We've measured many different immunological markers, both in the mucosa of the intestine and the lymphoid organs part of the intestine and we didn't see any inflammation there or changes in white blood cell number, Kaminski said. They also looked at the spleen where titanium dioxide was taken up into the bloodstream. You would expect [titanium dioxide] would be filtered out in the spleen and maybe induce inflammation there, but we did not see that, Kaminski added.

In 2017, French researchers from the Institut National de la Recherche Agronomique (INRAE) were among the first to examine the effects of E171 nanoparticles on the body. They fed rats a dose of 10mg of E171 per kilogram of body weight per day, which was similar to human exposure in food. The research, which was published in Scientific Reports, showed that E171 was able to traverse the intestinal barrier, pass into the bloodstream, and reach other areas of the body in rats. Researchers also found a link between immune system disorders and the absorption of titanium dioxide nanoparticles. 

The main food categories contributing to dietary exposure of E171 are fine bakery wares, soups, broths and sauces (for infants, toddlers and adolescents); and soups, broths, sauces, salads and savoury based sandwich spreads (for children, adults and the elderly). Processed nuts are also a main contributing food category for adults and the elderly.

RRAM and the New Computing Paradigm

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.

How can food businesses comply with this Regulation?

What are the different forms of titanium dioxide in beauty and personal care products?

Different dermal cell types have been reported to differ in their sensitivity to nano-sized TiO₂ . Kiss et al. exposed human keratinocytes (HaCaT), human dermal fibroblast cells, sebaceous gland cells (SZ95) and primary human melanocytes to 9 nm-sized TiO₂ particles at concentrations from 0.15 to 15 μg/cm² for up to 4 days. The particles were detected in the cytoplasm and perinuclear region in fibroblasts and melanocytes, but not in kerati-nocytes or sebaceous cells. The uptake was associated with an increase in the intracellular Ca²⁺ concentration. A dose- and time-dependent decrease in cell proliferation was evident in all cell types, whereas in fibroblasts an increase in cell death via apoptosis has also been observed. Anatase TiO₂ in 20–100 nm-sized form has been shown to be cytotoxic in mouse L929 fibroblasts. The decrease in cell viability was associated with an increase in the production of ROS and the depletion of glutathione. The particles were internalized and detected within lysosomes. In human keratinocytes exposed for 24 h to non-illuminated, 7 nm-sized anatase TiO_2, a cluster analysis of the gene expression revealed that genes involved in the “inflammatory response” and “cell adhesion”, but not those involved in “oxidative stress” and “apoptosis”, were up-regulated. The results suggest that non-illuminated TiO₂ particles have no significant impact on ROS-associated oxidative damage, but affect the cell-matrix adhesion in keratinocytes in extracellular matrix remodelling. In human keratinocytes, Kocbek et al. investigated the adverse effects of 25 nm-sized anatase TiO₂ (5 and 10 μg/ml) after 3 months of exposure and found no changes in the cell growth and morphology, mitochondrial function and cell cycle distribution. The only change was a larger number of nanotubular intracellular connections in TiO₂-exposed cells compared to non-exposed cells. Although the authors proposed that this change may indicate a cellular transformation, the significance of this finding is not clear. On the other hand, Dunford et al. studied the genotoxicity of UV-irradiated TiO₂ extracted from sunscreen lotions, and reported severe damage to plasmid and nuclear DNA in human fibroblasts. Manitol (antioxidant) prevented DNA damage, implying that the genotoxicity was mediated by ROS.

Titanium dioxide is typically micronized and coated for use in cosmetics products. The micronizing makes this somewhat heavy-feeling ingredient easier to spread on skin, plus a bit more cosmetically elegant. Micronized titanium dioxide is much more stable and can provide better sun protection than non-micronized titanium dioxide.

Among the raw materials for coating production, titanium dioxide is more ideal, followed by lithopone. The covering power of lithopone is only that of titanium dioxide, and the price of lithopone is much lower than that of titanium dioxide, so lithopone still occupies a large market share.

Health advocates urge US regulators to ban common food coloring additive, by Tom Perkins, The Guardian, June 2, 2023

Natural barite and anthracite containing more than 95% barium sulfate are mixed and fed at a ratio of 3:1 (mass). After being crushed to a diameter of less than 2cm, it enters the reduction furnace. The furnace temperature is controlled to be 1000-1200°C in the front section and 500-500 in the back section. 600°C, the reduction furnace rotates at a speed of 80 seconds per revolution, and the reaction conversion rate is 80% to 90%.

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.