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.

There are numerous manufacturers of titanium dioxide; the largest include Delaware-based Chemours (a spin-off of DuPont Chemical), Texas-based Kronos, and China-based Lomon Billions Group, all of which manufacture pigments for use in products like paints, coatings, and plastics. UK-based Venator is a major supplier of titanium dioxide used in food and cosmetics, along with paints, paper, plastic, and more. As a pigment, it is called Pigment White 6 (PW6), titanium white, or CI 77891. As a food additive, it is known as E171.

The cytotoxic effect was tested through the colorimetric assay employing 3′-[1-[(phenylamino) -carbonyl]−3,4-tetrazolium]-bis(4‑methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT) by reading the absorbance at 490 nm after 3 h of incubation post treatment [28]. The absorbance is proportional to the metabolic rate of viable (live) cells.

Organ accumulation

The FDA first approved the use of titanium dioxide in food in 1966, following its 1960 removal (along with the removal of other color additives) from the agency's original Generally Recognized as Safe list. In 1977, titanium dioxide joined the list of color additives that are exempt from certification, which means titanium dioxide doesn't have to be listed on the packaging of every product it's used in, Faber noted.

Titanium dioxide used for adhesive applications should contain an inorganic coating to control polarity, improve its ease of dispersion, and improve its weather resistance. The inorganic coating (zirconium dioxide, silica, alumina) is applied in the aqueous slurry by precipitation of one or more hydrated metal oxides and by neutralization of acidic and alkaline compounds.

In a small study published in the European Journal of Nutrition in 2020, researchers examined the effects of several food additives, including titanium dioxide, along with artificial sweeteners and cleaning products by testing the fecal samples of 13 people. Titanium dioxide was among the samples that “induced significant shifts in microbiome community structure.”  The growth of the bacterium species belonging to C. leptum, which has been shown to decrease in patients with inflammatory bowel disease, “significantly decreased in the presence of … titanium dioxide” among other additives and sweeteners tested.