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.”

Titanium dioxide manufacturer: Panzhihua Dongfang

Recent analyses of food-grade TiO₂ samples have found that a significant portion of particles may be within the nanoscale. These particles (also known as nanoparticles) range in size from 1 to 100 nm, where 1 nm equals 1 billionth of a metre (the width of a typical human hair is 80,000 to 100,000 nm).

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.

In summary, the Food Directorate's position is that there is no conclusive scientific evidence that the food additive TiO₂ is a concern for human health. This is based on a review of the available scientific data relevant to food uses of TiO₂. However, we will continue to monitor the emerging science on the safety of TiO₂ as a food additive and may revisit our position if new scientific information becomes available.

Lithopone 30% CAS No. 1345-05-7 / Nature and stability

This constant high rate of ROS production leads rapidly to extreme macromolecular oxidation, here it is observed in the AOPP and MDA detected after 3 h in samples treated with bare P25TiO₂NPs (Fig. 6, Fig. 7). Macromolecular oxidation includes, among others, both protein and lipid oxidation. The ROS causes protein oxidation by direct reaction or indirect reactions with secondary by-products of oxidative stress. Protein fragmentation or cross-linkages could be produced after the oxidation of amino acid side chains and protein backbones. These and later dityrosine-containing protein products formed during excessive production of oxidants are known as advanced oxidation protein products (AOPP). They absorb at 340 nm and are used to estimate the damage to structural cell amino acids. Lipid oxidation is detected by the conjugation of oxidized polyunsaturated lipids with thiobarbituric acid, forming a molecule that absorbs light at 532 nm. Polyunsaturated lipids are oxidized as a result of a free-radical-mediated chain of reactions. The most exposed targets are usually membrane lipids. The macromolecular damage could represent a deadly danger if it is too extensive, and this might be the case. Moreover, it could be observed that cellular damage continues further and becomes irrevocable after 6 h and MDA could not be detected. This may be due to the fact that the lipids were completely degraded and cells were no longer viable. Lipids from the cell membrane are the most prone to oxidation. In fact, lipid peroxidation biomarkers are used to screen the oxidative body balance [51]. At the same time, AOPP values are up to 30 times higher for bare nanoparticles in comparison to the functionalized ones.

A safety review conducted by the EFSA in 2021 assessed thousands of studies published on titanium dioxide.

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.

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