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Chronic exposure to excessive environmental fluoride has caused fluorosis to become a major public health problem worldwide. Although studies on stress pathways, signaling pathways, and apoptosis induced by fluoride have provided an in-depth understanding of the mechanism of this disease, its exact pathogenesis remains unclear. We hypothesized that the human gut microbiota and metabolome are associated with the pathogenesis of this disease. To get further insight into the profiles of intestinal microbiota and metabolome in coal-burning-induced endemic fluorosis patients, we conducted 16S rRNA sequencing of the intestinal microbial DNA and carried out non-targeted metabolomics of fecal samples from 32 patients with skeletal fluorosis and 33 matched healthy controls in Guizhou, China. We found that the gut microbiota of coal-burning endemic fluorosis patients displayed significant differences in composition, diversity, and abundance compared with healthy controls. This was characterized by an increase in the relative abundance of Verrucomicrobiota, Desulfobacterota, Nitrospirota, Crenarchaeota, Chloroflexi, Myxococcota, Acidobacteriota, Proteobacteria, and unidentified_Bacteria, and a significant decrease in the relative abundance of Firmicutes and Bacteroidetes at the phylum level. Additionally, at the genus level, the relative abundance of some beneficial bacteria, such as Bacteroides, Megamonas, Bifidobacterium, and Faecalibacterium, was significantly reduced. We also demonstrated that, at the genus level, some gut microbial markers, including Anaeromyxobacter, MND1, oc32, Haliangium, and Adurb.Bin063_1, showed potential for identifying coal-burning endemic fluorosis. Moreover, non-targeted metabolomics and correlation analysis revealed the changes in the metabolome, particularly the gut microbiota-derived tryptophan metabolites such as tryptamine, 5-hydroxyindoleacetic acid, and indoleacetaldehyde. Our results indicated that excessive fluoride might cause xenobiotic-mediated dysbiosis of human gut microbiota and metabolic disorders. These findings suggest that the alterations in gut microbiota and metabolome play vital roles in regulating disease susceptibility and multi-organ damage after excessive fluoride exposure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prolonged exposure to higher concentrations of fluoride (> 1.5 mg/L) is associated with dental and skeletal fluorosis. The effects of fluoride on dental and skeletal system have been studied extensively; however, the neurological consequences of fluoride in population-based studies are limited. The study aims to assess the epidemiology of neurological and other manifestations of fluorosis among rural populations living in the Main Ethiopian Rift valley. In this cross-sectional study, we enrolled 316 individuals from 23 rural communities in the Main Ethiopian Rift valley. Fluoride concentration was measured in drinking water samples collected from 23 community wells. Association between fluoride concentrations and clinical features of fluorosis was assessed using student t test, chi square, multivariable regression using adjusted odds ratio (OR). The mean fluoride concentration in the drinking water was 6.8 ± 4.3 mg/L (range: 0.3-15.5 mg/L). At least one clinical sign of skeletal fluorosis was observed in 54.4% (n = 175) of the study participants. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation, and skeletal fluorosis symptom, respectively. The mean fluoride level was higher for those individuals who reported paresthesia compared to those with no-paresthesia. Loss of appetite, constipation, and fatigue were reported by 48.0%, 45.6%, and 56.6% of the participants, respectively. Signs of crippling fluorosis were observed in small proportion (1.6%) of the participants. Individuals who reported headache are most likely exposed to higher fluoride concentrations in drinking water compared to those reported no-headache (p < 0.001). The study demonstrates high prevalence of neuro-medical manifestations of fluorosis in population living in the Main Ethiopian Rift valley. Fluoride concentration in drinking water and joint pain were independent predictors of fluorosis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Fluorosis is a major public health problem in the Rift Valley of Ethiopia. Low calcium (Ca) intake may worsen fluorosis symptoms. We assessed the occurrence of fluorosis symptoms among women living in high-fluoride (F) communities in South Ethiopia and their associations with dietary Ca intake. Women ( n = 270) from two villages provided clinical and questionnaire data. Dental fluorosis examination was done using Dean's Index, and skeletal and non-skeletal fluorosis assessment was carried out using physical tests and clinical symptoms. Daily Ca intake was estimated by a food frequency questionnaire. Food, drinking water and beverage samples were analyzed for F level. Many subjects (56.3%) exhibited dental fluorosis. One-third of the women were unable to perform the physical exercises indicative of skeletal fluorosis; about half had ≥2 symptoms of skeletal/non-skeletal fluorosis. The average F level in drinking water sources was ~5 mg/L. The F content in staple food samples varied from 0.8-13.6 mg/kg. Average Ca intake was 406 ± 97 mg/day. Women having ≤400 mg/day Ca intake had ~3 times greater odds of developing skeletal rigidity with joint pains [AOR = 2.8, 95%CI: 1.6, 5.0] and muscular weakness [AOR = 2.9, 95%CI: 1.3, 6.3] compared to those with higher intakes. No association of calcium intake was seen with dental fluorosis. As low dietary Ca intake was associated with symptoms related to skeletal and non-skeletal fluorosis, this warrants nutritional intervention on calcium intakes in this setting.

The study aimed to assess the levels of trace elements, minerals, and toxic elements as well as lipid peroxidation biomarkers (lipid acyl hydroperoxides, 2-thiobarbituric acid reactive substances (TBARS)) in the blood of children with chronic fluorosis from endemic fluorosis areas (Sosnivka village, Lviv region, western Ukraine). The results were compared with healthy children from Staryi Sambir (Lviv region, western Ukraine), whose drinking water contained permissible levels (< 1 ppm) of fluoride. Thirty-one children from the Sosnivka village in the Lviv region, including 16 females and 15 males aged 7-10 years, with clinically diagnosed fluorosis, were recruited for the study. The children had been exposed to fluoride (> 1.5 ppm) through drinking water for more than 5 years. In the blood, eight macro- and microelements (calcium, zinc, potassium, iron, copper, selenium, manganese, chromium), five additional elements (sulfur, bromine, chlorine, nickel, strontium), and four toxic elements (lead, mercury, cadmium, mercury) were assessed with the X-ray fluorescence method. The results of our study demonstrated a 14-fold decrease in the copper level, a 2.5-fold decrease in the calcium and zinc levels, and a 2-fold decrease in the selenium level in the blood of children with chronic fluorosis compared with the healthy children from the non-fluorosis area. In turn, a 1.7- and 1.4-fold increase in the strontium and lead content, respectively, was noted. The sulfur, chlorine, potassium, calcium, copper, zinc, and selenium levels in the blood samples of children with chronic fluorosis were lower than the reference value. The children had higher blood TBARS levels, while the acyl hydroperoxide levels were non-significantly increased in comparison with healthy children living in the non-fluorosis area. Additionally, the bromine level was correlated positively with the selenium level and acyl hydroperoxides. However, more studies are needed to clarify the relationship between blood mineral status, oxidative stress biomarkers, and chronic fluorosis.

Skeletal fluorosis is a rare toxic osteopathy characterized by massive bone fixation of fluoride. The disease occurs as an endemic problem in some parts of the world and is the result of prolonged ingestion or rarely by inhalation of high amounts of fluoride. Radiographic presentation is mainly characterized by bone changes with osteocondensation and later ossification of many ligaments and interosseous membranes. Skeletal fluorosis is not clinically obvious and can be confused with other rheumatologic disorders. Its severity lies in the development of skeletal deformities and neurological complications. Management of fluorosis generally focuses on symptom treatment.

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 B 12 depletion, 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., Competing Interests: None

Several million people are exposed to fluoride (F - ) via drinking water in the world. Current review emphasized the elevated level of fluoride concentrations in the groundwater and associated potential health risk globally with a special focus on Pakistan. Millions of people are deeply dependent on groundwater from different countries of the world encompassing with an elevated level of fluoride. The latest estimates suggest that around 200 million people, from among 25 nations the world over, are under the dreadful fate of fluorosis. India and China, the two most populous countries of the world, are the worst affected. In Pakistan, fluoride data of 29 major cities are reviewed and 34% of the cities show fluoride levels with a mean value greater than 1.5 mg/L where Lahore, Quetta and Tehsil Mailsi are having the maximum values of 23.60, 24.48, > 5.5 mg/L, respectively. In recent years, however, other countries have minimized, even eliminated its use due to health issues. High concentration of fluoride for extended time period causes adverse effects of health such as skin lesions, discoloration, cardiovascular disorders, dental fluorosis and crippling skeletal fluorosis. This review deliberates comprehensive strategy of drinking water quality in the global scenario of fluoride contamination, especially in Pakistan with prominence on major pollutants, mitigation technologies, sources of pollution and ensuing health problems. Considering these verities, health authorities urgently need to establish alternative means of water decontamination in order to prevent associated health problems.

The junction area of Yunnan, Guizhou, and Sichuan provinces is the heaviest coal-burning endemic fluorosis zones in China. To better understand the pathogenicity of endemic fluorosis in this area, 87 coal samples from the late Permian outcrop or semi-outcrop coal seams were collected in eight counties of the junction area of Yunnan, Guizhou, and Sichuan provinces. The total fluorine and sulfate content, etc. in the coal was determined using combustion-hydrolysis/fluoride-ion-selective electrode method and ion chromatography, respectively. The results show that the total fluorine concentrations in the samples ranged from 44 to 382 µg g -1 , with an average of 127 µg g -1 . The average pH of the coals is 5.03 (1.86-8.62), and the sulfate content varied from 249 to 64,706 µg g -1 (average 7127 µg g -1 ). In addition, the coals were medium- and high-sulfur coals, with sulfur mass fraction ranging from 0.08 to 13.41%. By heating the outcrop coals, HF release from the coal was verified quantitatively without exception, while simulated combustion directly confirmed the release of sulfuric acid (H 2 SO 4 ). The acid in coal may be in the form of acidic sulfate ([Formula: see text]/H 2 SO 4 ) because of a positive relationship between pH and [Formula: see text] in the acidic coal. The possible reaction mechanism would be that a chemical reaction between the acid (H 2 SO 4 or [Formula: see text]) and fluorine in the coal occurred, thereby producing hydrogen fluoride (HF), which would be the chemical form of fluorine released from coal under relatively mild conditions. The unique chemical and physical property of HF may bring new insight into the pathogenic mechanism of coal-burning endemic fluorosis. The phenomenon of coal-burning fluorosis is not limited to the study area, but is common in southwest China and elsewhere. Further investigation is needed to determine whether other endemic fluorosis areas are affected by this phenomenon.

India is one of the fluoride-endemic countries where the maximum numbers of ground or drinking water sources are naturally fluoridated. In India, a total of 23, out of 36 states and union territories have drinking water contaminated with fluoride in varying concentration. In the present scenario, especially in rural India, besides the surface waters (perennial ponds, dams, rivers, etc.), bore wells and hand pumps are the principal drinking water sources for domestic animals such as cattle (Bos taurus), water buffaloes (Bubalus bubalis), sheep (Ovis aries), goats (Capra hircus), horses (Equus caballus), donkeys (Equus asinus) and dromedary camels (Camelus dromedarius). Out of 23 states, 17 states, namely Andhra Pradesh, Assam, Bihar, Chhattisgarh, Gujarat, Haryana, Jharkhand, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Odisha (Orissa), Punjab, Rajasthan, Telangana, Uttar Pradesh and West Bengal, have fluoride beyond the maximum permissible limit of 1.0 or 1.5 ppm in drinking water. This situation is a great concern for the animal health because fluoride is a slow toxicant and causes chronic diverse serious health hazards or toxic effects. Despite the fact that domestic animals are the basic income sources in rural areas and possess a significant contributory role not only in the agriculture sector but also in the strengthening of economy as well as in sustainable development of the country, research work on chronic fluoride intoxication (hydrofluorosis) due to drinking of fluoridated water in domestic animals rearing in various fluoride-endemic states is not enough as compared to work done in humans. However, some interesting and excellent research works conducted on different aspects of hydrofluorosis in domesticated animals rearing in different states are briefly and critically reviewed in the present communication. Author believes that this review paper not only will be more useful for researchers to do some more advance research work on fluoride-induced toxicosis in different species of animals but will also be helpful in the making of health policy for domestic animals at state and national level for the mitigation of hydrofluorosis in India.

Fluoride is ubiquitous in environment and profound in bones, teeth and calcified tissues of human body. Fluoride has been the topic of regular discussion and investigations. Besides its toxicity, fluoride has also been examined for its beneficial effects like prevention and treatment of tooth decay, microbial infection, inflammation, cancer, occurrence of renal stone and many more. Since last many decades, several efforts have been made at pre-clinical and clinical level to understand role of fluoride in biological system. The present review gives a brief account of prevalence, sources of fluoride toxicity and pre-clinical and clinical studies carried out on effects of fluoride in last six decades., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Objectives: The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence., Methods and Study Design: A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride., Results: In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05)., Conclusion: Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.

Frequent and repetitive activities in job and awkward postures are shown as major contributors of musculoskeletal problems in most of the occupational health studies; however, efforts to explore newer risk factor are important to plan interventional measures. In this backdrop, this study examined contribution of fluoride exposure to musculoskeletal complaints. A cross-sectional interviewer-administered questionnaire survey was conducted involving 180 randomly selected subjects from a metal smelting industry. Clinical examination of the subjects was also performed to assess their health status and morbidity details. Assessment of personal exposure to particulate and gaseous fluoride at workplace was conducted. Urinary fluoride level was also examined in post-shift samples collected from study subjects. The mean age of the study subjects was 39.1 (±6.7) years. Majority of the workers (42.5%) were engaged in pot room. About 54% workers were suffering from backache and 66% subjects had joint pain. Exposure of workers to both particulate and gaseous fluoride and post-working shift urinary fluoride level was significantly higher in pot-room workers in comparison with all other workers. It was observed that age (odds ratio (OR): 1.62; 95% confidence interval (CI): 1.18-2.34), drinking untreated water (OR: 1.51; 95% CI: 1.03-2.76), working in pot room (OR: 1.44; 95% CI: 1.13-1.91) and urinary fluoride level (OR: 2.71; 95% CI: 1.81-3.75) had significant effects on musculoskeletal complaints. This study concludes that along with other predictors such as nature of work, posture at work and age of worker, exposure to fluoride also has significant role in the occurrence of musculoskeletal morbidity., (© The Author(s) 2015.)

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.

Purpose: The American Association of Poison Control Center's annual reports demonstrate that acute fluoride exposure is not an uncommon occurrence. Despite its prevalence, there has been little published research on the topic in the last 10 years. The purpose of this study was to calculate the incidence of acute fluoride toxicity and lethality as it occurs in New Jersey and provide a descriptive epidemiology of acute fluoride exposures., Methods: The study design was retrospective in nature. Records of phone calls made by individuals reporting excessive fluoride exposure (in an amount greater than directed/prescribed) to New Jersey's poison control center, known as Poison Information and Education System from the years 2010 through 2012, were extracted from Toxicall® (Computer Automatic Systems, Inc.) database. A total of 2,476 human-only exposure records met the inclusion criteria and were analyzed. Incidence rates were calculated, and population characteristics, circumstances and medical outcomes of acute fluoride exposure cases were assessed and categorized., Results: A total of 2,476 phone call records met the inclusion criteria. The fluoride exposures reported were from toothpaste with fluoride (49%, n=1,214), mouth rinse with fluoride (21.6%, n=536), multivitamin with fluoride (21.4%, n=530) and pure fluoride (0.08%, n=199). Medically speaking, 94.75% of calls were asymptomatic cases (n=2,346), 4.24% were symptomatic (n=105) and 1.01% were informational inquiries (n=25). Adverse symptoms reported were mostly minor (83.9% of symptomatic cases, n=88) and moderate (16.1% of symptomatic cases, n=17). The age group 18 months to 3 years of age showed the highest incidence of acute fluoride exposure (53.2%, n=1,317). There was a slightly higher incidence of acute fluoride exposures among males (n=1,317) vs. females (n=1,159). Most incidences occurred in the home (93.1% of records, n=2,305) and occurred unintentionally (96.7%, n=2,394). Calls were mainly made by the subject's mother (67.5%, n=1,671)., Conclusion: Based on the data, there were no reports of lethality or toxicity due to acute fluoride exposure in New Jersey from 2010 through 2012. Symptomatic reports and informational inquiries were few. All adverse outcomes due to excessive fluoride intake were remedied with calcium as the antidote. Dental hygienists should educate patients on safety measures of fluoride-containing products and evaluate overall fluoride exposure prior to making recommendations. However, findings in this study suggest that levels of fluoride in available commercial products will not produce life-threatening events, even if taken in doses higher than recommended., (Copyright © 2016 The American Dental Hygienists’ Association.)

In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia).

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.

Background: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development., Methods: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-IV) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models., Results: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-IV digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of -4.28 (95% CI -8.22, -0.33) and backward score with -2.13 (95% CI -4.24, -0.02)., Conclusions: This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The objective of the present study was to determine the plasma total oxidative status (TOS) and total antioxidant capacity (TAC) in patients with endemic fluorosis. A total of 79 (35 males and 44 females; mean age 44.0 ± 11.9 years) patients with endemic fluorosis and 55 (23 males and 32 females; mean age 48.3 ± 8.5 years) age-, sex- and body mass index-matched healthy controls were included in this study. The urine fluoride levels and plasma TOS and TAC levels were measured. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.91 ± 0.15 vs. 0.49 ± 0.13 mg/L, respectively; p < 0.001). TOS was significantly higher in fluorosis group than in control group (17.55 ± 3.82 vs. 15.06 ± 4.31 μmol H(2)O(2) Eq/L, respectively; p = 0.001). TAC was significantly lower in fluorosis group than in control group (1.60 ± 0.36 vs. 1.82 ± 0.51 mmol Trolox Eq/L, respectively; p = 0.004). Oxidative stress index (OSI) was significantly higher in fluorosis group than in control group (11.5 ± 3.8 vs. 8.8 ± 3.7, respectively; p < 0.001). Correlation analysis in all the groups indicated that TAC was negatively correlated with urine fluoride (r = -0.25, p = 0.003), TOS was positively correlated with urine fluoride (r = 0.34, p < 0.001) and OSI was positively correlated with urine fluoride (r = 0.36, p < 0.001). The results of our study demonstrate that oxidative stress plays an important role in the pathogenesis of the endemic fluorosis.

Objectives: Fluoride is one of the biological trace elements with a strong affinity for osseous, cartilaginous and dental tissue. The dental and skeletal effects of high fluoride intake have already been studied in the literature, but little is known about the effects of high fluoride intake on edentulous mandibles. The purpose of this study was to evaluate the effects of high fluoride intake on mandibular bone mineral density (BMD) measured by the dual-energy X-ray absorptiometry (DXA) technique in edentulous individuals with systemic fluorosis., Methods: 32 people who were living in an endemic fluorosis area since birth and 31 people who were living in a non-endemic fluorosis area since birth (control group) participated in this study. Systemic fluorosis was diagnosed in the patients using the sialic acid (NANA)/glycosaminoglycan (GAG) ratio. The BMDs of the mandibles were determined by the DXA technique., Results: The serum NANA/GAG ratios in the fluorosis group were significantly lower than those in the control group (p < 0.001). There was also a statistically significant difference in mandibular BMD measurements (p < 0.05) between the systemic fluorosis and control groups, as measured by the DXA technique. Mandibular body BMD measurements were higher in the fluorosis group (1.25 ± 0.24 g cm(-2)) than in the control group (1.01 ± 0.31 g cm(-2))., Conclusions: The results of the study showed that fluoride intake higher than the optimum level causes increased mandibular BMD in edentulous individuals. Further dose-related studies are needed to determine the effects of high fluoride intake on bony structures of the stomatognathic system.

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.

The aim of this study was to assess the value of the children's version of the Rey-Osterrieth Complex Figure Test as a screening test in a population exposed to different mixtures of neurotoxicants. Copy and Immediate Recall scores were evaluated through the test. Children were recruited from three sites; an area with natural contamination by fluoride and arsenic (F-As), a mining-metallurgical area with lead and arsenic contamination (Pb-As) and a malaria zone with the evidence of fish contaminated with dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). Children aged 6-11 years old, living in one of the three polluted sites since birth were recruited (n=166). The exposure was evaluated as follows: fluoride and arsenic in urine, lead in blood and DDT, dichlorodiphenyldichloroethylene (DDE) and PCBs in serum. To evaluate the test performance, z-scores for Copy and Immediate Recall were calculated. The proportion of children by residence area with performance lower than expected by age (below -1 SD) for Copy and Immediate Recall was in the F-As area (88.7% and 59%) and in the DDT-PCBs area (73% and 43.8%), respectively. In the Pb-As area, the proportion was 62% for both tests. After adjustment, Copy correlated inversely with fluoride in urine (r=-0.29; p<0.001) and Immediate Recall correlated inversely with fluoride in urine (r=-0.27; p<0.05), lead in blood (r=-0.72; p<0.01), arsenic in urine (r=-0.63; p<0.05) and DDE (r=-0.25; p<0.05). This study provided evidence that children included in this research are living in high risk areas and were exposed to neurotoxicants. Poor performance in the test could be explained in some way by F, Pb, As or DDE exposure, however social factors or the low quality of school education prevalent in the areas could be playing an important role.

Introduction: The people in Berhait block, Sahibganj district, Jharkhand state, India, have been exposed chronically to fluoridecontaminated groundwater. Hereby, we report the clinical effects of chronic exposure to fluoride., Methods: The study population was a convenience sample of 342 adults and 258 children living in the affected area. All volunteers filled out questionnaires and were examined. Well water from the six affected villages and urine samples were analyzed for fluoride using an ion-sensitive electrode., Results: Twenty nine percent of 89 well water samples had fluoride concentrations above the Indian permissible limit of fluoride in drinking water. Eighty-five children and 72 adults had clinical fluorosis. Urine fluoride concentrations in children were 0.758-2.88 mg/L whereas in adults they were 0.331-10.36 mg/L., Discussion: Clinical effects of fluoride included abnormal tooth enamel in children; adults had joint pain and deformity of the limbs and spine, along with ligamentous calcifications and exostosis formations in seven patients. Elevated urine fluoride concentrations supported the clinical diagnosis of fluorosis. Owing to insufficient fluoride-safe wells and lack of awareness of the danger of fluoride toxicity, villagers often drink fluoride-contaminated water., Conclusion: Villagers of Berhait block, including children, are at risk from chronic fluoride toxicity. To combat the situation, villagers need fluoride-safe water, education, and awareness of the danger about fluoride toxicity.

The prevalence of fluorosis is mainly due to the consumption of more fluoride through drinking water. It is necessary to find out the fluoride endemic areas to adopt remedial measures to the people on the risk of fluorosis. The objectives of this study are to estimate the fluoride exposure through drinking water from people of different age group and to elucidate the fluoride endemic areas through mapping. Assessment of fluoride exposure was achieved through the estimation fluoride level in drinking water using fluoride ion selective electrode method. Google earth and isopleth technique were used for mapping of fluoride endemic areas. From the study it was observed that Nilakottai block of Dindigul district in Tamil Nadu is highly fluoride endemic. About 88% of the villages in this block have fluoride level more than the prescribed permissible limit in drinking water. Exposure of fluoride among different age groups was calculated in this block, which comprises 32 villages. The maximum estimated exposure doses were 0.19 mg/kg/day for infants, 0.17 mg/kg/day for children and 0.10 mg/kg/day for adults. When compared with adequate intake of minimal safe level exposure dose of 0.01 mg/kg/day for infants and 0.05 mg/kg/day for other age groups, a health risk due to fluorosis to the people in Nilakottai block has become evident. From the results, the people in Nilakottai block are advised to consume drinking water with fluoride level less than 1 mg/l. It has been recommended to the government authorities to take serious steps to supply drinking water with low fluoride concern for the fluorosis affected villages.

Endemic skeletal fluorosis is widely prevalent in India and is a major public health problem. The first ever report of endemic skeletal fluorosis and neurological manifestation was from Prakasam district in Andhra Pradesh in the year 1937. Epidemiological and experimental studies in the endemic areas suggest the role of temperate climate, hard physical labor, nutritional status, presence of abnormal concentrations of trace elements like strontium, uranium, silica in water supplies, high fluoride levels in foods and presence of kidney disease in the development of skeletal fluorosis. Neurological complications of endemic skeletal fluorosis, namely radiculopathy, myelopathy or both are mechanical in nature and till date the evidence for direct neurotoxicity of fluoride is lacking. Prevention of the disease should be the aim, knowing the pathogenesis of fluorosis. Surgery has a limited role in alleviating the neurological disability and should be tailored to the individual based on the imaging findings.

An investigation was undertaken in three endemic fluorotic areas of Punjab State, India, to assess the prevalence of skeletal deformities. The concentration of fluoride in drinking water varies from 2.3 to 22.5 mg/L. The patients affected with skeletal fluorosis revealed joint pain in both upper and lower limbs, numbing and tingling of the extremities, back pains and knock-knees. Prevalence of skeletal fluorosis was found to be 29% of grade-I, 51% of grade-II and 20% of grade-III and was higher in males (63%) compared with females (37%).

Endemic dental fluorosis was first observed in Turkey in Isparta Province, located in the SW of Anatolia, with mottled enamel related to the high levels of fluoride (1.5-4.0 ppm) in drinking waters, about 55 years ago. The origin of fluoride was attributed to the contents of minerals in volcanic rocks, consisting of pyroxene, hornblende, biotite, fluorapatite and glassy groundmass minerals. It was also reported about 35 years ago that severe dental and skeletal fluorosis has been observed in human beings and livestock in Dogubeyazit and Caldiran areas, located around Tendurek Volcano in eastern Turkey, where natural waters contained fluoride levels between 2.5 and 12.5 ppm. It was hypothesised that fluoride, which might be transported by fumaroles or escaped from devitrified lavas, could be held on the surface of some minerals and then exchanged with OH(-) in ground waters with high pH at the foothills of the young Tendurek Volcano. Endemic dental and skeletal fluorosis was also observed in the inhabitants in Kizilcaoren Village of Beylikova Town in Eskişehir Province situated in the midwest of Turkey, where the fluoride content of the drinking waters ranged from 3.9 to 4.8 ppm. The origin of high fluoride in the natural waters was related to the fluorspar deposits, occurring in the catchment area near the village. During the survey in the Güllü Village of Esme-Usak, located in south-midwest of Turkey, it was observed that most of the inhabitants born and raised in the village and aged between 10 and 30 years, showed mild to moderate levels of mottled enamel. The fluoride contents of the deep well waters used for drinking in the village, varied from 0.7 to 2.0 ppm. Amorphous microscopic fluorite existing in the Pliocene lake limestones was considered as a possible origin of fluoride in the waters.

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.

Objective: To study the clinical and radiological prevalence of skeletal fluorosis among the retired employees of Wonji-Shoa sugar estate., Design: Retrospective and cross-sectional study., Setting: Wonji-Shoa sugar estate, an agro-industrial estate located in the Ethiopian Rift Valley., Subjects: Two hundred and sixty three employees of the estate who retired between 1995 and 1996., Main Outcome Measures: Clinical evidence of impaired squatting, neck and lumbar mobility, kyphosis, and X-ray evidence of fluorosis., Results: Skeletal fluorosis was more evident among the males (p<0.05), and the prevalence was higher among the factory and the agricultural workers than among the administrative workers (p<0.05). Clinical prevalence was 20% versus the radiological prevalence of 70.3%, indicating that many cases were asymptomatic. Impaired neck and lumbar mobility and impaired squatting significantly agreed with the radiological diagnosis (p<0.05) while kyphosis was not., Conclusion: Further clinical and epidemiological studies are suggested and strengthening of the existing defluoridation programmes within the area is recommended.

Purpose: The effects of menopause on bone mineral density (BMD) in women with endemic fluorosis were investigated., Materials and Methods: Eighty healthy Turkish women who lived in and around the city of Isparta were selected randomly and enrolled in this study. They were separated into four groups: group 1, 20 premenopausal women with regular menstrual cycles and endemic fluorosis; group 2, 20 postmenopausal women with endemic fluorosis; group 3, 20 premenopausal normal women constituting one control group; and group 4, 20 postmenopausal normal women constituting the other control group. Bone mineral density was measured in the lumbar spine and proximal femur using dual-energy x-ray absorptiometry., Results: In the premenopausal group, BMD values of vertebrae L2-L4 and Ward's triangle in women with endemic fluorosis were significantly greater than the respective values in women without endemic fluorosis (P = 0.024, P = 0.036). There were no differences between the groups in BMD values of the femoral neck (P = 0.156) and intertrochanteric area (P = 0.076). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward's triangle in the postmenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women without endemic fluorosis (P < 0.001, P = 0.015, P = 0.002, and P < 0.001, respectively). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward's triangle in the premenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women with endemic fluorosis (P = 0.010, P = 0.002, P = 0.004, and P = 0.010, respectively). The BMD values of the sites noted for the premenopausal controls were significantly greater than those of postmenopausal controls (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively)., Conclusions: Postmenopausal BMD values in both endemic fluorosis and controls were significantly less than premenopausal BMD values. Although the differences were less prominent in women with endemic fluorosis, menopause is still the major determinant of BMD in the spine and femur.

To investigate health impact of brick-tea type fluorosis in adults, the total daily fluorine intake, environment fluorine level were determined, the average urinary fluorine content assay and bone X-ray examination were conducted, the clinical manifestations were observed in the brick-tea type bone fluorosis epidemiological study conducted in Naqu County, Tibet at September, 2001. One hundred and eleven adults aged at 30-78 year-old were enrolled. It was found that the fluorine level of drinking water in Naqu County was 0.10 +/- 0.03 mg/L, but the brick-tea water processed foods-zamba and buttered tea had fluorine content of 4.52 +/- 0.74 mg/kg and 3.21 +/- 0.65 mg/kg respectively. The adult daily fluorine intake reached 11.99 mg, among which 99% is originated from the brick-tea containing foods. Positive detection rate of fluorosis osteopathy was 89% and the X-ray film confirmed that the diagnosis rate was 83%. Degenerative arthropathy and ossification of the interosteal membrane, calcification of the tendon were the characteristics that indicated by both the positive signs and reogenological examination. The prevalence of osteosclerosis type (bone matrix increased) was 74%. It is suggested that there were even more severe health impact compared with those in the water type and coal combustion type fluorosis.

Neurological manifestations of skeletal fluorosis have been attributed to compressive radiculomyelopathy. Experimental fluorosis has shown evidence of myopathic changes. Data on human muscle pathology is very scanty. This study included 22 patients with established osteofluorosis. 16 of them showed only EMG changes of neurogenic muscle disease. Histochemistry and histopathology of muscle biopsies showed features of muscle atrophy, evidenced by 'type I' atrophy and 'type I' grouping. No myopathic changes were observed. It may be concluded that the primary changes are related to the nerve, with muscle being affected secondarily. There was no evidence of any primary muscle pathology due to fluorosis.

Signs of dental discolouration, difficulty in mastication, bony lesions, lameness, debility and mortality in domesticated animals, reared around superphosphate fertiliser plants located approximately 15 km north of Udaipur, Rajasthan prompted us to investigate for the occurrence of fluorosis. Out of 166 animals clinically examined, the prevalence rate was 17.4% (4/23) in calves below 1 year of age, 37.2% (16/43) in cattle between 1 and 3 years, 61.3% (46/75) in cattle above 3 years and 72% (18/25) in buffalo above 1 year. Dental fluorosis was common in buffalo compared to cattle of all the age groups. Fluoride levels in fodder and water, consumed by the animals were much higher than the recommended permissible limit. Mean fluoride concentrations in serum and urine were 1.53 +/- 1.27 and 26.4 +/- 6.17 mg l(-1) in calves below 1 year of age, 0.56 +/- 0.17 and 26.2 +/- 3.86 mg l(-1) in cattle of 1-3 years, 0.49 +/- 1.13 and 27.5 +/- 4.63 mg l(-1) in cattle above 3 years and 0.60 +/- 0.07 and 28.6 +/- 4.73 mg l(-1) in buffalo over 1 year, respectively. The values were significantly (P < 0.01) higher than those of control animals kept over a 15-km distance from the factories. Fluoride concentrations in the environmental sample collected from the affected locality were 534.4 +/- 74.9 mg kg(-1) in fodder, 1.19 +/- 0.29 mg l(-1) in pond water and 0.479 +/- 0.351 mg l(-1) in tube well water. It was concluded that the consumption of fodder and water contaminated by the fumes and dusts emitting from superphosphate fertiliser plants resulted in the development of chronic fluorotic lesions in cattle and buffalo.

Having analyzed a total amount of all systems, the authors specified the most important genetic markers predisposing to chronic flour intoxication: the patients demonstrated higher frequency of ACP1*A and PGM1*1-alleles, phenotypes of acid phosphatase AA, of phosphoglucomutase 1+1+ and 2+2+, of dry cerumen consistence--d. The results could help to improve criteria of occupational selection and to specify practical recommendations on prophylaxis of chronic fluor intoxication.

A review and mapping of fluoride test data for 270 water sources in 126 communities and examination of the literature of fluorosis distribution in Ethiopia show that this health problem extends beyond the Rift Valley into some highland communities. Fluoride concentrations above 5.0 mg/l in the Rift Valley were found mostly in hot springs (100% of all sources), lakes (78%), shallow wells (54%) and boreholes (35%) and the lowest concentrations (below 1.5 mg/l) in springs and rivers. Analysis of hydrochemical, economic and demographic factors in the spatial distribution of high-fluoride domestic water sources indicates that the fluorosis problem has become more serious in the Rift Valley in recent decades. Considerable spatial variation in the occurrence of fluoride, even within the same communities, and the presence of some low-fluoride water sources in the Rift Valley offer possibilities for geochemical exploration for acceptable domestic sources. The defluoridation programme in the Wonji irrigation scheme illustrates the problems faced by a large rural community in a developing country. Possibilities for control are examined and recommendations made for the development of alternative water sources and promising defluoridation methods using locally available materials and technologies.

Beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary have been reported to have dental and bone abnormalities. To determine whether these lesions could be caused by high exposure to fluorides, we measured bone fluoride levels in eight beluga whales stranded on the shores of the St. Lawrence Estuary (Quebec, Canada), and in nine beluga whales killed by Inuit hunters in the Hudson Bay (North Western Territories, Canada). In both groups, fluoride concentrations were higher than those found in terrestrial mammals intoxicated by fluorides. Unexpectedly, fluoride concentration was significantly higher in beluga whales from the Hudson Bay (mean +/- SD: 10.365 +/- 1.098 ppm) than in beluga whales from the St. Lawrence Estuary (4.539 +/- 875 ppm) and was positively correlated with age in the latter population. Differences in diet might explain the differences in fluoride concentrations found between these two populations.

The authors report an uncommon complication in cervical skeletal fluorosis. It is a cervical spondylolisthesis at C5-C6 level complicated by a radiculomyelopathy described in a man living in an endemic area for fluorosis. After 3 years, a spontaneous stabilization of the cervical spine with a posterior calcification of the supraspinal and interspinal ligaments has caused an improvement of the neurological symptomatology.

In order to find out the situation of management and application of water defluoridation measures, as well as the effects on the prevention of endemic fluorosis in 10 provinces and cities with heavy endemic fluorosis from the drinking water sources, 1960 water engineering projects accounting for about 10% of all projects were investigated. The authors applied uniform method, criteria and forms to carry out the retrospective investigation. The data were entered into the computer database and analyzed statistically. The results demonstrate that all the defluoridation projects have significant effectiveness on the prevention of endemic fluorosis. The concentrations of water fluoride were below 1 mg/L. The prevalences of dental fluorosis were 30%-40% and the main type was light dental fluorosis. But with the time prolonging, less attention has been paid in man.

The concentration of fluoride was determined in water, forage and urine and serum samples of buffaloes from the Unnao district of India. The water and forage samples contained 2.01 +/- 0.51 and 22.50 +/- 0.82 ppm of fluoride, respectively. The analysis of biosamples collected from the affected animals revealed higher levels of fluoride in serum (0.58 +/- 0.05 ppm) and urine (10.64 +/- 1.23 ppm). Clinical examination identified a 40.34% prevalence rate of clinical lesions suggestive of fluorosis in buffalo of this locality. Dental lesions were present invariably in all affected animals whereas lameness, painful bony exostosis and emaciation were recorded in 28.17%, 8.45% and 76.00% of the animals. Based on the clinical lesions and fluoride content in water, serum and urine, it was concluded that the problem of fluorosis in buffalo is attributable to drinking water containing toxic levels of fluoride.

Objective: To determine the extent and confirm the cause of an August 1993 outbreak of acute fluoride poisoning in a small Mississippi community, thought to result from excess fluoride in the public water supply., Methods: State health department investigators interviewed patrons of a restaurant where the outbreak first became manifest and obtained blood and urine samples for measurement of fluoride levels. State health department staff conducted a random sample telephone survey of community households. Public health environmentalists obtained water and ice samples from the restaurant and tap water samples from a household close to one of the town's water treatment plant for analysis. Health department investigators and town water department officials inspected the fluoridation system at the town's main water treatment plant., Results: Thirty-four of 62 restaurant patrons reported acute gastrointestinal illness over a 24-hour period. Twenty of 61 households that used the community water supply reported one or more residents with acute gastrointestinal illness over a four-day period, compared with 3 of 13 households that did not use the community water supply. Restaurant water and ice samples contained more than 40 milligrams of fluoride per liter (mg/L), more than 20 times the recommended limit, and a tap water sample from a house located near the main treatment plant contained 200 mg/l of fluoride. An investigation determined that a faulty feed pump at one of the town's two treatment plants had allowed saturated fluoride solution to siphon from the saturator tank into the ground reservoir and that a large bolus of this overfluoridated water had been pumped accidentally into the town system., Conclusions: Correct installation and regular inspection and maintenance of fluoridation systems are needed to prevent such incidents.

Objective: This paper analyzes reports to the American Association of Poison Control Centers (AAPCC) of suspected overingestion of fluoride by children younger than 6 years of age between 1989 and 1994, and estimates the probably toxic amounts of various home-use fluoride products in children younger than 6 years of age., Methods: Annual incidence rates of reported fluoride exposures attributed to dietary supplements, toothpaste, and rinses were calculated. Probably toxic amounts of each product were calculated using the frequently cited dose of 5 mg/kg., Results: Children younger than 6 years of age accounted for more than 80 percent of reports of suspected overingestion. While the outcomes were generally not serious, several hundred children were treated at health care facilities each year. A 10 kg child who ingests 50 mg fluoride (10.1 g 1.1% NaF gel; 32.7 g 0.63% SnF2 gel; 33.3 g 1,500 ppm F toothpaste; 50 g 1,000 ppm F toothpaste; and 221 mL 0.05% NaF rinse) will have ingested a probably toxic dose., Conclusions: Overingestion of fluoride products in the home is preventable. Dentists and other health care providers should educate parents and child care providers about the importance of keeping fluoride products out of reach of children. Manufacturers should be encouraged by the ADA and the FDA to use child-resistant packaging for all fluoride products intended for use in the home.

A prospective case-controlled study was performed to evaluate the gastrointestinal symptoms and mucosal abnormalities occurring in patients with osteofluorosis. Ten patients with documented osteofluorosis and ten age- and sex-matched healthy volunteers were included in the study. Clinical evaluation, real-time ultrasound, and upper gastrointestinal endoscopy and biopsy from the gastric antrum and duodenum were performed in all subjects. The biopsies were subjected to a rapid urease test and light and electron microscopic examinations. Ionic fluoride levels were estimated in the drinking water, serum, and urine using an ION 85 ion analyzer. All patients with osteofluorosis had gastrointestinal symptoms, the most common being abdominal pain. Endoscopic abnormalities were found in seven patients with osteofluorosis. In all 7 of these patients, chronic atrophic gastritis was seen on histology. Electron microscopic abnormalities were observed in all 10 patients with osteofluorosis. These included loss of microvilli, cracked-clay appearance, and the presence of surface abrasions on the mucosal cells. None of the control subjects had any clinical symptoms or mucosal abnormalities. It was concluded that gastrointestinal symptoms as well as mucosal abnormalities are common in patients with osteofluorosis.