Review of Fluoride Intake and Appropriateness of Current Guidelines.

Since the classical epidemiological studies by Dean, it has been known that there should be an optimum level of exposure to fluoride that would be able to provide the maximum protection against caries, with minimum dental fluorosis. The "optimal" daily intake of fluoride for children (0.05-0.07 mg per kilogram bodyweight) that is still accepted worldwide was empirically determined. In the present review, we discuss the appropriateness of the current guidance for fluoride intake, in light of the windows of susceptibility to caries and fluorosis, the modern trends of fluoride intake from multiple sources, individual variations in fluoride metabolism, and recent epidemiological data. The main conclusion is that it is very difficult to think about a strict recommendation for an "optimal" range of fluoride intake at the individual level in light of existing knowledge of 1) the mechanisms of action of fluoride to control caries, 2) the mechanisms involved in dental fluorosis development, 3) the distinct factors that interfere in the metabolism of fluoride, and 4) the windows of susceptibility to both dental caries and fluorosis development. An "optimal" range of fluoride intake is, however, desirable at the population level to guide programs of community fluoridation, but further research is necessary to provide additional support for future decisions on guidance in this area. This list includes the effect of factors affecting fluoride metabolism, clinical trials on the effectiveness of low-fluoride dentifrices to prevent caries in the primary dentition, and validation of biomarkers of exposure to fluoride.

Current Guidance for Fluoride Intake: Is It Appropriate?

The purpose of this report is to examine critically the appropriateness of the current guidance for fluoride intake in the population (0.05-0.07 mg F/kg bodyweight/d), consider whether changes to the current guidance are desirable, and suggest further research that will strengthen the evidence base for future decisions on guidance/advice in this area. The benefits and the risks of using fluoride particularly concern preschool children because it is at this age that excessive fluoride intake may result in dental fluorosis. Data from mostly cross-sectional studies show a wide variation in exposure and a considerable variation in the amount of fluoride ingested. Fluorosis, mostly mild, is commonly observed. For considering changes in current guidance, there is a need for more knowledge on the relationship between exposure to fluoride at an early age and the development of fluorosis. For that, prospective epidemiological studies with sufficiently large and representative samples of children are required. It is also important to study children in communities both with and without water fluoridation and to include populations where salt or milk fluoridation is used. There is also a need for professional agreement on acceptable levels of mild and moderate/severe fluorosis and a more comprehensive knowledge on the appreciation of mild fluorosis among the public.

Prevention & control of fluorosis & linked disorders: Developments in the 21st Century - Reaching out to patients in the community & hospital settings for recovery.

The review on fluorosis addresses the genesis of the disease, diagnostic protocols developed, mitigation and recovery through nutritional interventions. It reveals the structural and functional damages caused to skeletal muscle and erythrocytes, leading to clinical manifestations in fluorosis. Hormonal derangements resulting in serious abnormalities in the health of children and adults are discussed. Fluoride toxicity destroys the probiotics in the gut, resulting in vitamin B12depletion, an essential ingredient in haemoglobin (Hb) biosynthesis. The article provides an overview of National Technology Mission on Safe Drinking Water and its contributions to fluorosis control. National Programme for Prevention and Control of Fluorosis is presently in operation in India and its focus cited. Major emphasis has been laid on a variety of disorders surfacing in India due to fluoride toxicity/fluorosis as 'fluorosis-linked disorders', viz. anaemia in pregnancy, schoolchildren, thyroid hormone abnormalities, hypertension, iodine deficiency disorders/goitre, renal failure and calcium+vitamin D-resistant rickets in children. The major action taken by the Indian Council of Medical Research (ICMR), Government of India in establishing a Centre of Excellence for Fluorosis Research in India and its contributions are highlighted.

Management of a Rare Case With Severe Hydrofluoric Acid Burns: Important Roles of Neutralizers and Continuous Renal Replacement Therapy.

Hydrofluoric acid (HF), a dangerous inorganic acid, is widely used in various industries and in daily life. Chemical burns caused by HF exposure occur more frequently in some regions worldwide. It has been reported that some cases with HF burns can be lethal due to the hypertoxicity of HF. In this article, we present a case of a 24-year-old worker who suffered HF burns by 53% HF solution to his face, neck, and nasal cavity. This patient quickly developed electrolyte disturbance, that is, hypocalcemia, and hypopotassemia, and myocardial injury after exposure. Multiple measures had been taken to treat this patient, including fluid resuscitation, electrolyte replacement, timely wound treatment with neutralizers, and respiratory tract care. Moreover, continuous renal replacement therapy was also employed to remove fluoride in the circulatory system and rectify the electrolyte disturbance and acid-base imbalance. The patient smoothly pulled though and survived. High fluoride levels in the dialysate solution were confirmed, indicating that continuous renal replacement therapy is an effective and potentially lifesaving treatment for acute HF poisoning.

Dietary Fluoride Intake and Associated Skeletal and Dental Fluorosis in School Age Children in Rural Ethiopian Rift Valley.

An observational study was conducted to determine dietary fluoride intake, diet, and prevalence of dental and skeletal fluorosis of school age children in three fluorosis endemic districts of the Ethiopian Rift Valley having similar concentrations of fluoride (F) in drinking water (~5 mg F/L). The duplicate plate method was used to collect foods consumed by children over 24 h from 20 households in each community (n = 60) and the foods, along with water and beverages, were analyzed for fluoride (F) content. Prevalence of dental and skeletal fluorosis was determined using presence of clinical symptoms in children (n = 220). Daily dietary fluoride intake was at or above tolerable upper intake level (UL) of 10 mg F/day and the dietary sources (water, prepared food and beverages) all contributed to the daily fluoride burden. Urinary fluoride in children from Fentale and Adamitulu was almost twice (>5 mg/L) the concentration found in urine from children from Alaba, where rain water harvesting was most common. Severe and moderate dental fluorosis was found in Alaba and Adamitulu, the highest severity and prevalence being in the latter district where staple foods were lowest in calcium. Children in all three areas showed evidence of both skeletal and non-skeletal fluorosis. Our data support the hypothesis that intake of calcium rich foods in addition to using rain water for household consumption and preparation of food, may help in reducing risk of fluorosis in Ethiopia, but prospective studies are needed.

Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers.

[THE RISK OF THE DEVELOPMENT OF OCCUPATIONAL CHRONIC FLUORIDE POISONING].

On the basis of individual occupational fluoride loads (IOFN) it was established that under current levels of air pollution of the working area by fluorine compounds, occupational fluorosis can occur in mostly sensitive workers with 66 or more years of accumulated period of work, while the most vulnerable are workers with of 9.4 or more years of accumulated period of work. The results obtained in comparison of clinical data with individual fluoride load, testify that in the high-risk group for the development of occupational fluoride intoxication include workers with an average accumulated period of work of 10.5 years or more and Individual Occupational Fluoride Load (IOFL) as 67,7 or more grams. In the high-risk group there are included workers with an average accumulated period ofwork of 13.7 years and IOFL as 89.8 grams or more. With the use of ultrasound densitometry there was revealed a clear cut dynamics of the increase of the speed of ultrasonic wave with the rise in the accumulated period of work at the plant, which indicates to a gradual increase in bone tissue density.

[Clinical and pathogenetic aspects of the chronic occupational intoxication with fluorine compounds in modern reality].

Multi-year follow-up of 358 workers of aluminum pot rooms, including 165 individuals suffering from fluorosis, has shown significant changes in the clinical picture of the chronic occupational fluorine intoxication, developed under modern conditions of production, at lower concentrations of fluorine compounds in the air of working area. In this connection, the pathology of the musculoskeletal system plays the dominating role in this clinical picture and has the large variability of combinations of the individual sections destructions of the bone tissue. The main criterion to establish the phase of the disease is still the number and severity of the signs of this destruction. The visceral pathology in contemporary production circumstances is registered with less frequency and loses a number of the previously described clinical manifestations, however, is still of some importance to identify the early signs of the disease and to prevent the dental fluorosis on time.

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.

Effect of fluoride on calcium ion concentration and expression of nuclear transcription factor kappa-B ρ65 in rat hippocampus.

The study investigated the neurotoxicity of drinking water fluorosis in rat hippocampus. Just weaning male Sprague-Dawley (SD) rats were given 15, 30, 60 mg/L NaF solution and tap water for 9 months. The calcium ion concentration ([Ca(2+)]) in synaptosomes was measured by double wavelength fluorescence spectrophotometer and the expression level of nuclear transcription factor kappa-B ρ65 (NF-κB ρ65) in hippocampal CA3 region was measured by immunohistochemistry. The results showed that [Ca(2+)] significantly increased (F = 33.218, P < 0.01) in moderate fluoride group compared with the control group, and the expression level of NF-κB ρ65 in CA3 region presented an increasing trend as fluoride concentration increased. These results indicate that increase of synaptosomes [Ca(2+)] and NF-κB ρ65 expression level may be the molecular basis of central nervous system damage caused by chronic fluoride intoxication. NF-κB ρ65 in CA3 region is probably a target molecule for fluorosis.

Percepción de ingesta de flúor a través del cepillado dental en niños colombianos / Perception of fluoride ingestion by dental brushing in Colombian children

Objetivo: describir la percepción de los padres sobre la ingesta de flúor a través del cepillado dental en los niños residentes en la ciudad de Cartagena de Indias, Colombia. Métodos: el universo del estudio lo constituyeron todos los padres residentes en la ciudad de Cartagena de Indias, con hijos en edades entre uno y cinco años. La muestra estuvo integrada por 420 individuos. Se utilizó un cuestionario estructurado, diligenciado por los participantes, con el cual se midieron tópicos relacionados con el uso de las cremas dentales a través del cepillado. Además se tuvieron en cuenta la edad, el género y el estrato socioeconómico. Los datos fueron analizados a través de pruebas de frecuencia; se asumieron intervalos de confianza al 95 por ciento. Para encontrar significación estadística se utilizó la prueba de X². Resultados: el 88,0 por ciento de los padres encuestados refiere usar el cepillado con crema dental. La edad promedio de cepillado es de 2,3 años (DE= 1,6). El 46 por ciento se cepilla dos veces al día; el tipo de crema dental más usada es la de adultos. La mayoría de los encuestados afirma que los niños han ingerido la pasta durante el cepillado. Con respecto al análisis bivariado, se encontraron diferencias entre el cepillado con crema dental y la edad (p= 0,0001), y con el estrato (p= 0,04). Además, el tipo de crema dental con la edad, (p= 0,0001) y la cantidad de pasta utilizada con la edad (p= 0,0001) y el estrato (p= 0,01). Conclusión: se perciben hábitos poco favorables, asociados al cepillado con pasta dental, los cuales pueden ser responsables de la ingestión de cantidades de flúor consideradas nocivas para la salud(AU)

Objective: To describe the parents perception on the fluoride ingestion with the use of dental brushing in the children residents in the city of Cartagena de Indias. Methods: Study universe included al parents residents in the city above mentioned whose children were aged 1-5. Sample included 420 subjects. A structural questionnaire was used headed by the participants allowing measurement of clichés related to the use of toothpastes ans brushes. Also, the gender and the socioeconomic status were took into account. Data were analyzed by frequency tests with 95 percent CI. For statistical significance we used the X2. Results: The 88 percent of parents polled refers on the use of toothpaste brushing. Mean age of brushing is of 2.3 years (SD= 1.6). The 46 percent use toothbrush twice a day, the more used toothpaste is that of adult persons. Most of polled confirms that children has ingested the toothpaste during brushing. Regarding the bivariant analysis there were differences between he brushing with toothpaste and the age (p= 0.0001) and with stratus (p= 0.04). Also, the type of toothpaste with age (p= 0.0001) and the quantity of toothpaste used according to age (p= 0.0001) and the stratum (p= 0.01). Conclusions: On note not much favourable associated with toothpaste brushing, which may account for ingestion of significant amounts of fluoride harmful for health(AU)

Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells.

Our proteomical analysis of osteoblasts exposed to fluoride revealed a distinctive upregulation of proteins in osteoblast. These upregulated proteins play key roles in the protein folding. The PRK-like ER kinase (PERK) signaling, one branch of unfolded protein response (UPR) to combat ER stress, is a transcription factor needed for osteoblast proliferation and differentiation. The mechanism of skeletal fluorosis by which fluoride regulates osteoblast is not fully defined. Here we studied the effect of fluoride on PERK signaling genes and x-box binding protein 1 (xbp-1) in OS7232 cells (human osteoblast-like cell line). Meantime, genes associated with bone turnover were examined in this study. We found that early and continuous fluoride exposure increased the binding immunoglobulin protein (BiP) expression and activated the PERK signaling pathway, resulting in activation of transcription factor 4 (ATF4) and nuclear factor erythroid 2-related factor 2 (Nrf2). The altered expression of cbfa1, osteoprotegerin (OPG)/nuclear factor kappa B ligand (RANKL) were viewed in this study. These results showed fluoride impelled a distinctive ER stress response in OS732 cells, primarily by activating PERK and PERK-dependent signaling. Little effects were viewed for activating xbp-1, a common target of the other two canonical sensors of ER stress, ATF6 and IRE1. In this study the altered expression of bone turnover genes were consistent with activation of ER stress and PERK signaling. This study proved that PERK signaling play major roles in action of fluoride on osteoblast, and suggested that bone response in skeletal fluorosis may be due in part to PERK signaling pathway.

Selenium increases expression of HSP70 and antioxidant enzymes to lessen oxidative damage in Fincoal-type fluorosis.

Fincoal type fluorosis has only been reported from China, but its pathogenesis is unclear. Many people believe that fluorosis is associated with oxidative stress. Oxidative stress can be reduced at higher selenium (Se) level. Heat shock protein (HSP70) is the most conserved and induced against different stressors. The aim of this study is to detect the expression of HSP70 in fluorosis patients and explore the role of Se in fluorosis protection. The subjects were divided into four groups: "High Se + F group" (n = 50), "High F group" (n = 50), "High Se group" (n = 20) and "Control group" (n = 46). Expression of HSP70 was evaluated by Western blotting and real-time PCR techniques. The concentration of fluoride, content of Se in hair, activity of antioxidant enzymes (GSH-Px, SOD, CAT) and content of malondialdehyde (MDA) were determined. The relative amount of HSP70 gene transcription was significantly higher in "High Se + F group" than the other groups. The same results were found for expression of HSP70 protein to beta-actin ratio. There was a significant difference between "High Se + F group" and "High F group" regarding MDA content and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activity. These results suggest that oxidative stress plays an important role in the pathogenesis of the Fincoal type fluorosis and it can be reduced at higher Se level.

Systemic fluoride poisoning and death from inhalational exposure to sulfuryl fluoride.

We report a poisoning death from inhalational exposure to the gas fumigants chloropicrin and sulfuryl fluoride. The patient displayed both local irritant effects of chloropicrin and systemic effects of sulfuryl fluoride. The clinical course, marked by initial hypocalcemia, delayed onset of ventricular dysrhythmias, and death, is consistent with fluoride being the predominant mechanism of toxicity with sulfuryl fluoride.

[Justifying the use of primary tissue culture method for evaluation of sodium fluoride safety in nutrition products].

Toxicity of sodium fluoride added to nutrition products is assessed through peculiarities of kidney tissue culture growth in vitro--over 75% inhibition of cell clumps growth supports high toxic influence of sodium fluoride, the growth decrease from 63% to 74% signifies lower degree, the growth inhibition less than 62% demonstrates very low toxicity of the chemical.

[Contrast analysis on two air fluorine content measurement methods].

OBJECTIVE: To take the two kinds of sampling and measurement methods of air fluorine content in the endemic fluorosis area to carry on the comparison, understanding their difference and inside relation. METHODS: Sampled 22 households random on the scene in the disease area with two samplers by two methods, at the position of which, at the same time, equidistance, same highness, as close as possible, but not produce interactive effect, to collect 34 of the air sample, and then gained the results by their respective methods of laboratory analysis and statistical analysis. RESULTS: The test of significance between two methods was P > 0.05, the coefficient of correlation was r = 0.7752, the test of significance was P < 0.01, the equation of linear regression between the GB method (X) and the manual method (Y) was Y = 1.1623X + 0.0008, the test of significance of coefficient of regression was P < 0.01. CONCLUSION: Two kinds of methods had no significant differences. They preset the medium degree positive correlation and a linear regression. The air fluoride in different granularity of suspended particles was not the same. The GB method was more applicable to research of synthesis damage towards the exposing crowd in burning coal fluorine, and manual method was more applicable to research of the damage resulting from the exposing crowd in burning coal fluorine through the breath system. Generally speaking, the results of the manual method was higher than the GB method.

[Current trends in fluorine research]. / Aktualne kierunki badaan nad fluorem.

PURPOSE: Current topics in fluorine research are presented with emphasis on findings by researchers in Szczecin and Poland, as well as in the world. Reports are cited on the distribution of fluorine compounds in the environment, routes of penetration into living organisms, and analytical methods for the quantitative determinations of fluorine content in air, water, soil, and foods. Important contributions have been made by Polish researchers on the role and patterns of fluorides in body fluids, soft and hard tissues, which remain in direct relationship to accumulation and elimination of fluorine. So far, comprehensive studies on mutagenic effects of fluorine and its potential role in bone neoplasms, Down syndrome, and other genetic disorders have not been carried out in Poland. Worthy of mention are reports on mechanisms of action of fluorine compounds on the cellular and subcellular level. CONCLUSIONS: Finally, two achievements of recent years in the field of fluorine research are discussed briefly. The first is concerned with the use in dentistry of chemical analysis for studying mineral reconstruction of teeth throughout the lifetime of an individual. The second is in the field of medicine where molecular modeling has been applied to explain the mechanism of action of aluminofluoride complexes (AlFx) as a messenger of false information during protein biosynthesis and their apparent role in the etiology of Alzheimer's disease.

Fluoride poisoning: a puzzle with hidden pieces.

Key industry data regarding harm from chronically inhaled fluoride have been unavailable publicly for decades. Recent unveiling of unpublished reports reveals three examples of data mishandling that disguised the need for more stringent occupational standards for particulate and gaseous fluorides and fluorine. Injury reports from workers handling chemicals show that unjustifiable reductions of injury and disability numbers in the process of publication shifted concern from respiratory to mineralized tissue damage. Selective editing and data omissions allowed bias that fluoride reduces caries without detrimental effects. Finally, industry's failure to publish an important industry-funded laboratory study buried knowledge of low thresholds for fluoride-induced lung disease. Data from that study are presented to clarify the dose- and duration-dependent changes caused by chronic inhalation of calcium fluoride.

Controlling the fluoride dosage in a patient with compromised salivary function.

BACKGROUND: High-concentration topical fluorides are used commonly to with compromised salivary function due to irradiation and chemotherapy. CASE DESCRIPTION: The authors describe a 50-year-old man with previously treated cancer who was using tray-applied topical fluoride gel. He complained of gastric symptoms, difficulty in swallowing, leg muscle soreness and knee joint soreness. A computed tomographic scan revealed thickening of the esophageal walls. An upper endoscopy revealed abnormal motility. The motility test indicated high-amplitude peristalsis and hypertensive lower esophageal sphincter, and urine testing indicated high levels of systemic fluoride. The patient's fluoride regimen was altered, and within a short period his urinary fluoride levels returned to normal and his symptoms resolved. CLINICAL IMPLICATIONS: Clinicians prescribing home-applied high-concentration fluorides need to be cognizant of the symptoms of fluoride toxicity, carefully monitor the patient's compliance with the treatment regimen, and adjust the dosage or mode of application to control the total ingested dose of fluoride.