Fig. 8. Selected images of skin stratus treated with P25TiO₂NPs 10% (left) and VitaminB2@P25TiO₂NPs 10% (right) under light, showing no penetration of the nanoparticles (white arrows) beyond the outer stratum corneum.

TiO₂ comes in many different forms. However, only a few of these forms are considered food-grade (acceptable to be added to food). Many studies that raised concern about the safety of TiO₂, including the concern for genotoxicity, used forms of TiO₂ that are not considered acceptable for use in food and have different properties than food-grade TiO₂. Other studies did use food-grade TiO₂, but took steps to break the material down into smaller particles than what would normally be found in food.

The gastrointestinal tract is a complex barrier/exchange system, and is the most important route by which macromolecules can enter the body. The main absorption takes place through villi and microvilli of the epithelium of the small and large intestines, which have an overall surface of about 200 m². Already in 1922, it was recognized by Kumagai, that particles can translocate from the lumen of the intestinal tract via aggregation of intestinal lymphatic tissue (Peyer’s patch, containing M-cells (phagocytic enterocytes)). Uptake can also occur via the normal intestinal enterocytes. Solid particles, once in the sub-mucosal tissue, are able to enter both the lymphatic and blood circulation.