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.

In the paper industry, art painting supplies level, use as a white opaque pigment for a variety of printing paper filler, white pigment for pencils, watercolors, art painting.

5. Is EFSA banning titanium dioxide? 

To be added to food, this additive must achieve 99% purity. However, this leaves room for small amounts of potential contaminants like lead, arsenic, or mercury (1Trusted Source).

In sunscreen, titanium dioxide is used as a barrier to keep the sun's ultraviolet (UV) rays from damaging your skin. It's processed into much smaller particles than what goes into food, called nanoparticles. In this form, it becomes transparent, and also absorbs UV light so it doesn't reach your skin.

We've used titanium dioxide safely for decades. However, recently its safety was called into question. 
 
At CRIS, we've explored the safety of titanium dioxide for nearly half a decade, including conducting double-blind research to test the safety of food-grade titanium dioxide (E171). Our study shows that when exposed to food-grade titanium dioxide in normal conditions, research animals did not experience adverse health outcomes.
 
It's important to emphasize that in a National Institutes of Health study, experimental animals were exposed to titanium dioxide in amounts as high as 5% of their diet for a lifetime and showed no evidence of adverse effects. 
 
A handful of studies greatly influenced the decisions made by the European Food Safety Authority (EFSA). Unfortunately, these studies did not consider that titanium dioxide exposure comes from food, not drinking water. Additionally, CRIS researchers could not reproduce the adverse outcomes identified by the studies through typical food ingestion. Regardless, the EFSA banned E171 as a food ingredient and for use in other capacities in the summer of 2022.
 
In 2022, the United States, United Kingdom, and Canada maintained that the scientific evidence supports that titanium dioxide (E171) is safe for humans to use and consume.

Nanotoxicology