③ Paper making industry: Paper making and paper products industry is the third largest application industry of titanium dioxide. Paper using titanium dioxide has good whiteness, high strength, luster, thin and smooth, and is not easy to penetrate when printing. Under the same conditions, the opacity is 10 times higher than that of paper using calcium carbonate and talc powder, and the weight can also be reduced by 15% to 30%. The amount of titanium dioxide in decorative paper accounts for 20%~40% of its raw materials, and the amount of titanium dioxide in other papers is about 1%~5%. Due to the continuous adjustment of the industrial structure of the paper products industry from 2016 to 2018, according to the data of China Paper Association, the output of China's paper products in 2019 was 72.19 million tons, a significant year-on-year increase of 29.4%, and the use of titanium dioxide increased significantly.

The updated evaluation revises the outcome of EFSA’s previous assessment published in 2016, which highlighted the need for more research to fill data gaps.  

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.

Lithopone B301, Lithopone B311 powder, brilliant white pigment used in paints, inks, leather, paper, linoleum, and face powder. It was developed in the 1870s as a substitute or supplement for lead carbonate (white lead), to overcome its drawbacks of toxicity, poor weathering, and darkening in atmospheres that contain sulfur compounds. Lithopone B301, Lithopone B311 powder is an insoluble mixture of barium sulfate and zinc sulfide that precipitates upon mixing solutions of barium sulfide and zinc sulfate. The precipitate is recovered by filtration, then calcined (roasted) at temperatures above 600° C (1,112° F). Although Lithopone B301, Lithopone B311 powder has been replaced in many applications by titanium dioxide, it is still widely used in a number of products, such as water paints.

It is opaque and glossy, and provides bright whiteness with blue undertones.

For research published in Archives of Toxicology in 2020, scientists fed one group of mice a solution containing titanium dioxide for one month, and compared it to those that did not receive the additive. They found “the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed” in the titanium dioxide group when compared with the control group. The tests also revealed that the titanium dioxide exposure could cause locomotor dysfunction, or mobility issues “by elevating the excitement of enteric neurons, which might spread to the brain via gut-brain communication by vagal pathway.” The researchers concluded: “These findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.”

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.”

CSPI’s Chemical Cuisine is the web’s definitive rating of the chemicals used to preserve foods and affect their taste, texture, or appearance. Besides titanium dioxide, the group recommends avoiding artificial sweeteners like aspartame, acesulfame potassium, and sucralose, as well as synthetic food dyes like Yellow 5 and Red 3. CSPI and others have recently asked the Food and Drug Administration to ban the latter dye in foods and ingested drugs because the FDA has already determined that it is a carcinogen unsafe for use in cosmetics.

As early as sixty years ago, zinc sulphide was first thought of as a pigment for coloring India rubber and a patent for the process of its manufacture was issued in England. But it was not until twenty years later that zinc sulphide and its manufacture was seriously considered as a pigment for paint, and in 1874 a patent was issued for a process of manufacturing a white pigment, composed of zinc sulphide and barium sulphate, known as Charlton white, also as Orr's white enamel. This was followed in 1876 by a patent issued to a manufacturer named Griffith and the product, which was similar in character to Charlton white, was known as Griffith's patent zinc white. In 1879 another patent for a more novel process was obtained by Griffith & Cawley, the product made under this process proving the best of the series placed upon the market up to that date. After that time many new processes were patented, all, however, tending to the same object, that of producing a white pigment, composed of zinc sulphide and barium carbonate, the results, however, in many cases ending with failure.

What exactly is titanium dioxide?