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.
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).
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.
This classification was given, as some animal studies found that inhaling titanium dioxide dust might cause the development of lung tumors. However, IARC concluded that food products containing this additive do not pose this risk (11).
Titanium dioxide can also be found in dairy products to make them whiter and brighter … like frosting or cottage cheese, Stoiber told USA TODAY, adding that the additive is used in other products – such as food or beverage instant mixes – as an anti-caking agent.
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.”
In a 2017 study published in Scientific Reports, researchers exposed rats to human-relevant levels of E171 to examine the effects of intestinal inflammation and carcinogenesis. They saw that “a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model.” They continued: “Stimulation of immune cells isolated from Peyer’s Patches [which are clusters of lymphoid follicles found in the intestine] showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased,” researchers wrote. “A 100-day titanium dioxide treatment promoted colon microinflammation and initiated preneoplastic lesions.” The scientists concluded: “These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.”
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Although barium sulfate is almost completely inert, zinc sulfide degrades upon exposure to UV light, leading to darkening of the pigment. The severity of this UV reaction is dependent on a combination of two factors; how much zinc sulfide makes up the pigments formulation, and its total accumulated UV exposure. Depending on these factors the pigment itself can vary in shade over time, ranging from pure white all the way to grey or even black. To suppress this effect, a dopant may be used, such as a small amount of cobalt salts, which would be added to the formulation. This process creates cobalt-doped zinc sulfide. The cobalt salts help to stabilize zinc sulfide so it will not have as severe a reaction to UV exposure.
There are numerous manufacturers of titanium dioxide; the largest include Delaware-based Chemours (a spin-off of DuPont Chemical), Texas-based Kronos, and China-based Lomon Billions Group, all of which manufacture pigments for use in products like paints, coatings, and plastics. UK-based Venator is a major supplier of titanium dioxide used in food and cosmetics, along with paints, paper, plastic, and more. As a pigment, it is called Pigment White 6 (PW6), titanium white, or CI 77891. As a food additive, it is known as E171.


Les pouvoirs couvrant et éclaircissant du lithopone normal sont supérieurs à ceux de la céruse et de l'oxyde de zinc, mais inférieurs au Dioxyde de Titane pur, étant le meilleur blanc sous tout rapport. C'est le sulfure de zinc qui, avec son indice de réfraction de 2,37, est l’élément opaque ; le 2nd composé, le sulfate de baryum, joue un rôle de diluant minéral et favorise l'efficacité de la diffusion du premier.
Still many experts say the body of research does not support the current health concerns being expressed about titanium dioxide.
The effects of TiO2 NPs in plants
Its chemical formula is TiO2, which means it consists of one titanium atom and two oxygen atoms (hence dioxide). It has a CAS (Chemical Abstracts Service) registration number of 13463-67-7.
From studies deemed relevant, the experts found that titanium dioxide as a food additive is poorly absorbed by the gastrointestinal tract of mice and rats, with no adverse effects observed in short-term studies in rodents receiving titanium dioxide in their diets. No observed adverse effect levels (NOAELs) of 15,000 milligrams per kilogram of bodyweight (mg/kg BW) per day and 5,000 mg/kg BW per day—the highest doses tested—were established for mice and rats, respectively.
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