Background 

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.

JECFA previously assessed titanium dioxide at its 13^th meeting, at which time the expert committee assigned a “not specified” ADI for the additive due to an absence of significant absorption and a lack of toxicological effects in the available experimental animal and human studies. Since its original evaluation by JECFA, titanium dioxide has become a public point of contention, with its ban being introduced (and then subsequently withdrawn) in California legislation in 2023, a legal battle playing out in the EU over the additive’s ban and classification as a carcinogen in 2022, and the European Food Safety Authority (EFSA) calling titanium dioxide unsafe. However, supporters of titanium dioxide say that claims about its dangers are founded in unreliable studies, and some recent research has supported its safety as a food additive.

TiO₂ NPs appeared to be more toxic to nematode Caenorhabditis elegans than submicron-sized TiO_2.  At a concentration of 1 mg/l, 7 nm particles affected its fertility and survival rate and were more toxic than 20 nm anatase particles. Similarly, Hu et al. showed that rutile particles (10–20 nm), at concentrations above 1 g/kg soil, can be bio-accumulated in earthworms, where they induce oxidative stress, inhibit the activity of cellulase and induce DNA and mitochondrial damage.

Applications:

What are the forms of titanium dioxide?

The pigment’s low Mohs hardness produces low abrasion compared to TiO2.

There seems to be a lot of misunderstanding about titanium dioxide, which can be used as a colorant in foods. While headlines may suggest titanium dioxide is a health concern, scientific research has actually shown titanium dioxide to be safe. So what is it used for and why is it used? Read on to learn more!