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In an early study Jani et al. administred rutile TiO₂ (500 nm) as a 0.1 ml of 2.5 % w/v suspension (12.5 mg/kg BW) to female Sprague Dawley rats, by oral gavage daily for 10 days and detected presence of particles in all the major gut associated lymphoid tissue as well as in distant organs such as the liver, spleen, lung and peritoneal tissue, but not in heart and kidney. The distribution and toxicity of nano- (25 nm, 80 nm) and submicron-sized (155 nm) TiO₂ particles were evaluated in mice administered a large, single, oral dosing (5 g/kg BW) by gavage. In the animals that were sacrificed two weeks later, ICP-MS analysis showed that the particles were retained mainly in liver, spleen, kidney, and lung tissues, indicating that they can be transported to other tissues and organs after uptake by the gastrointestinal tract. Interestingly, although an extremely high dose was administrated, no acute toxicity was observed. In groups exposed to 80 nm and 155 nm particles, histopathological changes were observed in the liver, kidney and in the brain. The biochemical serum parameters also indicated liver, kidney and cardiovascular damage and were higher in mice treated with nano-sized (25 or 80 nm) TiO₂ compared to submicron-sized (155 nm) TiO₂. However, the main weaknesses of this study are the use of extremely high single dose and insufficient characterisation of the particles.

The agency makes this exception for several approved color additives. 

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For research published in 2022 study in the journal Food and Chemical Toxicology, scientists examined “the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO2 nanomaterials in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs’ physiochemical characteristics.” They found a “DNA-damaging effect dependent on the nanomaterial,” along with the micronucleus assay suggesting “effects on chromosomal integrity, an indicator of cancer risk, in the HT29-MTX-E12 cells, for all the tested TiO2 nanomaterials.” Researchers concluded that the results showcase “evidence of concern” regarding titanium dioxide used as a food additive.

Titanium Dioxide Price Trends for the First Half of 2023

For that reason, the Center for Science in the Public Interest has graded titanium dioxide as a food additive that consumers should seek to “avoid.” Scientists at the nonprofit nutrition and food safety watchdog group today published a new entry for titanium dioxide in its Chemical Cuisine database of food additives.