According to the EFSA's Expert Panel on Food Additives and Flavorings 2021 opinion regarding titanium dioxide, it could not rule out a concern for genotoxicity from ingestion of the material based on a perceived gap in data on this risk, which serves as the basis for current ban, said a March report on the decision.

Here, NaOH or NH3 · H2O is used as a precipitant or pH regulator to react with FeSO4 to form ferrous hydroxide precipitation; Air is used as oxidant; The iron sheet reacts with sulfuric acid produced during the oxidative hydrolysis of FeSO4 to provide ferrous ions required in the reaction system and maintain the pH value of the solution. The alkali consumption of acid method is less and the particles are easy to wash. The relative rates of seed preparation and crystal growth determine the particle size, particle size distribution and particle morphology of iron yellow particles.

As mentioned above, these oxide NPs are harmful in part because both anatase and rutile forms are semiconductors and produce ROS. Particularly, P25 kind has band-gap energies estimated of 3.2 and 3.0 eV, equivalent to radiation wavelengths of approximately 388 and 414 nm, respectively. Irradiation at these wavelengths or below produces a separation of charge, resulting in a hole in the valence band and a free electron in the conduction band, due to the electron movement from the valence to conduction bands. These hole–electron pairs generate ROS when they interact with H₂O or O₂ [43,44]. It was described that they can cause an increase in ROS levels after exposure to UV-visible light [45]. The NBT assay in the studied samples showed that bare P25TiO₂NPs produce a large amount of ROS, which is drastically reduced by functionalization with vitamin B2 (Fig. 5). This vitamin, also known as riboflavin, was discovered in 1872 as a yellow fluorescent pigment, [46] but its function as an essential vitamin for humans was established more than sixty years later, and its antioxidant capacity was not studied until the end of the XX century [47,48]. This antioxidant role in cells is partially explained because the glutathione reductase enzyme (GR) requires it for good functionality. This enzyme is the one in charge of the conversion of oxidized glutathione to its reduced form which acts as a powerful inner antioxidant and can quench the ROS [49,50]. The cost of this action is that the glutathione is converted to the oxidized form and needs to be recovered by the GR. Consequently, the cells need more vitamin B2. Another glutathione action is the protection against hydroperoxide. This activity is also mediated by riboflavin. Therefore, local delivery of this vitamin seems to significantly help the cells in their fight to keep the oxidative balance, once they are exposed to high levels of ROS.