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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.

On absorption of UV light, photo-generated titanium dioxide particles create singlet oxygen, superoxide anions (O2-) and hydroxyl radicals (OH-) that are potent free radicals (1,2). Irradiated particles of titanium dioxide can induce oxidative damage to DNA (2) which can lead to the development of mutant cells and skin cancers (3,4,5,6) and lipid peroxidation of essential functions on the cell membrane (7).

Amount: if too little titanium dioxide is added, the distance between particles is too large and there is not enough opacity, while if the titanium content is too high, the particles interfere with each other and poor efficiency is obtained.

Lithopone has therefore traditionally been used in stoppers and putties, jointing compounds and sealing compounds, primers and undercoats and in road-marking paints.

Titanium dioxide is an insoluble mineral, meaning it cannot dissolve in water. Known for its bright, white pigment, manufacturers use titanium dioxide in many different capacities, including in cosmetics, foods, and drugs. 

In a 2019 study published in the journal Nanotoxicology, researchers recreated the first phase of digestion in mice and fed them titanium dioxide, then examined whether accumulation occurred in the organs. Researchers wrote: “Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO2 particles was also measured. Titanium accumulation in the liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine. Overall, [this] indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered.”

White powder

Colorectal tumors and preneoplastic lesions

Then, there’s ultrafine-grade, also known as nanoscale titanium dioxide. This is used for its ability to scatter lightly as an ultra-fine powder. This gives it the ability to lightly absorb into the skin while providing a bit of transparency. Below, we’ll go more into the cosmetic uses of these two forms of titanium dioxide.

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