“In the present study, fluoridated water did not seem to have a positive effect on dental health, as it might have been expected in a community with the respective caries prevalence.”

“Controlling for covariates, water fluoridation method was significant only in the models that included dwellings built before 1946 and dwellings of unknown age.”

“fluoridation was significantly associated with PbB [lead] concentration only for the “before 1946” (adjusted Wald-F= 2.8; p= 0.03) and “unknown” (adjusted Wald-F= 2.8; p= 0.03) strata. In the before-1946 model, however, none of the individual fluoridation categories (including the silicofluorides compounds) was significantly higher than the reference no-fluoride category. In the unknown-year model, the hydrofluosilicic acid category was significantly different than the no-fluoride category: the GM PbB concentration for hydrofluosilicic acid was 45% higher. This significant association between hydrofluosilicic acid and GM PbB concentration seen in the unknown-year stratum was not observed in the other strata. In addition, there was no trend toward increasing GM ratios for the silicofluoride categories with increasing dwelling age.”

"We have shown that 1 h after the intake of 1.44 mmol (60 mg) of NaF by fasting human volunteers, plasma fluoride increased up to 15 umol/L and insulin levels decreased significantly [1]. The same phenomenon was reproduced in rats. The oral administration of sodium fluoride [40 umol/100 g body weight) to fasting rats produced an immediate increase in plasma fluoride, a fall in insulin levels and the consequent increase in glycemia. With the washing-out of fluoride from plasma and soft tissues (4-5 h), glycemia and insulin returned to normal levels. The insulin secretion of isolated Langerhans islets perfused with solutions containing 5-20 umol/L fluoride was found significantly inhibited as a function of fluoride levels, both with basal and stimulatory concentrations of glucose [1]. In agreement, we have reported that in a group of 24 women and two men (44-66 years old, ex-residents of an area of endemic fluorosis) with fasting fluoremias of 0.5 to 9.2 umol/L, the area under the curve (AUC) of insulin during standard glucose tolerance tests showed an inverse relationship with fluoremia [2]. The overall information afforded by present experiments indicate that extracellular concentrations of fluoride above 5 umol/L [95 parts per billion] affect the insulin excretion. The results suggest that fluoride affects some stage of insulin secretion situated below the cascade of events that include the participation of calmodulin, protein-kinase C and cyclic AMP."

“Natural iodine deficiency and ambient air pollution with fluorine compounds were examined for their combined influence on the prevalence and severity of iodine-deficiency disorders. The excess intake of fluorine was shown to increase the incidence of thyroid diseases and to lower anthropometric indices in children. The preventive measures performed to eliminate iodine-deficiency disorders under intensive ambient air pollution with fluorine compounds were found to be insufficiently effective.”

“This study was designed to evaluate adverse health effects in adolescents from chronic exposure to various water fluoride concentrations in three communities located in northern Mexico: Ciudad Juarez, Samalayuca, and Villa Ahumada. In these communities the fluoride concentration in water averages 0.3, 1.0, and 5.3 mg/L, respectively. The residents of Villa Ahumada have been exposed to excessive levels of fluoride in drinking water since their birth. Using urinary fluoride as biomarker, we evaluated the effect of fluoride on dental fluorosis, growth, thyroid hormones, hepatic function, lipids, uric acid, and electrolytes. A total of 201 adolescents (106 female, 95 male), aged 15–20, were included in the study... In Villa Ahumada 97 percent of all adolescents exhibited dental fluorosis, and 18 percent of them have serious damage to their teeth. In Samalayuca 53 percent of all adolescents exhibited mild dental fluorosis, 15 percent of them have moderate dental fluorosis, and 2 percent showed serious damage in their teeth. In Villa Ahumada a significant inverse relationship was found between urine fluoride levels and stature; this association suggests that fluoride exposure may affect the teeth but also the growth of adolescents. Serum samples of these individuals showed elevated levels of alkaline phosphatase (ALP), potassium, magnesium, calcium, and phosphate, and decreased levels of thyroid hormone T3 and uric acid. These findings show that high fluoride ingestion has a definite relationship with the prevalence and severity of dental fluorosis, decrease of stature, and decrease of thyroid hormone secretion. Uric acid is one of the important antioxidants of plasma, and its level was lower in fluorotic adolescents, indicating that fluoride toxicity may involve a reduction on certain intrinsic scavengers resulting in an increased vulnerability to oxygen free radical toxicity.”

“SUMMARY: Thirty-two one-month-old Wistar albino rats were divided randomly into four equal groups of eight (female:male = 3:1). To assess damage to DNA in their thyroid gland cells, the first group (1) of rats served as the untreated control, the second group (2) was administered a high concentration of fluoride (HiF, 100 mg NaF/ L [45 mg F–/L] in their drinking water), the third group (3) was placed on a low iodine intake (LI, 0.0855 mg I/kg diet), and the fourth group (4) was exposed to the high fluoride and low iodine treatment combined (HiF+LI). At 20 months of age, the rats were sacrificed for experimental purpose and their thyroid gland cells were removed for single cell gel electrophoresis (SCGE = comet assay). In comparison with DNA damage in the thyroid gland cells of the control group 1 (10.74 ± 12.59%), such DNA damage in the LI, HiF, and HiF+LI groups 2, 3, and 4, was 83.50 ± 10.20%, 83.03 ± 12.11%, and 89.32 ± 8.21%, respectively. Moreover, the proportion of grade III thyroid gland cell damage increased by 32.26% in group 2, 47.83% in group 3, and 69.23% in group 4, as compared to the control group 1. These findings indicate that excessive long-term intake of fluoride, with or without adequate I intake, is a significant risk factor for the development of thyroid dysfunction.”

“SUMMARY: Thirty-two Wistar rats were divided randomly into four groups of six females and two males each. The experimental groups were exposed to high fluoride drinking water (45 mg F–/L from 100 mg NaF/L), low dietary iodine (0.0855 mg/kg), or both together in order to assess the effects of these three factors on the structure of the brain of the offspring rats. After the animal model was established, offspring rats were bred, and thirty-six rats from each group (female:male = 1:1) were used for the study. The treatment of the offspring rats was the same as that of their parents. In comparison with the control rats, the nuclei of many nerve cells were pyknosed and absent, the Nissl substance also showed various degrees of decrease, and the dendrites were elongated. The results indicate that the histopathological changes in the brain were initially due to lipid peroxidation caused by the interaction of high fluoride and low iodine. These changes in brain histopathology apparently occurred mainly during the period of embryonic development and in the early stage of brain development after birth.”

“In conclusion, DNA strands in brain cell are affected adversely when rats are exposed to high fluoride, low iodine, and the interactive combination of these two factors from the age of one month to 20 months. The rate and degree of DNA damage in brain cells is higher in the High Fluoride + Low Iodine group than in either the High Fluoride or Low Iodine group.”

“This study investigated the effects of arsenism and fluorosis on the mental ability (MA) and growth of children living in areas endemic for arsenism, fluorosis , or both. The children were divided into high arsenic/fluoride group (group 1), high fluoride group (group 2), high arsenic group (group 3), and control group. Group 2 [high fluoride group] showed significantly lower MA [mental ability] than the control group ( P<0.01). MA was lower in group 1 than in the control group (P<0.05), but was almost similar between group 1 and group 2 (P>0.05). Group 3 showed the lowest MA score among the groups (P <0.01). The MA score was negatively correlated with urinary arsenic (P<0.01) and fluoride levels (P<0.05). The height of group 2 and the body weight of group 3 children were significantly lower than those of the control group ( P<0.05). The vital capacity of group 1 was significantly lower than that of control children (P<0.05). It is concluded that high exposure to arsenic, fluoride, or both has significant negative effects on the MA and growth of children.”

“Objective: To determine radiological changes in bones and joints among patients in Dingbian County, China, where fluorosis is related to the supply of drinking water. Methods: Radiographic films of the pelvis, right forearm, and right leg were evaluated for randomly selected patients. Results: Based on the results of the radiographic films, the detection rate of skeletal fluorosis was 72.23%. Skeletal changes were seen more on the forearm and legs as compared to the pelvis. However, the radiographic diagnosis did not correspond to the clinical diagnosis. Radiographic changes were positively correlated with fluoride content in the drinking water. Thus, early diagnosis of fluorosis is difficult due to non-concordance of clinical features with radiographic changes.”

“The dose-response relationship between fluoride in brick-tea and the prevalence of skeletal fluorosis (SF) in adults was studied to determine a safe upper limit for fluoride intake from brick-tea. In brick-tea drinking endemic fluorosis areas of the Tibetan pastoral areas of Sichuan province, cluster sampling was conducted of residents above age thirty in Amu, Jiangrong, Anqu, Longrang, and Maiwashi villages of Hongyuang County in Aba state. X-ray technology was used to diagnose SF, and the daily fluoride intake of each person from bricktea infusions was determined by a retrospective cohort study. Results: Among the 207 residents examined, the X-ray standardized prevalence rate of SF was 49.76%, which increased with age and poor health, especially among persons over age forty. Both the amount of drinking brick-tea infusions and the amount of fluoride intake from them increased with age and were higher in the SF group than that in the unaffected group. The average daily fluoride intake was 4.49±1.51 mg/person/day) in the SF group and 1.86±1.46 mg/person/day in the unaffected group. The average daily fluoride intake of subjects with different stages or grades of SF was 3.36±1.35 mg (stage I), 4.96±1.44 mg (stage II), and 6.42±1.33 mg (stage III), respectively. There was a significant (p<0.05) positive linear correlation between the logarithm of daily fluoride intake from brick-tea and the prevalence of SF in each age group. The 95% normal upper-limit for daily fluoride intake from brick-tea was 3.37 mg/person/day, but the 90% unilateral upper-limit was 2.94 mg/person/day, which reflected the SF status more truly and avoided missing and misjudging diagnosis.”

”Brick tea infusion containing 100 mg/litre fluorine was made according to the methods used by inhabitants living in areas (in China) with endemic fluorosis. The infusion was diluted to 5 or 50 mg/litre fluorine concentrations, followed by the de-fluoridation. Wistar rats were randomly divided into 5 groups: Group A was given tap water (control); group B and C were given brick tea with serpentine at 5.0-1.5 and 50.0-1.5 mg/litre, respectively; group D and E were given brick tea at 5 and 50 mg/litre, respectively. Fluoride contents in serum, urine and bones were determined, and the morphological changes in bones, kidneys and liver were observed under light microscopy and transmission electron microscopy. The fluoride contents in the urine and bones of fluoride treated rats were higher than that in the controls. The pathological changes in the bones, kidneys and livers were significantly more pronounced in group E [50 ppm fluoride], and followed by group D [5 ppm fluoride].”

“Our earlier studies showed that the apoptosis of renal tubules can be induced by sodium fluoride (NaF). The present study was designed to estimated the effects of B-cell lymphoma/leukemia 2 (Bcl-2), Bcl-2-associated protein X (Bax), and osteopontin (OPN) on the apoptosis of renal tubular cells induced by NaF at different levels. The technique of reverse transcription-polymerase chain reaction and densitometer scanning volume density were used to evaluate the changes of Bcl-2, Bax, and OPN mRNA in tubular cells treated with different doses of NaF (0, 1, 5, 7.5, 12.5 mgF-/L) for 48 h. Compared to control, the level of Bax mRNA significantly increased at cells of the 7.5- and 12.5-mg F-/L groups and the expression of Bcl-2 mRNA obviously decreased at cells of the 5- and 7.5-mg F-/L groups. The NaF also enhanced the expression of OPN mRNA in a dose-dependent manner, but the strongest expression of OPN mRNA was observed at cells of the 7.5-mg F-/L group. The results suggested that NaF induces the apoptosis in renal tubules via activation of the Bax expression and Bcl-2 suppression; OPN probably acts as protective role against apoptosis in fluoride-treated renal cells.”

“An experiment was carried out on Sprague-Dawley rats (adult males) that for 50 days were administered, in the drinking water, NaF and NaF with caffeine (doses, respectively: 4.9 mg of NaF/kg body mass/24 h and 3 mg of caffeine/kg body mass/24 h). Disturbances were noted in the functioning of kidneys, which were particularly noticeable after the administration of NaF with caffeine. Changes in the functioning of kidneys were also confirmed by such parameters as the level of creatinine, urea, protein, and calcium. Modifications of the enzymatic antioxidative system (superoxide dismutase, catalase, and glutathione peroxidase) and lipid peroxidation (malondialdehyde) were also observed. Changes in the contents of the above parameters as well as pathomorphological examinations suggest increased diuresis, resulting in dehydration of the rats examined.”

“The effects of excessive fluoride intake on intracellular ionized calcium level and oxidative stress in kidneys of Wistar rats were determined. The rats were fed sodium fluoride in drinking water. The intracellular ionized calcium level was measured using fura-2/AM, and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were tested using biochemical methods. Results revealed that intracellular ionized calcium level was increased in fluoride-exposed group as compared to control group. The same increase was observed between the low calcium + fluoride group and low calcium group. SOD activity was lower, whereas MDA level was higher in low calcium + fluoride group than in low calcium group. It is suggested that the higher level of intracellular ionized calcium and oxidative stress are possibly significant in fluorosis pathology. The high level of intracellular ionized calcium and oxidative stress after excessive fluoride intake, along with low calcium, indicate that calcium nutrition has close connection with fluorosis mechanism.”