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Titanium Dioxide in Toothpaste: Genotoxicity Insights
Explore the evidence surrounding titanium dioxide (CI 77891) in toothpaste, its effects on oral mucosa, and the potential genotoxicity concerns. Learn about the unanswered questions in this critical analysis.
SCIENCE
Luigi Cellini
10/4/202613 min read
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Titanium Dioxide (CI 77891) in Toothpastes: What We Know and What Questions Remain Open
What is titanium dioxide?
Titanium dioxide (TiO₂) is a compound used in numerous products for its properties as a white pigment and opacifying agent.
In cosmetics it may appear in the ingredient list as Titanium Dioxide or under the designation CI 77891.
In a toothpaste its presence may primarily serve a technological and aesthetic function: providing whiteness and opacity to the product.
This means that its use is not necessarily related to the toothpaste's ability to remove plaque or clean the teeth.
But when a particulate substance is incorporated into a product intended to come into repeated contact with the oral cavity, the scientific question cannot be limited to its technological function.
We must also ask ourselves:
What happens to these particles when they come into contact with the oral mucosa once or several times a day over years?
"Titanium Dioxide" does not necessarily describe a single material
One of the first difficulties when discussing TiO₂ is that materials with different characteristics may exist under the same designation.
Crystal form, particle size and distribution, surface treatment and coatings can vary.
This distinction is toxicologically important.
In its 2024 assessment of TiO₂ used in cosmetic products that may produce oral exposure, the Scientific Committee on Consumer Safety (SCCS) of the European Commission examined 44 pigmentary grades and 40 nano grades.
The Committee concluded that the available evidence was not sufficient to exclude the genotoxic potential of almost all TiO₂ grades evaluated for oral cosmetic products [1].
The exception was two specific nano grades, RM09 and RM11, whose genotoxicity data did not indicate concern. However, even for these two materials the SCCS considered further information necessary on their possible uptake and cellular effects in the oral mucosa before they could be considered safe for oral care products.
SCCS Scientific Advice on Titanium Dioxide — European Commission, 2024
The mouth is not simply a route to the stomach
When analysing oral exposure to a substance it may be intuitive to focus on what happens after it is ingested.
But a toothpaste first comes into direct contact with teeth, gums and oral mucosa.
The question then is whether the TiO₂ particles simply remain on that surface until they are removed or ingested, or whether they can interact with the tissues.
The available experimental evidence shows that some TiO₂ particles can interact with the oral mucosa and penetrate epithelial models.
Penetration through the buccal mucosa
In 2014, Teubl and colleagues studied three different types of TiO₂ particles using, among other systems, an ex vivo porcine mucosa model and human epithelial cells [3].
Although the particles formed aggregates in the experimental medium, a proportion remained within the nanometric range. The researchers observed interaction with the mucus layer and penetration into the epithelium, with differences in depth related to the characteristics of the particles [3].
PubMed
Teubl et al. — The buccal mucosa as a route for TiO₂ nanoparticle uptake
A later study used reconstructed three-dimensional models of normal human buccal mucosa, obtained from human keratinocytes and fibroblasts [4].
After exposures of 20 minutes and 24 hours, the researchers detected nano-TiO₂ mainly within the epithelium. The observed penetration also depended on characteristics such as particle shape and dose.
Nano-TiO₂ penetration of oral mucosa — 3D model of human buccal mucosa
These experiments do not demonstrate that a toothpaste containing TiO₂ produces a clinical lesion during normal brushing.
But they do call into question an overly simple assumption: that the particles necessarily remain outside the oral tissue during contact with the mouth.
TiO₂ crossing the buccal mucosa: more recent experimental evidence
In 2023, Vignard and colleagues published a particularly relevant study [5].
The researchers deposited food-grade TiO₂ on the sublingual area of pigs. Thirty minutes later they observed individual particles and small aggregates in the mucosa; particles were subsequently recovered in the submandibular lymph nodes [5].
In parallel they studied human buccal epithelial cells.
The cells showed the ability to incorporate TiO₂ particles. Under the experimental conditions used, different effects were observed depending on the cellular state and the material studied, including cytotoxicity, genotoxicity and oxidative stress [5].
A particularly interesting result was the greater sensitivity of proliferative cells compared with differentiated ones. The authors noted that this result raises questions about a possible effect on the renewal of the oral epithelium [9].
Vignard et al., 2023 — TiO₂, buccal mucosa and genotoxicity in human oral epithelium
This study must be interpreted correctly: it does not demonstrate that using a toothpaste containing TiO₂ produces genotoxicity in humans.
It combines an animal model of transmucosal passage with cell experiments and uses food-grade TiO₂. Its results identify mechanisms and a possible route of exposure that require consideration; they are not equivalent to demonstrating clinical damage produced by a commercial toothpaste.
Why is genotoxicity a concern?
In 2021 the European Food Safety Authority (EFSA) re-evaluated titanium dioxide E171, which was then used as a food additive [2].
After reviewing the available evidence, EFSA concluded that TiO₂ particles have the potential to produce DNA strand breaks and chromosomal damage, although it found no evidence of gene mutations.
The decisive issue was that EFSA could not exclude a concern for genotoxicity [2]. Nor could it establish a particle size below or above which that concern would disappear, nor assume with sufficient certainty the existence of a safe threshold for this effect.
European Food Safety Authority
EFSA — Safety assessment of titanium dioxide (E171), 2021
This does not mean that EFSA demonstrated that TiO₂ causes cancer in people.
It means something different and scientifically important: with the available data it was not possible to adequately rule out the genotoxic concern.
And this distinction must be preserved.
Food and toothpaste: two different exposures
The evaluation of E171 as a food additive cannot be automatically transferred to a toothpaste.
A toothpaste is not intended to be ingested and the amounts, materials, particle characteristics and exposure conditions may be different.
Precisely for this reason, the specific assessment carried out by the SCCS for cosmetic products with oral exposure is especially important.
In 2024, after also considering EFSA's evaluation, the SCCS concluded that the available evidence did not allow the genotoxic potential of almost all TiO₂ grades evaluated for oral cosmetic products to be excluded [1].
The SCCS added another observation directly related to toothpastes:
cells of the oral mucosa can take up nanoparticles, including TiO₂ nanoparticles, and these can penetrate the mucous layer and be internalised in epithelial cells.
Therefore, taking into account that products such as toothpastes may be used every day and potentially more than once a day, the Committee considers further research necessary to exclude risks arising from repeated long-term exposure of the oral mucosa.
But what happens if the oral mucosa is not intact?
At this point a second question arises.
The oral mucosa of a real person is not necessarily always in ideal conditions.
There may be inflammation, gingivitis, mouth ulcers, small lesions, irritation or transient alterations of the epithelial barrier.
Moreover, the mucosa does not come into contact with TiO₂ alone.
A toothpaste is a complex formulation whose different components come into contact simultaneously with the tissues.
And some ingredients used in oral hygiene products have experimentally demonstrated the ability to modify the properties of the mucosa.
The example of Sodium Lauryl Sulfate (SLS)
Sodium Lauryl Sulfate (SLS) is a surfactant used in numerous oral hygiene products.
A study carried out on human oral mucosa specifically investigated its effects on the permeability barrier.
Experimental exposure for 15 minutes to SLS produced a significant increase in water permeability compared with the control tissue and a marked histological alteration of the epithelial surface [8].
But the same study contains a particularly instructive result: when SLS was used in combination with triclosan and zinc, the increase in permeability was not observed and the tissue was histologically comparable to the control.
Healy et al. — SLS, triclosan, zinc and oral mucosa permeability
This demonstrates something that is important far beyond SLS:
the behaviour observed for an isolated ingredient does not necessarily allow prediction of what will happen within a complete formulation.
The interaction between components matters.
Scientific References
[1] Scientific Committee on Consumer Safety (SCCS). Scientific Advice on Titanium dioxide (TiO₂) (CAS/EC numbers 13463-67-7/236-675-5, 1317-70-0/215-280-1, 1317-80-2/215-282-2). SCCS/1661/23. European Commission; 2024. Adopted on 13 May 2024.
Scientific Advice — European Commission / SCCS
This is the key document for the assessment of TiO₂ in cosmetic products involving oral exposure. The SCCS evaluated 44 pigmentary grades and 40 nano grades and concluded that the available evidence was not sufficient to exclude the genotoxic potential of almost all the TiO₂ grades evaluated. Public Health
[2] EFSA Panel on Food Additives and Flavourings (FAF). Safety assessment of titanium dioxide (E171) as a food additive. EFSA Journal. 2021;19(5):6585. DOI: 10.2903/j.efsa.2021.6585.
EFSA full assessment of E171
EFSA concluded that a concern for genotoxicity could not be ruled out, that no particle-size cut-off could be identified with respect to genotoxicity, and that E171 could no longer be considered safe when used as a food additive. This conclusion concerns the use of E171 in food and should not automatically be extrapolated to toothpaste. EFSA
[3] Teubl BJ, Leitinger G, Schneider M, Lehr CM, Fröhlich E, Zimmer A, Roblegg E. The buccal mucosa as a route for TiO₂ nanoparticle uptake. Nanotoxicology. 2015;9(2):253–261. DOI: 10.3109/17435390.2014.921343.
PubMed study
Experimental study investigating the interaction and penetration of different TiO₂ particles using, among other models, ex vivo porcine buccal mucosa and human epithelial cells. PubMed
[4] Konstantinova V, Ibrahim M, Lie SA, et al. Nano-TiO₂ penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models. Journal of Oral Pathology & Medicine. 2017;46(3):214–222. DOI: 10.1111/jop.12469.
PubMed study
In three-dimensional models reconstructed from normal human buccal mucosal cells, nano-TiO₂ was detected mainly within the epithelium following exposures of 20 minutes and 24 hours. PubMed
[5] Vignard J, et al. Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium. Particle and Fibre Toxicology. 2023.
PubMed study
This study investigated the transmucosal passage of food-grade TiO₂ in pigs and its effects on human buccal epithelial cells. Particles were observed in the mucosa following sublingual exposure and subsequently in submandibular lymph nodes; cytotoxicity, genotoxicity and oxidative stress were also investigated in the cellular model. PubMed
[6] Teubl BJ, Schimpel C, Leitinger G, Bauer B, Fröhlich E, Zimmer A, Roblegg E. Interactions between nano-TiO₂ and the oral cavity: impact of nanomaterial surface hydrophilicity/hydrophobicity. Journal of Hazardous Materials. 2015;286:298–305. DOI: 10.1016/j.jhazmat.2014.12.064.
PubMed study
Research investigating how the surface characteristics of TiO₂ nanoparticles influence their interaction with the environment of the oral cavity. PubMed
[7] Kim DH, Kundu J, Chae IG, Lee JK, Heo JS, Chun KS. Titanium dioxide nanoparticles induce COX-2 expression through ROS generation in human periodontal ligament cells. Journal of Toxicological Sciences. 2019;44(5):335–345. DOI: 10.2131/jts.44.335.
PubMed study
In human periodontal ligament cells, TiO₂ nanoparticles increased reactive oxygen species and activated molecular mechanisms associated with inflammatory responses, including NF-κB and COX-2. This is experimental cellular evidence and does not demonstrate clinical disease caused by toothpaste. PubMed
[8] Healy CM, Cruchley AT, Thornhill MH, Williams DM. The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa. Oral Diseases. 2000;6(2):118–123. DOI: 10.1111/j.1601-0825.2000.tb00112.x.
PubMed study
Experimental exposure of human oral mucosa to SLS produced a significant increase in water permeability and alteration of the epithelial surface. The same study found that the SLS/triclosan/zinc combination did not produce this increase, illustrating the importance of also investigating interactions within a formulation. PubMed
[9] Neppelberg E, Costea DE, Vintermyr OK, Johannessen AC. Dual effects of sodium lauryl sulphate on human oral epithelial structure. Experimental Dermatology. 2007. DOI: 10.1111/j.1600-0625.2007.00567.x.
PubMed study
Study using a reconstructed three-dimensional model of human oral epithelium to investigate the biological effects of SLS at concentrations relevant to oral hygiene products. PubMed
[10] Herlofson BB, Barkvoll P. Desquamative effect of sodium lauryl sulfate on oral mucosa. A preliminary study. Acta Odontologica Scandinavica. 1993;51(1):39–43. DOI: 10.3109/00016359309041146.
PubMed study
A double-blind, crossover experimental study examining oral epithelial desquamation using toothpastes containing different concentrations of SLS. PubMed
[11] Pérez-López D, Varela-Centelles P, García-Pola MJ, Castelo-Baz P, García-Caballero L, Seoane-Romero JM. Oral mucosal peeling related to dentifrices and mouthwashes: A systematic review. Medicina Oral, Patología Oral y Cirugía Bucal. 2019;24(4):e452–e460. DOI: 10.4317/medoral.22939.
Systematic review — PubMed
Systematic review of the available clinical evidence concerning oral mucosal peeling associated with toothpastes and mouthwashes. Among the cases included, SLS was implicated in some of the reported episodes; the authors also highlight methodological limitations in the available evidence.
[12] Lesch CA, Squier CA, Cruchley A, Williams DM, Speight P. The permeability of human oral mucosa and skin to water. Journal of Dental Research. 1989. DOI: 10.1177/00220345890680091101.
PubMed study
Study examining differences in permeability among different regions of human oral mucosa. The findings show that oral mucosa does not constitute a uniform barrier: permeability varies considerably according to anatomical region.
Important note on interpretation
References [3–7] provide evidence concerning the interaction of TiO₂ with the oral environment, mucosal models or oral cells. References [8–12] provide evidence concerning the characteristics of the oral mucosal barrier and the ways in which it may be altered under certain conditions.
None of these studies directly demonstrates that SLS-induced alteration of the oral mucosa increases TiO₂ penetration during normal toothbrushing.
This distinction is essential. The two bodies of evidence support the scientific relevance of asking the question, but they do not provide the answer.
Toothpastes and oral mucosal peeling
A systematic review published in 2019 examined the relationship between toothpastes, mouthwashes and oral mucosal peeling, that is, desquamation of the oral mucosa [11].
Of 410 references initially identified, 15 reports were selected. In the cases collected, certain oral hygiene products were related to desquamation and SLS was involved in some of the cases; moreover, the extent of desquamation was related to its concentration in the available data [11]. The authors themselves noted the limitations and methodological differences of the included evidence [10].
Systematic review — Oral mucosal peeling related to dentifrices and mouthwashes
This also does not demonstrate that any toothpaste with SLS necessarily damages the mucosa.
It demonstrates that the conditions of the oral barrier can change as a consequence of certain products and formulations under certain circumstances.
And we then arrive at a question that, from a safety point of view, is difficult to ignore.
What happens when both circumstances coincide?
We know that certain TiO₂ particles can interact with the oral mucosa, penetrate epithelial models and be internalised by cells [3] [5]. PubMed
We also know that certain pathological, mechanical or chemical conditions can alter the integrity of the mucosa and that some components used in oral hygiene products can, under certain experimental conditions, modify its surface or permeability [8]. PubMed
Therefore, a specific question arises:
What happens when we brush our teeth with a toothpaste containing TiO₂ if the oral mucosa is inflamed, damaged or its barrier function has been altered by other components of the toothpaste itself or by other substances with which the mouth has accidentally come into contact?
Does an altered mucosal barrier modify the penetration of particles?
Does the number of particles that can be internalised change?
Does their depth of penetration change?
Could the cellular response change?
Is repeated exposure on an intact mucosa the same as on a mucosa periodically subjected to inflammation, irritation or microlesions?
Two known pieces of evidence. One interaction still to be demonstrated.
Here we must establish a very clear boundary.
We have not found clinical evidence demonstrating that the SLS in a toothpaste increases the penetration of TiO₂ into the human mucosa during normal brushing.
Nor have we found evidence allowing us to state that the combination SLS + TiO₂ in a toothpaste itself produces greater genotoxic damage in humans.
To assert this would go beyond the available data.
But the absence of such a demonstration does not answer the previous question.
We have independent evidence for the two components of the problem:
A) certain TiO₂ particles can interact with and penetrate models of oral mucosa;
B) the oral mucosal barrier can be altered under certain circumstances and some ingredients can experimentally modify its permeability [8] [12].
What is missing is to adequately characterise A + B under conditions representative of exposure to toothpastes.
We know that the oral barrier can be altered. We know that certain TiO₂ particles can interact with that barrier. What we still need to know is what happens when both circumstances occur simultaneously during repeated exposure.
There is currently insufficient data to answer this question. Why?
This is another legitimate question.
Because reproducing realistically a chronic exposure on an altered mucosa is experimentally difficult?
Because these scenarios have not been considered a priority?
Because sufficiently representative models are lacking?
Because the numerous possible combinations between particles, concentrations, formulations and mucosal states make their study especially complex?
Or simply because the available research has not yet reached the point of answering these questions?
With the available evidence we cannot know.
And it would be incorrect to attribute a specific cause to this absence of information without having proof.
What we can state is that the question remains open.
The safety of a substance does not exist in isolation from its formulation
This problem reveals a general difficulty in the evaluation of complex products.
The consumer does not use TiO₂, SLS, a preservative, an abrasive or a flavouring in isolation.
They use all of them simultaneously within a formulation.
And that formulation does not necessarily come into contact with a perfect and always identical mucosa either.
Therefore, knowing the individual toxicology of each ingredient is indispensable, but may not by itself answer all the questions relating to a real exposure.
The experiment on SLS, triclosan and zinc itself demonstrates the importance of this question: a combination of ingredients modified an effect observed with SLS alone.
This does not allow prediction of a specific interaction with TiO₂.
But it does demonstrate why studying a formulation and studying its ingredients separately are not necessarily the same scientific question.
What does the European scientific authority currently say?
The position of the SCCS in 2024 can be summarised with caution.
For almost all TiO₂ grades considered in its assessment of oral cosmetic products, the available data did not allow the genotoxic potential to be excluded.
For two specific nano grades, the data provided did not indicate genotoxic concern, but the Committee requested further information on their uptake and cellular effects in the oral mucosa before they could be considered safe for oral hygiene products.
In addition, the SCCS specifically noted the need to better investigate repeated and long-term exposure of the oral mucosa to TiO₂ nanoparticles from products such as toothpastes.
The scientific evaluation is not definitively closed either: in September 2025 the European Commission issued a new mandate to the SCCS to assess the safety of nano and non-nano titanium dioxide in cosmetic products.
European Commission — new SCCS mandate on Titanium Dioxide, 2025
What can we conclude?
The available evidence does not demonstrate that the normal use of a toothpaste containing Titanium Dioxide / CI 77891 produces cancer, mucosal lesions or genetic damage in people.
To assert this would be scientifically incorrect.
But it would also be incorrect to state that all questions relating to its oral safety are resolved.
There is experimental evidence of interaction and penetration of certain TiO₂ particles in models of oral mucosa. There are experimental results of cytotoxicity, oxidative stress and genotoxicity under certain conditions. EFSA could not exclude a genotoxic concern for TiO₂ present in E171, and subsequently the SCCS could not exclude the genotoxic potential of almost all grades evaluated for cosmetic products with oral exposure [1]. Public Health
And a question especially relevant for products used daily remains open:
what happens with repeated exposure to these particles when the oral mucosal barrier is not in normal conditions?
Currently we do not have sufficient evidence to answer definitively.
That does not constitute a demonstration of danger.
But neither does it constitute a demonstration of absence of risk.
Science does not only advance through the answers it manages to demonstrate. It also advances by identifying the relevant questions that have not yet been answered.
A more natural smile for a cleaner world.
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