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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.

Titanium dioxide (TiO₂) is a naturally occurring mineral that is mined from the earth, processed and refined, and added to a variety of foods, as well as other consumer products. White in color, it is used to enhance the color and sheen of certain foods and is also key for food safety applications. In its natural state it exists in different bulk crystalline forms, such as anatase and rutile, but during processing it is ground into a very fine powder.

In its statement to USA TODAY, the FDA maintained that, in all post-approvals for food additives, our scientists continue to review relevant new information to determine whether there are safety questions and whether the use of such substance is no longer safe under the Federal Food, Drug, and Cosmetic Act.

Permanence and Stability

Having thus described the origin and uses of the pigment, we now come to the question, what is lithopone? It is, in short, a chemical compound usually consisting of 30.5 per cent zinc sulphide, 1.5 per cent zinc oxide and 68 per cent barium sulphate, but these proportions vary slightly in the different makes. Lithopone of this composition is sold as the highest grade, either as red seal or green seal, as it best suits the idea of the manufacturer. Many manufacturers, especially in Europe, sell and also export other brands under other seals, containing 24, 20, 18 and as little as 12 per cent of zinc sulphide with very small percentages of zinc oxide, the balance being usually barium sulphate, but sometimes certain portions of China clay or gypsum (calcium sulphate) or whiting (calcium carbonate). Such brands are not a chemical compound, but mechanical mixtures of the chemically compounded lithopone and the admixtures referred to.

Titanium dioxide manufacturer: CHTI

French researchers studied how and where E171 nanoparticles enter the bloodstream, first studying the route through pigs and then in vitro with human buccal cells, for a 2023 study published in the journal Nanotoxicology. The research showed that the nanoparticles absorbed quickly through the mouth and then into the bloodstream, before damaging DNA and hindering cell regeneration.

Zhu et al. were the first to provide evidence that TiO₂ NPs (21 nm) can transfer from daphnia to zebrafish by dietary exposure. Hence, dietary intake could be a major route of exposure to NPs for high trophic level aquatic organisms. Ecological research should therefore focus, not only on the concentration of NPs in the environment, but also on its bioconcentration, bioaccumulation and biomagnification. In addition it has been shown that TiO₂ NPs can increase accumulation of other environmental toxicants: enhanced accumulation of cadmium (Cd) and arsenic (As) was found in carp in the presence of TiO₂ NPs. The strong adsorption capacity for Cd and As was explained by the large specific surface area and strong electrostatic attraction of TiO₂ NPs that contribute to facilitated transport into different organs.

The FDA has not updated its general guidance on safety assessments since 2007. Within that time, there has been a significant increase in research on the confluence of toxicology, nanotechnology and human health. The EU updates its guidance regularly with new science available to offer proper safety assessments, with its most recent update published in 2021.