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VeilleNanos - Risks associated with the ingestion of titanium dioxide nanoparticles

Risks associated with the ingestion of titanium dioxide nanoparticles

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Risks associated with the ingestion of titanium dioxide nanoparticles

By the AVICENN team – Last updated in March 2024

Titanium dioxide (TiO2) is a white colorant in powder form, with a significant portion of its particles being of nanoscale size1smaller than 100 nanometers (1 nm = 0.001 µm = 1 billionth of a meter). It has been prohibited in foodstuffs in France in 2020, an in the entire European Union in 2022, following an opinion from the European Food Safety Agency (EFSA). Responding to suspicions of colon carcinogenicity, EFSA analyzed thousands of publications and concluded a potential genotoxic risk (DNA strand breaks and chromosomal damage) associated with TiO22See : Titanium dioxide: E171 is no longer considered safe as a food additive, EFSA, May 6, 2021, particularly with its nanoparticles. For now, titanium dioxide is still allowed at the non-nano scale for other oral cosmetic uses, such as toothpastes or lipsticks and balms (where it can be identified by the code CI 77891)3An opinion from the European Consumer Safety Committee (ECCS) is expected shortly..

Regarding medicinal products, the European Commission has laid the groundwork for a potential ban that could come into effect from 2025. Emphasizing that “it is crucial that the pharmaceutical industry makes every effort to accelerate research and development of alternative solutions to replace titanium dioxide (E171) in medicines”4See our fact sheet“Towards the suspension of titanium dioxide in cosmetics and medicines” for more information..

How is TiO2 absorbed, diffused and accumulated in the body during and after ingestion?

Laboratory research has shown that TiO2 nanoparticles can be absorbed through the oral mucosa,5See :
Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium, Vignard J et al, Nanotoxicology, 2023 : “The data presented here provide evidence that under realistic exposure conditions in terms of dose and duration of exposure, food-grade TiO2 may translocate through the oral mucosain an in vivo pig model of buccal mucosa that is close to the human mouth. We also report the high permeability of human buccal epithelial cells to TiO2 particles in vitro. After these cells were exposed to the food additive for 2 h, TiO2 particles generated oxidative and genotoxic stresses that were detrimental to proliferating cells mainly. This raises the issue of possible adverse consequences regarding the constant turnover of the buccal mucosa or during wound repair and regeneration.”
The buccal mucosa as a route for TiO2 nanoparticle uptake, Teubl et al, Nanotoxicology, 2015
cross the intestinal barrier,6See :
Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice, Coméra et al., Particle and Fibre Toxicology, 2020
Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status, Talamini et al, Nanotoxicology, 2019 : Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO2 particles was also measured. Titanium accumulation in liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine. Overall, the present study indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered.”
distribute into the bloodstream7See:
Pharmaceutical/food grade titanium dioxide particles are absorbed into the bloodstream of human volunteers, Pele et al, Particle and Fibre Toxicology, 2015
, and accumulate in various organs8See:
Silicon Dioxide and Titanium Dioxide Particles Found in Human Tissues, Peters et al, Nanotoxicology 14, 2020
Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats Kreyling et al, Nanotoxicology2017: the authors observed the passage of the gastrointestinal barrier for a small fraction of TiO2 in rats (0.6% of the administered dose), which was found after 7 days accumulated in various organs, mainly the liver, lungs, kidneys, brain, spleen, uterus and skeleton (cited by the HCSP in its report Review of knowledge on the effects of titanium dioxide (TiO2) nanoparticles on human health; characterization of population exposure and management measures, April 2018)
(liver, kidney, spleen, stomach, brain, lungs, testicles, ovaries, uterus, placenta, mammary glands, etc.) with possible transmission from mother to offspring during pregnancy9Titanium dioxide nanoparticles: E171 crosses the placental barrier, INRAE, October 7, 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, Guillard et al, Particle and Fibre Toxicology, 2020 and breastfeeding10Toxic effects of TiO2 NPs in the blood-milk barrier of the maternal dams and growth of offspring, Yao et al, Ecotoxicology and Environmental Safety, 2021:”Collectively, this study presented the deleterious pathological effects of oral exposure to TiO2 NPs in the mammary gland tissues and blood-milk barrier via the production of reactive oxygen species (ROS) in dams and developmental concerns in offspring.”.

What are the adverse effects of ingesting TiO2?

Accumulating studies report :

More generally…

Scientific publications on the health risks associated with titanium dioxide (TiO2) nanoparticles have been accumulating for about two decades now. In 2006 and again in 2019, TiO2 was classified as a potential carcinogen by inhalation by the International Agency for Research on Cancer (IARC) and the European Commission. This classification is contested by companies that manufacture or use TiO2,despite its role in informing workers about the risks they face so that they can better protect themselves.

TiO2 nanoparticles have a slow elimination rate, raising concerns about the long-term impacts of repeated exposure and the bioaccumulation of these particles26Avisde l’ANSES relatif à l’évaluation du risque de la fraction nanométrique de l’additif alimentaire E171, October 27, 2022. Those not stored in the human body but excreted and released in wastewater pose a risk of toxicity to terrestrial and aquatic ecosystems when dispersed in the environment27See:
Getting fat and stressed: Effects of dietary intake of titanium dioxide nanoparticles in the liver of turbot Scophthalmus maximus, Fonseca et al, Journal of Hazardous Materials, Volume 548, 2023
Toxicity of TiO2 nanoparticles to the marine microalga Chaetoceros muelleri Lemmermann, 1898 under long-term exposure, Bameri L et al, Environmental Science and Pollution Research, 29: 30427-30440, 2022
Proteomics reveals multiple effects of titanium dioxide and silver nanoparticles in the metabolism of turbot, Scophthalmus maximus, Araújo MJ et al, Chemosphere, 2022
Zinc oxide, titanium dioxide and C60 fullerene nanoparticles, alone and in mixture, differently affect biomarker responses and proteome in the clam Ruditapes philippinarum, Marisa I et al, Science of the Total Environment, 838 (2), 2022
Toxicity of titanium nano-oxide nanoparticles (TiO2) on the pacific oyster, Crassostrea gigas: immunity and antioxidant defence, Arash Javanshir Khoei and Kiadokht Rezaei, Toxin Reviews, 41, 2022
. It is also scientifically proven, albeit still underestimated, that titanium dioxide (nano)particles, combined with other substances (pesticides, nano-plastics, silica nanoparticles, etc.) can lead to more harmful “cocktail effects”28See :
Estimation of genomic and mitochondrial DNA integrity in the renal tissue of mice administered with acrylamide and titanium dioxide nanoparticles, Mohammed et al. Scientific reports, 2023
TiO2 nanoparticles combined with polystyrene nanoplastics aggravated reproductive toxicity in female mice via exacerbating intestinal barrier disruption, Zhang et al, Journal of the Science of food and agriculture, 2023
Nanoplastics enhance the toxic effects of titanium dioxide nanoparticle in freshwater algae Scenedesmus obliquus, Das et al, Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, Volume 2056, 2022
than the effects of these substances taken individually.

Literature reviews to take you further

Some warnings and stances by scientists

  • In a study published in 2022, researchers from the University of Franche-Comté conclude that “the addition of nanoparticles to food simply for ‘aesthetic’ reasons should be reconsidered.”29Cf Ingestion of titanium dioxide nanoparticles: a definite health risk for consumers and their progeny, Cornu R, Arch Toxicol. 2022.
  • In a literature review published in 2021 on the risks associated with the ingestion of titanium dioxide nanoparticles, researchers from the Portuguese National Institute of Health affirm that “From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA)”30cf : Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review, Rolo et al, Nanomaterials, 2022.
  • An INRAE statement raises awareness “about the importance of assessing the risk related to the presence of nanoparticles in this common additive in light of the proven exposure of pregnant women.” This is due to the fact that the exposure of pregnant women to titanium dioxide leads to the accumulation of TiO2 nanoparticles in the placenta and contamination of the fetus, as indicated in a study conducted by scientists from INRAE, LNE, Rouen Materials Physics Group, CHU Toulouse, University of Picardie Jules Verne, and the National Veterinary School of Toulouse, published in October 2020.
  • According to Laurence Macia from the University of Sydney, “titanium dioxide interacts with intestinal bacteria and alters some of their functions, which can lead to the onset of diseases. Its consumption should be better regulated by food authorities.”31Refer to “Common food additive found to affect gut microbiota,” The University of Sydney, May 13, 2019, and “Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction,” Pinget G. et al., Front. Nutr., 2019 (May 2019).
  • According to Fabrice Nesslany from the Pasteur Institute, “the utility is so low, and with the doubts that can still persist today (…), it serves no purpose, so while awaiting more consolidated studies, let’s not use it.” 32Cf. Video of Fabrice Nesslany (Pasteur Institute of Lille) at the Nano Symposium at the Maison de la Chimie, November 7, 2018.
  • According to Héloïse Proquin from Maastricht University in the Netherlands33Beyond the white: effects of the titanium dioxide food additive E171 on the development of colorectal cancer, Proquin, H, Maastricht: Gildeprint Drukkerijen, 2018,”The classification of E171 as free from toxic effects on the account of its insolubility and inertness is no longer valid (…) the presence of inflammation that was found in animal models after E171 ingestion could aggravate inflammatory bowel diseases and potential adverse effects towards enhancement of colorectal cancer. Therefore, we recommend that the experiments described here above, with an emphasis on actual testing in humans, should be performed for a further evaluation of E171 on its potential adverse effects on the enhancement of cancer, dysregulation of the immune system, and inflammation“.
  • In a study published in 2017 in the journal Experimental and Toxicologic Pathology, iranian researchers warn about the potentially devastating consequences of exposure to nanoparticles « These findings provide strong evidence that maternal exposure to TiO2-NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and their offspring across the world is potentially devastating »34Cf Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis, Ebrahimzadeh Bideskan A. et al., Exp Toxicol Pathol., 5;69(6): 329-337,  2017.
  • According to Gerhard Rogler from the University of Zurich, “patients with impaired intestinal barrier function, as in colitis, should refrain from consuming foods containing titanium dioxide” (July 2017)35Cf. Titanium Dioxide Nanoparticles Can Exacerbate Colitis, University of Zurich, July 19, 2017: Researchers at the University of Zurich sound the alarm about the inflammation and damage caused by titanium dioxide nanoparticles on the intestinal mucus of mice. They recommend individuals with colitis to avoid foods containing these titanium dioxide particles.
  • According to Francelyne Marano from the University Paris-Diderot, “when their addition does not serve a specific purpose other than enhancing the product’s attractiveness, for example, in candies or chewing gums (…), [titanium dioxide nanoparticles] should be prohibited as they bring no advantage” (2016 and 2018)36Cf. Francelyne Marano, Should We Fear Nanos?, Buchet Chastel, April 2016. Also, see her recent intervention during the Health Environment Debate: “Chemical Substances: Does Europe Protect Us?” at the French Ministry of Ecological and Solidarity Transition, (1h55min), October 18, 2018.

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