Fluoride Exposure Research Articles

The Association between Fluoride and Bone Mineral Density in US Children and Adolescents: A Pilot Study.

The aim of this study was to examine the association between fluoride exposure and bone mineral density (BMD) in children and adolescents. We used data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016. The fluoride concentrations in the water samples, plasma samples, and urine samples were measured electrometrically using an ion-specific electrode. Total body less head BMD (TBLH BMD) was measured using dual-energy X-ray absorptiometry (DXA). Weighted generalized linear regression models and restricted cubic splines (RCS) regression models were used to analyze the relationships between the three types of fluoride exposure and TBLH BMD. We performed subgroup analyses stratified by sex. A total of 1413 US children and adolescents were included in our study. In our linear regression models, we found inverse associations between fluoride concentrations in water and plasma and TBLH BMD. Additionally, we discovered a non-linear association between fluoride concentrations in water and plasma and TBLH BMD. No significant association or non-linear relationship was found between urine fluoride levels and TBLH BMD. This nationally representative sample study provides valuable insight into the intricate connection between fluoride exposure and skeletal health in children and adolescents.

P10-16 The role of gut microbiota in reproductive toxicity caused by fluoride and arsenic exposure

P10-16 The role of gut microbiota in reproductive toxicity caused by fluoride and arsenic exposure

Morphological changes in the fetal kidney induced by exposure to fluoride during pregnancy

To determine if fluoride’s established negative impact on adult kidney health begins during gestation, an intergenerational model of Wistar rats was exposed to two doses of fluoride (2.5 or 5.0 mg/kg/day via gavage) 20 days before mating and during gestation (20 days). The results revealed that fluoride was distributed to the amniotic fluid and fetus, resulting in lower weight, more pronounced fetal restriction, and decreased creatinine, osmolarity, and amniotic fluid volume. At the kidney level, less development in the nephrogenic and cortical zones was observed in the fluoride treatment groups, with an imbalance in the number of glomeruli and "S" shaped bodies, an increase in the immunoexpression of the marker of proliferation Ki-67 in the nephrogenic zone, an increase in the expression of Wnt4 and more maturation of the renal tubules, indicating that fluoride exposure during pregnancy alters kidney development and promotes early maturation of tubular segments.

Mapping the Environmental Risk of Fluoride Exposure of Drinking Water in a Community of Zacatecas, Mexico

Fluoride (iF) is an inorganic element commonly present in groundwater in central Mexico and is considered a health risk when it exceeds the Mexican drinking water standard of 1.5 mg/L. Prolonged exposure to iF can cause various adverse health effects, such as dental fluorosis and neurological effects, particularly in children. A rapid and cost-effective strategy to identify possible areas where the resident population may be at risk of exposure to this contaminant is the health risk estimation methodology of the Pan American Health Organization (PAHO). The aim of this study was to estimate the environmental risk of iF exposure in residents of Jerez, Zacatecas, Mexico, and subsequently construct risk maps to identify areas of the city where there is a higher risk of exposure. Fifty-five tap water samples were collected from households to determine iF concentrations using the ion-selective electrode method. Based on these environmental values, the hazard quotient (HQ) was estimated following the health risk estimation methodology. Subsequently, risk maps were generated from these values to visualize the spatial distribution of high-risk areas within the city. The iF concentrations in tap water ranged from 1.3 to 7.3 mg/L (ppm), with only one sample below the standard of 1.5 mg/L. We estimated HQ values ranging from 0.63 to 3.73. Exposure to iF in tap water is a health problem that must be addressed, necessitating risk communication actions that enable the population to safeguard its health through simple measures, thereby avoiding future health costs.

Comparative assessment of fluoride and arsenic mobilization mechanisms among the groundwater of the major affected river basins of India

ABSTRACT The high exposure of fluoride and arsenic in the groundwater of India is a serious challenge that is currently threatening human health, agriculture, livestock, and livelihood. The increased dependency on groundwater due to monsoonal uncertainties amplifies the risk by several folds. Due to the high population density in the affected regions, policies on prevention, monitoring, and mitigation have become extremely challenging to implement. The pursuit of improved human health in the affected regions cannot be completed until and unless there is sufficient urbanization and industrialization to support the livelihood, which again aggravates the situation due to improper disposal of anthropogenic contaminants owing to the lack of knowledge about the natural cycle of contaminants. The present review article is an attempt to understand the problem of fluoride and arsenic in the scenario of Indian floodplains by first explaining the globally identified mobilization mechanisms of these contaminants and then developing a compendium of knowledge through which the risk on the Indian floodplains can be analysed. Then the study compares the similarity/dissimilarity in the enrichment mechanism followed by a detailed investigation of the available mitigation techniques. In totality, the present study adds a new dimension to our understanding of the risk due to contaminants.

Fluoride-Induced Alterations in the Pancreas of Mammals: A Meta-analysis.

This review explores the diverse effects of fluoride on pancreatic function, encompassing both in vitro and in vivo studies. Fluoride exposure induces notable alterations at the cellular and molecular levels, affecting pancreatic morphology, histology, and enzymatic activity. In vitro studies demonstrate significant inhibition of pancreatic α-amylase activity and apoptosis in pancreatic beta cells. In vivo investigations reveal structural abnormalities in pancreatic cells, including mitochondrial damage, vacuolation, and nuclear damage. Moreover, fluoride exposure disrupts antioxidant enzyme activity, exacerbating oxidative stress and lipid peroxidation. Changes in digestive enzyme activity, such as the inhibition of pancreatic lipase and α-amylase, further contribute to pancreatic dysfunction. Additionally, alterations in hormone secretion, notably insulin levels and disturbed glucose homeostasis, highlight the complex effects of fluoride on the pancreatic endocrine system. These findings underscore fluoride-induced pancreatic toxicity and highlight the need for a comprehensive understanding and mitigation strategies to safeguard pancreatic health.

Development and Psychometric Validation of Population-Based Knowledge Attitudes and Practices-Questionnaire on Fluoride (PBKAP-QF).

Fluoride exposure is a global public health concern. Understanding the knowledge, attitudes, and practices (KAP) of affected populations is essential for effective community management. This study aimed to develop and validate a KAP questionnaire to assess fluoride and its risk in general population.An extensive literature review and focus group discussions were conducted to construct the questionnaire. Content validity was assessed using the Content Validity Index (CVI) based on expert feedback. Factor analysis was performed for final tool validation, and item characteristics were analyzed using IBM SPSS v. 27 and IBM AMOS v. 26.A total of 300 responses were collected. Initially, 41 items were included in the questionnaire, which were reduced to 25 after expert review. The final version included 19 items, with an I-CVI ranging from 0.80 to 1.00, indicating no issues with item difficulty or discrimination. Cronbach's alpha ranged from 0.88 to 0.90, demonstrating good internal consistency. The Kaiser-Meyer-Olkin (KMO) value was 0.848, and Bartlett's test (χ2 = 6860.978, df = 156, p < 0.01) confirmed data suitability for factor analysis. Three constructs were extracted with factor loadings greater than 0.5. Confirmatory factor analysis demonstrated a good model fit.This study developed and validated a robust 19-item KAP questionnaire for assessing knowledge, attitudes, and practices related to fluoride exposure. The tool demonstrated excellent reliability, validity, and internal consistency, supporting its use in guiding effective community-level management and public health interventions in fluoride-endemic areas.

Assessing variability and hydrochemical characteristics of groundwater fluoride contamination and its associated health risks in East Singhbhum district of Jharkhand, India

Groundwater pollution caused by fluoride is a significant concern for the global population owing to its toxicity, which has negative health consequences. Industrial discharges, agricultural practices, and improper waste disposal are primary concerns in evaluating the degree of fluoride contamination in the selected districts of Eastern India. In a targeted area sampling approach, exactly 196 samples were collected during pre- and post-monsoon, and precise fluoride detection was performed using Ion-Selective Electrodes. Fluoride levels in pre-monsoon water were observed within a range of 0.02 to 2.7 mg/L, with an average abundance of 0.4 ± 0.50. In post-monsoon, the concentration ranged from 0.02 to 4.7 mg/L (mean 0.53 ± 0.60). The study found that 97 % of groundwater samples had acceptable fluoride levels within the 1.5 mg/L limit during pre and post-monsoon. Moreover, approximately 87 % of the samples exhibit fluoride content below the 1 mg/L limit. The hazard quotient was observed to be 0.17 to 0.58 in adults, 0.23 to 0.79 in children and 0.36 to 1.26 in infants during pre-monsoon, whereas 0.05 to 0.55 in adults, 0.12 to 0.74 in children and 0.11to 1.19 in infants during post monsoon. The above data indicates that infants had the highest risk of fluoride exposure, with a significant negative correlation between fluoride and calcium ions. Fluoride had minimal to no link with other ions, a modest positive correlation with sulfate, and a weak negative relationship with overall hardness and alkalinity across both seasons. The present study contributes towards the identification of fluoride levels in various areas, making society aware of water contamination and its health impacts.

Association Between Environmental Fluoride Exposure and Bone Speed of Sound (SOS) at One Year Postpartum

Association Between Environmental Fluoride Exposure and Bone Speed of Sound (SOS) at One Year Postpartum

Epigenome-wide association study of fluoride exposure and DNA methylation among U.S. children

Epigenome-wide association study of fluoride exposure and DNA methylation among U.S. children

Salivary proteomic signatures in severe dental fluorosis

The relationship between dental fluorosis and alterations in the salivary proteome remains inadequately elucidated. This study aimed to investigate the salivary proteome and fluoride concentrations in urine and drinking water among Thai individuals afflicted with severe dental fluorosis. Thirty-seven Thai schoolchildren, aged 6–16, were stratified based on Thylstrup and Fejerskov fluorosis index scores: 10 with scores ranging from 5 to 9 (SF) and 27 with a score of 0 (NF). Urinary and water fluoride levels were determined using an ion-selective fluoride electrode. Salivary proteomic profiling was conducted via LC–MS/MS, followed by comprehensive bioinformatic analysis. Results revealed significantly elevated urinary fluoride levels in the SF group (p = 0.007), whereas water fluoride levels did not significantly differ between the two cohorts. Both groups exhibited 104 detectable salivary proteins. The NF group demonstrated notable upregulation of LENG9, whereas the SF group displayed upregulation of LDHA, UBA1, S100A9, H4C3, and LCP1, all associated with the CFTR ion channel. Moreover, the NF group uniquely expressed 36 proteins, and Gene Ontology and pathway analyses suggested a link with various aspects of immune defense. In summary, the study hypothesized that the CFTR ion channel might play a predominant role in severe fluorosis and highlighted the depletion of immune-related salivary proteins, suggesting compromised immune defense in severe fluorosis. The utility of urinary fluoride might be a reliable indicator for assessing excessive fluoride exposure.

Knockdown of SMYD3 by RNA Interference Regulates the Expression of Autophagy-Related Proteins and Inhibits Bone Formation in Fluoride-Exposed Osteoblasts.

This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/β-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/β-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.

NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review.

Fluoride is a common exposure in our environment that comes from a variety of sources and is widely promoted for its dental and overall oral health benefits. Contributions to an individual's total exposure come primarily from fluoride in drinking water, food, beverages and dental products. A 2006 evaluation by the National Research Council (NRC) found support for an association between consumption of high levels of naturally occurring fluoride in drinking water and adverse neurological effects in humans and recommended further investigation. The evidence reviewed at that time was from dental and skeletal fluorosis-endemic regions of China. Since the NRC evaluation, the number and location of studies examining cognitive and neurobehavioral effects of fluoride in humans have grown considerably, including several recent North American prospective cohort studies evaluating prenatal fluoride exposure. In 2016, the National Toxicology Program (NTP) published a systematic review of the evidence from experimental animal studies on the effects of fluoride on learning and memory. That systematic review found a low-to-moderate level of evidence that deficits in learning and memory occur in non-human mammals exposed to fluoride. To conduct a systematic review of the human, experimental animal, and mechanistic literature to evaluate the extent and quality of the evidence linking fluoride exposure to neurodevelopmental and cognitive effects in humans. A systematic review protocol was developed and utilized following the standardized OHAT systematic review approach for conducting literature-based health assessments. This monograph presents the current state of evidence associating fluoride exposure with cognitive or neurodevelopmental health effects and incorporated predefined assessments of study quality and confidence levels. Benefits of fluoride with respect to oral health are not addressed in this monograph. The bodies of experimental animal studies and human mechanistic evidence do not provide clarity on the association between fluoride exposure and cognitive or neurodevelopmental human health effects. Human mechanistic studies were too heterogenous and limited in number to make any determination on biological plausibility. This systematic review identified studies that assessed the association between estimated fluoride exposure and cognitive or neurodevelopmental effects in both adults and children, which were evaluated separately. The most common exposure assessment measures were drinking water concentrations and estimates of total fluoride exposure, as reflected in biomarkers such as urinary fluoride. In adults, only two high-quality cross-sectional studies examining cognitive effects were available. The literature in children was more extensive and was separated into studies assessing intelligence quotient (IQ) and studies assessing other cognitive or neurodevelopmental outcomes. Eight of nine high-quality studies examining other cognitive or neurodevelopmental outcomes reported associations with estimated fluoride exposure. Seventy-two studies assessed the association between fluoride exposure and IQ in children. Nineteen of those studies were considered to be high quality; of these, 18 reported an inverse association between estimated fluoride exposure and IQ in children. The 18 studies, which include 3 prospective cohort studies and 15 cross-sectional studies, were conducted in 5 different countries. Forty-six of the 53 low-quality studies in children also found evidence of an inverse association between estimated fluoride exposure and IQ in children. Existing animal studies provide little insight into the question of whether fluoride exposure affects IQ. In addition, studies that evaluated fluoride exposure and mechanistic data in humans were too heterogenous and limited in number to make any determination on biological plausibility. The body of evidence from studies in adults is also limited and provides low confidence that fluoride exposure is associated with adverse effects on adult cognition. There is, however, a large body of evidence on associations between fluoride exposure and IQ in children. There is also some evidence that fluoride exposure is associated with other neurodevelopmental and cognitive effects in children; although, because of the heterogeneity of the outcomes, there is low confidence in the literature for these other effects. This review finds, with moderate confidence, that higher estimated fluoride exposures (e.g., as in approximations of exposure such as drinking water fluoride concentrations that exceed the World Health Organization Guidelines for Drinking-water Quality of 1.5 mg/L of fluoride) are consistently associated with lower IQ in children. More studies are needed to fully understand the potential for lower fluoride exposure to affect children's IQ.

Prenatal Fluoride Exposure Linked to Behavioral Problems in Children

Prenatal Fluoride Exposure Linked to Behavioral Problems in Children

Apoptosis and Inflammation Involved with Fluoride-Induced Bone Injuries.

Excessive fluoride exposure induces skeletal fluorosis, but the specific mechanism responsible is still unclear. Therefore, this study aimed to identify the pathogenesis of fluoride-induced bone injuries. We systematically searched fluoride-induced bone injury-related genes from five databases. Then, these genes were subjected to enrichment analyses. A TF (transcription factor)-mRNA-miRNA network and protein-protein interaction (PPI) network were constructed using Cytoscape, and the Human Protein Atlas (HPA) database was used to screen the expression of key proteins. The candidate pharmacological targets were predicted using the Drug Signature Database. A total of 85 studies were included in this study, and 112 osteoblast-, 35 osteoclast-, and 41 chondrocyte-related differential expression genes (DEGs) were identified. Functional enrichment analyses showed that the Atf4, Bcl2, Col1a1, Fgf21, Fgfr1 and Il6 genes were significantly enriched in the PI3K-Akt signaling pathway of osteoblasts, Mmp9 and Mmp13 genes were enriched in the IL-17 signaling pathway of osteoclasts, and Bmp2 and Bmp7 genes were enriched in the TGF-beta signaling pathway of chondrocytes. With the use of the TF-mRNA-miRNA network, the Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7 genes were identified as the key regulatory factors. Selenium methyl cysteine, CGS-27023A, and calcium phosphate were predicted to be the potential drugs for skeletal fluorosis. These results suggested that the PI3K-Akt signaling pathway being involved in the apoptosis of osteoblasts, with the IL-17 and the TGF-beta signaling pathways being involved in the inflammation of osteoclasts and chondrocytes in fluoride-induced bone injuries.

Dental dilemma: escalating out-of-pocket expenditure trends

The increase in global oral diseases is driven by urbanization, inadequate fluoride exposure, easy access to sugary foods, and limited oral health care. Aggressive marketing of sugary products and tobacco/alcohol further worsens the situation, impacting both oral health and overall well-being. American Dental Association (ADA) report "oral health and well-being". It reveals that a sizeable fraction of the population 38% has lower life satisfaction as a result of oral health problems. one in five persons’ experience anxiety, and twenty-three percent feel embarrassed about the state of their mouths and teeth. This affects social relationships in addition to being an emotional burden, as shown by the 1 in 4 individuals who avoid smiling and the 22% of young adults who avoid social situations because they are self-conscious about their teeth.

Glutamine metabolism in fluorosis: Integrated metabolomics and transcriptomics analysis

ObjectiveTo identify the potential metabolic biomarkers of fluorosis and the pathogenesis of fluorosis. MethodsSprague Dawley rats in this study were randomly divided into fluoride exposure and control groups. In the fluoride exposure group, six offspring rats without dental fluorosis were defined as group A, and six offspring rats with dental fluorosis were defined as group C. Eight offspring rats in the control group were defined as group B. The metabolites in plasma were determined using GC–MS, with differential metabolites (DMs) identified using VIP > 1, and P < 0.05. Cluster analysis, KEGG pathway enrichment analysis and Receiver Operating Characteristic (ROC) analysis were subsequently performed. The DMs which were caused by fluoride exposure in the previous study were used to verify our results. The GSE70719 from GEO database were used to support this research at the mRNA level and in vitro experiment were selected to verify above results. ResultsThe 13 up-regulated and 4 down-regulated DMs were identified in the group A + C, the 18 up-regulated and 4 down-regulated DMs were identified in group A, and the 12 up-regulated and 2 down-regulated DMs were identified in group C. All groups showed enrichment in Aminoacyl-tRNA synthesis, D-glutamine and D-glutamate metabolism, Nitrogen metabolism, and Purine metabolism pathways. ROC analysis revealed that L-glutamine had excellent diagnostic ability for fluorosis (AUC > 0.85, P < 0.05). Changes in major DMs (L-glutamine, 4-hydroxyproline and L-alanine) were consistent with previous findings. Transcriptomic results showed the significant alteration of GLS gene in the fluoride exposure group. In vitro experiments confirmed decreased GLS and SLC1A5 genes expression. ConclusionL-glutamine emerges as a potential biomarker for fluorosis. Glutamine metabolism was involved in the pathogenesis of fluorosis.

Fluoride-related changes in the fetal cord blood proteome; a pilot study

BackgroundFluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes.ResultsPathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation.ConclusionMaternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

Epigenome-wide association study of fluoride exposure during early adolescence and DNA methylation among U.S. children

Exposure to fluoride in early childhood has been associated with altered cognition, intelligence, attention, and neurobehavior. Fluoride-related neurodevelopment effects have been shown to vary by sex and very little is known about the mechanistic processes involved. There is limited research on how fluoride exposure impacts the epigenome, potentially leading to changes in DNA methylation of specific genes regulating key developmental processes. In the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride adjusted for specific gravity (CUFsg) concentrations. Whole blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip 850 k Array. In a cross-sectional analysis, we interrogated epigenome-wide DNA methylation at 775,141 CpG loci across the methylome in relation to CUFsg concentrations in 272 early adolescents at age 12 years. Among all participants, higher concentrations of CUF were associated with differential methylation of one CpG (p < 6 × 10−8) located in the gene body of GBF1 (cg25435255). Among females, higher concentrations of CUFsg were associated with differential methylation of 7 CpGs; only three CpGs were differentially methylated among males with no overlap of significant CpGs observed among females. Secondary analyses revealed several differentially methylated regions (DMRs) and CpG loci mapping to genes with key roles in psychiatric outcomes, social interaction, and cognition, as well as immunologic and metabolic phenotypes. While fluoride exposure may impact the epigenome during early adolescence, the functional consequences of these changes are unclear warranting further investigation.

Association between fluoride exposure and psychiatric disorders in adults

ABSTRACT To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.