Over the last 100-120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment. To give a better overview, various connected topics are also discussed: reasons and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and finally biomarkers of fluoride exposure.

Chemical Aspects of Human and Environmental Overload with Fluorine

Dental caries has declined in the 40 years since fluoridated toothpastes were introduced. Much has been learned about why fluoride is so effective and how this knowledge can be used to optimise programmes for caries prevention. Fluoride works through enhancing the remineralisation of early stages of caries and by inhibiting demineralisation, which would lead to dental caries. Remineralisation involves the deposition of calcium phosphates from saliva to rebuild partly dissolved enamel crystallites. When fluoride is incorporated the dissolution of these reinforced crystallites will be reduced during a subsequent sugar-induced and bacteria-mediated acid attack. Fluoride works primarily when it is present in the oral cavity. Based on our understanding of the fluoride mode of action the following advice can be given from clinicians to their patients: The fluoride concentration in oral products is related to efficacy but the concentration does not necessarily need to be high to be efficacious. Fluoride availability throughout the day is important; this can be achieved when fluoride products are used as part of the daily hygiene routine (F-brushing or rinsing). Alternatively, when fluoride is provided in the drinking water or through professionally applied F-varnishes or gels, the patient will benefit without requiring daily compliance to its use. The latter methods are particularly effective as additional treatments in high caries individuals.

/pdf/contemporary-perspective-on-the-use-of-fluoride-products-in-3cbmj1l9dc.pdf

Contemporary perspective on the use of fluoride products in caries prevention

Dental caries is one of the most common microbe-mediated oral diseases in human beings. At present, the accepted etiology of caries is based on a four-factor theory that includes oral microorganisms, oral environment, host, and time. Excessive exposure to dietary carbohydrates leads to the accumulation of acid-producing and acid-resistant microorganisms in the mouth. Dental caries is driven by dysbiosis of the dental biofilm adherent to the enamel surface. Effective preventive methods include inhibiting the cariogenic microorganisms, treatment with an anti-biofilm agent, and sugar intake control. The goal is to reduce the total amount of biofilm or the levels of specific pathogens. Natural products could be recommended for preventing dental caries, since they may possess fewer side effects in comparison with synthetic antimicrobials. Herein, the mechanisms of oral microbial community development and functional specialization are discussed. We highlight the application of widely explored natural products in the last five years for their ability to inhibit cariogenic microorganisms.

/pdf/microbial-etiology-and-prevention-of-dental-caries-4ch86z70kc.pdf

Microbial Etiology and Prevention of Dental Caries: Exploiting Natural Products to Inhibit Cariogenic Biofilms.

Humans have co-evolved with micro-organisms and have a symbiotic or mutualistic relationship with their resident microbiome. As at other body surfaces, the mouth has a diverse microbiota that grows on oral surfaces as structurally and functionally organised biofilms. The oral microbiota is natural and provides important benefits to the host, including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and colonisation by exogenous microbes. On occasions, this symbiotic relationship breaks down, and previously minor components of the microbiota outcompete beneficial bacteria, thereby increasing the risk of disease. Antimicrobial agents have been formulated into many oral care products to augment mechanical plaque control. A delicate balance is needed, however, to control the oral microbiota at levels compatible with health, without killing beneficial bacteria and losing the key benefits delivered by these resident microbes. These antimicrobial agents may achieve this by virtue of their recommended twice daily topical use, which results in pharmacokinetic profiles indicating that they are retained in the mouth for relatively long periods at sublethal levels. At these concentrations they are still able to inhibit bacterial traits implicated in disease (e.g. sugar transport/acid production; protease activity) and retard growth without eliminating beneficial species. In silico modelling studies have been performed which support the concept that either reducing the frequency of acid challenge and/or the terminal pH, or by merely slowing bacterial growth, results in maintaining a community of beneficial bacteria under conditions that might otherwise lead to disease (control without killing).

/pdf/ecological-approaches-to-oral-biofilms-control-without-sbq0ao4yh6.pdf

Ecological Approaches to Oral Biofilms: Control without Killing

A brief review on experimental fluorosis.

Post-tooth brushing rinsing behaviours have the potential to either reduce or enhance the effectiveness of fluoride toothpaste and show wide variation in the general population. There is a lack of high-quality evidence to support definitive guidance in this area. However, the currently available international guidelines provide consistent recommendations despite the limited evidence. To explore the available evidence base and recommendations on optimal post-brushing rinsing behaviour relating to the use of both water and mouth rinses, a meeting was held between the authors and other experts. This paper reports the consensus views of those present at the meeting concerning what advice we should give our patients. A full list of meeting attendees is provided at the end of this article.

/pdf/post-brushing-rinsing-for-the-control-of-dental-caries-4ewqfkf69g.pdf

Post-brushing rinsing for the control of dental caries: exploration of the available evidence to establish what advice we should give our patients

Fluoridated toothpaste is effective for dental caries control, yet may be a risk factor for dental fluorosis. This study aimed to quantify fluoride ingestion from toothpaste by children and to investigate the effects of age, gender, and social class on the amount of fluoride ingested per toothbrushing session. Sixty-one children, 4-6 yr of age, were recruited: 38 were from low socio-economic (LSE) areas of Newcastle, UK, and 23 were from high socio-economic (HSE) areas of Newcastle, UK. All expectorated saliva, rinse water (if used), and residual toothpaste were collected after brushing at home and were analysed for fluoride. Of the children, 74% and 69% from HSE and LSE areas, respectively, claimed that they brushed twice per day. The mean (SD) weight of toothpaste dispensed was 0.67 (0.36) g. The mean (SD) amount of fluoride ingested per toothbrushing session and per day was 17.0 (14.7) and 29.3 (32.8) μg kg(-1) of body weight, respectively. Daily fluoride intake per kilogram of body weight did not differ significantly between children from LSE and HSE areas. Fluoride intake per toothbrushing session was significantly influenced by weight of toothpaste, its fluoride concentration, and the child's age. Whilst the average amount of toothpaste used per toothbrushing session was more than twice the recommended amount (of 0.25 g), only one child had a daily fluoride intake that exceeded the tolerable upper intake level of 0.1 mg kg(-1) of body weight for this age group.

Fluoridated toothpaste: usage and ingestion of fluoride by 4- to 6-yr-old children in England

In terms of novel formulations, there seems to have been a shift in emphasis from anti-caries/anti-gingivitis to anti-calculus/whitening toothpastes in recent years. The anti-calculus and whitening effects of toothpastes are to some extent based on the same active ingredients: compounds of high affinity for tooth mineral. Due to this affinity, crystal growth may be hindered (anti-calculus) and chromophores be displaced (whitening). Besides these common ingredients, both types of toothpaste may contain agents specifically aimed at each condition. Clinical studies have shown that these active ingredients can be successfully formulated in fluoride toothpastes to give significant reductions in supragingival calculus and stain formation and facilitate their removal. Some of the ingredients are formulated in toothpastes that additionally contain anti-plaque and anti-gingivitis ingredients, making these toothpastes (together with the fluoride) truly multi-functional. The development of these products is not straightforward because of interaction between formulation components and because the active ingredients must maintain their beneficial characteristics during the shelf life of the paste. Neither a therapeutic benefit (in terms of less gingivitis or less caries) nor a societal benefit (in terms of less treatment demand) has been demonstrated as a result of the anti-calculus and whitening effects of toothpastes.

Anti-calculus and whitening toothpastes

/pdf/the-impact-of-nutrition-and-diet-on-oral-health-2kbf3cgt3k.pdf

The Impact of Nutrition and Diet on Oral Health.

The amount of fluoride retained in the mouth following the application of dentifrices, mouthwashes, etc. may be important in determining their anticaries efficacy. In this study we investigated the relationship between the salivary flow rate and salivary fluoride clearance. Ten adults tested six mouthrinses, consisting of aqueous sodium fluoride solutions (0.013, 0.026 mol/l) with and without added sodium chloride (1.28 mol/l) or sucrose (0.44 mol/l), in a randomised order. Prior to each test, subjects swallowed, rinsed for 2 min with 2 ml water and then expectorated into a preweighed container to obtain a measure of initial saliva flow rate. Next, the procedure was repeated using one of the test rinses. Finally, samples of unstimulated whole saliva were collected for up to 3 h after each mouthrinse application and analysed for fluoride. Salivary fluoride concentrations were significantly lower after application of mouthrinses that contained either sucrose or NaCl, both of which compounds markedly enhanced salivary flow, than after the use of corresponding mouthrinses without any additive. Area under the salivary fluoride clearance curve (AUC) values were inversely correlated with salivary flow rate on an individual basis (p < 0.01). The observed behaviour could not be completely attributed to treatment dilution by saliva at the time of application.

On the relationship between the rate of salivary flow and salivary fluoride clearance.

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