For research published in 2022 study in the journal Food and Chemical Toxicology, scientists examined “the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO2 nanomaterials in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs’ physiochemical characteristics.” They found a “DNA-damaging effect dependent on the nanomaterial,” along with the micronucleus assay suggesting “effects on chromosomal integrity, an indicator of cancer risk, in the HT29-MTX-E12 cells, for all the tested TiO2 nanomaterials.” Researchers concluded that the results showcase “evidence of concern” regarding titanium dioxide used as a food additive.

Below 10% substitution, 1 kg of TiO2 should be replaced by 1 kg of Lithopone 30%.  

Fig. 4. Hemolysis (%) values of samples, A: 0.2 mg/mL P25TiO₂NPs; B: 0.02 mg/mL P25TiO₂NPs; C: 0.2 mg/mL VitaminB2@P25TiO₂NPs; D: 0.02 mg/mL VitaminB2@P25TiO₂NPs after 3 h of irradiation (red) and 6 h (blue). SD <5 for all samples and p <0.05 between C-D and A-B.

Overall, the Food Directorate's comprehensive review of the available science of TiO₂ as a food additive showed:

North America