Titanium dioxide: the mouth, the primary route of E171 into the bloodstream

The use of E171 in food has been banned in Europe since 2022. Pioneering work by INRAE had shown that this food additive passes into the bloodstream and has toxic effects in the intestine. In recent work, INRAE researchers, in collaboration with the LNE, took the analysis a step further. The results, published on 17 May in Nanotoxicology, show that the nanoparticles that make up this additive can pass directly through the mucous membranes of the mouth.

E171 is a food additive that, until recently, was used as a white colouring agent and opacifier in many products such as pastries, sweets, sauces and ice cream. It is composed of micro- and nanoparticles of titanium dioxide, TiO₂.

These titanium dioxide nanoparticles are being closely studied by the scientific community. Previous studies on animal models have shown that they can cause the appearance of precancerous cells in the colon, among other effects on the body. Based on the precautionary principle, the use of E171 in food was banned in France in 2020 and in Europe in 2022.

Once ingested, nanoparticles accumulate in the liver and spleen after being absorbed from the intestine, but also in the placenta, contaminating the foetus.³ But are there other pathways for these nanoparticles?

To answer this question, scientists from INRAE, in collaboration with the LNE (National Metrology and Testing Laboratory, Paris), studied its absorption by the mucous membranes of the oral cavity. They first studied their passage through the mouths of pigs (histologically very similar to that of humans), then the effect of nanoparticles on human oral cells in culture. Under these in vivo and in vitro conditions, respectively, the tests show that they are indeed rapidly absorbed. Once absorbed, they damage the DNA of the cells by subjecting them to oxidative stress, affecting the survival of growing cells, an effect that is likely to affect the renewal of the oral epithelium*.

These results confirm not only that these nanoparticles pass through the oral mucosa to reach the bloodstream, well before being absorbed in the intestine, but also that they can affect cell regeneration within these same mucous membranes.

This research highlights the importance of taking into account the direct exposure of the oral cavity to the food additive E171 when assessing risks to humans, both when used in food products and in cosmetics (particularly toothpaste) and pharmaceutical products.

*The buccal epithelium is the mucous membrane that lines the inner surface of the lips and the oral cavity.

See also

https://www.inrae.fr/actualites/dioxyde-titane-bouche-premiere-voie-passage-du-e171-sang

Reference

Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium. Nanotoxicology, 2023. https://doi.org/10.1080/17435390.2023.2210664

Bibliography
1) Bettini S., Boutet-Robinet E., Cartier C. et al. (2017). Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Sci Rep., 7, 40373. doi: 10.1038/srep40373.
2) Bischoff N.S., de Kok T.M., Sijm D.T.H.M. et al. (2020). Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System. Int J Mol Sci., 22 (1), 207. doi: 10.3390/ijms22010207.
3) Guillard A., Gaultier E., Cartier C. et al. (2020). Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model.Part Fibre Toxicol., 17 (1), 51. doi: 10.1186/s12989-020-00381-z.