Food, Global Health 2 min
Titanium dioxide: E171 first enters the blood via the mouth
PRESSE RELEASE - The use of E171 in food has been banned in Europe since 2022. Pioneering work by INRAE has 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, have taken their 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 buccal mucosa.
Published on 17 May 2023
E171, a food additive, has been used until recently as a whitening and opacifying agent in many products such as pastries, sweets, sauces and ice cream. It is composed of micro- and nanoparticles of titanium dioxide, or TiO2.
The scientific community has been scrutinising these titanium dioxide nanoparticles. Previous studies on animal models have shown that they can cause the appearance of pre-cancerous cells in the colon[1] among other effects in the body[2]. On the basis of the precautionary principle, the use of E171 in food has been banned in France from 2020. All of Europe followed suit in 2022.
Once ingested, nanoparticles accumulate in the liver and spleen after absorption from the intestine, but also in the placenta, until they contaminate the foetus[3]. Scientists then wondered if there were other routes of exposure of the body to these nanoparticles.
To answer this question, researchers from INRAE, in collaboration with the LNE (Laboratoire National de métrologie et d'Essais, Paris), studied its absorption by the buccal cavity. They first studied their passage through the mouth of pigs (histologically very similar to that of humans), then the effect of the nanoparticles on human buccal cells in culture. Under these conditions, in vivo and in vitro respectively, 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 may affect the renewal of the oral epithelium[4].
These results not only confirm that these nanoparticles pass through the oral mucosa to reach the bloodstream, thus well before their absorption in the intestine, but also that they can affect cell regeneration within these same mucosa.
This work highlights the importance of taking into account 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 pharmaceuticals.
E171 is used as a white food colouring and opacifying agent. It is still used in pharmaceutical preparations and toothpastes, and outside Europe in food. In this study, scientists tracked TiO2 particles using electron microscopy coupled with titanium spectrometry. They also used the "nanoparticle-scope", an innovative technology to map their distribution in tissues at the nanometre scale.
[1]Bettini S, Boutet-Robinet E, Cartier C, Coméra C, Gaultier E, Dupuy J, Naud N, Taché S, Grysan P, Reguer S, Thieriet N, Réfrégiers M, Thiaudière D, Cravedi JP, Carrière M, Audinot JN, Pierre FH, Guzylack-Piriou L, Houdeau E. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Sci Rep. 2017 Jan 20;7:40373. DOI: 10.1038/srep40373.
[2]Bischoff NS, de Kok TM, Sijm DTHM, van Breda SG, Briedé JJ, Castenmiller JJM, Opperhuizen A, Chirino YI, Dirven H, Gott D, Houdeau E, Oomen AG, Poulsen M, Rogler G, van Loveren H. Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System.
Int J Mol Sci. 2020 Dec 28;22(1):207. DOI: 10.3390/ijms22010207.
[3]Guillard A, Gaultier E, Cartier C, Devoille L, Noireaux J, Chevalier L, Morin M, Grandin F, Lacroix MZ, Coméra C, Cazanave A, de Place A, Gayrard V, Bach V, Chardon K, Bekhti N, Adel-Patient K, Vayssière C, Fisicaro P, Feltin N, de la Farge F, Picard-Hagen N, Lamas B, Houdeau E. 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. 2020 Oct 7;17(1):51. DOI: 10.1186/s12989-020-00381-z.
[4] The oral epithelium is the mucous membrane on the inner lining of the lips and the oral cavity.
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.