A 2022 review on past studies of titanium dioxide and rat lung cancer, for instance, said the original study was under extreme conditions and its effects were not replicated in other animal species. Additionally, the review concluded that the few studies which did directly focus on titanium dioxide's impact on humans did not end up showing any increased cancer risk.

The skin of an adult person is, in most places, covered with a relatively thick (∼10 μm) barrier of keratinised dead cells. One of the main questions is still whether TiO₂ NPs are able to penetrate into the deeper layers of the skin. The majority of studies suggest that TiO₂ NPs, neither uncoated nor coated (SiO₂, Al₂O₃ and SiO₂/Al₂O₃) of different crystalline structures, penetrate normal animal or human skin. However, in most of these studies the exposures were short term (up to 48 h); only few long-term or repeated exposure studies have been published. Wu et al.83 have shown that dermal application of nano-TiO₂ of different crystal structures and sizes (4–90 nm) to pig ears for 30 days did not result in penetration of NPs beyond deep epidermis. On the other hand, in the same study the authors reported dermal penetration of TiO₂ NPs with subsequent appearance of lesions in multiple organs in hairless mice, that were dermal exposed to nano-TiO₂ for 60 days. However, the relevance of this study for human exposure is not conclusive because hairless mice skin has abnormal hair follicles, and mice stratum corneum has higher lipid content than human stratum corneum, which may contribute to different penetration. Recently Sadrieh et al. performed a 4 week dermal exposure to three different TiO₂ particles (uncoated submicron-sized, uncoated nano-sized and coated nano-sized) in 5 % sunscreen formulation with minipigs. They found elevated titanium levels in epidermis, dermis and in inguinal lymph nodes, but not in precapsular and submandibular lymph nodes and in liver. With the energy dispersive X-ray spectrometry and transmission electron microscopy (TEM) analysis the authors confirmed presence of few TiO₂ particles in dermis and calculated that uncoated nano-sized TiO₂ particles observed in dermis represented only 0.00008 % of the total applied amount of TiO₂ particles. Based on the same assumptions used by the authors in their calculations it can be calculated that the total number of particles applied was 1.8 × 10¹³ /cm² and of these 1.4 x10⁷/cm² penetrated. The surface area of skin in humans is around 1.8 m²  and for sun protection the cream is applied over whole body, which would mean that 4 week usage of such cream with 5 % TiO₂ would result in penetration of totally 2.6 × 10¹⁰ particles. Although Sadrieh et al.concluded that there was no significant penetration of TiO₂ NPs through intact normal epidermis, the results are not completely confirmative.

A study published in the Journal of Agricultural and Food Chemistry in 2019 sought to examine the effects of titanium dioxide on intestinal inflammation. Researchers did this by feeding rats titanium dioxide nanoparticles and found that, after the course of two to three months, the animals had lower body weights and induced intestinal inflammation. The researchers also found the nanoparticles altered gut microbiota composition and aggravated chronic colitis. The rats also experienced reduced populations of CD4+T cells (which are cells that help organize immune responses by prompting other immune cells to fight infection), regulatory T cells, and white blood cells in mesenteric lymph nodes. The researchers wrote: “Dietary TiO2 nanoparticles could interfere with the balance of the immune system and dynamic of gut microbiome, which may result in low-grade intestinal inflammation and aggravated immunological response to external stimulus, thus introducing potential health risk.”

Titanium dioxide can boost and brighten colors because of how well it absorbs and also scatters light. In food and drugs, this additive is known as E171 and helps define colors clearly and can prevent degradation (cracking and breakdown of materials) from exposure to sunlight.

Genotoxicity Assessment