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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.

2. Relative density: 4.136 to 4.39 g/mL.

Tioxide process. This process is similar to that used to produce fumed silicas. Ultra-low particle size titanium dioxide (15-35 nm) is obtained for use as photocatalyst or UV absorber (for instance in sun protective creams).

Nano-sized P25TiO₂NPs were kindly donated by Dr. Scaiano, Ottawa University (Canada). Riboflavin (vitamin B2) was from Sigma and ascorbic acid (vitamin C) and KBr (for IR pills) were from Cicarelli. Base cream for the animal experiments was purchased from Todo Droga and the LED panel was built ad hoc.

Potential hazards of oral exposure to TiO₂ NPs 

Safety

Despite a bullish trends ruling the market for the bulk of the period, the North American market had mixed sentiments in the fourth quarter of 2021. This was mostly due to the adequate pushback from the supply-demand imbalance, which was further compounded by rising natural gas prices, which had taken a proper toll on the future production of numerous minerals, including titanium dioxide. An increase in COVID instances had prompted concerns in ore feedstock. As a result, during the fourth quarter of 2021, the FD UGSC (USA) quarterly average negotiations for the chemical CP Rutile Grade were finalised at USD 4434 per tonne.

Lithopone is an inorganic white pigment, obtained from co-precipitation of Zinc sulfide (ZnS) and Barium sulfate (BaSO4). Titanium Dioxide (TiO2) has replaced Lithopone as a white pigment in majority applications as TiO2 is more durable. However, it is much cheaper than TiO2 and has advantages such as low binder requirement and good dispensability. As a white pigment, it can improve the substrate's weather resistance, and improve the fungicidal properties of paint formulations. Some of the major applications of Lithopone include manufacturing of paint pigments, plastic & rubber products, paper, printing inks, cosmetics, and leather & linoleum products. It is commercially available under names such as pigment white 5, Barium zinc sulfate sulfide, Becton White, C.I. 77115, Charlton White, Enamel White, and Zincolith. On the basis of content of ZnS, Lithopone is available at 28%-30% Lithopone and 60% Lithopone.

Due to its low binder requirement, lithopone provides paints with good flow and application properties. In the plastic processing industry, it is added to plastics to increase the plastic product’s UV tolerance, thus increasing its outdoor life. In the leather industry, it is one of the sulfide-based white pigments. It is also used in the production of linoleum floorings.