In 2019, EFSA published a statement on the review of the risk related to the exposure to food additive titanium dioxide (E171) performed by the French Agency for Food, Environment and Occupational Health Safety (ANSES). In its statement, EFSA highlighted that the ANSES opinion reiterated the uncertainties and data gaps previously identified by EFSA and did not present findings that invalidated the Authority’s previous conclusions on the safety of titanium dioxide.

The EU expert panel did not identify an immediate health concern linked to TiO₂ when used as a food additive. However, due mainly to uncertainties concerning the safety of TiO₂ nanoparticles, the panel concluded that TiO₂ as a food additive (E171) could no longer be considered safe.

Production

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.

The evidence also suggests that the toxicity of TiO₂ particles may be reduced when eaten as part of the diet. This is because proteins and other molecules in a person's diet can bind to the TiO₂ particles. This binding alters the physical and chemical properties of the particles, which influences how they interact with cells, tissues and organs.

Finally, it's important to consider the global trends impacting the pigment industry as a whole. Environmental regulations, technological advancements, and sustainable practices are increasingly becoming part of the conversation. Suppliers that prioritize eco-friendly production methods or offer biodegradable alternatives may appeal to buyers willing to pay a higher price for sustainably sourced materials.

What titanium dioxide is really emblematic of ... is the failure of FDA to look back at these old decisions and ask whether its decisions that were made in this case ... 56 years ago (in the 1966 approval) still hold up, he said.

Worldwide Lithopone Industry to 2027 - Use of Lithopone in the Paints & Coatings Industry is Driving Growth - ResearchAndMarkets.com

The most significant uncertainty identified by the EU experts was the concern that TiO₂ particles may have genotoxic effects. Genotoxicity refers to the ability of a chemical to directly damage genetic material within a cell (DNA), which may lead to cancer in certain situations. Although the experts did not conclude that TiO₂ particles in E171 are genotoxic, they could not rule out the concern that they might be.

Overwhelmingly, research that’s relevant to human eating patterns shows us that E171 is safe when ingested normally through foods and drugs (1,2).