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.

In short, no, research demonstrates that E171 is safe when consumed in normal situations.

Moreover, how we're exposed to an ingredient matters significantly in terms of our health and potential toxicity.   

Research shows that inhaling titanium dioxide particles in significant quantities over time can cause adverse health outcomes. Unless you work in an industrial setting, inhaling substantial amounts of titanium dioxide is highly unlikely. 

Research supports that applying titanium dioxide to the skin in the form of sunscreens, makeup, and other topical products does not pose a health risk. 

Overwhelmingly, research that's relevant to human exposure shows us that E171 is safe when ingested normally through foods and drugs (1,2).

Again, other research suggests that E171 could cause harm; however, those research processes did not design their studies to model how people are exposed to E171. Research that adds E171 to drinking water, utilizes direct injections, or gives research animals E171 through a feeding apparatus is not replicating typical human exposure, which occurs through food and medicine consumption.

Read more in-depth about the titanium dioxide risk at go.msu.edu/8Dp5. 

Lithopone was discovered in the 1870s by DuPont. It was manufactured by Krebs Pigments and Chemical Company and other companies.^[2] The material came in different seals, which varied in the content of zinc sulfide. Gold seal and Bronze seals contain 40-50% zinc sulfide, offering more hiding power and strength.^[3] Although its popularity peaked around 1920, approximately 223,352 tons were produced in 1990. It is mainly used in paints, putty, and in plastics.^[1]

Assessment of biocompatibility in eukaryotic cells

Le lithopone, blanc de lithopone ou blanc de Comines est un pigment blanc composé d'un mélange de sulfure de zinc et de sulfate de baryum, généralement en proportions équimolaires.

European food safety regulators have since labeled titanium dioxide as no longer safe for human consumption, due to its potential toxicity. 

In a study published in the journal Environmental Toxicology and Pharmacology in 2020, researchers examined the effects of food additives titanium dioxide and silica on the intestinal tract by grouping and feeding mice three different food-grade particles — micro-TiO2, nano-TiO2, and nano-SiO2.  With all three groups, researchers observed changes in the gut microbiota, particularly mucus-associated bacteria. Furthermore, all three groups experienced inflammatory damage to the intestine, but the nano-TiO2 displayed the most pronounced changes. The researchers wrote: “Our results suggest that the toxic effects on the intestine were due to reduced intestinal mucus barrier function and an increase in metabolite lipopolysaccharides which activated the expression of inflammatory factors downstream. In mice exposed to nano-TiO2, the intestinal PKC/TLR4/NF-κB signaling pathway was activated. These findings will raise awareness of toxicities associated with the use of food-grade TiO2 and SiO2.”

Titanium dioxide in sunscreen

I don't see the scientific evidence in the literature that would cause people any concern, said Kaminski.

Yes. According to the FDA and other regulatory agencies globally, “titanium dioxide may be safely used for coloring foods”. Titanium dioxide is safe to use, and the FDA provides strict guidance on how much can be used in food. The amount of food-grade titanium dioxide that is used is extremely small; the FDA has set a limit of 1 percent titanium dioxide for food. There is currently no indication of a health risk at this level of exposure through the diet.

Scrap zinc or concentrated zinc ores are dissolved in sulfuric acid, the solution is purified and the two solutions are reacted. A heavy mixed precipitate results that is 28 to 30% zinc sulfide and 72 to 70% barium sulfate.

Furthermore, the use of titanium dioxide in rubber helps to reduce the environmental impact of rubber manufacturing processes. As a non-toxic and environmentally friendly material, titanium dioxide is safe for use in rubber products that come into contact with food, water, or other sensitive materials. This makes it an attractive choice for manufacturers looking to produce eco-friendly and sustainable rubber goods.

Production of TiO₂ Pigment

Lithopone in plastics and masterbatch