Titanium dioxide as used in sunscreens is commonly modified with other ingredients to ensure efficacy and stability. Examples of what are known as surface modifier ingredients used for titanium dioxide include stearic acid, isostearic acid, polyhydroxystearic acid, and dimethicone/methicone copolymer.

Skin-penetration studies 

In an early study Jani et al. administred rutile TiO₂ (500 nm) as a 0.1 ml of 2.5 % w/v suspension (12.5 mg/kg BW) to female Sprague Dawley rats, by oral gavage daily for 10 days and detected presence of particles in all the major gut associated lymphoid tissue as well as in distant organs such as the liver, spleen, lung and peritoneal tissue, but not in heart and kidney. The distribution and toxicity of nano- (25 nm, 80 nm) and submicron-sized (155 nm) TiO₂ particles were evaluated in mice administered a large, single, oral dosing (5 g/kg BW) by gavage. In the animals that were sacrificed two weeks later, ICP-MS analysis showed that the particles were retained mainly in liver, spleen, kidney, and lung tissues, indicating that they can be transported to other tissues and organs after uptake by the gastrointestinal tract. Interestingly, although an extremely high dose was administrated, no acute toxicity was observed. In groups exposed to 80 nm and 155 nm particles, histopathological changes were observed in the liver, kidney and in the brain. The biochemical serum parameters also indicated liver, kidney and cardiovascular damage and were higher in mice treated with nano-sized (25 or 80 nm) TiO₂ compared to submicron-sized (155 nm) TiO₂. However, the main weaknesses of this study are the use of extremely high single dose and insufficient characterisation of the particles.

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Another vital aspect to consider when working with a lithopone pigment pricelist is the effect of quality on pricing. Higher purity pigments generally command a premium price because of their enhanced performance characteristics. When choosing a supplier, it’s essential to look for manufacturers who adhere to strict quality control standards. This ensures that the pigment not only meets industry standards but also performs reliably in various applications, thus justifying any additional costs.

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Hemolysis was studied on suspensions of P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL), vitaminB2@P25TiO₂NPs (0.2 mg/mL and 0.02 mg/mL) and vitamin B2 (0.2 mg/mL and 0.02 mg/mL) were prepared and mixed with 500 μL of anticoagulated blood (donated by Laboratorio de Hemoderivados, UNC) in a rate of 1/10. A solution of NaCl 10% was used as the positive control and PBS as the negative control. Then, the samples were irradiated using the LED described above for 3 and 6 h to simulate the light penetration into the skin. Also, a set of samples was kept in the dark as control. Finally, the samples were centrifuged and the absorbance at 540 nm was measured in the supernatants. The experiment was reproduced twice; the standard deviation was calculated and p-value < 0.05 were considered significant.

Of the products that include the additive in their labels, Thea Bourianne, senior manager at data consultant Label Insights, told Food Navigator USA in May 2021 that more than 11,000 products in the company's database of U.S. food and beverage products listed titanium dioxide as an ingredient. Non-chocolate candy led those numbers at 32%. Cupcakes and snack cakes made up 14%, followed by cookies at 8%, coated pretzels and trail mix at 7%, baking decorations at 6%, gum and mints at 4% and ice cream at 2%.

Different dermal cell types have been reported to differ in their sensitivity to nano-sized TiO₂ . Kiss et al. exposed human keratinocytes (HaCaT), human dermal fibroblast cells, sebaceous gland cells (SZ95) and primary human melanocytes to 9 nm-sized TiO₂ particles at concentrations from 0.15 to 15 μg/cm² for up to 4 days. The particles were detected in the cytoplasm and perinuclear region in fibroblasts and melanocytes, but not in kerati-nocytes or sebaceous cells. The uptake was associated with an increase in the intracellular Ca²⁺ concentration. A dose- and time-dependent decrease in cell proliferation was evident in all cell types, whereas in fibroblasts an increase in cell death via apoptosis has also been observed. Anatase TiO₂ in 20–100 nm-sized form has been shown to be cytotoxic in mouse L929 fibroblasts. The decrease in cell viability was associated with an increase in the production of ROS and the depletion of glutathione. The particles were internalized and detected within lysosomes. In human keratinocytes exposed for 24 h to non-illuminated, 7 nm-sized anatase TiO_2, a cluster analysis of the gene expression revealed that genes involved in the “inflammatory response” and “cell adhesion”, but not those involved in “oxidative stress” and “apoptosis”, were up-regulated. The results suggest that non-illuminated TiO₂ particles have no significant impact on ROS-associated oxidative damage, but affect the cell-matrix adhesion in keratinocytes in extracellular matrix remodelling. In human keratinocytes, Kocbek et al. investigated the adverse effects of 25 nm-sized anatase TiO₂ (5 and 10 μg/ml) after 3 months of exposure and found no changes in the cell growth and morphology, mitochondrial function and cell cycle distribution. The only change was a larger number of nanotubular intracellular connections in TiO₂-exposed cells compared to non-exposed cells. Although the authors proposed that this change may indicate a cellular transformation, the significance of this finding is not clear. On the other hand, Dunford et al. studied the genotoxicity of UV-irradiated TiO₂ extracted from sunscreen lotions, and reported severe damage to plasmid and nuclear DNA in human fibroblasts. Manitol (antioxidant) prevented DNA damage, implying that the genotoxicity was mediated by ROS.