis after oral TiO2 exposure compared to those reported in obese or diabetic patients, and to highlight potential mechanisms by which foodborne TiO2 nanoparticles may increase the susceptibility to develop obesity-related metabolic disorders.” The study authors discovered recurrent changes in the gut microbiota composition when exposed to titanium dioxide nanoparticles, with an imbalance of intestinal symbiotic microbiota. These changes and imbalances were also reported and played a role in the development of obesity, the authors wrote. This highlights “foodborne TiO2 nanoparticles as an endocrine disruptor-like chemical promoting obesity-related disorders,” the authors concluded.

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Toxic effects of TiO₂ NPs on aquatic organisms