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.

This cytotoxic effect was also reported before; i.e. Natarajan et al. conducted an experiment that found a strong oxidative stress, morphological changes in mitochondria and substantial loss in the fusion of primary hepatocytes exposed to P25TiO₂NPs [52].

In addition to its aesthetic benefits, lithopone also offers practical advantages for leather suppliers. Due to its low cost and wide availability, lithopone is a cost-effective option for leather manufacturers looking to minimize production expenses without compromising on quality. Its stable chemical properties also make it easy to work with during the manufacturing process, resulting in a smooth and efficient production line.

Increased severity of ulcerative colitis

Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters. The researchers wrote: “Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.” After reviewing dozens of studies, the scientists concluded: “Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”

The US and Canada, however, approve the use of titanium dioxide as a food additive. Canada's recent review of titanium dioxide reconfirmed its safety and pointed out that many of the toxicity studies the EU reviewed were not relevant to the safety of titanium dioxide as a food ingredient, and that the ban is based on an abundance of caution and uncertainty.

Lithopone, a white pigment composed of a mixture of barium sulfate and zinc sulfide, is commonly used in the leather industry as a coloring agent. Leather suppliers around the world rely on lithopone to achieve the desired color and finish on their products.