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.

Lithopone is an inorganic white pigment, obtained from co-precipitation of Zinc sulfide (ZnS) and Barium sulfate (BaSO4). Titanium Dioxide (TiO2) has replaced Lithopone as a white pigment in majority applications as TiO2 is more durable. However, it is much cheaper than TiO2 and has advantages such as low binder requirement and good dispensability. As a white pigment, it can improve the substrate's weather resistance, and improve the fungicidal properties of paint formulations. Some of the major applications of Lithopone include manufacturing of paint pigments, plastic & rubber products, paper, printing inks, cosmetics, and leather & linoleum products. It is commercially available under names such as pigment white 5, Barium zinc sulfate sulfide, Becton White, C.I. 77115, Charlton White, Enamel White, and Zincolith. On the basis of content of ZnS, Lithopone is available at 28%-30% Lithopone and 60% Lithopone.

CSPI says it might reconsider its rating if specifications for food-grade titanium dioxide in the U.S. are updated to ensure nanoparticles are minimized, and new studies are conducted to assess its capacity to cause cancer or other health problems.