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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.

The toxicity of P25TiO₂NPs under UV radiation could be even higher when combined with other usual components of sunscreens Indeed, Soler de la Vega et al. advise that combination with parabens increases the toxicity of the final cosmetic mixture [53].

Molar mass: 412.23

For research published in Archives of Toxicology in 2020, scientists fed one group of mice a solution containing titanium dioxide for one month, and compared it to those that did not receive the additive. They found “the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed” in the titanium dioxide group when compared with the control group. The tests also revealed that the titanium dioxide exposure could cause locomotor dysfunction, or mobility issues “by elevating the excitement of enteric neurons, which might spread to the brain via gut-brain communication by vagal pathway.” The researchers concluded: “These findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.”

In conclusion, the demand for dyes and pigments is on the rise, and having a reliable titanium dioxide factory like CAS 13463-67-7 is essential for meeting this demand. With its dedication to quality, sustainability, and innovation, CAS 13463-67-7 is well-positioned to continue serving the needs of its customers and the industry as a whole.

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