A safety review conducted by the EFSA in 2021 assessed thousands of studies published on titanium dioxide.

In a study published in the journal Toxicology, researchers examined the effects of exposing human colon cancer cell line (HTC116) titanium dioxide food additives in vitro. “In the absence of cytotoxicity, E171 was accumulated in the cells after 24 hours of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization,” the scientists wrote. Researchers removed the additive from the culture, then examined the results 48 hours later. They found, “The removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.”

Moreover, titanium dioxide is also used in rubber formulations to improve the processing and curing properties of rubber compounds. It acts as a catalyst in the vulcanization process, speeding up the cross-linking of rubber molecules and enhancing the overall performance of the final product. This results in rubber products that are stronger, more flexible, and better suited for a wide range of applications.

Although the evidence for general toxic effects was not conclusive, on the basis of the new data and strengthened methods we could not rule out a concern for genotoxicity and consequently we could not establish a safe level for daily intake of the food additive, commented Matthew Wright, member of the EFSA's Food Additives and Flavourings Panel in a press statement.

TiO₂ NPs appeared to be more toxic to nematode Caenorhabditis elegans than submicron-sized TiO_2.  At a concentration of 1 mg/l, 7 nm particles affected its fertility and survival rate and were more toxic than 20 nm anatase particles. Similarly, Hu et al. showed that rutile particles (10–20 nm), at concentrations above 1 g/kg soil, can be bio-accumulated in earthworms, where they induce oxidative stress, inhibit the activity of cellulase and induce DNA and mitochondrial damage.

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.