Dispersion in the polymer: optimum dispersion should produce a good distribution and separation of titanium dioxide particles in the formulation.

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.

Titanium dioxide (TiO₂). Titanium dioxide is the most common white pigment used today. As a pigment, titanium dioxide is unique because it combines both high colouring and high opacifying capacity. This is mainly due to its high refractive index (2.7). Furthermore, titanium dioxide is an excellent UV absorber (it is used in sun protective creams). Some typical properties are: density 3.3-4.25 g/cm³; pH of water suspension 3.5-10.5; particle size 8–300 nm; oil absorption 10–45 g/100 g; specific surface area 7–160 m²/g. Most titanium dioxide is produced from the rutile (TiO₂) or ilmenite (titanate of ferrous iron). Titanium dioxide can be obtained using different processes.