In 2022, a year after the EFSA recommended against the use of E171, the Food Standards Australia New Zealand (FSANZ) conducted its own reassessment of titanium dioxide as a food additive. The agency concluded that titanium dioxide was indeed safe to use as a food additive. The United Kingdom and Canada came to similar conclusions.

The cytotoxic effect was tested through the colorimetric assay employing 3′-[1-[(phenylamino) -carbonyl]−3,4-tetrazolium]-bis(4‑methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT) by reading the absorbance at 490 nm after 3 h of incubation post treatment [28]. The absorbance is proportional to the metabolic rate of viable (live) cells.

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The safety of the food additive E 171 was re-evaluated by the EFSA ANS Panel in 2016 in the frame of Regulation (EU) No 257/2010, as part of the re-evaluation programme for food additives authorised in the EU before 20 January 2009.  

Research supports that applying titanium dioxide to the skin in the form of sunscreens, makeup, and other topical products does not pose any health risks. 

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

Assessment of skin penetration and biohazard in vivo

Still many experts say the body of research does not support the current health concerns being expressed about titanium dioxide.

Europe

That came after a 2021 report from an expert panel at the European Food Safety Authority, which reviewed data on titanium dioxide safety. The panel said it couldn’t rule out concerns that the food additive might be able to damage DNA and possibly lead to cancer. They explained that after you eat something that has titanium dioxide in it, your body absorbs low levels of its particles – but the particles can build up as you eat more foods with this additive.

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.

Although cosmetics are not meant for consumption, there are concerns that titanium dioxide in lipstick and toothpaste may be swallowed or absorbed through the skin.

Nanotoxicology 

1. Lithopone is used as an inert pigment in paints, inks and cosmetics.

Suppliers of lithopone have recognized the growing need for high-quality, reliable products that meet both industry standards and consumer preferences. They have invested in advanced production techniques and stringent quality control measures to ensure that their lithopone products deliver consistent performance. This commitment to quality allows paint formulators to achieve the desired properties in their final products, such as enhanced durability, improved hiding power, and superior color stability over time.

Lithopone 30% CAS No. 1345-05-7

Experimental

In recent years, there has been growing interest in the development of novel applications for Chinese anatase titanium dioxide, such as in the field of energy storage and conversion. For example, it has been investigated as a potential electrode material for lithium-ion batteries, due to its high conductivity and stability. Furthermore, its photocatalytic activity has been explored for use in dye-sensitized solar cells, where it can help to improve the efficiency of solar energy conversion.