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.

What titanium dioxide is really emblematic of ... is the failure of FDA to look back at these old decisions and ask whether its decisions that were made in this case ... 56 years ago (in the 1966 approval) still hold up, he said.

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.

This article reviews the uses, benefits, and safety of titanium dioxide.

Fig. 3. Cell survival measured on samples of MSSA with bare and functionalized P25TiO₂NPs after 6 h of irradiation. A: P25TiO₂NPs, B:vitaminB2@P25TiO₂NPs, C: vitaminC@P25TiO₂NPs in concentrations of 0.2 μg/mL (red) and 0.2 mg/mL (blue). p <0.05.

The basic scenario of resistive switching in TiO₂ (Jameson et al., 2007) assumes the formation and electromigration of oxygen vacancies between the electrodes (Baiatu et al., 1990), so that the distribution of concomitant n-type conductivity (Janotti et al., 2010) across the volume can eventually be controlled by an external electric bias, as schematically shown in Figure 1B. Direct observations with transmission electron microscopy (TEM) revealed more complex electroforming processes in TiO₂ thin films. In one of the studies, a continuous Pt filament between the electrodes was observed in a planar Pt/TiO₂/Pt memristor (Jang et al., 2016). As illustrated in Figure 1C, the corresponding switching mechanism was suggested as the formation of a conductive nanofilament with a high concentration of ionized oxygen vacancies and correspondingly reduced Ti³⁺ ions. These ions induce detachment and migration of Pt atoms from the electrode via strong metal–support interactions (Tauster, 1987). Another TEM investigation of a conductive TiO₂ nanofilament revealed it to be a Magnéli phase Ti_nO_2n−1 (Kwon et al., 2010). Supposedly, its formation results from an increase in the concentrations of oxygen vacancies within a local nanoregion above their thermodynamically stable limit. This scenario is schematically shown in Figure 1D. Other hypothesized point defect mechanisms involve a contribution of cation and anion interstitials, although their behavior has been studied more in tantalum oxide (Wedig et al., 2015; Kumar et al., 2016). The plausible origins and mechanisms of memristive switching have been comprehensively reviewed in topical publications devoted to metal oxide memristors (Yang et al., 2008; Waser et al., 2009; Ielmini, 2016) as well as TiO₂ (Jeong et al., 2011; Szot et al., 2011; Acharyya et al., 2014). The resistive switching mechanisms in memristive materials are regularly revisited and updated in the themed review publications (Sun et al., 2019; Wang et al., 2020).