Toxic effects of TiO₂ NPs on aquatic organisms

On the other hand, the U.S. Food and Drug Administration (FDA) in their Final Administrative Order on Sunscreen Drug Products posted in September 2021 still accepts titanium dioxide up to 25% in the list of Generally Recognized As Safe and Effective (GRASE) in the main document, without further clarification on what kind or size of particles [9]. However, on page 24 (Sunscreen containing nanomaterials) FDA clearly “distinguish nanomaterials from other forms of these ingredients'' (zinc oxide and titanium dioxide) and ask for comments on “any particular nanomaterials that you believe should not be permitted for use in OTC sunscreen products”. To the best of our knowledge, this Agency did not ban the use of nanoparticulate titanium dioxide in any form, even though it is mentioned on page 34 that the anatase form is the more photoactive one, due to the lack of evidence with real sunscreens OTC (over the counter) in vivo. Moreover, other regulations in Latin America (MERCOSUR agreement, 2006) do not state clearly their position on the use of nanoparticulate TiO₂NPs [10].

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.

2. Lithopone is widely used in the plastic industry.