Genotoxic evaluation of chronic fluoride exposure: sister-chromatid exchange study

As part of a continuing investigation, this study was conducted to examine the genotoxic effects of chronic exposure to sodium fluoride (NaF) in drinking water on the frequency of sister-chromatid exchange (SCE) in the bone-marrow cells of male Chinese hamsters. Animals at about 3 weeks of age were randomly assigned to 6 groups, each with at least 3 hamsters, and were maintained on a low fluoride diet (less than 0.2 ppm F) throughout the experiment. At 4 weeks of age, the animals in groups I-V began to receive drinking water containing fluoride at concentrations of 0, 1, 10, 50 and 75 ppm, respectively. Group VI was treated with cyclophosphamide and served as the positive control. The animals were sacrificed at 24 weeks of age by cervical dislocation. The humeri and plasma were analyzed for fluoride content, which was found to increase with the increase in fluoride concentration in drinking water. Slides of chromosomes from bone-marrow cells were prepared and blindly examined for the frequency of SCE. The mean scores of SCE for the hamsters receiving drinking water containing F concentrations up to 75 ppm for 21 weeks ranged from 4.28 to 6.28 per cell, and were not significantly different from those of the negative controls (4.60-5.44/cell). The results indicated that chronic fluoride exposure had no effect on the frequency of SCE in Chinese hamster bone-marrow cells under the conditions of the present investigation.     

Effect of drinking waters of high fluorine content on the urinary fluoride level.

The urinary fluoride level has been studied in 307 subjects consuming drinking waters of different fluoride concentrations. The urinary fluoride level was found to increase with the fluoride content of the drinking water. The urinary F level of the population group drinking water of optimum fluoride concentration was 1.14 mg of fluoride per litre. Thus, in regions where the drinking water contains an insufficient amount of fluoride, the fluoride content of domestic salt must be adjusted so as to ensure an about 1.14 mg/litre urinary F level of the population.     

Fluoride and environmental health: a review

The relationship between environmental fluoride and human health has been studied for over 100 years by researchers from a wide variety of disciplines. Most scientists believe that small amounts of fluoride in the diet can help prevent dental caries and strengthen bones, but there are a number of adverse affects that chronic ingestion at high doses can have on human health, including dental fluorosis, skeletal fluorosis, increased rates of bone fractures, decreased birth rates, increased rates of urolithiasis (kidney stones), impaired thyroid function, and lower intelligence in children. Chronic occupational exposure to fluoride dust and gas is associated with higher rates of bladder cancer and variety of respiratory ailments. Acute fluoride toxicity and even death from the ingestion of sodium fluoride pesticides and dental products have also been reported. The distribution of fluoride in the natural environment is very uneven, largely a result of the geochemical behavior of this element. Fluorine is preferentially enriched in highly evolved magmas and hydrothermal solutions, which explains why high concentrations are often found in syenites, granitoid plutonic rocks, alkaline volcanic, and hydrothermal deposits. Fluoride can also occur in sedimentary formations that contain fluoride-bearing minerals derived from the parent rock, fluoride-rich clays, or fluorapatite. Dissolved fluoride levels are usually controlled by the solubility of fluorite (CaF₂); thus, high concentrations are often associated with soft, alkaline, and calcium-deficient waters. Although much is known about the occurrence and health effects of fluoride, problems persist in Third World countries, where populations have little choice in the source of their drinking water and food. However, even in developed nations, fluoride ingestion can exceed the recommended dose when sources other than drinking water are ignored.     

Variations in concentration of fluoride in blood plasma of pregnant women and their possible consequences for amelogenesis in a fetus

The aim of the study was to assess the fluoride exposure of pregnant women living in Poznan (Poland) by examination of fluoride levels in blood plasma.

The subjects of the study were 31 pregnant women aged 22–34 years in the course of regular pregnancy. Data concerning the sources of fluoride exposure such as diet, oral hygiene measures and topical application of fluoride procedures, were collected from each individual with a questionnaire. Samples of blood plasma were drawn in the 28th, 33rd week of pregnancy and during delivery. The analysis evaluating the fluoride concentration in the samples was carried out with the use of fluoride electrode ORION (model 96-09). The data were statistically analyzed using the program Statistica for Windows.

Mean value of fluoride concentration in the samples of blood plasma from the 28th week of pregnancy was lower than the mean concentration detected in the 33rd week of pregnancy (3.29 and 3.73 μmol/l, respectively). These values suggest that apart from drinking water, there were other important sources of fluoride in the examined sample.

The results indicate that a reliable assessment of fluoride exposure in a given population cannot be based solely on the concentration of fluoride in drinking water. Relatively high levels of fluoride in blood plasma of examined women suggest that there is no need for fluoride supplementation in this group of patients.     

Fluoride exposure and factors affecting dental caries in preschool children living in two areas with different natural levels of fluorides

BackgroundSuccessful oral health interventions must be based on the specific needs of the population that they serve. Evaluation of habits related to dental caries development and estimation of fluoride exposure in a target group of young patients helps to plan effective and safe caries prevention strategies.ObjectivesThe study aimed to evaluate factors affecting dental caries experience and sources of fluoride exposure in preschool children living in two areas: with optimal and low natural content of fluoride in drinking water.Materials and methodsThe study included a group of 73 children of both sexes aged 4–7 years attending two kindergartens in Środa Wielkopolska and Turek (Wielkopolska Voivodeship, Poland), where the content of fluoride in drinking water according to data obtained in the sanitary station ranged from 0.68 to 0.74 mg/L (optimal concentration of fluoride) and from 0.19 to 0.30 mg/L (low concentration of fluoride), respectively. Parents of patients completed a survey about diet, hygiene, and dental care, taking into account the child's fluoride exposure. The calibrated dentist assessed the oral health condition using a mirror, a CPI probe, and a headlamp. Oral hygiene was recorded using the Silness and Löe plaque index, caries experience by calculating the numbers of decayed, missing, and filled primary, and permanent teeth (dmf and DMF, respectively) while caries frequency by calculating the percentage of children with caries experience above 0. In order to assess the fluoride concentrations in urine and drinking water, parents were asked to provide a urine sample collected on fasting and a tap water sample. Fluoride concentrations were assessed using a 09–37 (MARAT) fluoride ion-selective electrode and a RAE 111 silver-chloride reference electrode. Statistical analysis was conducted using the data analysis software system Statistica (version 12, StatSoft, Inc. 2014), assuming a statistical significance level p < 0.05.ResultsNo statistically significant differences were found between caries indices of the examined children in each kindergarten (p > 0.05). Urinary fluoride levels were higher in children who tended to swallow toothpaste or used fluoride rinses and positively correlated with fluoride concentrations in the drinking water. Dental caries experience in the examined children depended on the effectiveness and frequency of oral hygiene procedures and dietary habits.ConclusionsThe strategy aimed at improving the oral health of the examined group of children should include accomplishing oral hygiene, promoting a non-cariogenic diet, and, finally, controlling fluoride exposure from at-home fluoride products. Caries prevention program ought to be adjusted to individual characteristics of each child, taking into consideration oral hygiene practices, dietary habits and total fluoride intake.     

Health-risk assessment related to the fluoride,nitrate, and nitrite in the drinking water in the Sanandaj,Kurdistan County,Iran

The concentration of fluoride and nitrate in groundwater is usually higher than that of surface water. The main objective of this study was to estimate the health-risk assessment associated with fluoride, nitrate, and nitrite in drinking water in Sanandaj and its villages. The number of samples in the Sanandaj and its rural was 106. The average concentration of fluoride in urban and rural drinking water was 0.22 mg/l and 0.27 mg/l, respectively. Fluoride concentration was also close to urban and rural drinking water. The concentration of nitrate in urban and rural drinking water was in the range between 0.28–27.77 mg/l and 1.28–80 mg/l, respectively. The concentration of nitrate reported in rural samples was higher than that of urban samples. The maximum concentration of nitrate reported in this study was 80 mg/l. The mean CDI for nitrate in the men, women, and children was 0.4258, 0.5110, and 1.1454, respectively. The findings of this study indicated that all three groups studied were exposed to nitrate contact hazards (HQ > 1). Therefore, the HQ in each of the three groups was higher than 1, which should be carefully monitored and necessary measures should be performed.     

Activity of pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication.

The aim of this work was to examine the effect of fluoride ions on antioxidative enzyme activity in the pancreas of rats exposed during 4 months to NaF in drinking water. The study was carried out in 30 four-week-old male Wistar FL rats, that were randomly assigned to three equal groups and given distilled water ad libitum for three weeks. Subsequently, two examined groups of animals were exposed to NaF in drinking water: group 1 (10 rats) at 50 mg F(-)/L (2.63 mmol/L), group 2 (10 rats) at 100 mg F(-)/L (5.26 mmol/L). The control group (10 rats) received distilled water. After 4 months the animals were anesthetized with ether prior to collection of pancreas and cardiac blood. Serum concentrations of glucose and fluoride, as well as activities of the cytoplasmic (CuZn-SOD) and the mitochondrial (Mn-SOD) superoxide dismutase, glutathione peroxidase (GSH-Px) and concentrations of malondialdehyde (MDA) in the homogenized pancreas were measured. The activity of CuZn-SOD was reduced by 50% and a tendency to lower activities of Mn-SOD was observed. No changes were noted in the activity of GSH-Px or concentrations of MDA. We conclude that: 1) the fluoride caused hyperglycemia in rats in this study is not accompanied by an activation of the free radical production in the pancreas; 2) the hyperglycemia in the exposed rats cannot be attributed to pancreatic damage caused by fluoride ions (the cause in this case appears to be extrapancreatic); 3) the inhibition of pancreatic CuZn-SOD is probably due to the direct action of fluoride on the enzyme.     

Association of Hypertension,Body Mass Index,and Waist Circumference with Fluoride Intake; Water Drinking in Residents of Fluoride Endemic Areas,Iran

Hypertension is becoming a global epidemic for both rural and urban populations; it is a major public health challenge in Iran. Fluoride can be a risk factor for hypertension. Cross-sectional analysis was conducted in two study areas to assess the relation of fluoride with blood pressure prevalence, BMI, waist circumference, and waist-to-hip ratio (WHR) among different age groups in both sexes. The mean value of fluoride concentration in the drinking water from the four study villages varied from 0.68 to 10.30 mg/L. The overall prevalence of HTN and prehypertension in all subjects was 40.7%. The prevalence of isolated systolic hypertension, isolated diastolic hypertension, systolic-diastolic hypertension, and prehypertension in the total sample population was 1.15, 0.28, 9.53, and 29.76%, respectively. The odd ratio of hypertension in residents who drank water with high fluoride levels was higher than that in residents who drank water with lower level of fluoride (OR 2.3, 1.03–5.14). Logistic regression results showed that age (P?<?0.001), sex (P?=?0.018), BMI (P?=?0.015), and the fluoride level in drinking water (P?=?0.041) had a significant relationship with increased blood pressure. There were no statistically significant correlations between fluoride and BMI, hip circumference, and waist to hip ratio (WHR). The findings of this study are important for health care personnel and policymakers.     

Bone age of children in 2 communities in Hungary with different fluoride levels in the drinking water

The adverse effects of ingested fluoride were investigated. The bone-age of children consuming drinking water containing optimum (about 1 mg/l) fluoride concentration with regard to caries prophylaxis was compared with the bone-age of those consuming drinking water containing low (0.14-0.26 mg/l) fluoride concentration. The examinations were conducted on 7-14-year old Hungarian children. The bone-age was determined by the TW2 method. No significant difference was found between the bone-age of the children belonging to the group consuming water with optimum fluoride concentration and those in the other group consuming water with low fluoride concentration.     

Bone-fracture incidence rate in two Italian regions with different fluoride concentration levels in drinking water.

The effect of the fluoride concentration in drinking water on the prevention of fractures related to osteoporosis has been questioned or contradicted in several recent studies. These studies have been mostly performed using water with artificially added fluoride, at the optimum level of about 1 mg/l. In the present study authors have investigated the effect of equal or greater fluoride concentrations (mean 1.45 mg/l) naturally present in waters supplied for human consumption to a population of 72.756 (Bracciano county), in comparison with a population of 126.189 (Avezzano county), supplied with low fluoride concentration water (mean 0.05 mg/l). The incidence of fractures in the years 1990 and 1991 was evaluated in the two areas (Bracciano and Avezzano), which are located in central Italy and where population have a similar life style, economic and social level and employment structure. The incidence data were obtained from the registers of the public hospital taken as a reference in each district. The authors noticed a significantly greater rate of fracture incidence at several parts of the body, in particular femur fractures (relative risks for males 4.28 and for females 2.64), in the population of the district of Avezzano than in the population of Bracciano. The greater concentration of fluoride in waters distributed for human consumption in Bracciano district seems to have the effect of protecting its inhabitants against fractures.     

Safety Evaluation of Fluoride Content in Tea Infusions Consumed in the Azores—a Volcanic Region with Water Springs naturally Enriched in Fluoride

Tea is the second most commonly consumed beverage in the world. It is well recognized that the consumption of tea in high quantities can promote the development of fluorosis. The main objective of this study is to estimate the exposure to fluoride in the Azores through drinking tea prepared with water from different volcanic locations, by i) investigating the fluoride (F) content of various commercial brands of tea (Camellia sinensis) marketed in Azores and ii) comparing tea releasing rates of F according to brewing time, considering the fluoride concentration in the different types of water used for the infusion. Fluoride contents were determined by ion-selective electrode in 30 samples of drinking water from three different locations and in 450 samples of tea (black and green tea) from three different brands. Fluoride concentration in water ranged from 0.29 to 1.56 ppm (Porto Formoso and Sete Cidades village, respectively). Fluoride concentrations increased with brewing time, reaching the highest values in the Azorean black and green tea infusions. For all the studied brands, a negative correlation was found between tea fluoride contents and the pH of the water used to prepare the infusion. Fluoride concentration in infusions was significantly associated with the background fluoride concentration in drinking water. Since the fluoride concentration in groundwater varies accordingly to the geological conditions and tea consumption can contribute to fluoride intake, it is important to define the limits for tea consumption, particularly in fluoride-rich areas.

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Graphical Abstract Fluoride concentrations in black and green tea for 3 minutes of brewing time and, association between fluoride concentration and pH with brewing time

     

Effect of fluorine on heart arrhythmias in rats

The antiarrhythmic activity of fluoride was studied in a model of CaCL2-induced heart arrhythmias in male albino rats. The prolonged intake of sodium fluoride with drinking water (2 mg/l for 1 month) significantly reduced the severity of arrhythmias that was evident as an increase in the latency and a decrease in the frequency and duration of arrhythmias. A less pronounced effect was noted when the concentration of sodium fluoride was increased to 5 mg/l. At larger concentrations (11 mg/l) the fluoride exerted a toxic effect and potentiated the arrhythmogenic action of CACL2. The antiarrhythmic action of fluoride in low concentrations may be associated with the blockade of an inward Ca current.     

Effect of Fluoridated Water on Plasma Insulin Levels and Glucose Homeostasis in Rats with Renal Deficiency

Glucose intolerance in fluorosis areas and when fluoride is administered for the treatment of osteoporosis has been reported. Controlled fluoridation of drinking water is regarded as a safe and effective measure to control dental caries. However, the effect on glucose homeostasis was not studied so far. The aim of this study was to evaluate the effect of the intake of fluoridated water supply on glucose metabolism in rats with normal and deficient renal function. Male Sprague–Dawley rats were divided into eight groups of four rats. Renal insufficiency was induced in four groups (NX) which received drinking water containing 0, 1, 5, and 15 ppm F (NaF) for 60 days. Four groups with simulated surgery acted as controls. There were no differences in plasma glucose concentration after a glucose tolerance test between controls and NX rats and among rats with different intakes of fluoride. However, plasma insulin level increased as a function of fluoride concentration in drinking water, both in controls and in NX rats. It is concluded that the consumption of fluoridated water from water supply did not affect plasma glucose levels even in cases of animals with renal disease. However, a resistance to insulin action was demonstrated     

Effect of Fluoride on Insulin Level of Rats and Insulin Receptor Expression in the MC3T3-E1 Cells

Studies on the role of insulin and insulin receptor (InsR) in the process of skeletal fluorosis, especially in osteogenic function, are rare. We evaluated the effect of increasing F^? doses on the marker of bone formation, serum insulin level and pancreatic secretion changes in vivo and mRNA expression of InsR and osteocalcin (OCN) in vitro. Wistar rats (n?=?50) were divided into two groups, i.e. a control group and fluoride group. The fluoride groups were treated with fluoride by drinking tap water containing 100?mg?F^?/L. The fluoride ion-selective electrode measured the fluoride concentrations of femurs. The alkaline phosphatase (ALP), OCN, insulin and glucagon of serum were tested to observe the effect of fluoride action on them. Meantime, the pancreas pathological morphometry analysis via ?? cells stained by aldehyde fuchsin showed the action of fluoride on pancreas secretion. MC3T3-E1 cells (derived from newborn mouse calvaria) were exposed to varying concentrations and periods of fluoride. The mRNA expression of InsR and OCN was quantified with real-time PCR. Results showed that 1-year fluoride treatment obviously stimulated ALP activity and OCN level along with increase of bone fluoride concentration of rats, which indicated that fluoride obviously stimulated osteogenic action of rats. In vitro study, the dual effect of fluoride on osteoblast function is shown. On the other hand, there was a significant increase of serum insulin level and a general decrease of glucagon level, and the histomorphometry analysis indicated an elevated insulin-positive area and increase in islet size in rats treated with fluoride for 1?year. In addition, fluoride obviously facilitated the mRNA expression of InsR in vitro. To sum up, there existed a close relationship between insulin secretion and fluoride treatment. The insulin signal pathway might be involved in the underlying occurrence or development of skeletal fluorosis.     

Effect of Fluoride Exposure on Serum Glycoprotein Pattern and Sialic Acid Level in Rabbits

This study describes the effects of fluoride exposure on the protein profile, glycoprotein pattern, and total sialic acid concentration of serum in rabbits. For this aim; 20 healthy New Zealand rabbits were used. The rabbits were divided into two equal groups each with ten animals according to their weighing: control group and experimental group. The rabbits in control group were given drinking tap water containing 0.29 mg/l sodium fluoride and experimental group received the same tap water to which was added 40 mg/l sodium fluoride for 70 days. Blood samples were taken from each rabbit on day 70. Serum fluoride concentrations were measured by a fluoride-specific ion electrode in serum. The fluoride levels in the serum were found as 18.4 (±1.58) μg/L in control and 301.3 (±52.18) μg/L in fluoride exposed rabbits. The sialic acid levels were found as 69.2 (±0.32) mg/dL in control and 43.4 (±0.13) mg/dL in fluoride exposed group. The electrophoretic patterns of serum proteins, glycoproteins, and total sialic acid concentration were determined. Fifteen different protein fractions with molecular weights ranging from 22 to 249 kDa were displayed in the serum protein electrophoretic gel of both groups. The raw concentrations of the protein fractions decreased in fluoride exposed rabbits as compared with the control rabbits. The serum glycoprotein pattern revealed seven major protein bands from 47 to 167 kDa in experimental and control groups. The slight decrease of raw concentration of the protein bands in glycoprotein pattern of serum was observed in fluoride toxication comparing to control. The results suggest that serum TSA determination and serum protein electrophoresis can be used to evaluate prognosis of fluoride exposure as a supplementary laboratory test in combination with clinical and other laboratory findings of fluorosis.     

Fluoride-induced lesions in the teeth of the short-tailed field vole (Microtus agrestis): A description of the dental pathology

The effect of fluoride on the appearance of the teeth of the short-tailed field vole. Microtus agrestis, was investigated in both wild animals collected from field sites affected by different levels of industrial fluoride contamination and laboratory-reared animals consuming experimental grass diets of known fluoride concentration or with known fluoride concentrations in drinking water. The extent and severity of lesions on the surface and structure of both incisors and molars are described as six lesion types and related to the amount of biologically available orally ingested fluoride. In the incisors of voles consuming relatively low fluoride diets, lesions are mainly confined to those resulting from disruption of enamel pigmentation expressing itself as concentric bands of pigmentation-free areas on incisor surfaces. The visible effects on molars at low fluoride levels are confined to minor alterations in surface appearance. At higher levels of available dietary fluoride, effects on enamel pigmentation are superseded by alterations in the formation, composition, and strength of both enamel and dentine. The incisors exhibit a marked to severe increase in the cutting tip erosion rates with comparable increases in the extent of abnormal surface changes (enamel hypoplasia) and loss of enamel pigmentation. The grinding surfaces of molars from animals exposed to high levels of dietary fluoride exhibit increasingly severe erosion of outer enamel regions, combined with cavitation and staining of the exposed central dentine. The mechanisms through which fluoride elicits increasingly visible and pathological alterations to the surface and subsurfaces of rodent teeth are discussed. J Morphol 232: 155–167, 1997. © 1997 Wiley-Liss, Inc.     

Spatial distribution and seasonal variation in fluoride enrichment in groundwater and its associated human health risk assessment in Telangana State,South India

Groundwater is a vital source of drinking water in Siddipet rural and urban regions of Central Telangana, South India and it is a major cause of fluoride toxicity in humans. The intake of elevated fluoride has a significant impact on human health, especially immediate problems that are seen in children's teeth. The primary aim of the study was to identify the seasonal variation in fluoride concentration and associated health risks in the residents of the study region. To assess the fluoride contamination in groundwater, a total of 158 samples were analyzed in two seasons. The mean concentrations of fluoride 1.26 mg/L and 2.21 mg/L were 1.46 and 2.8 times higher than the acceptable limit of 1.5 mg/L, before and after monsoon respectively. To estimate the human health risks due to the ingestion of elevated fluoride through drinking water, hazard quotient fluoride (HQ_Fluoride) was calculated using the United States Environmental Protection Agency method. HQ_Fluoride values were 0.44–2.44 and 0.89–4.67 for children, 0.36–2.00 and 0.73–3.82 for females, and 0.41–2.26 and 0.82–4.31 for males in pre- and post-monsoon seasons respectively, suggesting emphatically greater risk than the acceptable limits (HQ_Fluoride > 1), which generates health risks.     

Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice

Arsenic and fluoride are potent toxicants, widely distributed through drinking water and food and often result in adverse health effects. The present study examined the effects of sodium meta-arsenite (100 mg/l in drinking water) and sodium fluoride (5 mg/kg, oral, once daily), administered either alone or in combination for 8 weeks, on various biochemical variables indicative of tissue oxidative stress and cell injury in Swiss albino male mice. A separate group was first exposed to arsenic for 4 weeks followed by 4 weeks of fluoride exposure. Exposure to arsenic or fluoride led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by increased level of blood and tissues reactive oxygen species (ROS) level. An increase in the level of liver and kidney thiobarbituric acid reactive substance (TBARS) along with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and reduced GSH content were observed in both arsenic and fluoride administered mice. The changes were significantly more pronounced in arsenic exposed animals than in fluoride. It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone. In some cases antagonistic effects were noted following co-exposure to arsenic and fluoride. Arsenic and fluoride concentration increased significantly on exposure. Interestingly, their concentration decreased significantly on concomitant exposure for 8 weeks. However, the group which was administered arsenic for 4 weeks followed by 4 weeks of fluoride administration showed no such protection suggesting that the antagonistic effect of fluoride on arsenic or vice versa is possible only during interaction at the gastro intestinal sites. These results are new and interesting and require further exploration.     

Exposure to Fluoride in Drinking Water and Hip Fracture Risk: A Meta-Analysis of Observational Studies

BackgroundMany observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk.MethodsPubMed and EMBASE databases were searched to identify relevant observational studies from the time of inception until March 2014 without restrictions. Data from the included studies were extracted and analyzed by two authors. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Finally, publication bias was assessed.ResultsFourteen observational studies involving thirteen cohort studies and one case-control study were included in the meta-analysis. Exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs, 1.05; 95% CIs, 0.96–1.15). Sensitivity analyses based on adjustment for covariates, effect measure, country, sex, sample size, quality of Newcastle–Ottawa Scale scores, and follow-up period validated the strength of the results. Meta-regression showed that country, gender, quality of Newcastle–Ottawa Scale scores, adjustment for covariates and sample size were not sources of heterogeneity. Little evidence of publication bias was observed.ConclusionThe present meta-analysis suggests that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture. Given the potential confounding factors and exposure misclassification, further large-scale, high-quality studies are needed to evaluate the association between exposure to fluoride in drinking water and hip fracture risk.     

Influence of Methionine and Vitamin E on Fluoride Concentration in Bones and Teeth of Rats Exposed to Sodium Fluoride in Drinking Water

Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. This study evaluates the influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats subjected to long-term exposure to sodium fluoride in drinking water. The study was conducted in 30 3-month-old female Wistar FL rats. The animals were divided into five groups, six rats per group. The control group consisted of rats receiving only distilled water as drinking water. All other groups received NaF in the amount of 10 mg/kg of body mass/day in their drinking water. In addition, respective animal groups received: NaF + Met group—10 mg of methionine/kg of body mass/day, NaF + Met + E group—10 mg of methionine/kg of body mass/day and 3 mg of vitamin E (tocopheroli acetas)/rat/day and NaF + E group—3 mg of vitamin E/rat/day. Femoral bones and incisor teeth were collected for the study, and the fluoride concentration was determined using a fluoride ion-selective electrode. Fluoride concentration in both bones and teeth was found to be higher in the NaF and NaF + Met groups compared to the control group. In groups NaF + Met + E and NaF + E, the study material contained much lower fluoride concentration compared to the NaF group, while the effect was more prominent in the NaF + E group. The results of the studies indicate that methionine and vitamin E have opposite effects on accumulation of fluorides in hard tissue in rats. By stimulating fluoride accumulation, methionine reduces the adverse effect of fluorides on soft tissue, while vitamin E, which prevents excessive accumulation of fluorides in bones and teeth, protects these tissues from fluorosis. Therefore, it seems that combined application of both compounds would be optimal for the prevention of the adverse effects of chronic fluoride intoxication.