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Fig. 7. Lipid peroxidation measured on samples of MSSA with: A) 0.2 mg/mL P25TiO₂NPs; B) 0.02 mg/mL P25TiO₂NPs; C) 0.2 mg/mL VitaminB2@P25TiO₂NPs; D) VitaminB2@P25TiO₂NPs 0.02 mg/mL after 3 h of irradiation (red) and 6 h (blue). MDA could not be detected after 6 h of irradiation in a sample with P25TiO₂NPs. Error bars are too small to be seen in graphic and p < 0.05 between C-D and A-B.

Infrared spectra were performed (from 400 to 4000 cm⁻¹) in vitamins@P25TiO₂NPs samples and the vitamins alone as controls, employing a Nicolet AVATAR 360 Fourier transform infrared spectrophotometer.

The Evolution and Impact of Anatase Titanium Dioxide Manufacturers

Prof. Maged Younes, Chair of EFSA’s expert Panel on Food Additives and Flavourings (FAF), wrote of the decision: “Taking into account all available scientific studies and data, the Panel concluded that titanium dioxide can no longer be considered safe as a food additive. A critical element in reaching this conclusion is that we could not exclude genotoxicity concerns after consumption of titanium dioxide particles. After oral ingestion, the absorption of titanium dioxide particles is low, however they can accumulate in the body.”

Currently, titanium dioxide as a food additive is classified as GRAS, or “generally recognized as safe.” 

This regulation entered into force on 7 February 2022. However, the Regulation included a six-month transitional period to allow food businesses time to phase out the use of this food additive and to reformulate their products using suitable alternatives. This period will end on 7 August 2022.

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.

3. Regulatory Compliance It is crucial for suppliers to adhere to industry regulations, especially in sectors like food, pharmaceuticals, and cosmetics. Reliable suppliers will ensure their products meet relevant regulatory standards, providing proper documentation and certifications.

In 2019, EFSA published a statement on the review of the risk related to the exposure to food additive titanium dioxide (E171) performed by the French Agency for Food, Environment and Occupational Health Safety (ANSES). In its statement, EFSA highlighted that the ANSES opinion reiterated the uncertainties and data gaps previously identified by EFSA and did not present findings that invalidated the Authority’s previous conclusions on the safety of titanium dioxide.

In addition to pigments and sunscreens, titanium dioxide is also used in the production of paper, food products, and pharmaceuticals. In the paper industry, titanium dioxide is added to paper coatings to improve brightness, smoothness, and printability. In the food industry, titanium dioxide is used as a whitening agent in products such as candies, chewing gum, and icing. In the pharmaceutical industry, titanium dioxide is used as a coloring agent in tablets and capsules.