Other scientists, however, have called into question the experimental designs of such studies, citing inconsistent results specifically in studies used to test DNA damage.

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.

Conclusion

In terms of manufacturers, there are many companies that produce calcium carbonate and titanium dioxide. Some of the top manufacturers of calcium carbonate include Omya, Imerys, and Minerals Technologies. These companies have large mining operations and production facilities in regions where calcium carbonate is abundant.

Exposure routes are the pathways that allow ingredients to enter our bodies. Primary exposure routes include: 

Titanium is a metal element found naturally in the environment. When it's exposed to oxygen in the air, it forms titanium oxides that are contained in many minerals, sands, soils, and dusts.