Is there any association between fluoride exposure and thyroid function modulation? A systematic review.

Numerous pre-clinical and observational studies have explored the potential effects of fluoride (F) at varying concentrations on diverse systems and organs. While some have assessed the endocrinological conditions of children and adults, a consensus regarding the interaction between F and the thyroid remains elusive. This systematic review aimed to gather primary evidence on the association between F and changes in the thyroid at optimal and high levels in water supply as stipulated by the World Health Organization. A search strategy, incorporating terms pertinent to the studies, was employed across PubMed, Scopus, Web of Science, Lilacs, and Google Scholar. Following the review of studies, data were extracted and analyzed using the Grading of Recommendations, Assessment, Development, and Evaluations to assess the quality of the evidence. Our results yielded 3,568 studies, of which seven met the inclusion criteria for this review. Five of the seven studies identified an association between high F exposure and thyroid function. In the analysis of methodological quality, every study was found to have major or minor methodological issues and significant risk of bias. The overall confidence in the evidence was deemed low for all outcomes in the seven studies. The evidence compiled in this review suggests a potential association between chronic high levels of F exposure and thyroid damage. Nonetheless, further studies with robust design and high methodological quality are required to provide evidence for policy makers and health care practitioners.

Effect of Calcium Supplementation and TMEM16A Inhibition on Endoplasmic Reticulum Stress Induced by Dental Fluorosis in Mice.

BACKGROUND: Dental fluorosis is a discoloration of the teeth caused by the excessive consumption of fluoride. It represents a distinct manifestation of chronic fluorosis in dental tissues, exerting adverse effects on the human body, particularly on teeth. The transmembrane protein 16a (TMEM16A) is expressed at the junction of the endoplasmic reticulum and the plasma membrane. Alterations in its channel activity can disrupt endoplasmic reticulum calcium homeostasis and intracellular calcium ion concentration, thereby inducing endoplasmic reticulum stress (ERS). This study aims to investigate the influence of calcium supplements and TMEM16A on ERS in dental fluorosis. METHODS: C57BL/6 mice exhibiting dental fluorosis were subjected to an eight-week treatment with varying calcium concentrations: low (0.071%), medium (0.79%), and high (6.61%). Various assays, including Hematoxylin and Eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qPCR), and Western blot, were employed to assess the impact of calcium supplements on fluoride content, ameloblast morphology, TMEM16A expression, and endoplasmic reticulum stress-related proteins (calreticulin (CRT), glucose-regulated protein 78 (GRP78), inositol requiring kinase 1α (IRE1α), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)) in the incisors of mice affected by dental fluorosis. Furthermore, mice with dental fluorosis were treated with the TMEM16A inhibitor T16Ainh-A01 along with a medium-dose calcium to investigate the influence of TMEM16A on fluoride content, ameloblast morphology, and endoplasmic reticulum stress-related proteins in the context of mouse incisor fluorosis. RESULTS: In comparison to the model mice, the fluoride content in incisors significantly decreased following calcium supplements (p < 0.01). Moreover, the expression of TMEM16A, CRT, GRP78, IRE1α, PERK, and ATF6 were also exhibited a substantial reduction (p < 0.01), with the most pronounced effect observed in the medium-dose calcium group. Additionally, the fluoride content (p < 0.05) and the expression of CRT, GRP78, IRE1α, PERK, and ATF6 (p < 0.01) were further diminished following concurrent treatment with the TMEM16A inhibitor T16Ainh-A01 and a medium dose of calcium. CONCLUSIONS: The supplementation of calcium or the inhibition of TMEM16A expression appears to mitigate the detrimental effects of fluorosis by suppressing endoplasmic reticulum stress. These findings hold implications for identifying potential therapeutic targets in addressing dental fluorosis.

Evaluation of possible role of fluoride in pathogenesis of oral submucous fibrosis: A pilot study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls. METHODS: The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR). RESULTS: OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = -0.158, p = 0.334). CONCLUSION: The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.

Fluoride and caries prevention: a scoping review of public health policies.

Background: Dental caries is the most common infectious disease, affecting approximately 60 to 90% of the world population, especially young children, and disadvantaged communities. Due to the extremely high prevalence and the significant negative impact on general health, well-being, and quality of life it is considered a global public health problem. Despite the improvement of policies to promote oral health care in the past decades, dental caries is still a healthcare challenge, characterized by increasing disparities among different social groups between and within countries. Fluoride-based prevention of dental caries is a cost-effective approach, that has been implemented since 1940's. It includes systemic and topical administrations, through community-based or individual programs. Preventive interventions should be tailored to individual and community caries risk assessment and estimate of cumulative fluoride intake, in order to maximize the preventive effect and avoid the risk of potential adverse effects associated with excessive fluoride exposure. Regulation of public health policies plays a major role in this context. Study design: Scoping review. Methods: The aim of this scoping review was to report an overview of current guidelines regarding fluoride-based preventive strategies for dental caries and relevant policies on the matter, as well as to address current issues related to public health aspects of dental caries prevention. We searched for the relevant literature on the matter, focusing on policy documents, such as recommendations, position papers and guidelines, issued from the major scientific and regulatory institutions involved in oral health promotion and on publications concerning relevant aspects of public health law. Results: Prevention of dental caries through fluoride can rely on topical fluorides for home-use (toothpastes and mouthrinses), professionally applied topical fluorides (gels, varnishes, silver diamine fluoride, fluoride-releasing restorative materials and sealants), fluoride supplements (tablets and drops), and community-based strategies (community water fluoridation, fluoridated salt and milk). Current relevant guidelines for all these preventive aids are outlined in the paper. A significantly greater preventive effect of topical fluorides has been widely established in the recent past, as compared to systemic effects. Furthermore, increasing concerns have emerged on potential adverse effects on general health associated with early and excessive systemic exposure to fluoride, especially for children, supported by recent meta-analyses. Also, community water fluoridation has raised significant aspects of relevance for health law and policies. In a public health perspective, healthcare policymakers should tackle social iniquities by promoting information and oral health literacy, through community and school-based programs, ensuring access to early dental visits and basic dental care and improving availability and affordability of fluoride topical products. Conclusions. Fluoride-based prevention can provide a simple and cost-effective approach to reduce the incidence of dental caries and the associated social burden. Among fluoride-based preventive strategies, systemic community-based administration of fluoride should be considered with great caution, due to the unfavorable risk-benefit ratio currently established. Topical fluoridated pro-ducts are generally preferred, given the optimal risk-benefit ratio. Further efforts must be made to identify and tackle the barriers to dental caries prevention and related social iniquities from a public health perspective. Policies and laws on oral health should promote access to caries prevention with targeted comprehensive strategies.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort.

BACKGROUND: Fluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. OBJECTIVES: We examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. METHODS: We measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. RESULTS: A 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: -0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05-0.32 mg/L), those with levels in the third quartile (0.49-0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13-0.52 mg/L) and third (0.52-0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04-0.13 mg/L). Adjustment for maternal iodine status did not change the results. DISCUSSION: Fluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.

Voriconazole-induced periostitis in a patient with HIV treated for coccidioidomycosis meningitis.

Voriconazole-induced periostitis is a rare adverse effect in patients on long-term therapy, characterised by periosteal inflammation and associated bony pain. The accompanying lab abnormalities (elevated serum alkaline phosphatase and fluoride) and characteristic imaging findings (uptake of radionuclide tracer on nuclear bone scan) are critical for diagnosis. The disease process is thought to be secondary to excess fluoride from voriconazole which stimulates bone formation and decreases osteoclast bone resorption. Management includes stopping voriconazole and switching to another agent.

Environmental fluoride exposure and implications on potential pediatric kidney health risks: an approach with urinary biomarkers.

BACKGROUND: Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. METHODS: Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11-18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). RESULTS: UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. CONCLUSIONS: Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions.

Prevalence of Skeletal Fluorosis in Northern Tanzania: A Follow-Up Study.

OBJECTIVES: Skeletal fluorosis is a metabolic bone disease caused by excessive exposure to fluoride, predominantly through contamination of drinking water. This study aimed to identify all cases of skeletal fluorosis in Tindigani village situated in Northern Tanzania. This was done following changes in drinking water sources after a previous prevalence study in 2009 in this population. METHODS: In a door-to-door cross-sectional study of Tindigani village, a sample of residents was assessed for skeletal fluorosis and dental fluorosis. Diagnosis of skeletal fluorosis was based on pre-defined angles of deformity of the lower limbs. Dental fluorosis was diagnosed and graded using the Thylstrup and Fejerskov Index. Samples from current drinking water sources underwent fluoride analysis. RESULTS: Tindigani village had a population of 1,944 individuals. Of the 1,532 individuals who were screened, 45 had skeletal fluorosis, giving a prevalence of 3.3% (95% CI=2.4, 4.3). Dental fluorosis was present in 82.5% of those examined (95% CI=79.8, 85.3). Dental fluorosis was present in all individuals with skeletal fluorosis and at higher grades than in the rest of the population. Drinking water samples were collected from 28 sources. These included piped, surface, well, and borehole water sources. Fluoride concentrations ranged from 0.45-38.59 mg/L of fluoride. CONCLUSIONS: Skeletal fluorosis is an ongoing but preventable health problem in the current population. The delivery of sustainable low fluoride piped water to this community would be of clear health benefit. This has been addressed at a local level.

Variability of groundwater fluoride and its proportionate risk quantification via Monte Carlo simulation in rural and urban areas of Agra district, India.

This study quantifies the groundwater fluoride contamination and assesses associated health risks in fluoride-prone areas of the city of Taj Mahal, Agra, India. The United States Environmental Protection Agency (USEPA) risk model and Monte Carlo Simulations were employed for the assessment. Result revealed that, among various rural and urban areas Pachgain Kheda exhibited the highest average fluoride concentration (5.20 mg/L), while Bagda showed the lowest (0.33 mg/L). Similarly, K.K. Nagar recorded 4.38 mg/L, and Dayalbagh had 1.35 mg/L. Both urban and rural areas exceeded the WHO-recommended limit of 1.5 mg/L, signifying significant public health implications. Health risk assessment indicated a notably elevated probability of non-carcinogenic risk from oral groundwater fluoride exposure in the rural Baroli Ahir block. Risk simulations highlighted that children faced the highest health risks, followed by teenagers and adults. Further, Monte Carlo simulation addressed uncertainties, emphasizing escalated risks for for children and teenagers. The Hazard Quotient (HQ) values for the 5th and 95th percentile in rural areas ranged from was 0.28-5.58 for children, 0.15-2.58 for teenager, and 0.05-0.58 for adults. In urban areas, from the range was 0.53 to 5.26 for children, 0.27 to 2.41 for teenagers, and 0.1 to 0.53 for adults. Physiological and exposure variations rendered children and teenagers more susceptible. According to the mathematical model, calculations for the non-cancerous risk of drinking water (HQ-ing), the most significant parameters in all the targeted groups of rural areas were concentration (CW) and Ingestion rate (IR). These findings hold relevance for policymakers and regulatory boards in understanding the actual impact and setting pre-remediation goals.

Toothpaste ingestion-evaluating the problem and ensuring safety: systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the ingestion of toothpaste and its sequelae. The study adhered to the PRISMA guidelines and was registered in the PROSPERO database. A comprehensive search strategy was conducted across multiple databases, resulting in the inclusion of 18 relevant publications. Eligible studies encompassed various designs and included both children and adults as the study population. Data extraction was carried out systematically, and relevant information on study characteristics, interventions, and outcomes were collected. The assessment of bias was performed using the Joanna Briggs Institute's Critical Appraisal Tools showing variations of bias among the included studies. The overall risk of systemic toxicity was found to be low, and no severe or life-threatening events were reported in the included studies. Furthermore, some toothpaste formulations containing higher concentrations of fluoride were associated with an increased risk of dental fluorosis. These findings have several implications for practice and policy. Healthcare providers and dental professionals should emphasize the importance of promoting safe toothpaste use, especially in vulnerable populations such as young children who are more prone to accidental ingestion. Public health campaigns and educational initiatives should aim to raise awareness about appropriate toothpaste usage and the potential risks. In addition, toothpaste manufacturers and regulatory bodies should consider revising guidelines and regulations to ensure the safety of oral care products, including the appropriate concentration of active ingredients. Future research should focus on investigating the long-term effects of toothpaste ingestion, exploring potential interactions between different active ingredients, and evaluating the efficacy of current preventive measures.

Fluoride distribution in selected foodstuffs from Nakuru County, Kenya, and the risk factors for its human overexposure.

Critical data on the impacts of fluoride (F) in food systems along the Eastern Africa Rift Valley System (EARS) is needed for public health risk assessment and for the development of strategies for ameliorating its deleterious effects among the affected communities. Long-term F overexposure causes dental and skeletal fluorosis, and leads to neurotoxicity, which impacts several important body functions. Investigating F exposure pathways is of essence to inform and safeguard public health of the affected communities. The current study assessed the F levels in potatoes (Solanum tuberosum L.), beans (Phaseolus vulgaris L.) and garden peas (Possum sativa) from Nakuru County, Kenya, by potentiometric analysis using F ion-selective electrodes. It then evaluated the risk factors for excessive human exposure to F through contaminated foodstuffs. The mean F levels in the potatoes (8.50 ± 4.70 mg/kg), beans (8.02 ± 4.12 mg/kg) and peas (4.99 ± 1.25 mg/kg) exceeded recommended dietary allowances (RDA) level of 4 mg/kg endorsed by US Institute of Medicine for the different categories of people. The F distribution trends in beans and potatoes reflected the environmental patterns of F contamination of the study area but the spatial extent Fin the peas indicated existence of partial resistance of the pea plants to environmental F uptake. The results indicated that both the beans and the potatoes were more liable to accumulating greater amounts of F from the environment than garden peas and that all the three foodstuffs contained high F levels that posed greater risk of F overexposure and its deleterious impacts among the young children, male populations, and in people of greater body weight and high physical activity levels.

Nanocrystal-induced chronic tubular-nephropathy in tropical countries: diagnosis, mitigation, and eradication.

In tropical countries, a mysterious tubulo-interstitial chronic renal disease (CKD), unrelated to diabetes, hypertension, and immunological causes, manifested four decades ago. Approximately 25,000 primarily middle-aged male farmers succumb annually to this crystal-tubular nephropathy (CTN). Without any known causative factors, it was identified as CKD of unknown aetiology (CKDu). Because multiple factors contribute to causing it later, was changed to CKD of multi-factorial (CKDmfo). Despite no evidence, it was hypothesised to cause by agrochemicals or heavy metals in food or drinking contaminated water. However, current data suggest that the CKD-CTN is due to natural geogenic water contamination. Consumption of concentrated stagnant groundwater from deep-dug wells and tube wells containing hard water and fluoride, overdecades is necessary for its clinical manifestations. In all affected countries have prolonged annual dry seasons that led to the evopo-concentration of ions and minerals in groundwater, making hard water even more unpalatable, thus, peasants consume lesser amounts of water. They develop chronic dehydration from daily exposure to hot climatic conditions aggravated by regular alcohol intake. These conditions provide a highly conducive environment-a perfect storm for calcium phosphate (CaPO4) crystal formation in renal tissues. Our recent histological and preliminary electron microscopic data reveal deposition of CaPO4 crystals and nano-tubes in kidneys. While CaPO4 nano-minerals are unstable, the presence of fluoride ions stabilises and allows their growth. This new concept paves the path for highly cost-effective, straightforward local solutions to protect farm workers and eliminate the disease, without embarking on expensive medications, interventions, or building hospitals. Chronic dehydration-associated CKD-CTN is preventable by increased consumption of potable water. Increasing clean water consumption reduces CKD-CTN incidence, and associated morbidities and premature deaths. However, the damage becomes irreversible when the disease advances beyond CKD stage IIIB. The incidence of this deadly renal failure can be prevented by its education, lifestyle changes, and increased water consumption, not by treating the renal disease or expanding dialysis centres/hospitals, or transplantation services. Eradication of CKD-CTN cost significantly less than the current approach of treating affected persons and unnecessarily expanding health infrastructure. Since the manifestation of CKD-CTN is due to consuming naturally contaminated drinking water (with calcium containing hard water and fluoride), it is not difficult to remove these to prevent CKD-CTN: thus, international assistance is unwarranted for its eradication. The straightforward approaches described here will prevent CKD-CTN and save thousands of lives in affected farming communities.

Associations of gestational and early-life exposure to toxic metals and fluoride with a diagnosis of food allergy or atopic eczema at 1 year of age.

Studies have indicated that early-life exposure to toxic metals and fluoride affects the immune system, but evidence regarding their role in allergic disease development is scarce. We aimed to evaluate the relations of exposure to such compounds in 482 pregnant women and their infants (4 months of age) with food allergy and atopic eczema diagnosed by a paediatric allergologist at 1 year of age within the Swedish birth-cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Urinary cadmium and erythrocyte cadmium, lead, and mercury concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), urinary inorganic arsenic metabolites by ICP-MS after separation by ion exchange chromatography, and urinary fluoride by an ion-selective electrode. The prevalence of food allergy and atopic eczema was 8 and 7%, respectively. Gestational urinary cadmium, reflecting chronic exposure, was associated with increased odds of infant food allergy (OR [95% CI]: 1.34 [1.09, 1.66] per IQR [0.08 µg/L]). Both gestational and infant urinary fluoride were associated, albeit at a statistically non-significant level, with increased atopic eczema odds (1.48 [0.98, 2.25], 1.36 [0.95, 1.95], per doubling, respectively). By contrast, gestational and infant erythrocyte lead was associated with decreased odds of atopic eczema (0.48 [0.26, 0.87] per IQR [6.6 µg/kg] and 0.38 [0.16, 0.91] per IQR [5.94 µg/kg], respectively), and infant lead with decreased odds of food allergy (0.39 [0.16, 0.93] per IQR [5.94 µg/kg]). Multivariable adjustment had marginal impact on the estimates above. After additional adjustment for fish intake biomarkers, the methylmercury associated atopic-eczema odds were considerably increased (1.29 [0.80, 2.06] per IQR [1.36 µg/kg]). In conclusion, our results indicate that gestational cadmium exposure might be associated with food allergy at 1 year of age and, possibly, early-life exposure to fluoride with atopic eczema. Further prospective and mechanistic studies are needed to establish causality.

Susceptibility of fluorotic enamel to dental erosion-abrasion.

Dental hard tissue conditions can be of pre- or post-eruptive nature, such as enamel fluorosis and erosive tooth wear (ETW), respectively. Dental enamel fluorosis is caused by the chronic and excessive intake of fluoride during enamel development, leading to increased fluoride concentration and increased porosity. ETW has become a common clinical condition and often impairs dental function and aesthetics. This in vitro study tested the hypothesis that fluorotic enamel presents different susceptibility to dental erosion-abrasion. It consisted of a 3×3×2 factorial design, considering a) fluorosis severity: sound (TF0), mild (TF1-2), moderate (TF3-4); b) abrasive challenge: low, medium, and high; and c) erosive challenge: yes or no. A total of 144 human teeth were selected according to the three fluorosis severity levels (n=48), and subdivided into six groups (n = 8) generated by the association of the different erosive and abrasive challenges. Enamel blocks (4×4 mm) were prepared from each tooth and their natural enamel surfaces subjected to an erosion-abrasion cycling model. After cycling, the depth of the lesions in enamel was assessed by profilometry. ANOVA showed that the three-way and two-way interactions among the factors were not significant (p > 0.20). Enamel fluorosis level (p=0.638) and abrasion level (p = 0.390) had no significant effect on lesion depth. Acid exposure caused significantly more enamel surface loss than water (p < 0.001). Considering the limitations of this in vitro study, fluorosis did not affect the susceptibility of enamel to dental erosion-abrasion.

[Spatial correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in a typical coal-fired pollution fluorosis area].

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy.

The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.

Millennial drinks: acidity, fluoride content, and enamel softening.

This in vitro study aimed to evaluate the acidity and fluoride content of beverages commonly consumed by millennials and the enamel-softening effect of these drinks on tooth enamel. The study included 13 beverages in 4 categories: energy (sports) drink, flavored sparkling water, kombucha, and other (an unsweetened iced tea, a vegetable-fruit juice blend, and a soft drink). The acidity was measured with a pH/ion meter, and the fluoride concentration was measured with a combined fluoride electrode coupled to the meter (n = 10 measurements per beverage). The Vickers hardness number of extracted molars was measured before and after a 30-minute immersion in 4 representative beverages via 2 immersion protocols (n = 10 per beverage per protocol): (1) immersion in the beverage only and (2) immersion alternating between the beverage and artificial saliva every other minute. The pH and fluoride concentrations of the beverages ranged from 2.652 to 4.242 and from 0.0033 to 0.6045 ppm, respectively. One-way analysis of variance (ANOVA) revealed that all differences between beverages in pH values were statistically significant, as were the majority of differences in fluoride concentrations (P < 0.001). The beverages and the 2 immersion methods significantly affected enamel softening (2-way ANOVA, P = 0.0001 to 0.033). The representative energy drink (pH 2.990; 0.0102 ppm fluoride) caused the greatest enamel softening followed by the representative kombucha (pH 2.820; 0.2036 ppm fluoride). The representative flavored sparkling water (pH 4.066; 0.0098 ppm fluoride) caused significantly less enamel softening than the energy drink and kombucha. A root beer (pH 4.185; 0.6045 ppm fluoride) had the least enamel softening effect. All tested beverages were acidic and had a pH below 4.5; only some contained fluoride. Flavored sparkling water, likely due to its higher pH, caused less enamel softening than the tested energy drink and kombucha. The fluoride content of kombucha and root beer lower their enamel-softening effects. It is imperative that consumers be aware of the erosive potential of beverages they consume.

A National Study Exploring the Association Between Fluoride Levels and Dental Fluorosis.

Importance: While the effects of fluoride on health have been widely researched, fewer high-quality studies examine the association of fluoride levels in water and dental fluorosis. Objective: To investigate the association between fluoride exposure from drinking water and dental fluorosis. Design, Setting, and Participants: This cross-sectional study used the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) data (January 1, 2013, through December 31, 2016). NHANES uses a complex sampling technique to develop nationally representative sample estimates of the US population that consists of interviews and physical assessments. Children and adolescents aged 6 to 15 years were included because NHANES contains their data for all 3 forms of fluoride measures: plasma fluoride levels, water levels of fluoride, and dietary fluoride supplementation. Data were analyzed from January 1 to April 30, 2023. Exposures: Water and plasma fluoride levels were measured by laboratory personnel. Dietary fluoride supplement data were self-reported. Main Outcomes and Measures: The Dean's Fluorosis Index was used to evaluate fluorosis status for each tooth. The dental fluorosis severity value was based on the second most affected tooth. Independent variables included plasma and water fluoride concentrations and dietary fluoride supplementation. An independent samples t test was used to compare fluoride exposures between groups, and Pearson correlation assessed the association between plasma and water fluoride levels. To assess whether fluoride exposures were associated with dental fluorosis, logistic regression analyses were conducted. Results: There were 1543 participants in the 2013-2014 NHANES cycle (weighted proportion male, 51.9%; mean [SD] age, 11.0 [2.7] years) and 1452 in the 2015-2016 cycle (weighted proportion male, 52.6%; mean [SD] age, 11.1 [2.8] years). A weighted 87.3% exhibited some degree of fluorosis in the 2013-2014 cycle and 68.2% in the 2015-2016 cycle. Higher fluoride levels in water and plasma were significantly associated with higher odds of dental fluorosis (adjusted odds ratios, 2.378 [95% CI, 2.372-2.383] in the 2013-2014 cycle and 1.568 [95% CI, 1.564-1.571] in the 2015-2016 cycle). Conclusions and Relevance: The findings of this cross-sectional study suggest that exposure to higher concentrations of fluoride in water and having higher plasma levels of fluoride were associated with a greater risk of dental fluorosis. Further research can help policy makers develop policies that balance substantial caries prevention with the risk of dental fluorosis.

[Correlation analysis and benchmark dose study on bone metabolic biochemical index of low doses of exposed hydrogen fluoride workers].

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.

Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies.

Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case-control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case-control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.