On the other hand, titanium dioxide is a synthetic mineral that is produced through a chemical reaction involving the mineral ilmenite or rutile. It is used in industries such as cosmetics, paint, and sunscreen as a whitening agent and pigment. The manufacturing process of titanium dioxide involves extracting the mineral from ores, purifying it through chemical processes, and then grinding it into a fine powder.

The lack of clear regulations and controls explains that P25TiO₂NPs are still found in many of the commercialized sunscreens in the market. Some of them are coated to reduce the photoactivity of the anatase form, which is known to be responsible for tissue damage, but not enough studies were made on these coated forms. The anatase photoactivity could trigger the production of reactive oxygen species (ROS) generation, as it was stated before. The ROS are chemically reactive species containing oxygen, such as peroxides, superoxide, hydroxyl radical, and singlet oxygen. They are regularly produced in the biological milieu and counterbalanced by physiological antioxidant defense mechanisms. However, an abrupt increase of ROS may result in non-reversible damage to the skin cells. The effects of coated and uncoated P25TiO₂NPs need therefore to be studied, and articles on this topic present different conclusions. [11], [12], [13] Recent literature on this topic found that TiO₂NPs inhalation provokes serious genotoxicity and DNA damage [14], [15], [16], [17]. On the other hand, some studies in rats have reported no significant harm to genetic material [18], [19], [20], [21], [22].

Most notably, a European Food Safety Authority safety assessment published in May 2021 pointed to genotoxicity concerns, as suggested by previous research. Genotoxicity is the ability of chemicals to damage genetic information such as DNA, which may lead to cancer.

In a study published in the journal Toxicology, researchers examined the effects of exposing human colon cancer cell line (HTC116) titanium dioxide food additives in vitro. “In the absence of cytotoxicity, E171 was accumulated in the cells after 24 hours of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization,” the scientists wrote. Researchers removed the additive from the culture, then examined the results 48 hours later. They found, “The removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.”