Hemolysis was studied on suspensions of P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL), vitaminB2@P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL) and vitamin B2 (0.2 mg/mL and 0.02 mg/mL) were prepared and mixed with 500 μL of anticoagulated blood (donated by Laboratorio de Hemoderivados, UNC) in a rate of 1/10. A solution of NaCl 10% was used as the positive control and PBS as the negative control. Then, the samples were irradiated using the LED described above for 3 and 6 h to simulate the light penetration into the skin. Also, a set of samples was kept in the dark as control. Finally, the samples were centrifuged and the absorbance at 540 nm was measured in the supernatants. The experiment was reproduced twice; the standard deviation was calculated and p-value < 0.05 were considered significant.

The aim of this work was to examine particularly the Degussa P25 titanium dioxide nanoparticles (P25TiO₂NPs) because they are among the most employed ones in cosmetics. In fact, all kinds of titanium dioxide nanoparticles (TiO₂NPs) have gained widespread commercialization over recent decades. This white pigment (TiO₂NPs) is used in a broad range of applications, including food, personal care products (toothpaste, lotions, sunscreens, face creams), drugs, plastics, ceramics, and paints. The original source is abundant in Earth as a chemically inert amphoteric oxide, which is thermally stable, corrosion-resistant, and water-insoluble. This oxide is found in three different forms: rutile (the most stable and substantial form), brookite (rhombohedral), and anatase (tetragonal as rutile), of these, both rutile and anatase are of significant commercial importance in a wide range of applications [3]. Additionally, the nano-sized oxide exhibits interesting physical properties, one of them is the ability to act as semiconducting material under UV exposure. In fact, TiO₂NPs are the most well-known and useful photocatalytic material, because of their relatively low price and photo-stability [4]. Although, this photoactivity could also cause undesired molecular damage in biological tissues and needs to be urgently assessed, due to their worldwide use. However, not all nanosized titanium dioxide have the same behavior. In 2007, Rampaul A and Parkin I questioned: “whether the anatase/rutile crystal form of titanium dioxide with an organosilane or dimethicone coat, a common titania type identified in sunscreens, is appropriate to use in sunscreen lotions” [5]. They also suggested that with further study, other types of functionalized titanium dioxide could potentially be safer alternatives. Later, Damiani found that the anatase form of TiO₂NPs was the more photoactive one, and stated that it should be avoided for sunscreen formulations, in agreement with Barker and Branch (2008) [6,7].

Prof Maged Younes, Chair of EFSA’s expert Panel on Food Additives and Flavourings (FAF), said: “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”. 

The FDA continues to allow for the safe use of titanium dioxide as a color additive in foods generally according to the specifications and conditions, including that the quantity of titanium dioxide does not exceed 1% by weight of the food, the FDA said in a statement to USA TODAY.

Following the EU’s ban on E171, the FDA told the Guardian that, based on current evidence, titanium dioxide as a food additive is safe.  “The available safety studies do not demonstrate safety concerns connected to the use of titanium dioxide as a color additive.”

In a 2021, Chinese researchers examined the impact of E171 on lipid digestion and vitamin D3 bioaccessibility in a simulated human gastrointestinal tract model. They examined Vitamin D’s bioaccessibility, or the amount it was released in the gastrointestinal tract, becoming available for absorption, and found it “significantly decreased from 80% to 74%” with the addition of E171. In the experiment, E171 decreased lipid digestion dose-dependently. Researchers wrote: “The findings of this study enhance our understanding toward the potential impact of E171 on the nutritional attributes of foods for human digestion health.”  The study was published in the Journal of Agricultural and Food Chemistry, 

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Titanium dioxide prices in the Asian market skyrocketed due to high demand and limited stock availability. Prices in the Chinese market surged significantly, reaching 2875 USD /MT at the end of March, well above the USD 2015/MT level in January 2021.