High Fluoride Exposure Research Articles

Effects of high fluoride and iodine combined exposure on thyroid nodules and goiter in school-age children in Jiangsu, China

Effects of high fluoride and iodine combined exposure on thyroid nodules and goiter in school-age children in Jiangsu, China

Assessment of fluoride accumulation in various vegetable and leafy greens consumed in Morocco

Fluoride is an essential element in preventing tooth decay, but excessive consumption can be harmful to health. There are various sources of fluoride exposure, including oral intake from water, tea, dates, toothpaste, and green vegetables; however, the extent of exposure varies among different groups in the population. Therefore, it is crucial to monitor the consumption of these sources to avoid the risk of excessive fluoride intake. Our study, analyzing 33 varieties of root, fruit, tuber, and leaf vegetables produced in the Rabat-Salé-Kenitra region of Morocco, should be aiming to understand fluoride accumulation in vegetables, classify different varieties based on their fluoride content, and assess the risks associated with high fluoride exposure through vegetable consumption. The results revealed fluoride levels ranging from 2.3 to 36.2 mg/kg for leaves of consumable plants, 0.17 to 13.2 mg/kg for leafy vegetables, 0 to 5.19 mg/kg for fruit vegetables, 1.45 to 3.66 mg/kg for tuber vegetables, 1.62 to 8.33 mg/kg for bulb vegetables, and 0.85 to 3.40 mg/kg for root vegetables. This study emphasizes the significance of understanding fluoride concentrations in vegetables. It suggests classifying different varieties based on their fluoride content to prevent the risks associated with excessive fluoride exposure from consuming these vegetables. High fluoride exposure through vegetables can result in various health problems, including dental, skeletal, and other types of fluorosis.

Fluoride exposure and pediatric kidney health in dry, wet and intermediate climatic zone communities in Sri Lanka: Implications from urinary Cystatin-C, and albumin-creatinine ratio

BackgroundHigh fluoride exposure is increasingly discussed attributing to kidney injury as a causative factor. Depending on geochemistry, differential fluoride levels in drinking water are identified in different regions in Sri Lanka. However, the levels of fluoride exposure, and associations with kidney health has not been adequately studied in Sri Lanka, particularly in pediatric communities. Hence, the present study aimed to assess fluoride exposure in selected pediatric communities in the dry, wet and intermediate climatic zones in Sri Lanka, along with an assessment of renal health using urinary Cystatin-C (uCys-C), and albumin-creatinine ratio (uACR). MethodsWe conducted a cross-sectional study with school students in selected education zones representing dry (N = 331), wet (N = 152), and intermediate (N = 292) climatic zones in Sri Lanka. Fluoride contents in urine and drinking water were assessed as measures of fluoride exposure. ResultsThe median (interquartile distance) urinary fluoride levels of participants in the dry, wet and intermediate zones were 1.63(1.04–2.85), 1.29(0.85–2.21), and 1.07(0.61–1.98) mg/gCr while the fluoride contents of drinking water samples were 1.76(1.36–2.30), 0.25(0.18–0.37), and 0.43(0.26–0.63) ppm respectively with significant differences among the three groups. Median uCys-C level (ng/mgCr) of the participants in intermediate zone [30.26(8.49–71.44)] was significantly low (p < 0.05) compared to that of the participants in dry zone [56.19(7.08–211.8)], and wet zone [66.29(30.43–125.20)]. The incidences of elevated uCys-C levels above reference intervals in participants of dry zone (47.7%), and wet zone (50.0%) were significantly high (p < 0.001) compared to the intermediate zone (26.4%). ConclusionRelatively high fluoride exposure is likely in dry and wet zone communities compared to the intermediate zone along with significantly higher incidence of uCys-C levels above reference intervals in study groups with higher fluoride exposure. However, to conclude a clear link between fluoride exposure and kidney health we need in-depth studies.

Effect of zinc intake on association between fluoride exposure and abnormal sex steroid hormones among US pubertal males: NHANES, 2013-2016.

Excessive fluoride exposure can disturb the balance of sex hormones. Zinc is essential for sex hormone synthesis and spermatogenesis. But it is not clear how zinc affects the relationship of fluoride exposure with abnormal sex steroid hormones. Here, a total of 1008 pubertal males from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2013-2014, 2015-2016) were enrolled. The concentrations of water fluoride and plasma fluoride and the levels of serum testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured. Two 24-h dietary recall interviews were conducted to assess the dietary zinc intake. The relationships of fluoride exposure and zinc intake with sex hormones were examined using linear regression and logistic regression models, while the generalized additive model was used to evaluate their non-linear relationship. Our findings revealed that for every two-fold increase in plasma fluoride concentration, testosterone levels decreased by 7.27% (95% CI - 11.49%, - 2.86%) and estradiol levels decreased by 8.73% (95% CI - 13.61%, - 3.57%). There was also significant non-linear association observed between zinc intake and SHBG levels. Being in the first tertile of plasma fluoride had a 60% lower risk of high SHBG (OR = 0.40, 95% CI 0.18, 0.89) compared with being in the second tertile. When compared to the first tertile, being in the second tertile of zinc intake was associated with a 63% (OR = 0.37, 95% CI 0.14, 0.98) lower risk of high SHBG. Furthermore, we observed an interactive effect between the plasma fluoride and zinc intake on estradiol and SHBG, as well as the risk of high SHBG (P-interaction < 0.10). These findings suggest that fluoride exposure and zinc intake can affect sex steroid hormone levels and the risk of high SHBG. Notably, zinc intake may alleviate the increased risk of high SHBG and the abnormal changes of estradiol and SHBG caused by higher fluoride exposure.

A brief review of industrial fluorosis in domesticated bovines in India: Focus on its socio-economic impacts on livestock farmers

An excessive and repeated high fluoride exposure over a long period of time is harmful to the health of humans and domestic animals and causes several toxic effects in the form of fluorosis disease. If fluoride exposure is due to industrial fluoride, the disease is known as industrial fluorosis. In recent years, due to rapid industrialization in India, various health problems are increasing continuously among domesticated bovine animals, cattle (Bos taurus) feed and water buffalo (Bubalus bubalis) living and grazing in industrial areas due to industrial fluoride pollution. In fact, many coal-burning and industrial activities, such as power generating stations and the manufacturing of steel, iron, aluminum, zinc, phosphorus, chemical fertilizers, bricks, cement, hydrofluoric acid, etc are generally discharging fluoride into their surrounding areas which create industrial fluoride pollution. An industrially emitted fluoride not only contaminates the surrounding environment including soil, air and fresh water reservoirs, but also contaminates vegetation, agricultural crops, and many other biological communities on which bovines generally survive. These animals develop a number of toxic effects on their teeth (dental fluorosis), bones (skeletal fluorosis) and soft organs (non-skeletal fluorosis) due to chronic industrial fluoride intoxication. Due to industrial fluorosis, bovine animals become physically weak and lame, and diverse health problems, such as anemia, gastrointestinal discomforts, polyuria, polydipsia, impaired reproduction, etc. are also found in them. In the country, many domesticated bovines are suffering with industrial fluorosis. In these animals, the maximum prevalence, 84.11% of industrial dental fluorosis and 72.0% of skeletal fluorosis has been reported. In the country, the research works done so far on industrial fluorosis in bovines are briefly and critically reviewed in the present communication. Along with this, the focus has also been on the adverse socio-economic impacts of industrial fluorosis on livestock farmers and how to prevent this disease in these animals.

Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children

To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children. A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF >1.41mg/L) and low fluoride exposure group (LFG, CUF ≤1.41mg/L) according to the median concentration of CUF (1.41mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models. Negative and positive associations between serum TT4 level (β=-0.721, 95%CI: -1.209, -0.234) and Tvol (β=0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P<0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P<0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P<0.05, respectively). Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

Fluoride contamination in drinking water and associated health risk assessment in the Malwa Belt of Punjab, India

• We report fluoride levels in 745 groundwater samples from the Malwa Belt, Punjab. • 49.7% of the samples exceeded the WHO guideline value of 1.5 mg L −1 . • High fluoride levels are observed in industrial and agricultural predominant areas. • Health risk assessment was computed for different age groups through ingestion. • Children and teenagers are more vulnerable to high fluoride exposure than infants. This study highlights fluoride concentrations, the associated non-carcinogenic risk for various age groups (infants, children, teenagers, adults, and senior citizens), and physicochemical parameters in 745 groundwaters from 7 districts of Punjab. The fluoride levels varied from 0.1 to 17.5 mg L −1 with an average value of 2.1 ± 1.8 mg L −1 and a median of 1.5 mg L −1 , and 49.7% of samples exceeded the permissible limit of 1.5 mg L −1 prescribed by the Bureau of Indian Standards and World Health Organization. The mean fluoride concentrations in the seven districts followed the order of Bathinda (3.2 mg L −1 ) > Muktsar (2.6 mg L −1 ) > Faridkot (2.4 mg L −1 ) > Mansa (2.3 mg L −1 ) > Fazilka (1.3 mg L −1 ) > Barnala (1.1 mg L −1 ) > Moga (1.0 mg L −1 ). Fluoride in groundwater showed a significant relationship with total dissolved solids in all the districts except the Moga district. The results showed that mean hazard quotients (HQs) were greater than 1 for all age groups in Bathinda, Mansa, Faridkot, and Muktsar districts. The non-carcinogenic risk among the investigated age groups was in the order of children > teenagers > adults > senior citizens > infants. The results revealed that the groundwater is unfit for human consumption. Further investigations are required in the study region to measure the daily fluoride exposure in other drinking water sources such as canal water, municipal reverse osmosis water, and bottled water.

Necessity to Pay Attention to the Effects of Low Fluoride on Human Health: an Overview of Skeletal and Non-skeletal Damages in Epidemiologic Investigations and Laboratory Studies.

Due to the implementation of water improvement and fluoride reduction plans supported by central and local governments in recent years, areas with high fluoride exposure are being gradually decreased. Therefore, it is of practical importance to study the effect of low fluoride on human health. Epidemiologic investigations and in vivo and in vitro studies based on low fluoride have also confirmed that fluoride not only causes skeletal damage, such as dental fluorosis, but also causes non-skeletal damage involving the cardiovascular system, nervous system, hepatic and renal function, reproductive system, thyroid function, blood glucose homeostasis, and the immune system. This article summarizes the effects of low fluoride on human and animal skeletal and non-skeletal systems. A preliminary exploration of corresponding mechanisms that will help to fully understand the harm of low fluoride on human health was undertaken to provide the basis for establishing new water fluoride standards and help to implement individual guidance.

Preventive effects of Lactobacillus johnsonii on the renal injury of mice induced by high fluoride exposure: Insights from colonic microbiota and co-occurrence network analysis

Fluoride (F) exposure was widely reported to be associated with renal diseases. Since absorbed F enters the organism from drinking water mostly through the gastrointestinal tract, investigating changes of gut microbes may have profound implications for the prevention of chronic F exposure because increasing evidence supported the existence of the gut-kidney axis. In the present study, we aimed to explore the potential positive effects of probiotics on high F exposure-induced renal lesions and dysfunction in mice by the modulation of the colonic microbiota. Mice were fed with normal (Ctrl group) or sodium-fluoride (F and Prob groups; 100 mg/L sodium fluoride (NaF)) drinking water with or without Lactobaillus johnsonii BS15, a probiotic strain proven to be preventive for F exposure. Mice fed with sodium-fluoride drinking water alone exhibited renal tissue damages, decreased the renal antioxidant capability and dysfunction. In contrast, L. johnsonii BS15 reversed these F-induced renal changes. 16S rRNA gene sequencing shows that L. johnsonii BS15 alleviated the increased community diversity (Shannon diversity) and richness index (number of observed features) as well as the distured structure of colon microbiota in F-exposed mice. A total of 13 OTUs with increased relative abundance were identified as the keystone OTUs in F-exposed mice based on the analysis of degree of co-occurrence and abundance of OTUs. Moreover, Spearman’s rank correlation shows that the 13 keystone OTUs had negative effect on renal health and intestinal integrity. L. johnsonii BS15 reversed four of keystone OTUs (OTU 5, OTU 794, OTU 1035, and OTU 868) changes which might be related to the underlying protected mechanism of L. johnsonii BS15 against F-induced renal damages.

A systematic review and meta-analysis of the association between fluoride exposure and neurological disorders

Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to “Humans”; “Central nervous system”; “Fluorides”; and “Neurologic manifestations” were searched in a systematic way on PubMed, Scopus, Web of Science, Lilacs, Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.

Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects

BACKGROUND AND AIM: People of all ages are exposed to fluoride from a variety of sources including dental products, drinking water, food, beverages and pharmaceuticals. In some developed countries, fluoride is added to municipal water systems to prevent tooth decay. The National Toxicology Program (NTP) conducted a systematic review of the human, experimental animal, and mechanistic literature to evaluate the extent and quality of the evidence about whether fluoride exposure is associated with neurodevelopmental and cognitive effects. METHODS: A systematic review protocol was developed and utilized following the Office of Health Assessment and Translation (OHAT) approach for conducting literature-based health assessments. RESULTS:The literature search and screening process identified 159 published human studies, 339 published experimental animal studies, and 60 in vitro/mechanistic studies. While the animal data provide some evidence of effects of fluoride on neurodevelopment, the human evidence base is large, directly addresses cognitive neurodevelopmental effects, and is most informative concerning the effects of fluoride on cognitive neurodevelopment in children. CONCLUSIONS:The human body of evidence provides a consistent and convincing pattern of findings that higher fluoride exposure (e.g., 1.5 mg/L in drinking water) is associated with lower measures of cognitive neurodevelopment, primarily in measures of children’s IQ. When focusing on findings from studies with fluoride exposures in ranges typically found in drinking water in the United States (0.7 mg/L for optimally fluoridated community water systems), effects on cognitive neurodevelopment of children are inconsistent, and therefore unclear. The evidence for effects of fluoride exposures on cognition in adults is also limited. The evidence from animal studies is difficult to directly relate to the observed cognitive effects in humans, and the mechanisms underlying fluoride-associated cognitive neurodevelopmental effects are not well characterized. KEYWORDS: Fluoride, systematic review, children's IQ

Environmental fluoride exposure disrupts the intestinal structure and gut microbial composition in ducks

Fluorine (F) and its compounds produced from industrial production and coal combustion can cause air, water and soil contamination, which can accumulate in animals, plants and humans via food chain threatening public health. Fluoride exposure affects liver, kidney, gastrointestinal and reproductive system in humans and animals. Literature regarding fluoride influence on intestinal structure and microbiota composition in ducks is scarce. This study was designed to investigate these effects by using simple and electron microscopy and 16S rRNA sequencing techniques. Results indicated an impaired structure with reduced relative distribution of goblet cells in the fluoride exposed group. Moreover, the gut microbiota showed a significant decrease in alpha diversity. Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in both control and fluoride-exposed groups. Specifically, fluoride exposure resulted in a significant decrease in the relative abundance of 9 bacterial phyla and 15 bacterial genera. Among them, 4 phyla (Latescibacteria, Dependentiae, Zixibacteria and Fibrobacteres) and 4 genera (Thauera, Hydrogenophaga, Reyranella and Arenimonas) weren’t even detectable in the gut microbiota of the ducks. In summary, higher fluoride exposure can significantly damage the intestinal structure and gut microbial composition in ducks.

Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects

Background: People of all ages are exposed to fluoride from a variety of sources including dental products, drinking water, food, beverages and pharmaceuticals. In some developed countries, fluoride is added to municipal water systems to prevent tooth decay. Methods: The National Toxicology Program (NTP) conducted a systematic review of the human, experimental animal, and mechanistic literature to evaluate the evidence and develop hazard conclusions about whether fluoride exposure is associated with neurodevelopmental and cognitive effects. Results: The literature search and screening process identified 185 published human studies, 339 published experimental animal studies, and 60 in vitro/mechanistic studies. Conclusion: Although draft conclusions were reached by integrating evidence from human and animal studies with consideration of relevant mechanistic data, the conclusions are based primarily on the human evidence. The body of human evidence provides a consistent pattern of findings, across several different populations, that high fluoride exposure is associated with lower intelligence quotient (IQ) in children. These consistent findings are based primarily on studies with higher levels of fluoride exposure (i.e., &gt;1.5 ppm in drinking water). When focusing on findings from studies with exposures in ranges typically found in the United States (approximately 0.03 to 1.5 ppm in drinking water) that can be evaluated for dose response, effects on cognitive neurodevelopment are inconsistent, and therefore unclear. There is inadequate evidence to determine whether fluoride exposure lowers IQ or impairs cognitive function in adults. The evidence from animal studies is inadequate to inform conclusions on cognitive effects, and the mechanisms underlying fluoride-associated cognitive neurodevelopmental effects are not well characterized. The NTP will develop hazard conclusions for children and adults on a 4-level scale for hazard classification (“known”, “presumed”, “suspected”, “not classifiable”). Keywords: Fluoride, exposure, systematic review, epidemiology.

Fluoride Exposure and Blood Pressure: a Systematic Review and Meta-Analysis.

Fluoride exposure may cause changes in blood pressure, but this conclusion is controversial. Therefore, this meta-analysis aims to investigate the potential relationship between fluoride exposure and blood pressure or hypertension. PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG MED ONLINE, and Chinese Scientific Journals Full-Text Databases (VIP) were searched; in addition, two related studies were added manually. In total, 7 observational studies were identified, the pooled odds ratios (ORs) for hypertension between high and reference fluoride exposure groups were calculated, and the pooled standardized weighted mean difference (SMD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was estimated using an inverse-variance weighted random-effects model; next, sensitivity analysis and subgroup analysis were used to assess potential sources of heterogeneity; furthermore, publication bias was assessed using the Begg and Egger test. In brief, there were no statistical differences between exposure groups and control groups in terms of blood pressure or hypertension when all included studies considered. However, subgroup analysis indicated that blood pressure will rise with the increase of fluoride exposure concentrations in endemic fluorosis areas. The corresponding pooled SMD estimates were 0.31 (95% CI 0.11, 0.51) and 0.27 (95% CI 0.11, 0.43) for SBP and DBP. Funnel plots suggested no asymmetry. Our findings support the possibility of a positive correlation between fluoride exposure and blood pressure in endemic fluorosis areas. Additional evidence is needed to assess the dose-response relationship between fluoride exposure and blood pressure.

Controversy: The evolving science of fluoride: when new evidence doesn't conform with existing beliefs.

Over the past 75 years, health authorities have declared that community water fluoridation-a practice that reaches over 400 million worldwide-is safe. Yet, studies conducted in North America examining the safety of fluoride exposure in pregnancy were nonexistent. When a Canadian study reported that higher fluoride exposure in pregnant women was associated with lower IQ scores in young children, critics attacked the methodology of the study and discounted the significance of the results. Health authorities continued to conclude that fluoride is unequivocally safe, despite four well-conducted studies over the last 3 years consistently linking fluoride exposure in pregnancy with adverse neurodevelopmental effects in offspring. We describe the challenges of conducting fluoride research and the overt cognitive biases we have witnessed in the polarized fluoride debate. The tendency to ignore new evidence that does not conform to widespread beliefs impedes the response to early warnings about fluoride as a potential developmental neurotoxin. Evolving evidence should inspire scientists and health authorities to re-evaluate claims about the safety of fluoride, especially for the fetus and infant for whom there is no benefit.

Key Role of Pro-inflammatory Cytokines in the Toxic Effect of Fluoride on Hepa1-6 Cells.

The role of pro-inflammatory cytokines in the toxicity of fluoride to tumor cells was investigated by culturing Hepa1-6 cells in medium containing gradient concentrations of fluoride (0, 0.5, 1, 1.5, 2, 3, 4, and 5 mmol/L). The viability of Hepa1-6 cells was detected via MTT assay. Interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and IL-1β levels in the supernatant were determined via an enzyme-linked immunosorbent assay, and the protein expression levels of these enzymes in Hepa1-6 cells were evaluated by immunofluorescence staining. Results showed that the viability of Hepa1-6 cells remarkably decreases after fluoride exposure, especially at concentration of 3, 4, and 5 mmol/L fluoride. Levels of IL-2, TNF-α, and IL-1β in the supernatant markedly decreased when cells were exposed to fluoride at concentrations of 1 mmol/L or higher. However, levels of TNF-α and IL-1β substantially increased and IL-2 showed no remarkable change when the fluoride concentration was 0.5 mmol/L. The content of IL-6 remarkably increased with increasing fluoride concentrations up to 2 mmol/L, and then markedly decreased at 3, 4, and 5 mmol/L fluoride; the decreasing trend of IL-6 content under high fluoride exposure is consistent with the decrease in Hepa1-6 cell viability observed at the same concentration. The protein expression levels of IL-2, IL-6, TNF-α, and IL-1β were in accordance with their contents in the supernatant. In summary, our study demonstrated that fluoride inhibits Hepa1-6 cell growth and results in disorders in the expression and secretion pro-inflammatory cytokines.

Serum and urine fluoride levels in populations of high environmental fluoride exposure with endemic CKDu: a case-control study from Sri Lanka.

Chronic kidney disease of uncertain etiology (CKDu) is a common health issue among farming communities in the dry zone of Sri Lanka where groundwater fluoride is known to be higher than recommended levels. Excessive environmental ingestion of fluoride is widely considered as a possible factor for the onset of CKDu. This study was carried out to evaluate the serum and urine fluoride levels in biopsy-proven, non-dialysis CKDu patients. Control subjects were selected from the same area without any deteriorated kidney functions. Serum and urine fluoride levels were determined by ion-selective electrode method. Higher content of serum and urine fluoride levels were observed in patients with chronic renal failures. In CKDu cases, the serum fluoride concentrations ranged between 0.47 and 9.58mg/L (mean 1.39 ± 1.1mg/L), while urine levels were varied between 0.45 and 6.92mg/L (mean 1.53 ± 0.8mg/L). In patients, urine fluoride levels showed a significant difference with the CKDu stage; however, no difference was obtained between genders and age. In endemic controls, serum and urine fluoride levels ranged between 0.51 and 1.92mg/L (mean = 1.07 ± 0.3mg/L) and 0.36 and 3.80mg/L (mean = 1.26 ± 0.6mg/L), respectively. Significantly higher fluoride in serum and urine was noted in CKDu patients compared to endemic control groups. Higher fluoride exposure via drinking water is possibly the reason for higher fluoride in serum, while excessive urinary excretion would be due to deterioration of the kidney, suggesting a possible nephrotoxic role of environmental fluoride exposure.

Low-to-moderate fluoride exposure in relation to overweight and obesity among school-age children in China

High fluoride exposure has been related to harmful health effects, but the impacts of low-to-moderate fluoride on child growth and obesity-related outcomes remain unclear. We performed a large-scale cross-sectional study to examine the association between low-to-moderate fluoride in drinking water and anthropometric measures among Chinese school-age children. We recruited 2430 resident children 7–13 years of age, randomly from low-to-moderate fluorosis areas of Baodi District in Tianjin, China. We analyzed the fluoride contents in drinking water and urine samples using the national standardized ion selective electrode method. Multivariable linear and logistic analyses were used to assess the relationships between fluoride exposure and age- and sex-standardized height, weight and body mass index (BMI) z-scores, and childhood overweight/obesity (BMI z-score > 1). In adjusted models, each log unit (roughly 10-fold) increase in urinary fluoride concentration was associated with a 0.136 unit increase in weight z-score (95% CI: 0.039, 0.233), a 0.186 unit increase in BMI z-score (95% CI: 0.058, 0.314), and a 1.304-fold increased odds of overweight/obesity (95% CI: 1.062, 1.602). These associations were stronger in girls than in boys (Pinteraction = 0.016), and children of fathers with lower education levels were more vulnerable to fluoride (Pinteraction = 0.056). Each log unit (roughly 10-fold) increase in water fluoride concentration was associated with a 0.129 unit increase in height z-score (95% CI: 0.005, 0.254), but not with other anthropometric measures. Our results suggest low-to-moderate fluoride exposure is associated with overweight and obesity in children. Gender and paternal education level may modify the relationship.

Osseointegration of titanium dental implant under fluoride exposure in rabbits: Micro-CT and histomorphometry study.

This study aims to investigate the influence of fluoride exposure on implant osseointegration. A total of 24 male New Zealand white rabbits were randomly divided into the control group and the fluoride exposure group. Rabbits in the control group were fed with tap water, while those in the fluoride exposure group were given 200mg/L sodium fluoride solution. After 2-month feeding, implants were inserted into the extraction socket immediately after extraction of rabbit mandibular anterior teeth. Four rabbits in each group were sacrificed to collect the implants samples at 1, 2, and 3months post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the condition of implant osseointegration. Bone volume around the implants increased in a time-dependent manner in both groups. Micro-CT images illustrated that the bone mineral density (BMD) in the fluoride exposure group was significantly lower than that in the control group after implantation for 2 and 3months. The bone-implant contact ratio (BIC) in the fluoride exposure group was much lower than that of the control group at 3months post-implantation according to histomorphometry examination. In rabbit animal model, high fluoride exposure affected the quality of bone surrounding the implant and significantly reduced bone integration of the implant, especially in the late stage of osseointegration.

Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers.

Long-term occupational exposure to low level of fluoride can induce oxidative stress and apoptosis in many cells, including lymphocyte. However, the underlying mechanism remains unclear. Hence, this study was designed to explore the potential oxidative stress and apoptosis of long-term occupational exposure to low level of fluoride in aluminum smelter workers. A total of 120 aluminum smelter workers were recruited in control, low-, middle-, and high-fluoride exposure groups with 30 workers for each group. The peripheral blood samples were collected, centrifuged, and isolated to obtain serum and lymphocyte suspensions. The air and serum fluoride concentrations were detected by fluoride ion-selective electrode method. The lymphocytic apoptosis rate, DNA damage, oxidative stress, and mRNA levels of p53, Bcl-2, and Bax were assessed by Annexin V/PI staining, comet assay, attenuated total reflectance Fourier transform infrared spectroscopy and real-time polymerase chain reaction, respectively. Results showed that the air and serum fluoride concentrations of fluoride-exposed groups were higher than those of the control group (p < 0.05). Fluoride exposure might induce apoptosis, DNA damage and oxidative stress in a dose-dependent manner in lymphocytes (p < 0.05). The expression levels of p53 and Bax were increased with fluoride exposure in lymphocytes (p < 0.05), whereas the Bcl-2 expression was decreased but not significantly. Taken together, these observations indicate that long-term occupational exposure to low level of fluoride may lead to oxidative stress and induce apoptosis through the p53-dependent pathway in peripheral blood lymphocytes of aluminum smelter workers. Serum fluoride level may be the potential biomarker of fluoride exposure.