In vitro, in the hemocytes of the marine mussel Mytilus hemocytes, suspension of TiO₂ NPs (Degussa P25, 10 μg/ml) stimulated immune and inflammatory responses, such as lysozyme release, oxidative burst and nitric oxide production. Vevers and Jha demonstrated the intrinsic genotoxic and cytotoxic potential of TiO₂ NPs on a fish-cell line derived from rainbow-trout gonadal tissue (RTG-2 cells) after 24 h of exposure to 50 μg/ml. Reeves et al. demonstrated a significant increase in the level of oxidative DNA damage in goldfish cells, and suggested that damage could not repaired by DNA repair mechanisms. Another suggestion from the mentioned study was that hydroxyl radicals are generated also in the absence of UV light. It has been shown that fish cells are generally more susceptible to toxic/oxidative injury than mammalian cells.

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.

The toxicity of P25TiO₂NPs was evaluated in both prokaryotic (Fig. 3) and eukaryotic cells (Fig. 4). The XTT assay was chosen to measure the cell viability in bacterial cultures of MSSA, a normal skin microbiota microorganism. The reduction in the viability of samples with bare NPs is notorious, possibly due to the described ROS production from the interaction of P25TiO₂NPs with light [37]. This effect seems to be avoided when they are functionalized with vitamin B2. Also, the most concentrated vitaminB2@P25TiO₂NPs sample (0.2 mg/mL) shows up to 60% more absorbance after 6 h compared to the bare NPs (due to normal cell replication). This may indicate that the antioxidant effect of the vitamin B2 coating is greater than the oxidation damage produced by the NPs. This protective capacity could be attributed to the glutathione redox cycle and the conversion of reduced riboflavin to its oxidized form [38]. Values of cell viability greater than 100% are not rare and could be understood because the XTT assay actually measure metabolic activity when reducing the tetrazole to formazan. It is usually assumed that conversion is dependent on the number of viable cells, but it could also be related to an expected increased enzymatic activity when cells are exposed to small doses of some new substance. Further analysis showed that this effect was not the only one responsible for better cell viability of vitaminB@P25TiO₂NPs treated samples.

The US and Canada, however, approve the use of titanium dioxide as a food additive. Canada's recent review of titanium dioxide reconfirmed its safety and pointed out that many of the toxicity studies the EU reviewed were not relevant to the safety of titanium dioxide as a food ingredient, and that the ban is based on an abundance of caution and uncertainty.

Here it has been shown that functionalization of P25TiO2NPs with vitamin B2 was able to significantly decrease the oxidative stress produced when they are exposed to sunlight. This finding is of main importance to prevent skin damage and toxicity of sunscreens containing this form of untreated titanium dioxide and should be taken into consideration when updating the regulations mentioned above .

Risk managers at the European Commission and in EU Member States have been informed of EFSA’s conclusions and will consider appropriate action to take to ensure consumers’ protection.

Titanium dioxide holds exceptional significance as a white pigment due to its superior scattering capabilities, remarkable chemical stability, and non-toxic nature. Among all white pigments, it surpasses others in terms of its ability to scatter light effectively. Consequently, titanium dioxide stands as the most significant inorganic pigment, accounting for the highest quantity in usage. The majority part of the global production of ilmenite and rutile is dedicated to the production of TiO2 pigments. The remaining portion is utilized for the manufacturing of titanium metal and in the production of welding electrodes.

Asia-Pacific accounted for the largest revenue share in 2019. China and India are the key markets in the region that have a growing paint and plastics industry, owing to rise in urbanization and industrial developments such as in automotive and construction domains.