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.

The FDA first approved the use of titanium dioxide in food in 1966, following its 1960 removal (along with the removal of other color additives) from the agency's original Generally Recognized as Safe list. In 1977, titanium dioxide joined the list of color additives that are exempt from certification, which means titanium dioxide doesn't have to be listed on the packaging of every product it's used in, Faber noted.

But in the U.S., titanium dioxide is found all over the grocery shelves. Candy like Skittles, Starbursts, and Jell-O, gum like Trident White peppermint gum and Mentos Freshmint Gum, cake products like Duncan Hines Creamy Vanilla Frosting, and Nabisco Chips Ahoy! cookies are just a few of the myriad food items that contain the additive.

Europe

Some food products will include titanium dioxide on their nutrition label. But again, it can be hard to tell for those who don't list the ingredient. 

≥30.0