Various Concentrations Of Fluoride Research Articles

(Invited) Electrochemically Driven Ion-Exchange Remediation of Water Containing High Fluoride Content

Remediation of water contaminated by anthropogenic activities is required to provide clean water for human consumption and prevent damage to the environment. The scale of the challenge is signaled by its inclusion in the UN 17 Sustainable Development Goals [1]. Major contributors to the problem are industrial activity and agriculture. The former commonly results in the release of metals; analysis and separation of such cationic species have received considerable attention [2]. In the latter instance, run-off of fertilizers used to enhance crop yields can result in unacceptable levels of nitrate or phosphate in natural waters. While monitoring of anionic species is widely undertaken using ion selective electrodes [3], the promise of electrochemical separation technologies [4] in this area is less well developed.For anthropogenic causes, remediation is the last resort following failure to prevent release of toxic materials into the environment. In contrast, there are instances where the “contaminant” is natural: fluoride is a prime example. The beneficial dental health effects of fluoride are widely appreciated, but excessive amounts are harmful to teeth, bones and various organs [5]. The World Health Organization (WHO) identifies the optimum fluoride level in drinking water to be 0.5-1.0 mg/L. In many regions, water is fluoridated to realize the health benefits. However, local geological conditions many countries can result in natural water fluoride levels significantly above the recommended upper limit of 1.5 mg/L.This presentation addresses the challenges associated with remediation of anions, with particular focus on fluoride. At the outset, it is recognized that for potable water the requirement is not full de-ionization but selective removal of contaminants: this is a separation challenge. The attributes, performance and potential for scale-up of a range of (electro)chemical remediation strategies will be discussed in general. We then focus on electrochemically switched ion-exchange (ESIX) [6], for which application to water softening [7] and perchlorate removal [8] has been demonstrated.We explore the facility of aniline-based (co-)polymer films to reversibly extract and eject fluoride ions as the charge (oxidation state) of the films are subject to electrochemical control. Homopolymer and copolymer films based on aniline, o-aminophenol and o-toluidine were deposited potentiodynamically. Film thickness was controlled via the number of potential cycles: the resultant electroactive site population was assayed coulometrically in monomer-free background electrolyte. Film mass was assayed gravimetrically using the EQCM. For relatively thin films, correlation of film mass and charge capacity revealed the solvent content. During deposition of thicker films, acoustic admittance data revealed the progressive evolution of viscoelastic effects. Co-monomer feedstock has a significant influence on film deposition rate, absolute solvent population and redox-driven solvent population change [9].The ion-exchange capacity of the films for redox-driven fluoride uptake was determined upon exposure to aqueous solutions of varying fluoride concentration, both in the absence and presence of chloride as a competing anion. EQCM mass and charge responses, respectively, provide overall “ion+solvent” and “solvent” population changes: correlation permits separation of fluoride and water uptake/release. Copolymer composition significantly influences the ease of fluoride uptake and release and reveals ion trapping. Complementary data on the dynamics of ion and solvent transfers are provided by shorter timescale experiments, involving voltammetry at faster scan rates and chronoamperometry. Correlation of gravimetric and coulometric data permits temporal separation of fluoride and solvent entry and exit.Practical exploitation of these promising fundamental observations will require scale-up and optimization of cycle life, film viscoelasticity and response time as functions of film thickness. We speculate that spatially variant film solvation will be a critical parameter. To this end, we consider the viability of neutron reflectivity measurements with isotopic substitution to determine the spatial distributions of fluoride and solvent in films of graded composition.

Fluoride and Biological Calcification I: Effect of Fluoride on Collagen-Induced In Vitro Mineralization and Demineralization Reactions.

An in vitro system employing collagen isolated from the sheep tendons to induce mineralization and demineralization reactions was used not only to study the effect of various concentrations of fluoride on the collagen-induced mineralization and demineralization reactions but also to compare their action with the inhibitors of mineralization and/or demineralization. Studies demonstrated that under physiological conditions, at lower concentrations (5 × 10-6 to 5 × 10-5 M) fluoride inhibited while at higher concentrations (> 10-4 M), it stimulated the collagen-induced in vitro mineralization. At higher concentrations, fluoride was also found to inhibit the demineralization of the collagen bound preformed mineral phase. At low concentrations, fluoride acted like Mg2+ to inhibit mineralization while at higher concentration, it acted like crystal poisons (e.g., pyrophosphate phosphonates, citrate) to inhibit demineralization. However, unlike magnesium and pyrophosphate, fluoride at its higher concentrations was found to stimulate rather than inhibit the process of mineralization.

Effect of fluoride on photosynthetic pigment content and antioxidant system of Hydrilla verticillata

ABSTRACTFluoride can either inhibit or enhance the growth of aquatic macrophytes, depending upon fluoride concentration and exposure time. To investigate fluoride toxicity, the submerged plant Hydrilla verticillata was treated with various concentrations of fluoride (F) (0, 10, 20, and 40 mg/L) for different lengths of time (7, 14, 21, and 28 days). At exposure to 10 mg/L F, the content of chlorophyll, protein, and carbohydrates content increased in leaves of H. verticillata, and the activity of guaiacol peroxidase (POD) and superoxide dismutase (SOD) slightly increased in plants compared with the control. When fluoride concentration increased to 20 mg/L, the toxic effect generated by fluoride led to a reduction of chlorophyll, protein, and carbohydrates in H. verticillata, but the activity of guaiacol peroxidase and SOD and the amount of ascorbic acid (AsA) and glutathione (GSH) were enhanced significantly. After exposure to fluoride at 40 mg/L for a long period, these physiological parameters showed a sharp decrease, and inactivation was observed in H. verticillata. These results suggested that a certain concentration of fluoride induced antioxidant response, and excess fluoride induced metabolism imbalance and oxidative damage in H. verticillata.

Elucidation of the sorptive uptake of fluoride by Ca 2+ -treated and untreated algal biomass of Nostoc sp. (BTA394): Isotherm, kinetics, thermodynamics and safe disposal

Abstract The present study explores the sorption mechanism of fluoride from aqueous solution on to live biomass of Nostoc sp. (BTA394). Adsorptive efficiency of the algal biomass both as Ca2+-treated and without Ca2+-treatment were studied in varying fluoride concentration. The influence of several parameters like initial fluoride concentration (5–20 mg/L), time (0–14 h), temperature (283.15–303.15 K) and calcium concentration (50–200 ppm) were considered. The effect of pH (1–11) was taken into account only for the untreated biomass. Instrumental analysis of the algal biomass was studied for better understanding of the adsorption mechanism. The removal process was found to follow Langmuir isotherm model (R2 = 0.9962 and 0.9945) with maximum adsorptive uptake of 4.72 mg/g and 3.49 mg/g by Ca2+-treated and Ca2+-untreated algal biomass respectively. The sorption process obeyed pseudo second order kinetic model. Thermodynamic study revealed the process to be endothermic, spontaneous and feasible in nature. The spent algal biomass was further modified which could be used as an ingredient in road construction or brick making thereby preventing the problems associated with waste disposal. Therefore, Ca2+-treated live algal biomass of Nostoc sp. (BTA394) could be a promising biosorbent for fluoride removal from aqueous solution.

Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts

ObjectiveThe aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. MethodsWe cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. ResultHigh fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. ConclusionsThese results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis.

Anodic Dissolution of Titanium in Acidic Fluoride Media - Effect of Varying Fluoride Concentration

Ti and Ti alloys are well known for their excellent chemical stability and biocompatibility. Ti metal shows high corrosion resistance due to the presence of protective native oxide film. Although TiO2 layer is stable and protective in action, it can be dissolved in HF [1-3]. Anodic dissolution of Ti in acidic fluoride medium shows three distinct regions, viz. active, passive and transpassive [1,2]. The anodic current increases with potential in the active region and it decreases with potential in the passive region. The current increases slowly with potential in the transpassive region. Transpassive dissolution has been extensively studied [1,3]. Using potentiodynamic polarization and electrochemical impedance spectroscopic data, the anodic dissolution of Ti in 0.1 M HF in the active and passive regime has been investigated recently and a four step mechanism has been proposed [2]. HF is a weak acid and is known to form various species in solution, as described in the equation below. HF ↔ H++F- HF+F-↔HF2 - HF+HF2 -↔H2F3 - The equilibrium constants for the above reactions are K1 = 6.84 × 10-4, K2 = 5 and K3 =0.58 respectively [4]. Although a four step mechanism has been proposed to explain the anodic dissolution of Ti in HF[2], the influence of HF concentration has not been incorporated in the mechanism yet. It is important to quantify each species present in solution and their influence on individual steps of the reaction. In this work, the effect of varying the concentration of HF on Ti dissolution was investigated. A rotating disk Ti electrode was used in a three electrode cell with Ag/AgCl (in 3.5 M KCl) as reference and Pt wire as counter electrode. HF concentration was varied from 25 mM to 1000 mM. In all the experiments, 1 M Na2SO4 was used as the supporting electrolyte. The electrode was rotated at 900 rpm. Potentiodynamic polarization experiments were conducted at a scan rate of 20 mV/s, starting at -250 mV below open circuit potential and ending in the transpassive regime on the anodic side. A few experiments were also conducted at a scan rate of 2 mV/s, in solutions of 50 mM, 500 mM and 1000 mM HF concentrations, and the current response was the same at both 2 mV/s and 20 mV/s scan rates. The results are presented in Fig. A. The anodic polarization curves (Fig. A) show that the active and passive regimes are clearly visible in all the HF concentrations studied here. The inset shows the results at lower concentrations, expanded for clarity. The peak current value increases with an increase in HF concentration. The location of peak potential also shifts to more anodic values at higher HF concentration. The potential and logarithm of the absolute value of current in the cathodic and anodic regime (active region only) are presented in Fig. B. The cathodic and anodic branches of potentiodynamic polarization were extrapolated to estimate the corrosion current. The estimated corrosion current values and the peak current values near active-passive transition were correlated with nominal HF concentration and as well as with the concentration of individual species occurring at equilibrium. In order to identify the effect of individual species unambiguously, a few experiments were also run by adding H2SO4 or KF to the experimental solutions (results not shown here). The corresponding changes in the peak current values and corrosion current estimates were also analysed. The results indicate the corrosion current and peak current can be expressed as proportional to [H+]α and [F-]β , where α is 0.72 and β is 0.92. This suggests that undissociated HF is likely to play a major role in Ti dissolution.

Hybrid sorbent-ultrafiltration systems for fluoride removal from water

ABSTRACTFluoride contaminated water sources are found in many parts of the world and the consumption of such water is causing dental and skeletal fluorosis in humans, especially in developing countries. Hybrid sorbent-ultrafiltration (UF) systems are proposed for the removal of fluoride from water for the first time in this study. Laterite and bone char were selected as they are low cost, accessible sorbents in developing countries. The performances of the laterite-UF and bone char-UF systems were compared in terms of fluoride removal and membrane permeability under varying fluoride concentration, solution pH, and sorbent load. For equilibrium fluoride concentration of 1.5 mg/L, the World Health Organization guideline for safe drinking water, the sorption capacity of bone char (1.1 mg/g) was larger than that of laterite (0.40 mg/g) and this was attributed to the larger surface area of bone char. For the laterite-UF system, increase in fluoride concentration resulted in a decline in UF permeability whereas for the bone char-UF system there was no influence of fluoride concentration on membrane permeability. The optimal solution pH at which the systems are operated at maximum sorption capacity while avoiding membrane fouling was determined as pH 5-6 for the laterite-UF and pH 7 for the bone char-UF system. For both systems, the permeability declined in a similar manner as the sorbent load increased. Although both systems require further optimization, they showed to be viable defluoridation technologies.

Effects of Different Concentrations of Fluoride in Oral Mucosal Cells in Albino Rats.

Fluoride has been described to be physiologically essential for the normal development and growth of human beings. However, it is well known that excessive fluoride causes skeletal, nonskeletal and dental complications. Therefore, outlining the cytogenetic effects induced by fluorosis is necessary. To evaluate the cytomorphology of exfoliated oral mucosal cells among various concentrations of fluoride. Study group comprised of 12 Albino Wistar rats, categorized into A,B and C groups (fed with 25 ppm,50 ppm and 100 ppm concentration of NaF), each group consisting of 4 rats, with 4 controls (fed with 1ppm concentration of NaF in distilled water). Each group was fed for a period of 42 days. Cytological smears were taken from the buccal mucosa of each group after 42 days of fluoride administration. The samples were stained with the papanicolaou method and assessed for Cytomorphometrical changes in maximum diameter of nucleus, minimum diameter of nucleus, perimeter of the nucleus, maximum diameter of the cell, minimum diameter of the cell and perimeter of the cell by image analysis software and the results were statistically analysed using SPSS software. Mean values of maximum diameter, minimum diameter and perimeter of the nucleus increased in fluoride induced study groups when compared to controls and the results showed that p-value was statistically significant (p-value: 0.000, 0.001). Mean value of maximum diameter, minimum diameter and perimeter of the cell decreased in fluoride induced subjects when compared with controls which were statistically not significant (p-value: 0.791, 0.600 & 0.719). A continuous increase in the nuclear size and decrease in the cell size was identified in fluoride induced groups as compared to controls. The observations of our present study revealed that cellular changes occur with severity of fluorosis. These cellular morphological changes may possibly eventuate into dysplastic alterations, which can progress to malignant changes.

Fluoride induced alterations in erythrocyte and related parameters of an Air-breathing fish, Channa punctatus (Bloch)

The effect of various concentrations of fluoride (NaF) (10, 20, 30 and 40ppm) after 15 days of exposure on some haematobiochemical parameters of Channa punctatus (Bloch) has been studied. Changes in the shape and size, cell membrane and nucleus of the R.B.C. were observed. Clumping of the R.B.C. cells was noted. Clumping becomes prominent in higher concentrations. The TEC, Hb, PCV, MCV, MCH and MCHC progressively decreased with an increase in the concentration of fluoride. The length/ breadth ratio of erythrocyte and erythrocyte nucleus do not depart significantly from normal values and as such there is no significant change in erythrocyte and nuclear surface area.

Relationship between Fluoride Concentration and Activity against Virulence Factors and Viability of a Cariogenic Biofilm: in vitro Study

Despite widespread use of various concentrations of fluoride for the prevention of dental caries, the relationship between fluoride concentration and activity against cariogenic biofilms has not been much studied. Herein we investigated the relationship between fluoride concentration and activity against virulence factors and viability of Streptococcus mutans biofilms. S. mutans biofilms were formed on saliva-coated hydroxyapatite discs. The 70-hour-old biofilms were exposed to 0, 1, 3, 10, 30, 100, 300, 1,000 or 2,000 ppm F^-. The changes of virulence factors and viability of the biofilms were analyzed using biochemical methods and laser scanning confocal fluorescence microscopy. At 1-2,000 ppm F^-, the activity of fluoride against acid production, acid tolerance, and extracellular polysaccharide formation of S. mutans biofilms accurately followed a sigmoidal pattern of concentration dependence (R² = 0.94-0.99), with EC₅₀ values ranging from 3.07 to 24.7 ppm F^-. Generally, the activity of fluoride against the virulence factors was concentration-dependently augmented in 10-100 ppm F^- and did not increase further at concentrations higher than 100 ppm F^-. However, fluoride did not alter glucosyltransferase activity and viability of S. mutans biofilm cells in all concentrations tested. These results can provide a basis for the selection of appropriate fluoride concentrations that reduce the physiological ability of cariogenic biofilms.

Effect of caries preventive products on the growth of bacterial biofilm on titanium surface

Fluorides may affect the oxide layer on titanium surface. Caries preventive mouthwashes or gels contain fluorides and are applied at low pH. The aim of the present work was to study whether various concentrations of fluoride at acidic pH cause changes in the surface structure on the polished region of Ti implants, and alter the adherence and colonization of bacteria. Commercially pure Ti grade 4 discs with a polished surface were treated with a mouthwash containing 0.025% fluoride, a gel containing 1.25% fluoride or a 1% aqueous solution of NaF (pH 4.5). The change of surface roughness of the samples and the colonization of Porphyromonas gingivalis strains were studied by scanning electron microscopy after 5 days of anaerobic incubation. The quantity of the bacterial protein was determined by protein assay analysis. Agents with high fluoride concentration at acidic pH increased the roughness of the Ti surface. A slight increase in the amount of bacteria was found on the surfaces treated with 1% NaF and gel in comparison with the control surface. This study suggested that a high fluoride concentration at acidic pH may hinder the development of a healthy transgingival epithelial junction on Ti implants, due to bacterial colonization.

Evidence-Based Clinical Recommendations Regarding Fluoride Intake From Reconstituted Infant Formula and Enamel Fluorosis: A Report of the American Dental Association Council on Scientific Affairs

This article presents evidence-based clinical recommendations regarding the intake of fluoride from reconstituted infant formula and its potential association with enamel fluorosis. The recommendations were developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs (CSA). The panel addressed the following question: Is consumption of infant formula reconstituted with water that contains various concentrations of fluoride by infants from birth to age 12 months associated with an increased risk of developing enamel fluorosis in the permanent dentition? A panel of experts convened by the ADA CSA, in collaboration with staff of the ADA Center for Evidence-based Dentistry (CEBD), conducted a MEDLINE search to identify systematic reviews and clinical studies published since the systematic reviews were conducted that addressed the review question. CEBD staff identified one systematic review and two clinical studies. The panel reviewed this evidence to develop recommendations. The panel suggested that when dentists advise parents and caregivers of infants who consume powdered or liquid concentrate infant formula as the main source of nutrition, they can suggest the continued use of powdered or liquid concentrate infant formulas reconstituted with optimally fluoridated drinking water while being cognizant of the potential risks of enamel fluorosis development. These recommendations are presented as a resource to be considered in the clinical decision-making process. As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences.

Fluoride‐induced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats

This study intended to determine the effects of various concentrations of fluoride (1, 10, 50 and 100 ppm) in drinking water for a period of 12 weeks on changes in haem biosynthesis pathway, oxidative stress and neurological variables supported by histopathological observations and fluoride in rats. The data indicates significant alterations in the parameters related to haeme synthesis pathway like inhibition of blood delta-aminolevulinic acid dehydratase, delta-aminolevulinic acid synthetase, oxidative stress like depletion of glutathione (GSH) and increase in oxidized glutathione (GSSG) and thiobarbituric acid reactive substances. These changes were accompanied by depletion in GSH:GSSG ratio, whole brain biogenic amine levels and a dose-dependent increase in fluoride concentration. Interestingly and most significantly, these changes were more pronounced at lower concentrations of fluoride compared with higher fluoride dose. Biochemical changes were supported by the histological observations, which also revealed that at high concentrations of fluoride, toxic effects and damages to organs were more pronounced. These changes support our earlier findings regarding the role of decreased ionic mobility of fluoride ion at higher concentrations, leading to less pronounced toxicity.

Role of Oxidative Stress in Osteoblasts Exposed to Sodium Fluoride

We investigated the relationship between oxidative stress and osteoblasts viability in osteoblasts exposed to various concentrations of fluoride in this study. Primary calvarial osteoblasts from neonatal Kunming mice were cultured and subcultured to the third generation. Osteoblasts were incubated with sodium fluoride (0, 0.5, 1, 2, 4, 8, 12, and 20 mgF(-)/L) for 24, 48, and 72 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis showed cell viability significantly increased after osteoblasts exposed to low concentrations of fluoride (0.5 to approximately 2 mgF(-)/L) for 24 to approximately 72 h. Oxidative stress analysis showed that low concentration of fluoride excited lipid peroxidation in osteoblasts and increased activity of antioxidant enzymes in varying degrees. We demonstrated that changes of osteoblasts viability of the low-dose fluoride groups are different from those of high-dose fluoride groups; however, both low and high doses of fluoride caused active state of oxidative stress in osteoblasts, which suggesting that oxidative stress may be excited by the active osteoblasts viability induced by a low dose of fluoride.

The Effect of Saliva on the Formation of KOH-Soluble Fluoride after Topical Application of Amine Fluoride Solutions of Varying Fluoride Concentration and pH

The effect of saliva on the amount of KOH-soluble fluoride formed on a sound enamelsurface after application of amine fluoride solution of varying fluoride concentrations (1, 0.5 and 0.25% F) and pH (5.3, 4.5 and 4.0) was examined in an in vitro study. The saliva pretreatment increased the amount of KOH-soluble fluoride at the highest pH value. For any given fluoride concentration, the presence of saliva did not influence the amount of KOH-soluble fluoride. These data suggest that saliva could enhance the amount of KOH-soluble fluoride if the topical fluoride preparations are not highly acid.

Combined Effects of Xylitol and a Low Concentration of Fluoride on Promotion of Remineralization of Human Enamel, an Experimental Study.

The purpose of this study is to evaluate the combined effects of xylitol and low concentrations of fluoride on the promotion of remineralization of human enamel. Demineralized enamel blocks were immersed in remineralizing solutions containing 10% xylitol and various concentrations of fluoride (0-1.2ppm). The remineralizing solution containing xylitol and fluoride was found to promote remineralization between 14 and 15 degrees of saturation with respect to fluoroapatite. Although both fluoride and xylitol are thought to promote remineralization, from this study, it can be suggested that for effective remineralization, the degree of saturation with respect to fluoroapatite should also be considered.

Fluoride intake in children living in a high‐fluoride area in Ethiopia – intake through beverages

The present study was conducted in Wonji Shoa, a sugar estate in the Ethiopian Rift Valley. Drinking water in the area is provided either by the Awash River or by high-fluoride ground water wells. Defluoridation plants have been installed, but are not in regular use, and fluorosis, dental as well as skeletal, is endemic. The aim of this study was to assess daily fluoride intake from drinking water and beverages in children from neighbouring villages with varying fluoride concentration in the drinking water. Thirty families were selected from two of the plantation villages (A and K). The criterion for being included in the project was the presence in the household of at least one child, fully weaned and below the age of 5 years. For sampling of beverages, the duplicate portion technique was used. The fluoride concentration in the beverage samples was determined using standard methods, using a fluoride ion-selective electrode. Ten of the selected households in Village A fetched water from the Awash River (1.8 mg F-/L) while five relied upon water from a local well (2.1 mg F-/L). All 15 households in Village K used water from a local well with fluoride concentration of 14.4 mg/L. The mean daily fluoride intake from drinking water and beverages during the four days, varied from 1.2 to 1.5 mg and 5.9 to 8.8 mg in Village A and K, respectively. Low variety in types of beverages consumed was reported both during the study period and through the questionnaire. Only local water was used for beverage preparation. Children who consumed milk had a reduced fluoride intake. Tea, which was part of the children's diet, was not found to be a main source of fluoride. A2n effective defluoridation of the drinking water or a change of water source would seem to be the only options for avoidance of dental and possibly skeletal fluorosis.

Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes.

The genetic toxicity of fluoride has been investigated extensively by various test systems. However, results obtained have been inconsistent. Fluoride has been reported to be non-genotoxic, genotoxic, and synergistic or antagonistic with certain mutagens. To date, there are no published human studies on the genotoxicity of fluoride. The purpose of this investigation was to determine genotoxic risks of long-term exposure to various concentrations of fluoride in drinking water in humans with normal or inadequate nutrition. Six groups of subjects with either normal or inadequate nutritional intakes were selected from areas of approximately 0.2, 1.0, or 4.8 ppm (10.5, 52.6, or 252.6 mumol/L) fluoride in water. The subjects had been continuous residents in the area for at least 35 years. Samples of drinking water, plasma, and urine were analyzed for fluoride content. Blood lymphocytes were examined to determine the frequency of sister chromatid exchange (SCE). Blood chemistry and electrolytes were also analyzed. The results showed that average daily fluoride intake as well as urine and plasma fluoride levels increased with increase in the fluoride content of the drinking water. The blood chemistry and electrolyte values were within the normal range for all populations, but several parameters were significantly different. While the numerical differences were small, the subjects with low fluoride in the water (0.11 and 0.23 ppm or 5.8 and 12.1 mumol/L) had significantly higher SCE frequencies than those with higher fluoride exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term effects of fluoride on biosynthesis of enamel-matrix proteins and dentine collagens and on mineralization during hamster tooth-germ development in organ culture

The effect of various concentrations of fluoride (F −) on cell proliferation, matrix formation and mineralization was examined in hamster molar tooth germs in premineralizing and mineralizing stages. The exposure lasted 16 h (mineralizing stages) and 24 h (premineralizing stages) and the F − levels ranged from 2.63 μM to 2.63 mM; [ 3H]-thymidine, [ 3H]-proline, 45Ca and 32PO 4 were used as markers for cell proliferation, matrix formation and mineralization, respectively. The proline-labelled amelogenins were isolated by sequential extraction with water and formic acid and their nature examined by SDS-urea-polyacrylamide electrophoresis. Digestion by collagenase was used to assess the amount of proline incorporated into collagens. F − in concentrations up to 1.31 mM inhibited neither biosynthesis of DNA and amelogenins, nor synthesis of collagens and their hydroxylation. Amelogenins extracted from F − induced, non-mineralizing enamel matrix had the same electrophoretic mobility and the same degree of phosphorylation as amelogenins from normal, mineralizing enamel. However, F − increased the uptake of 45Ca and TCA-soluble 32P dose-dependently, starting with 52 μM. Thus, interference with secretion of enamel matrix by F − takes place at much lower concentrations than required to inhibit biosynthesis of enamel matrix.

On the role of cyclic AMP in the cytotoxic effect of fluoride.

The possible role of adenosine 3',5'-monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl-cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP-formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP.