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.

≤0.3

Overall, titanium dioxide manufacturers play a crucial role in supplying this essential compound to industries around the world. By focusing on quality, sustainability, and innovation, manufacturers can ensure a stable supply of titanium dioxide for years to come.

Another common use of titanium IV oxide is in food coloring. Titanium dioxide is a FDA-approved food additive that is used to enhance the color of various food products. It is commonly used in candies, pastries, and dairy products to create vibrant colors. Titanium dioxide is a safe food additive that is used in small quantities to enhance the visual appeal of food products.

We've used titanium dioxide safely for decades. However, recently its safety was called into question. 
 
At CRIS, we've explored the safety of titanium dioxide for nearly half a decade, including conducting double-blind research to test the safety of food-grade titanium dioxide (E171). Our study shows that when exposed to food-grade titanium dioxide in normal conditions, research animals did not experience adverse health outcomes.
 
It's important to emphasize that in a National Institutes of Health study, experimental animals were exposed to titanium dioxide in amounts as high as 5% of their diet for a lifetime and showed no evidence of adverse effects. 
 
A handful of studies greatly influenced the decisions made by the European Food Safety Authority (EFSA). Unfortunately, these studies did not consider that titanium dioxide exposure comes from food, not drinking water. Additionally, CRIS researchers could not reproduce the adverse outcomes identified by the studies through typical food ingestion. Regardless, the EFSA banned E171 as a food ingredient and for use in other capacities in the summer of 2022.
 
In 2022, the United States, United Kingdom, and Canada maintained that the scientific evidence supports that titanium dioxide (E171) is safe for humans to use and consume.