Risks associated with the ingestion of titanium dioxide nanoparticles

Risks associated with the ingestion of titanium dioxide nanoparticles

By the AVICENN team – Last updated in June 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, 2015cross 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 pregnancy⁹– Titanium 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 breastfeeding¹⁰– Toxic 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 :

• risks to the liver, stomach, kidneys¹¹See:
  – Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure, Brand W et al, Nanotoxicology. 2020
  – Grape Seed Proanthocyanidin Extract Mitigates Titanium Dioxide Nanoparticle (TiO2-NPs)-Induced Hepatotoxicity through TLR-4/NF-κB Signaling Pathway, Mohammed et al, Biological Trace Element Research, 2020
  – Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles, Chen Z et al, Particle and Fibre Toxicology, 2019
  – Assessment of titanium dioxide nanoparticles toxicity via oral exposure in mice: Effect of dose and particle size, Ali et al., Biomarkers, 2019 :: “The effect of five days oral administration of TiO2 NPs (21 and 80 nm) with different doses was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment . In addition, the smaller particle size of TiO2 NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations . Toxicity of TiO2 NPs increases in a dose-dependent manner and vice versa with particles size . The evaluated biomarkers are good indicators for TiO2 NPs toxicity. More detailed studies are required before the recommendation of TiO2 NPS as food additives. .”
  – Effects of vitamin A and vitamin E on attenuation of titanium dioxide nanoparticles-induced toxicity in the liver of male Wistar rats, Moradi et al, Molecular Biology Reports 2019, 46, 2919-2932.
  – Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status, Talamini L et al, Nanotoxicology, 2019: “repeated oral administration of E171 to mice at a dose level (5 mg/kg body weight for 3 days/week for 3 weeks) comparable to estimated human dietary exposure, resulted in TiO2 deposition in the liver and intestine; 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.”.
  – Detection of titanium particles in human liver and spleen and possible health implicationsHeringa MB et al, Particle and Fibre Toxicology2018: this publication established the presence of titanium dioxide (TiO2) nanoparticles in the liver and spleen of 15 humans (no longer just laboratory rats). In half of the cases, the levels were above the level considered safe for the liver.
  –Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats, Morgan et al, Biomedicine and Pharmacotherapy, 2017, lungs¹²Telomere length and genotoxicity in the lung of rats following intragastric exposure to food-grade titanium dioxide and vegetable carbon particles, Jensen et al., Mutagenesis, Volume 34, 2019: “intragastric exposure to E171 is associated with reduced tight junction protein expression in the intestinal barrier and telomere length shortening in the lung in rats.”, ovaries and/or testicles¹³See:
  – Food-grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood-testis barrier disruption in mice, Rodríguez-Escamilla JC et al, Journal of applied toxicology, 2019 : “This study highlights the attention on matrix food containing E171 and possible adverse effects on testis when E171 is consumed in a liquid matrix.”.
  – Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations, Heringa MB et al, Nanotoxicology, October 2016 , …
• disturbances of the intestinal microbiota¹⁴See :
  – Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life, Carlé C et al., Particle and Fibre Toxicology, (20), 45, 2023
  – Oral exposure to Ag or TiO2 nanoparticles disrupted gut transcriptome and microbiota in a mouse model of ulcerative colitis, Wang et al, Food and Chemical Toxicology, 169(11):113368, 2022:”ingested _nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila.”
  – Impacts of foodborne inorganic nanoparticles on the gut microbiota-immune axis: potential consequences for host health, Lamas B, Particle and Fibre Toxicology, 2020
  – Foodborne titanium dioxide nanoparticles induce stronger adverse effects in obese mice than non-obese mice: gut microbiota dysbiosis, colonic inflammation, and proteome alterations, Cao et al., Small 16.36, 2020
  – Impacts of Additive Food E171 (Titanium Dioxide) on the Gut Microbiota and Colorectal Carcinogenesis in ApcMIN/+ Murine ModelBrugiroux S et al, GastroenterologyMay 2019 : “Additive E171 promotes colonic tumorigenesis and induces change in gut microbiota composition. Underlying carcinogenic mechanisms focusing on microbiota dysbiosis implication are in progress. This study supports the carcinogenic properties of TiO2 in the context of colorectal cancer.”., inflammation and damage to the intestinal barrier¹⁵See :
  – Food-Grade Titanium Dioxide Induces Toxicity in the Nematode Caenorhabditis elegans and Acute Hepatic and Pulmonary Responses in Mice, Sitia et al, Nanomaterials (Basel), 2022
  – Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer, Barreau et al, Particle and Fibre Toxicology, 18(26), 2021
  – Impact of Food Additive Titanium Dioxide on Gut Microbiota Composition, Microbiota-Associated Functions, and Gut Barrier: A Systematic Review of In Vivo Animal Studies, International Journal of Environmental Research and Public Health, 18(4):2008, 2021
  – The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro, Dorier M et al., Environ. Sci.: Nano, Advance Article, 2019: “Epithelial cells repeatedly exposed to TiO2 developed an inflammatory profile, together with increased mucus secretion. Epithelial integrity was unaltered, but the content of ATP-binding cassette (ABC) family xenobiotic efflux pumps was modified. Taken together, these data show that TiO2 moderately but significantly dysregulates several features that contribute to the protective function of the intestine .”
  – Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status, Talamini L et al, Nanotoxicology, 2019: “repeated oral administration of E171 to mice at a dose level (5 mg/kg body weight for 3 days/week for 3 weeks) comparable to estimated human dietary exposure, resulted in TiO2 deposition in the liver and intestine; 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.”. , risks of food intolerance and allergies¹⁶See :
  – Long-term exposure from perinatal life to food-grade TiO₂ alters intestinal homeostasis and predisposes to food allergy in young mice, Issa M et al., Allergy, Novembre 2023
  – The food additive titanium dioxide hinders intestinal production of TGF-β and IL-10 in mice, and long-term exposure in adults or from perinatal life blocks oral tolerance to ovalbumin, Lamas B et al., Food and Chemical Toxicology, 179, Septembre 2023
  – Perinatal exposure to foodborne inorganic nanoparticles: A role in the susceptibility to food allergy?, Issa M et al., Front. Allergy, Sec. Food Allergy, 3, Décembre 2022, of immune problems, of chronic illnesses¹⁷Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life, Carlé C et al., Particle and Fibre Toxicology, (20), 45, 2023 such as Crohn’s disease¹⁸See TiO2 nanoparticles abrogate the protective effect of the Crohn’s disease-associated variation within the PTPN22 gene locus, Schwarzfischer M et al, Gut, 2023, metabolic disorders such as glucose intolerance¹⁹See Dysregulation along the gut microbiota-immune system axis after oral exposure to titanium dioxide nanoparticles: A possible environmental factor promoting obesity-related metabolic disorders, Lamas B et al, Environmental Pollution, 330, 2023, or gestational diabetes²⁰– Exposure to Titanium Dioxide Nanoparticles During Pregnancy Changed Maternal Gut Microbiota and Increased Blood Glucose of Rat, Mao Z et al., Nanoscale Research Letters, 14:26, December 2019: “Our study pointed out that TiO2 NPs induced the alteration of gut microbiota during pregnancy and increased the fasting blood glucose of pregnant rats, which might increase the potential risk of gestational diabetes of pregnant women.” in pregnant women, as well as precancerous lesions in the colon²¹See :
  –The effects of the food additive Titanium dioxide (E171) on tumor formation and gene expression in the colon of a transgenic mouse model for colorectal cancer, Bischoff et al, Nanomaterials, 2022
  –Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon, Bettini S et al., Scientific Reports, 2017
• genotoxic effects* (DNA strand breaks and chromosomal damage)²²In response to suspicions of carcinogenicity in the colon, the European Food Safety Agency (EFSA) published an opinion in 2021 in which it concluded that TiO2, and more specifically its nanoparticles, posed a potential genotoxic risk (DNA strand breaks and chromosomal damage). Cf: Titanium dioxide: E171 is no longer considered safe as a food additive, EFSA, May 6, 2021even at low doses²³See :
  – DNA Damage and Apoptosis as In-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (_TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2, Ferrante et al, International Journal of Environmental Research and Public Health, 2023
  – A weight of evidence review of the genotoxicity of titanium dioxide (TiO2), Kirkland et al, Regulatory Toxicology and Pharamcology, Volume 136, December 2022
  – Investigation of the genotoxicity of digested titanium dioxide nanomaterials in human intestinal cells, Vieira et al, Food and Chemical Toxicology, Volume 161, 2022
  – Scientific opinion on the safety assessment of titanium dioxide as a food additive (E171), EFSA, 2021
  – TiO2 genotoxicity: An update of the results published over the last six years, Carrière et al, Mutation Research Genetic Toxicology and Environmental Mutagenesis, 2020
  – Assessment of the in vitro genotoxicity of TiO2 nanoparticles in a regulatory context, Charles et al, Nanotoxicology, 2018
  – Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress, Dorier M et al., Nanotoxicology, 2017
  – Titanium dioxide nanoparticle-induced oxidative stress triggers DNA damage and hepatic injury in mice, Shukla et al, Nanomedicine, 2014
• impacts on cardiac and neurobehavioral performance and metabolic profile²⁴Oral administration of TiO2 nanoparticles during early life impacts cardiac and neurobehavioral performance and metabolite profile in an age- and sex-related manner, Mortensen et al, Particle and Fibre Toxicology, 19, 2022
• adverse consequences for offspring²⁵See :
  – Effect of chronic prenatal exposure to the food additive titanium dioxide E171 on respiratory activity in newborn mice., Colnot E, O’Reilly J and Morin D, Frontiers in Pediatrics, 12:1337865, 2024 : “this is the first study to demonstrate that in utero, exposure to E171 alone can impair postnatal respiratory function in mice”
  – Multigenerational inheritance of breathing deficits following perinatal exposure to titanium dioxide nanoparticles in the offspring of mice, Boulain M et al., Discover Nano, 19, 16, 2024
  – Consequences of perinatal exposure to titanium dioxide nanoparticles on newborn development and behavior in mice, Marie Boulain, neuroscience thesis, University of Bordeaux, December 2022
  – Chronic maternal exposure to titanium dioxide nanoparticles alters breathing in newborn offspring, Colnot et al, Particle and Fibre Toxicology, 19, 57, 2022 :“We show that a chronic exposure to _TiO2 NPs during pregnancy alters the respiratory activity of offspring, characterized by an abnormally elevated rate of breathing.”
  – 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 : “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”.(respiratory, cardiovascular or neurological problems, stunted growth, behavioral changes, anxiety disorders, etc.).
  

* In its Scientific Advice on Titanium dioxide (TiO2) 1661/23 published in May 2024, the European Scientific Committee on Consumer safety (SCCS) considers that the available evidence, provided by industry for 44 pigmentary et 40 nano TiO2 grades, is not sufficient to exclude the genotoxicity potential of almost all of the types of TiO2 grades²⁶(82 our of 84) used in oral cosmetic products and thus, that more experimental data are needed to exclude the genotoxicity potential of the grades of TiO2 (both pigmentary and nano) used in oral cosmetic products, except for two nano grades²⁷(RM09 and RM11, for which the provided genotoxicity data indicate no genotoxicity concern).
The SCCS also adds that, considering that oral mucosal cells are prone to the uptake of nanoparticles (including TiO2 nanoparticles) and that some oral products containing TiO2 nanoparticles such as toothpastes, will be used every day and potentially more than once a day, further investigations are needed to exclude the risk to the consumer from longterm repeated exposures of the oral mucosa to TiO2 nanoparticles.

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 particles²⁸Avisde 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 environment²⁹See:
– 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”³⁰See :
– 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.

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.”³¹Cf 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)”³²cf : 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.”³³Refer 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.” ³⁴Cf. 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 Netherlands³⁵Beyond 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 »³⁶Cf 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)³⁷Cf. 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)³⁸Cf. 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.