At the present JECFA meeting, the committee considered additional toxicological studies relevant to the safety assessment of the chemical that investigated its toxicokinetics, acute toxicity, short-term toxicity, long-term toxicity and carcinogenicity, genotoxicity, and reproductive and developmental toxicity, as well as special studies addressing its short-term initiation/promotion potential for colon cancer. The experts acknowledged that a large number of toxicological studies have been conducted using test materials, including nanoparticles, having size distributions and physico-chemical properties not comparable to real-world uses of titanium dioxide as a food additive. The studies on non-representative materials were evaluated by JECFA, but the committee concluded that such studies are not relevant to the safety assessment of the additive.

References

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.

Testing samples were made mixing 100 uL of TiO₂NPs suspensions (0.2 mg/mL and 0.02 mg/mL) and vitamins@P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL) with 100 μL ATCC 29,213 methicillin-sensitive Staphylococcus aureus (MSSA) (10⁷ in PBS, pH 7). Controls were made replacing nanoparticles with the same volume of PBS. The concentrations of nanoparticle suspensions were chosen based on the FDA approved maximal and the minimal amount usually found in sunscreens, which are 20% and 2% (this is equivalent to 0.2 mg/mL and 0.02 mg/mL for nanoparticles suspensions). The cream concentration, on the other hand, was an intermediate value of 10%.