Fluoride and Oral Health.

The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of 'Fluoride and Oral Health' has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature.

Validation of fingernail fluoride concentration as a predictor of risk for dental fluorosis.

The aim of this study was to validate the use of fingernail fluoride concentrations at ages 2-7 years as predictors of the risk for developing dental fluorosis in the permanent dentition. Fifty-six children of both genders (10-15 years of age) had their incisors and premolars examined for dental fluorosis using the Thylstrup-Fejerskov index. Fingernail fluoride concentrations were obtained from previous studies when children were 2-7 years of age. Data were analyzed by unpaired t test, ANOVA, and Fisher's exact test when the fingernail fluoride concentrations were dichotomized (≤ 2 or >2 µg/g). Children with dental fluorosis had significantly higher fingernail fluoride concentrations than those without the condition, and the concentrations tended to increase with the severity of fluorosis (r(2) = 0.47, p < 0.0001). Using a fingernail fluoride concentration of 2 µg/g at ages 2-7 years as a threshold, this biomarker had high sensitivity (0.84) and moderate specificity (0.53) as a predictor for dental fluorosis. The high positive predictive value indicates that fingernail fluoride concentrations should be useful in public health research, since it has the potential to identify around 80% of children at risk of developing dental fluorosis.

Skeletal fluorosis due to excessive tea and toothpaste consumption.

We describe the case of a 53-year-old woman who presented with a metatarsal fracture and was found to have a bone mineral density (BMD) T-score of +11 in the lumbar spine and +7.6 in the hip. Subsequent investigation revealed very high serum, urine and tissue fluoride levels, associated with excessive tea and toothpaste consumption. The case emphasises the need to exclude fluorosis in individuals with unexpectedly high BMD levels.

Development of gold standard ion-selective electrode-based methods for fluoride analysis.

BACKGROUND/AIMS: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. METHODS: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. RESULTS: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. CONCLUSION: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.

Fluoride uptake by plaque from water and from dentifrice.

It has been suggested that fluoride retention in plaque is limited by available binding sites. We determined the effects of fluoridated or placebo dentifrices on plaque and salivary fluoride concentrations [F]s in communities with different water fluoride concentrations (0.04, 0.85, 3.5 ppm). After one week of dentifrice use, samples were collected 1.0 and 12 hrs after the last use of dentifrices. After the use of fluoridated dentifrice, plaque fluoride concentrations were higher at both times, except at 12 hrs in the 3.5-ppm community. Plaque concentrations at 1.0 hr after the use of fluoridated dentifrice increased almost constantly (6.5 mmol/kg), but then decreased approximately 50% at 12 hrs in each community. Unlike previous studies, the present findings suggest that the use of fluoridated dentifrice is likely to increase plaque fluoride concentrations significantly for up to 12 hrs in areas where the water contains fluoride close to 1.0 ppm. As previously reported, plaque fluoride concentrations were directly related to calcium concentrations.

pH-dependent fluoride transport in intestinal brush border membrane vesicles.

Fluoride (F) absorption from the rat stomach and urinary bladder, hamster cheek pouch, and the renal tubules of several species are pH gradient-dependent. These observations led to the hypothesis that F crosses these epithelia in the form of the undissociated acid, HF. Several recent reports, however, have provided evidence that F absorption from the rat small intestine is insensitive to the lumenal pH. We report here our evidence that F uptake by rabbit intestinal brush border membrane vesicles (BBMV) occurred rapidly and with an overshoot only in the presence of an inward-directed proton gradient. In the absence of a proton gradient or in the presence of an outward-directed gradient, F uptake was slow and without an overshoot. In the presence of an inward-directed proton gradient, F uptake was partially inhibited by DIDS and DEP but not by diBAC. PCMBS inhibited F uptake by up to 83% in a dose-response manner. DiBAC appeared to reduce intravesicular pH slightly but the other reagents had no effect. When the uptake buffer contained chloride or nitrate, F uptake was partially inhibited compared to the mannitol or gluconate controls. It was concluded that F transport across the rabbit intestinal BBMV occurs via a carrier-mediated process which may involve cotransport of F with H+ or exchange of F with OH-. The inhibitory effects of DIDS, DEP and PCMBS may occur by affecting this carrier-mediated transport.

Calcium-induced inhibition of taurine transport in brush-border membrane vesicles from rabbit small intestine.

The influence of Ca2+ on the activity of the taurine transport system was investigated in rabbit small intestinal brush-border membrane vesicles. Preincubation of the brush-border membrane vesicles with Ca2+ prepared by the Mg2(+)-aggregation method markedly decreased the NaCl gradient-dependent uptake of taurine in these vesicles. Uptake of glucose and alanine, both dependent on a Na+ gradient, were also decreased by Ca2(+)-treatment, but their reduction was very small compared with that of taurine uptake. The inhibitory effect of Ca2+ was dose- and time-dependent. The inhibition was reduced by the presence of ethylene glycol-bis(beta-amino ethyl ether)-N,N,N'-N'-tetraacetic acid during treatment of the membrane vesicles with Ca2+. Neomycin partially protected the taurine transporter activity from the Ca2(+)-induced inhibition, but indomethacin did not. 5-Nitro-2-(3-phenylpropylamino)benzoate, a Cl(-)-channel blocker, did not increase taurine uptake in the Ca2(+)-treated membrane vesicles. It is concluded that the Ca2(+)-induced inhibition of taurine uptake in rabbit intestinal brush-border membrane vesicles is not due to accelerated dissipation of the ion gradient driving forces across the membrane but rather to a direct effect on the transporter, most likely mediated by the activation of the membrane-bound phospholipase C.

Oxolinic acid in urinary tract infection: a multi-centre trial.

A single-blind trial of oxolinic acid (750 mg. twice-daily for 14 days) and ampicillin (500 mg. 3-times daily for 14 days) in 60 cases with urinary tract symptoms showed superior results with oxolinic acid: 94% of pathogens were sensitive to oxolinic acid and 69% were sensitive to ampicillin. Sympotomatic relief and bacterial eradication occurred earlier in the oxolinic acid group.

The physiological and toxicological characteristics of fluoride.

The metabolism and toxicity of fluoride are discussed with emphasis on new scientific findings. The gastric absorption, tissue distribution, and renal excretion of the ion are all influenced by the magnitude and direction of the pH gradient between adjacent body fluid compartments. This mechanism explains the asymmetric distribution of fluoride across cell membranes, and the manipulation of transmembrane pH gradients has proven efficacious in acute fluoride toxicity. The comparative metabolism and relative toxicities of ionic fluoride and monofluorophosphate are discussed. It is no longer certain that there is a difference between the acute toxic potentials of sodium fluoride and those of MFP. It is concluded that the "probably toxic dose" or PTD of fluoride--the dose which should trigger therapeutic intervention and hospitalization--is 5 mg/kg of body weight. As currently packaged, many dental products contain sufficient fluoride to exceed the PTD for young children. There is a need for additional research into the sources, effects, and fate of strongly bound or organic fluoride compounds. Attention is drawn to the fact that, while the metabolic characteristics and effects of fluoride in young and middle-aged adults have received considerable research attention, there is a paucity of such information for young children and the elderly. The increasing prevalence of dental fluorosis is addressed. It is concluded that nondietary sources of fluoride, mainly fluoride-containing dental products, are a major source of ingested fluoride. The article concludes with 12 recommendations for future research.

Fluoride in dental products: safety considerations.

This review summarizes the nature of acute fluoride toxicity, its time-course, and the fluoride doses that are involved. The generally accepted "certainly lethal dose" range for 70 kg adults, i.e., from 5 to 10 g of sodium fluoride or from 32 to 64 mg fluoride/kg, is discussed. Based on recent case reports of fluoride-induced fatalities, it is concluded that this dose range has little utility in cases involving young children. The concept of a "probably toxic dose" (PTD) is advanced. The PTD, 5.0 mg F/kg, is defined as the dose of ingested fluoride that should trigger immediate therapeutic intervention and hospitalization because of the likelihood of serious toxic consequences. The concentrations and quantities of fluoride in selected dental products are discussed in relation to the PTD. It is concluded that, as these products are currently packaged, most of them contain quantities of fluoride sufficient to exceed the PTD for young children. Recommendations are made to reduce the risk of toxicity associated with their use.

Systemic absorption of fluoride from alginate impression material in humans.

Thirty minutes after routine alginate impressions in five adult subjects, plasma fluoride levels increased by an average of 2.6 times over control values. Urinary fluoride excretion rates increased approximately 2.9 times during the first two hours after the impressions. Average whole saliva fluoride levels at 15 minutes were over 100 times the average control concentration. When small amounts of alginate were deliberately ingested, plasma fluoride levels and urinary excretion rates increased sharply.

Lack of significant effect of coffee and caffeine on fluoride metabolism in rats.

It has been reported that rat plasma fluoride (F) concentrations are higher by up to 100% when F is administered ig in coffee or a caffeine solution compared with when it is administered in water. It was hypothesized that the consumption of caffeinated beverages has contributed to the prevalence of dental fluorosis. The present studies were done to determine the physiological mechanisms for these effects. For approximately 2 h after F was administered in coffee, plasma F concentrations were higher than when administered in water, decaffeinated coffee, or a caffeine solution (3 mg/kg), but the intergroup differences were small and generally not statistically significant. The 4-hour plasma AUC values did not differ with statistical significance. There were no differences among the groups in the renal or extrarenal (skeletal) clearances of F, which suggested that the higher plasma F concentrations in the coffee groups may have been due to a slight and transient increase in absorption rate. The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given. In addition, the renal excretion, clearance, and fractional renal clearance of calcium did not differ among the groups. The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma and developing enamel fluoride concentrations during chronic acid-base disturbances.

Mild acid-base disturbances were induced in rats for 30 days. These disturbances did not affect % ash of maxillary incisors or % P of the developing enamel from mandibular incisors. Total fluoride intake (food and water) among groups drinking fluoride-free water was constant. Nevertheless, average plasma and developing enamel fluroide concentrations were highest in the acidotic group and lowest in the alkalotic group. Among groups drinking water containing 50 ppm fluoride, total fluoride intake was highest by the alkalotic group and lowest by the acidotic group. Plasma and enamel fluoride concentrations, however, were highest in the acidotic group. It is concluded that plasma and developing enamel fluoride levels can be independent of, or inversely related to, fluoride intake.

The biologic availability of fluoride from alginate impressions and APF gel applications in children.

Ten child volunteers received routine alginate impressions and APF gel topical applications during separate visits. Whole saliva, urine, and surface enamel fluoride concentrations were measured before and after these procedures. Significant increases in salivary, urinary, and enamel fluoride concentrations were observed following APF gel application but only in whole saliva following alginate impressions.

Environmental and physiological factors affecting dental fluorosis.

In addition to differences in fluoride intake and possibly to calcium deficiency or malnutrition, there are several factors which may account for individual differences in the occurrence of dental fluorosis. Disorders in acid-base balance affect the renal handling of fluoride such that, in acidosis, the excretion rate is diminished and, in alkalosis, the excretion rate is enhanced. Thus, any factor that can decrease urinary pH would be expected to increase the likelihood of dental fluorosis and vice versa. Results from studies with both rats and dogs have shown that acid-base disturbances per se, especially acidosis, adversely affect the mineralization of enamel in a manner that resembles fluorosis. It has been found that the retention and tissue levels of fluoride are increased by residence at high altitude. It has also been found that, in the absence of fluoride exposure, residence at high altitude per se can have a profound disruptive effect on amelogenesis which could be confused with fluorosis. The effects of diseases which lead to increases in urinary flow rate and water intake on the likelihood of the occurrence of dental fluorosis are also discussed.

Dentin permeability: a comparison of functional versus anatomical tubular radii.

Two independent techniques (filtration and surface tension) were developed to measure the functional tubular radii of 11 dentin and 2 glass discs. Anatomic radii were determined using SEM for comparative purposes. The functional radii of the dentin discs ranged from 5 to 40% of the anatomic radii. This differences was due to the fact that SEM visualizes only the surface while the functional techniques measure the radii within dentin tubules. It is concluded that the functional methods are preferred whenever the dynamics of fluid flow through dentin are under consideration.

A comparative study of fluoride pharmacokinetics in five species.

This study was designed to quantitate and compare the major features of the short-term pharmacokinetics of fluoride--i.e., the plasma (Cp), renal (Cr), and extra-renal (Cer) clearances--in young adult dogs, cats, rabbits, rats, and hamsters. Plasma and urine samples were collected for seven h after the iv administration of fluoride (0.5 mg F/kg). Cp ranged from 3.5 to 8.6 mL/min/kg in the dog and hamster, respectively. Cr ranged from less than 1.5 mL/min/kg in the dog and rabbit to about 3.5 mL/min/kg in the rat and hamster. Cer ranged from 2.1 mL/min/kg in the dog to over 4.5 mL/min/kg in the cat, rabbit, and hamster. It was concluded that (1) there are major quantitative differences in the metabolic handling of fluoride among the five species, and that (2) Cp, Cr, and Cer values of the young adult dog, when factored for body weight, resemble those of the young adult human most closely.

Subcutaneously implanted alginate as a continuous-release source of fluoride.

The fluoride concentrations of seven brands of alginate ranged from 8600 to 30,500 ppm. In acute and chronic in vivo studies, fluoride was continuously released from subcutaneously implanted alginate cylinders for up to three weeks. This technique is a simple and economical method for elevating soft and hard tissue fluoride levels.

Topical fluorides: effects on physiologic and biochemical processes.

The ingestion of fluoride from dentifrices or mouthrinses can contribute substantially to the total daily intake of the ion, even in communities that provide optimally fluoridated drinking water. It is concluded that the frequent and unsupervised use of these products by children six years of age or younger, especially those living in areas with water fluoridation, places them at risk of dental fluorosis. Recommendations to reduce the risk are presented. The use of 1.23% (12,300 ppm) APF gels, particularly in the absence of suctioning during the application and expectoration after the application, is associated with the swallowing of relatively large quantities of fluoride. The resulting increases in plasma fluoride levels may be sufficient to cause dental fluorosis, as judged by studies with laboratory animals, and a reduction in the kidney's ability to concentrate the urine, as judged by studies with both laboratory animals and humans. The epigastric distress experienced by some patients during or after APF gel applications appears to be due, at least in part, to a direct toxic effect of fluoride on the gastric mucosa. Data from studies with humans and laboratory animals indicate that there may also be associated changes in plasma and tissue cAMP levels, glucose metabolism, and salivary amylase secretion. There is an immediate need for the dissemination to the dental profession of standardized methods for gel application that will minimize the quantities of fluoride available for ingestion and systemic absorption.

Blood and urinary 18F pharmacokinetics following parenteral administration in the rat.

Blood and urinary excretion time courses of 18F administered parenterally to rats were monitored for two hours. The intraperitoneal, subcutaneous, and intravenous routes gave kinetically indistinguishable results after ten minutes following the dose. The blood time course during the first hour following intramuscular dosing showed a relative constancy and suggested a delayed absorption time.