Lithopone B301, Lithopone B311 powder, brilliant white pigment used in paints, inks, leather, paper, linoleum, and face powder. It was developed in the 1870s as a substitute or supplement for lead carbonate (white lead), to overcome its drawbacks of toxicity, poor weathering, and darkening in atmospheres that contain sulfur compounds. Lithopone B301, Lithopone B311 powder is an insoluble mixture of barium sulfate and zinc sulfide that precipitates upon mixing solutions of barium sulfide and zinc sulfate. The precipitate is recovered by filtration, then calcined (roasted) at temperatures above 600° C (1,112° F). Although Lithopone B301, Lithopone B311 powder has been replaced in many applications by titanium dioxide, it is still widely used in a number of products, such as water paints.

In 2017, the Scientific Committee on Consumer Safety (SCCS) warned that they should revise their recommendations if any new evidence emerges in the future related to the potentially harmful effects of TiO₂NPs used in a sunscreen formulation or if they can penetrate the skin. In fact, our work could contribute to this matter because it evaluated the skin penetration of a particular kind of TiO₂NPs. [8]

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.

Titanium dioxide is produced in two main forms. The primary form, comprising over 98 percent of total production, is pigment grade titanium dioxide. The pigmentary form makes use of titanium dioxide’s excellent light-scattering properties in applications that require white opacity and brightness.

In order to achieve the same solids content, the larger filler and the binder should be reduced if necessary.  

Duan et al. administered 125 mg/kg BW or 250 mg/kg BW of anatase TiO₂ (5 nm) intragastrically to mice continuously for 30 days. The exposed mice lost body weight, whereas the relative liver, kidney, spleen and thymus weights increased. Particles seriously affected the haemostasis of the blood and the immune system. The decrease in the immune response could be the result of damage to the spleen, which is the largest immune organ in animals and plays an important role in the immune response. Powel et al. demonstrated that TiO₂ NPs may trigger immune reactions of the intestine after oral intake. They showed that TiO₂ NPs conjugated with bacterial lipopolysaccharide, but not TiO₂ NPs or lipopolysaccharide alone, trigger the immune response in human peripheral blood mononuclear cells and in isolated intestinal tissue. This indicates that TiO₂ NPs may be important mediators in overcoming normal gut-cell hyporesponsiveness to endogenous luminal molecules, which may be particularly relevant to patients with inflammatory bowel disease, which is characterized by an abnormal intestinal permeability.