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The additives that received a “no safety concern” conclusion based on current estimated dietary exposure are as follows:

3. Safety measures The MSDS should provide recommendations for safe handling, storage, and disposal of lithopone. This may include guidelines for personal protective equipment, proper ventilation, and spill response procedures.

Drobne et al. used the terrestrial arthropod Porcellio scaber as a test organism for determining the cytotoxic effect of TiO₂ NPs (anatase). The animals were exposed to TiO₂ NPs of two different sizes (25 nm and 75 nm) in the concentration range 10–1000 μg TiO₂/g dry food for 3 to 14 days. No adverse effects, such as mortality, body weight changes or reduced feeding, were observed. In fact, quite the opposite, an enhanced feeding rate, food absorption efficiency and increase in catalase activity were observed. The intensity of these responses appeared to be time- but not dose-dependent. It should also be noted that the concentrations tested in this study were much higher than the predicted concentration (4.8 μg/g soil) at high emission scenario of nano-sized TiO₂. Using the same test organism another group showed that exposure to TiO₂ NPs induced destabilization of cell membrane in the epithelium of digestive glands isolated from exposed animals. They also showed that this effect can be observed after just 30 minutes of exposure.

The production of ROS was studied on white blood cells as a model to screen the effect on eukaryotic cells after being exposed to samples and solar simulated irradiation (according to the level of penetration under the skin). For that purpose, the leukocytes were separated from anticoagulated fresh blood using the Ficoll-Hypaque reactive in a well-known technique [33]. Then, 50 μL of 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 50 μL of white blood cells suspension. A solution of 3% H₂O₂ was used as positive control and PBS as negative control. Then, the samples were irradiated using the LED panel 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 ROS were detected through the colorimetric assay employing the nitroblue tetrazolium salt (NBT salt) and the absorbance at 650 nm was measured. The experiment was reproduced twice; the standard deviation was calculated and p-value < 0.05 were considered significant.

It's also added directly to food; mainly for coloring, but also as a thickener and to keep some powdered food, like confectioner's sugar, from clumping.   

A significant body of research, mostly from rodent models and in vitro studies, has linked titanium dioxide with health risks related to the gut, including intestinal inflammation, alterations to the gut microbiota, and more. It is classified by the International Agency for Research on Cancer (IARC) in Group 2B, as possibly carcinogenic to humans.