Genotoxicity and cytotoxicity 

In 2017, French researchers from the Institut National de la Recherche Agronomique (INRAE) were among the first to examine the effects of E171 nanoparticles on the body. They fed rats a dose of 10mg of E171 per kilogram of body weight per day, which was similar to human exposure in food. The research, which was published in Scientific Reports, showed that E171 was able to traverse the intestinal barrier, pass into the bloodstream, and reach other areas of the body in rats. Researchers also found a link between immune system disorders and the absorption of titanium dioxide nanoparticles. 

Recent policy changes in regard to titanium dioxide

In 2023, California and New York proposed banning several food additives that are banned in Europe but legal in the United States. Titanium dioxide was among the five proposed to be banned, but in September, the additive was removed from the list of additives from the California ban list.

One of the key players in the titanium dioxide manufacturing industry is CAS 13463-67-7. This factory is known for its high-quality products and state-of-the-art facilities. With a focus on innovation and sustainability, CAS 13463-67-7 has become a go-to choice for companies looking to source titanium dioxide for their dyes and pigments.

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.