Discussion of study results

This study shows that the two tested commercially available fluoride toothpastes for children aged up to 24 months were significantly overdosed by parents: Fluoride toothpaste A was overdosed by a factor 5.9 and fluoride toothpaste B was overdosed by a factor 7.2 (Tables 4, 5 and Figs. 2, 3). This is in line with other studies with older children who should use a pea-size amount of toothpaste but overdosed [28, 29]. Huebner et al. found that parents dosed 0.36?±?0.26?g toothpaste for 12-35-months-old children, 0.28?±?0.19?g for 36–59-months-old children, and 0.38?±?0.26?g for 60–71-months-old-children when asked to dose the amount of toothpaste they usually do at home [30]. Martin et al. found that 26.7% of the parents did not dose a smear-size amount of toothpaste for their 21-months-old children (mean age) [31]. These findings are relevant for the risk assessment of fluoride since e.g., Naccache et al. stated that “(…) the quantity of dentifrice used was the most important factor affecting the ingestion of fluoride through toothbrushing by young children.” [33]

It is challenging to calculate the overall fluoride intake for children up to 24 months because of the various sources of fluoride including food, supplements, drinking water etc. [15,16,17]. Moreover, country-specific aspects of fluoride exposure such as artificially fluoridated drinking water, use of fluoridated salt etc. must be considered. However, just taking into account the dose of fluoride toothpaste in this study, the fluoride intake exceeds the ‘upper limit’ of fluoride to avoid the development of dental fluorosis [25]; see Tables 7 and 8 for calculations using the example of a 12-months-old child. For these calculations a 2-times and a 3-times daily application of the toothpaste were assumed (Table 6). Hong et al. studied the correlation between fluoride intake and fluorosis and found that “(…) Average daily intake of 0.04–0.06?mg?F/kg/bw showed a significantly elevated risk for fluorosis (23.0% for maxillary central incisors, 14.5% for first molars), while fluorosis risk was even higher for average intake above 0.06?mg?F/kg/bw (38.0% for maxillary central incisors, 32.4% for first molars). (…)” [25] (see Table 11 for details).

For a comprehensive risk assessment, fluoride intake also from other sources should be added. This has not been performed in this study because of the complexity of various fluoride sources, see above. However, the fluorosis risk will further increase when all possible additional fluoride sources will be added to the fluoride exposure from fluoride toothpaste. Moreover, and based on recent in vivo studies, dental fluorosis should not be the only endpoint to perform a comprehensive risk assessment of fluoride but other endpoints such as neurotoxicity should be also included in future studies [10, 14]. It has been clearly stated that when parents use a fluoride toothpaste for the oral care of their children that: “The toothpaste should be applied by parents in correct dose to reliably avoid excessive intake.” [7] However, as shown in this study, parents included in our study did not dose the correct amount of fluoride toothpaste as recommended [6, 7], but significantly overdosed.

In the field of toothpastes it is important to emphasize that, in contrast to adults, children up to 24 months swallow most or all of the toothpaste [24], i.e., the use of fluoride toothpaste at this age must be seen as systemic fluoride exposure.

It is important to note that two commonly used toothpastes with 1000 ppm fluoride specifically formulated for children from the first tooth on were used in original toothpaste with the original diameter of the opening was used. Thus, the resulted presented here are representative of how parents dose fluoride toothpaste for their children at home.

In the scientific literature there have been attempts described to limit the dose of fluoride children’s toothpaste (e.g., by using a dispensing device [34]), however, this has not been established on the market. Additionally, verbal instructions do not seem to be useful as Hubner et al. conclude that: “(…) Most parents use more fluoridated toothpaste than is recommended for young children and verbal instructions to limit the dose are ineffective. (…).” [30] Furthermore, the excess doses sized of toothpastes in TV commercials are, besides favorable flavor for children [27], likely to be another reason why young children are overdosed with respect to the amount of toothpaste place on their toothbrushes [32]. An interesting study in this field was published by Basch et al. on the advertisement of children’s toothpaste in parenting magazines in the US [35]. They found that “(…) Of the 31 advertisements that depicted a picture of a toothbrush with toothpaste, all but one (96.8%) depicted a full swirl of toothpaste covering the entire toothbrush head, which is well over the recommended amount. (…)” [35].

There are papers stating that there are fixed-values for the weight of a grain of rice-size amount of toothpaste (i.e., 0.125?g) and a pea-size amount of toothpaste (i.e., 0.25?g) [6]. However, we found that an ‘optimal’ dose of a rice size-amount of toothpaste was even smaller than 0.125?g for the tested toothpastes (in our study: fluoride toothpaste A: 0.045?±?0.006?g; fluoride toothpaste B: 0.039?±?0.012) (Table 4). This may be explained by different toothpaste formulations which may lead to different densities of toothpastes. However, the density of the tested toothpastes described in the dose study by Creeth et al. was almost identical to the density of the tested toothpastes in our study (i.e., around 1.3?g/mL) [28]. Since the label text on toothpaste tubes for children with 1000 ppm fluoride in the Germany recommends grain of rice-size amounts of toothpaste for children up to 24 months (and not the dose of a weight of 0.125?g toothpaste) we used the reference weights determined with an ‘optimal’ grain of rice-dose of the toothpastes.

It is important to mention that a notable proportion of parents (39.3%) in our study were not aware about the special conditions of use and warnings in relation to fluoride toothpastes with 1000 ppm fluoride for children [5,6,7] (Table 9). In future studies it should be determined if another presentation of the label text (e.g., with special graphics and/or enlarged text) would increase the awareness of the special conditions of use and warnings mandatory for toothpastes with 1000 ppm fluoride for children. In a study by Chen et al. 66% of parents were not aware of the special recommendations of dose for fluoride toothpaste for children [36]. Moreover, in this published study, even if the parents were familiar with the guidelines, they, nevertheless, over dispensed a smear-size amount of toothpaste, i.e., the mean 0.21?g but it should have been 0.09?g, as well as they over dispensed a pea-size amount of toothpaste, i.e., the mean was 0.44?g but it should have been 0.22?g [36].

Finally, it is important to note that there are some parents (14.7%) who used not only fluoride toothpaste for their children up to 24 months but also fluoride tablets (Table 10), which can further increase to risk of developing fluorosis.

This study has some limitations which are described below. A limitation of this study is that only two children’s toothpaste and one toothbrush were tested. Thus, a future study could include also other toothpaste and toothbrush brands. Moreover, studies with more participants from different regions in Germany (as well as from other countries) and with a more detailed analysis, e.g., on gender and age as well as on the socioeconomic background of the parents, could be performed. Parents were asked one-time to dose the toothpastes, thus, future studies could analyze the dosing behavior over a longer period.

A strength of our study is that parents were asked to dose the amount they dose at home for their children and not to dose an amount that was shown to them, i.e., this study tested the real-life scenario.

Fluoride-free toothpastes for children aged up to 24 months

Taken together, the results of this study show that correct dose of a grain of rice size amount of fluoride toothpaste was not dispensed. Thus, to reduce the overall fluoride intake and to prevent the development of dental fluorosis and to avoid other side effects associated with fluoride, fluoride-free toothpaste could be a viable option for the oral care of infants and toddlers. It is important to emphasize that fluoride-free toothpastes should include an anti-caries agent [2].

With a rice-size amount of fluoridated toothpaste, it is not known if such a drastic reduction in the amount of fluoride in a single dose would still be anti-cariogenic. There is at least one clinical trial where a grain of rice-size fluoride toothpaste was tested and it seem to still be effective [37].

Different fluoride-free active ingredients based on calcium phosphates have been described in oral care, e.g., hydroxyapatite, casein phosphopeptide-amorphous calcium phosphate, calcium sodium phosphosilicate, and ?-tricalcium phosphate [38]. Out of those fluoride alternatives, hydroxyapatite has been studied most [38].

The clinical efficacy of hydroxyapatite toothpastes in caries protection has been clinically demonstrated [39,40,41,42,43,44,45]. This active ingredient mimics the human enamel crystallites [46], and is safe if accidently swallowed and does not pose a fluorosis-risk [47], i.e., it is ideally suited for the oral care of infants and toddlers [48]. Hydroxyapatite has been shown to remineralize early caries in human primary teeth and to prevent demineralization under in situ conditions [43]. Additionally, hydroxyapatite reduces the bacterial colonization to tooth surfaces without having biocide properties [49].

A general advantage of fluoride-free toothpastes for children is that they can be dosed in higher amounts (i.e., the dose is not limited to grain of rice-size or pea-size amounts) which significantly increase the cleaning efficacy of the toothpaste (Table 12) [50].