Fluoride (F) is added to many dental care products as well as in drinking water to prevent dental decay. However, recent data associating exposure to F with some developmental defects with consequences in many organs raise concerns about its daily use for dental care. This systematic review aimed to evaluate the contribution of dental care products with regard to overall F intake through drinking water and diet with measurements of F excretion in urine used as a suitable biomarker. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using keywords related to chronic exposure to F in the human population with measurements of F levels in body fluids, 1,273 papers published between 1995 and 2021 were screened, and 28 papers were finally included for data extraction concerning daily F intake. The contribution of dental care products, essentially by toothbrushing with kinds of toothpaste containing F, was 38% in the mean regardless of the F concentrations in drinking water. There was no correlation between F intake through toothpaste and age, nor with F levels in water ranging from 0.3 to 1.5 mg/L. There was no correlation between F intake and urinary F excretion levels despite an increase in its content in urine within hours following exposure to dental care products (toothpastes, varnishes, or other dental care products). The consequences of exposure to F on health are discussed in the recent context of its suspected toxicity reported in the literature. The conclusions of the review aim to provide objective messages to patients and dental professionals worried about the use of F-containing materials or products to prevent initial caries or hypomineralized enamel lesions, especially for young children.
*Read full study online at https://www.frontiersin.org/articles/10.3389/froh.2022.916372/full
The present systematic review showed that the mean contribution of F-containing dental care products, mainly toothpastes, is 38% regardless of the age of children or F concentration in drinking water. These data are slightly lower than those published earlier by Paiva et al. , reporting a 65% contribution. The difference may be either due to the method of collecting data or to evolution of the use of less fluoridated toothpastes.
The contribution of F intake was not correlated with the age of children. However, children under 4 years old presented a very high TDFI as well as some adults who did not respect the good practice of dental care uses. Those two cases highlight the importance of: (i) dental products on the exposome, (ii) the types of F, bio-assimilation, and concentrations in the dental care products, and (iii) the importance of dental care products adapted to age, but more importantly, the results show the importance of good dental care habits (no swallowing, rinsing with water after toothbrushing, exposure to F after meals, and use of appropriate amount of toothpaste). The variation of F intake from the diet seemed to be less sensitive to the water concentration than the variation due to the concentration and good use of dental care products in the different areas. Therefore, despite the fact that studies in this field are lacking especially for adults, impact of dental care products on TDFI for adults should not be negligible. This requests to be further investigated in the case of misconducted use as it can increase the risk of excessive F intake.
The increase in F intake, especially due to dental care products did not necessarily correlate with the amount of F excretion. This result can be explained by the fact that we were looking at the reported means, which smoothed the values. The lack of correlation between DUFE and TDFI can also be due to (i) poor estimation of F inputs (additional sources and under or overestimation), and/or (ii) bias of the methodological and/or analytical quantification of urinary excretion (data were reported in means for each publication, choice of collection, and measure of the F into the urine), and/or (iii) variability of excretion capacity for each organism. In addition, these data were based on nine publications which could be a limitation of the study.
Urine is the only biomarker capable of measuring F excretion. However, urine may not be the most pertinent biomarker for the estimation of TDFI especially in children due to F accumulation during bone growth and mineralization. Children can retain more F in their skeleton (~50%) than adults (approximately 36%), with inverse retention in bone with age of the children and with the excess of F excreted in urine . The absence of correlation between DUFE and TDFI suggests that there is a variability but a non-negligible amount of F was not eliminated from the organism. Our data showed a variation of DUFE between 65.2 and 691 ?g/day that may have informed on the F bioavailability, its residence time (clearance), and its interactions with different tissues. The majority of body F is bound in hard tissues, such as bones and teeth, and <1% can be found in soft tissues .
Further investigation combining measures of F in plasma and urine could be informative on the bioavailability of F and its interactions with different organs. Once absorbed, F reaches peak serum concentrations after 20–60 min, and then returns to the baseline after approximately 15 h suggesting that part of the oral F passes through systemic route [56, 57, 68, 69]. This is probably the reason why a relation has been reported between supplement use or the amount of toothpaste used for brushing and child’s fluorosis scores . Most pharmacokinetic analyses showed a transient increase in the urinary F excretion approximately 1–3 h after topical application of fluoridated varnishes in adults and in children, after the use of a fluoridated mouthrinse solution, or after brushing with F-containing toothpastes [42, 56–58, 60, 64, 66]. A return to baseline is reported by all the studies 24–72 h after the end of the exposure, irrespective of the source. The minimal recommended period of urine collection is 24 h to obtain good estimations of the daily amount of F excretion. The DUFE is the variable generally recommended for the estimation of the daily F exposure. The amount of excreted F is obtained by multiplying the 24-h urinary volume by its F concentration .
As a consequence, we have proposed an experimental model of cumulative F exposure following the age of the individuals considering three different thresholds of 30, 300, and 1,300 ug F/day (Supplementary Figure 3) and a model of mixed exposures (1,300 ug F/day until 4 years, then 300 ug F/day until 8 years, and 30 ug F/day until 16 years). The thresholds have been defined based on the estimated F retention. Those values were obtained by subtracting the DUFE from the TDFI and were estimated between a few ug and 1,890 ug/day. Thus, this model is a cumulative representation, which includes daily F bone retention to estimate the trapped F into the body over a span of several years. According to this model, early age exposure could drastically affect the total F retention into the organism. Even though the residence time (i.e., half-life) of F into the different organs remains not well known, the exposure to a high absorption of dental care products may print a high F content over the years. In addition, bad habits of dental care products may impact F exposure for the adults. Therefore, these data showing a non-negligible contribution to daily F intake through toothbrushing using F-containing toothpastes may be discussed in the light of the literature as F was reported to pass through the blood-placental barrier and the blood-brain barrier thus subsequently cause learning problems . In fact, most of studies on the safety of toothpastes and dental care products are short-term pharmacokinetics studies that do not consider long-term effects, whereas F accumulated in bone may be released in specific situations associated to skeletal loss, such as lactation . However, we found no study that has explored the contribution of dental care products to total F exposure in pregnant and lactating women nor studies taking into account the gender, especially in young children. This concern is even more important considering that recent studies reported a relation between prenatal F exposure and lower performance intelligence quotient (IQ) in boys, but not in girls . An increase of 0.5 mg/L of F concentration in the water (approximately equal to the difference between fluoridated and non-fluoridated regions) was associated with a 7.9-point lower IQ score in formula-fed infants and 6.3-point lower IQ score in breastfed children in both boys and girls, suggesting that postnatal exposure to F may affect both sexes . Sex-dependent susceptibility to F may be due to multiple biological and behavioral reasons, they have also been reported in several experimental studies in rodents, and more recently in zebrafish [12, 13].
In conclusion, our review highlights the major F contribution from dental care products regardless of the area or F concentration in drinking water. This additional source presents a large variability depending on the concentration, chemical forms, and amount of the dental product used. However, the good usage of these products also seems to be determinant for the contribution to TDFI. Therefore, the contribution of F intake through toothpaste can be easily controlled and adapted to the patient. Consequently, the future studies on F exposure and toxicity need to take into consideration exposure to F-containing dental care products, habits of use, and individual features (gender, age, diet, caries, etc.). Furthermore, considering the contribution of dental care products to the TDFI, the “optimal daily F intake” estimated approximately 50–70 ug/kg bw/day by EFSA could be reevaluated to determinate the optimal DDFI depending on each individual. The contribution of ~39–51% due to dental care products suggests that the optimal daily dietary F may be half of the EFSA values.
The study was funded by the French National Institute of Health and Medical Research (INSERM), the Université Paris Cité (Idex Project FLUOREMAIL), and the National Agency for Safety of Food and Environment (ANSES) (Grant 2019/1/230).
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/froh.2022.916372/full#supplementary-material
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Keywords: fluoride, drinking water, diet, toothpaste, dental products, urine
Citation: Saad H, Escoube R, Babajko S and Houari S (2022) Fluoride Intake Through Dental Care Products: A Systematic Review. Front. Oral. Health 3:916372. doi: 10.3389/froh.2022.916372
Received: 09 April 2022; Accepted: 04 May 2022;
Published: 10 June 2022.
Rogelio González-González, Juárez University of the State of Durango, Mexico
Jesus Lavalle-Carrasco, Juárez University of the State of Durango, Mexico
Omar Tremillo Maldonado, Juárez University of the State of Durango, Mexico
Copyright © 2022 Saad, Escoube, Babajko and Houari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sylvie Babajko, email@example.com
*Original full study online at https://www.frontiersin.org/articles/10.3389/froh.2022.916372/full
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Fluoride Dentrifice and Stomatitis
Statistical data of 133 patients who have been using fluoride dental cream or powder have been presented. Each has developed intraoral ulcerative lesions. Many have been treated for other complaints without clearance of the lesions. Age is not significant. Repeated insults with the fluoride dentrifices produced increasingly severe excoriations. There seems to be nothing specific about the lesions to differentiate them from other diseases of an oral nature.
Fluoride Toothpaste: A Cause of Perioral Dermatitis
We have gathered clinical and historical data implicating fluoride dentrifices as an important etiologic factor in this dermatosis. The following two cases support this observation.
Allergy to Fluoride
Six children and one adult exhibited various allergic reactions after the use of toothpaste and vitaimin preparations containing fluoride. The following conditions were encountered: Urticaria, exfoliative dermatitis, atopic dermatitis, stomatitis, gastro-intestinal and respiratory allergy.
Fluoride & Perioral Dermatitis
Perioral dermatitis (PD) is a common rosacea-like dermatitis that was never reported prior to the mid-fifties. Although it can affect both sexes and all ages, most patients are women ages 20-50 years. Patients with PD frequently report a pre-existing tendency to blush. This disease is most likely multifactorial in origin, and fluoride preparations in dentrifices probably have played a role as precipitator.
Acute Fluoride Toxicity from Toothpaste Ingestion
The Food & Drug Administration now requires that all fluoride toothpastes sold in the United States bear the following poison warning: "WARNING: Keep out of reach of children under 6 years of age. If you accidentally swallow more than used for brushing, seek professional help or contact a poison control center immediately." The
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