Available studies in humans and postmortem analysis of tissues suggested that the oral bioavailability of titanium dioxide in humans is very low. JECFA noted that there are currently no epidemiological studies that allow any conclusions to be drawn with respect to an association between dietary exposure titanium dioxide and human health effects.

You can find more information about EFSA’s work in the area of food additives on our website

What is an exposure route? 

In industrial settings, people can be exposed to titanium dioxide through inhalation. Inhalation exposure to titanium dioxide is exceedingly rare for most people. 

In a 2021, Chinese researchers examined the impact of E171 on lipid digestion and vitamin D3 bioaccessibility in a simulated human gastrointestinal tract model. They examined Vitamin D’s bioaccessibility, or the amount it was released in the gastrointestinal tract, becoming available for absorption, and found it “significantly decreased from 80% to 74%” with the addition of E171. In the experiment, E171 decreased lipid digestion dose-dependently. Researchers wrote: “The findings of this study enhance our understanding toward the potential impact of E171 on the nutritional attributes of foods for human digestion health.”  The study was published in the Journal of Agricultural and Food Chemistry, 

Macromolecular oxidation was detected in proteins by the colorimetric measurement of Advanced Oxidation Protein Products (AOPP) and in lipids by the colorimetric quantification of malondialdehyde (MDA). Standard curves were run with chloramine-T and 1,1,3,3 tetraethoxypropane (TEP) for AOPP and MDA methods, respectively [29], [30], [31]. Values were normalized to initial protein content in samples, measured with Bradford reagent [32]. The standard deviation of at least six measures was calculated and p-value < 0.05 were considered significant.

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.