Where is Crest toothpaste made

Surfactants in toothpastes: a concern for the oral mucosa?

The use of toothpastes is not an invention of modern medicine; As early as 3,000 to 5,000 years before the birth of Christ, the ancient Egyptians used a powder made from beaten eggs and ashes to remove plaque from their teeth [7]. The composition of toothpaste naturally changed over the millennia, with the most important change being the introduction of fluoride into everyday oral hygiene. The addition of fluorides to the toothpaste led to a significant reduction in caries and can undoubtedly be viewed as a milestone in caries prophylaxis [12]. In addition to fluoride, the most important active ingredient, numerous other ingredients can be found in toothpastes today.

Ingredients of modern toothpastes

To put it simply, one can differentiate between active ingredients such as fluorides, anti-plaque and anti-gingivitis substances, substances against bad breath, tartar formation, tooth neck hypersensitivity, erosive events or for whiter teeth and between so-called auxiliary substances. The auxiliary materials include abrasives, modifiers for a suitable viscosity and good flow properties, humectants, preservatives, water and also surfactants. Surfactants are responsible for the foaming properties of the toothpaste and thus lead to a suitable distribution of other ingredients throughout the oral cavity [7]. Furthermore, thanks to their special chemical properties, they support the cleaning effect of toothpastes. Sodium lauryl sulfate is one of the most widely used surfactants, but it has already been associated with undesirable reactions such as the repeated occurrence of aphthae and irritation of the oral mucosa [6,10]. However, detailed studies on this subject are extremely rare.

Two laboratory studies on the effect of different surfactants on cell cultures

Study 1: Adult Toothpastes

  • Tab. 1: Toothpastes for adults with the surfactants and other ingredients they contain [4].
    © Cvikl
In a laboratory study by the authors, toothpastes with different surfactants were examined with regard to their effects on the viability of oral fibroblasts and epithelial cells [4]. For this purpose, human cells of the oral mucosa (gingival fibroblasts and epithelial cells) as well as a mouse cell line, which is routinely used for cytotoxicity tests, were cultivated. These cells were then exposed to a liquid toothpaste suspension and analyzed. The toothpastes were all commercially available, fluoride-containing toothpastes for adults with four different surfactants. Five products contained sodium lauryl sulfate: Colgate® Total, Crest® Cavity Protection, Elgydium Anti-Plaque, Odol-med3® Original and Oral-B® Pro-Expert; one product contained amine fluoride: Elmex® caries protection; one product contained Steareth-20: Curaprox Enzycal; and two products contained cocamidopropyl betaine: Emoform® actifluor Protect and Sensodyne® fluoride. Table 1 shows the toothpastes used with the respective surfactants and other ingredients.

The individual toothpastes were dissolved in a medium customary in cell culture in a concentration of 50% (or in a concentration of 72% for the Curaprox Enzycal and Sensodyne® fluoride toothpastes). In order to remove the solid components of the toothpaste-medium mixture, the mixture was centrifuged and the liquid supernatant was sterile filtered for use in cell culture. Before the experimental application, the liquid obtained was diluted to a final concentration of 0.3% toothpaste in the liquid.

The cultured cells (gingival fibroblasts, epithelial cells and mouse fibroblasts) were then brought into contact with different concentrations of the toothpaste supernatants for 2 minutes each and then rinsed with a neutral liquid (PBS - phosphate-buffered saline). Immediately afterwards, the cells were analyzed with regard to their viability and their growth behavior. The so-called LC 50 value (mean lethal concentration), the concentration at which 50% of the cells died and 50% of the cells were alive, was calculated from the data from the study on viability. In addition, live / dead staining of the treated cells was carried out for better illustration.

Sodium lauryl sulfate and amine fluoride reduced cell viability

Without going into the individual results of the different analysis methods - the results of the different methods mutually confirm each other - the following statements could be made: The toothpastes that contain sodium lauryl sulfate as a surfactant all showed an LC50 value of less than 5%. This means that only 5% toothpaste in the liquid (equivalent to 0.5 g / 10 ml) is necessary to kill half of the cells analyzed. The toothpastes with amine fluoride as surfactant also showed an LC50 value of less than 5%. In contrast to this, the results of the toothpastes with cocamidopropyl betaine or steareth-20 as surfactant: LC 50 values ​​of 8%, 24% and even 75% were measured. In summary, also considering the results of the growth behavior and the live / dead coloration, the in vitro study presented here showed that toothpastes for adults with sodium lauryl sulfate and amine fluoride, but not with cocamidopropyl betaine or steareth-20, reduce the viability of the examined cells significantly reduced.

Study 2: Children's toothpastes

  • Tab. 2: Toothpastes for children with the surfactants and other ingredients they contain [5].
    © Cvikl
The question that now arose was what effects toothpastes for children have on cells of the oral mucosa [5]. There were already clear differences in the composition of the children's toothpastes compared to the adult toothpastes. Regardless of the lower fluoride content, which according to the guidelines of the dental societies was 500 ppm for children's toothpastes and 1,000 ppm for toothpastes for young people, there was a large number of different surfactants and also diverse combinations of the individual surfactants. This suggests that manufacturers are already trying to reduce the concentration of sodium lauryl sulfate, at least in toothpastes for children and adolescents, possibly in order to take into account the particularly sensitive conditions of children's mucous membranes. Due to this large number of different surfactants and their combinations, it was not possible for us to carry out a primary classification according to the surfactants used, as in the study on adult toothpastes already described. As a result, 17 commercially available toothpastes for children up to 6 years and for adolescents up to 12 years were examined [5]. Three of the toothpastes examined had cocamidopropyl betaine as the only surfactant in their ingredients: Blendi up to 6 years, Sensodyne® Junior 6–12 years and Theramed up to 6 years; two toothpastes only contained sodium lauryl sulfate: Colgate® up to 6 years and Mentadent Kids up to 6 years; one toothpaste contained a combination of cocamidopropyl betaine and sodium lauryl sulfate: Theramed Junior 6–12 years and one toothpaste contained amine fluoride as the sole surfactant: Elmex® Junior 6–12 years. All other toothpastes for children and young people had different surfactants: Candida Kids up to 6 years and Candida Junior 6–12 years, Dontodent Junior 6–12 years as well as nenedent®baby 0.5–2 years and nenedent® children's toothpaste up to 6 years; or a mixture of cocamidopropyl betaine and other surfactants: Dontodent Kids up to 6 years, Elmex® up to 6 years, Odol-med3® milk tooth 0.5–5 years, Odol-med3® milk tooth up to 6 years, Odol-med3® Junior 6– 12 years. Table 2 lists the toothpastes with the surfactants they contain and other ingredients.

The procedure of the laboratory study was identical to that of the first study on adult toothpastes. A toothpaste slurry (with cell medium instead of saliva as in everyday life) was produced, the solid components were centrifuged out and the supernatants obtained in various concentrations (from 80% to 0.4%) were transferred to cells of the oral cavity for 2 minutes Mucous membrane or added to the mouse fibroblasts already described and then washed off. Investigations on cell viability, growth behavior and live / dead staining were then carried out. From the results of the viability studies, the LC50 value, also described, was calculated for each individual toothpaste in order to know which toothpaste concentration is toxic for 50% of the treated cells.

Evaluation according to survival rate shows clear differences

If you look at the results - here again in particular the results of the LC50 values, as these are the most descriptive for everyday clinical practice and were also confirmed by the other test methods - the following conclusions can be drawn: There were three groups of toothpastes, which differed statistically significantly. One group with toothpastes Dontodent 6–12, Mentadent Kids up to 6, Candida up to 6, Theramed 6–12, Elmex® 6–12, Colgate® up to 6, Dontodent up to 6, Odol-med3® 6–12, Candida 6– 12 and Odol-med3® to 6 showed LC50 values ​​of less than 5%. This means that as little as 0.5 g of toothpaste per 10 ml of liquid, half of the treated cells have died. A second group with the toothpastes Elmex® up to 6, Odol-med3® up to 5, nenedent®baby up to 2 and nenedent® up to 6 showed LC50 values ​​between 5% and 20%. The third group of toothpastes with Sensodyne® Junior 6–12, Theramed Junior 1–6 and Blendi up to 6, however, showed LC50 values ​​of over 95%, ie even when the toothpaste was used almost undiluted, 50% of the treated cells were still on Life.

Discussion points of the two investigations

The use of a toothpaste containing fluoride for daily oral hygiene is out of the question to maintain healthy teeth. Which toothpaste and in particular which surfactant contained in the toothpaste should be used, unfortunately, cannot be answered so clearly. In the studies described, it could be clearly shown that certain surfactants were less good for the treated cells than others. For example, toothpastes with sodium lauryl sulfate and amine fluoride had a more negative effect on cells of the oral mucosa than toothpastes with cocamidopropyl betaine or steareth-20 as a surfactant. These results are largely consistent with the existing literature on the subject. In another laboratory study, sodium lauryl sulfate reduced the viability of keratinocytes after a 2-minute exposure time [8]. In contrast to the studies presented, cocamidopropyl betaine showed toxic effects in other laboratory tests [1,8]. On the other hand, studies exist in which cocamidopropyl betaine shielded cells from the negative effects of sodium lauryl sulfate [2]. The experimental setup of the two studies presented differs from other studies in one not insignificant point. In order to come as close as possible to the clinical situation, the toothpastes were examined as a whole and not just the individual surfactants, whereby other factors or ingredients could also be examined. However, it is undisputed that toothpastes with certain surfactants are more damaging to cells than toothpastes with other surfactants.

The trend for toothpastes for children was similar to that for toothpastes for adults. Children's toothpastes with sodium lauryl sulfate showed very low LC50 values ​​of less than 5%, whereas children's toothpastes with cocamidopropyl betaine as the sole surfactant had LC50 values ​​of over 95%. However, as soon as Cocamidopropyl Betaine was mixed with another surfactant or other surfactants were used, significantly lower LC50 values ​​were again detectable.

Clinical relevance

The clinical relevance of the two studies presented must of course be assessed with caution [3]. The two studies are purely laboratory studies in which all influences, be it from the user of the toothpaste or from the environment, were excluded. For example, it must be remembered that the oral mucosa is normally protected by several factors, whereas the cells in the laboratory test were exposed to the toothpaste protrusions without protection. Protection by the natural saliva film was not simulated, nor was the natural barrier of the tissue or a possible immunological response taken into account. In this respect, it can be assumed that much higher concentrations are necessary in everyday use in order to provoke any damage to the mucous membrane. Clinical reports confirm that damage can occur, however [6,9,11]. It should also be borne in mind that some surfactants have caused little or no damage even in the vulnerable system of cell culture. The statement that cocamidopropyl betaine is equally toxic or even more toxic than sodium lauryl sulfate in various studies cannot be confirmed by the two studies described and requires further investigations.

Conclusion and recommendations for practice

In summary, it can be said without a doubt that the type of surfactants in the toothpaste has an influence on the cells of the oral mucosa. As a result, we recommend that sensitive adults, especially those with repeated aphthous ulcers, pay close attention to the ingredients and, in particular, to the surfactants used. For children, age-appropriate toothpastes should be used, also due to the fluoride concentration, and attention should also be paid to the ingredients here. Across all age groups, we recommend rinsing your mouth with at least a little water after brushing your teeth. People / children with a high risk of tooth decay can then rinse with a fluoride-containing mouth rinse in order to take advantage of the fluoride depot on the oral mucosa, without keeping other components of the toothpaste in the mouth for longer than necessary.