Kinetics of fluoride after brushing with the no-rinse method.

BACKGROUND: Fluoride plays a vital role in preventing dental caries, with its addition to oral care products significantly promoting oral hygiene. A no-rinse brushing method aims to increase fluoride retention in the oral cavity, as rinsing with water decreases fluoride levels in saliva, which could affect remineralization. While the no-rinse brushing method holds promise for improving fluoride retention in the oral cavity, critical inquiries persist regarding its safety. This study investigated the kinetics of oral fluoride and potential risks to fully assess its effectiveness and implications for oral health. METHODS: Ten healthy adults participated in a crossover study comparing the no-rinse with the rinse method. All subjects followed American Dental Association (ADA) brushing guidelines. Levels of fluoride in saliva (supernatant and sediment) and urine were measured over time, and plasma fluoride was measured one hour after brushing. Pharmacokinetic parameters were also calculated from the data. RESULTS: Participants using the no-rinse method had higher fluoride levels in supernatant immediately and up to 30 min post-brushing compared to the rinse method. Fluoride levels in sediment were higher only immediately after brushing. The total fluoride concentration in saliva remained elevated for up to 5 min with the no-rinse method. Systemic fluoride absorption showed no significant difference between the two methods based on blood and urine analysis. CONCLUSION: This research indicates that the no-rinse method can enhance fluoride retention in the oral cavity for up to 30 min after a single brushing. In addition, our findings suggest that this method does not significantly influence systemic fluoride levels or toxicity. REGISTRY: Thai Clinical Trials Registry, TCTR ( http://thaiclinicaltrials.org ). CLINICAL TRIAL REGISTRATION NUMBER: TCTR20231104001 (4/11/2023).

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.

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.

A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months.

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

Salivary and urinary assessment of fluoride and silver ion concentrations after silver diamine fluoride application in children: a prospective cohort study.

PURPOSE: The purpose of the study was to determine the fluoride (F) and silver (Ag) ions levels in the saliva and urine of healthy children after silver diamine fluoride (SDF) application on dental carious lesions. METHODS: Sixty children (4-6 years with ≥ 3 caries lesions) were recruited from the outpatient department of Pediatric Dentistry. From each child, 3 ml unstimulated saliva samples were collected at baseline, one hour, and 24 h after SDF application. Similarly, 3 ml urine samples were collected prior to and after 24 h of SDF application. F and Ag ion concentrations were determined by fluoride ion-selective electrode (ISE) and inductively coupled plasma mass spectrometry (ICPMS), respectively. RESULTS: The mean ± standard deviation (SD) baseline, 1-h, and 24-h salivary F concentrations (ppm) were 0.07 ± 0.07, 0.93 ± 0.48, and 0.19 ± 0.19, respectively, while the mean baseline and 24-h urinary F concentrations (ppm) were 0.33 ± 0.20 ppm and 0.43 ± 0.25 ppm, respectively. The mean baseline, 1-h, and 24-h salivary Ag concentrations (ppb) were 4.22 ± 3.15, 4198 ± 350, and 56.93 ± 37, respectively. The mean baseline and 24-h urinary Ag concentrations (ppb) were 2.80 ± 2.93 ppb and 4.72 ± 4.0 ppb, respectively. There were statistically elevated F and Ag ion concentrations at 1 h and 24 h after SDF application as compared to the baseline. CONCLUSION: Salivary and urinary F and Ag ions concentrations elevated significantly at 24 h following SDF applications in children. A significant high recovery of these ions in urine indicates minimal systemic absorption, thus intermittent topical application of 38% SDF has a minimal risk of toxicity.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

Flawed MIREC fluoride and intelligence quotient publications: A failed attempt to undermine community water fluoridation.

OBJECTIVE: To assess the evidence presented in a set of articles that use the Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study database to claim that community water fluoridation (CWF) is associated with harm to foetal and infant cognitive development. METHODS: Critical appraisal of measurements and processes in the MIREC database, and articles derived therefrom. MIREC's cohort is approximately 2000 pregnant women recruited in 10 centres across Canada, 2008-2011, leading to measuring 512 children aged 3-6 years in six cities. Fluoride exposure was measured by city fluoridation status, self-reports and maternal spot urine samples. Intelligence Quotient (IQ) was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) by different assessors in each city. RESULTS: MIREC's fluoride and IQ measurements are invalid and therefore cannot support the claim that CWF is associated with IQ decline in children. CONCLUSIONS: The MIREC fluoride-IQ articles' results should be considered unacceptable for legal and policy purposes; other water fluoridation studies and systematic reviews show no effect of fluoridation on cognition.

Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California.

BACKGROUND: Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California. METHODS: Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal-Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. RESULTS: Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three. CONCLUSIONS: MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.

Association between fluoride exposure in drinking water and cognitive deficits in children: A pilot study.

Fluoride (F) exposure in drinking water may lead to reduced cognitive function among children; however, findings largely remain inconclusive. In this pilot study, we examined associations between a range of chronic F exposures (low to high: 0.4 to 15.5 mg/L) in drinking water and cognition in school-aged children (5-14 years, n = 74) in rural Ethiopia. Fluoride exposure was determined from samples of community-based drinking water wells and urine. Cognitive performance was measured using: 1) assessments of ability to draw familiar objects (donkey, house, and person), and 2) a validated Cambridge Neuropsychological Test Automated Battery's (CANTAB) Paired Associate Learning (PAL), which examines memory and new learning and is closely associated with hippocampus function of the brain. Associations between F and cognitive outcomes were evaluated using regression analysis, adjusting for demographic, health status, and other covariates. The median (range) of water and urine F levels was 7.6 (0.4-15.5 mg/L) and 6.3 (0.5-15.7 mg/L), respectively; these measures were strongly correlated (r = 0.74), indicating that water is the primary source of F exposure. Fluoride in drinking water was negatively associated with cognitive function, measured by both drawing and CANTAB test performance. Inverse relationships were also found between F and drawing objects task scores, after adjusting for covariates (p < 0.05). Further analysis using CANTAB PAL tasks in the children confirmed that F level in drinking water was positively associated with the number of errors made by children (p < 0.01), also after adjusting for covariates (p < 0.05). This association between water F and total errors made became markedly stronger as PAL task difficulty increased. Fluoride exposure was also inversely associated with other PAL tasksthe number of patterns reached, first attempt memory score and mean errors to success. These findings provide supportive evidence that high F exposures may be associated with cognitive deficits in children. Additional well-designed studies are critically needed to establish the neurotoxicity of F in children and adults exposed to both low levels known to protect dental caries, as well as excess F levels in drinking water.

Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (ß = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION: Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.

A Phase 1 Trial to Evaluate the Relationship Between Fluoride Intake and Urinary Fluoride Excretion in Healthy Participants.

Chronic overexposure to fluoride can have deleterious effects in the musculoskeletal system. Some fluorine-containing therapeutics, such as voriconazole, release fluoride through metabolism. Therefore, drug-related fluoride exposure should be assessed for novel therapeutics suspected of releasing fluoride through metabolism. Two trials were conducted to identify the optimal method of assessing drug-related fluoride exposure. In trial 1, designed to assess reproducibility of fluoride pharmacokinetics in urine and plasma, 14 participants were administered a fluoride-restricted diet and once-daily doses of sodium fluoride (2.2 mg [1 mg of fluoride] on days 1 and 2; and 13.2 mg of sodium fluoride [6 mg of fluoride] on days 3 and 4). In trial 2, designed to confirm the selected method for fluoride detection, 12 participants were administered a fluoride-restricted diet and randomized to receive voriconazole (400 mg twice, 12 hours apart, on day 1 [131 mg/d of fluoride maximum], then 3 doses of 200 mg every 12 hours [65.3 mg/d of fluoride maximum]) or placebo. Plasma fluoride concentrations and urinary fluoride excretion were assessed in each trial. Assessment of plasma fluoride concentrations in trial 1 was limited by 301 of 854 samples (35.2%) below the lower limit of quantitation. Urine fluoride excretion was readily measured and demonstrated a decrease from baseline during the fluoride-restricted diet phase, as well as dose-proportional increases with fluoride administration. In trial 2, increases in urine fluoride were successfully observed in participants administered voriconazole. In conclusion, fluoride exposure was optimally assessed by urinary fluoride excretion in conjunction with strict dietary fluoride restrictions, as measurements were consistent and reproducible.

Fluoride Pharmacokinetics in Urine and Plasma Following Multiple Doses of MK-8507, an Investigational, Oral, Once-Weekly Nonnucleoside Reverse Transcriptase Inhibitor.

MK-8507 is an investigational HIV-1 nonnucleoside reverse transcriptase inhibitor being developed for the treatment of HIV-1 infection. MK-8507 contains 2 trifluoromethyl groups that may result in fluoride release through metabolism, but the extent of MK-8507-related fluoride release in humans has yet to be determined. This double-blind, placebo-controlled, 2-period, parallel-group, multiple-dose trial in healthy participants without HIV-1 who were administered a fluoride-restricted diet and once-weekly doses of MK-8507 aimed to estimate the relationship between MK-8507 dose and fluoride exposure. A total of 15 adult male and 3 adult female (of non-childbearing potential) participants were randomized to receive MK-8507 200 mg (n = 6), MK-8507 800 mg (n = 6), or placebo (n = 6). Change from baseline in mean daily fluoride excretion averaged over 7 days following the administration of MK-8507 200 mg resulted in a net mean increase of 19.8 µmol (90% confidence interval, 12.2-27.4) relative to placebo and did not exceed 57 µmol, a threshold related to the mean difference between the daily reference dose set by the US Environmental Protection Agency and the average dietary fluoride intake in the United States. However, daily urinary fluoride excretion exceeded the threshold following administration of 800 mg MK-8507 (75.1 µmol [90% confidence interval, 67.5-82.7]). Assuming a linear relationship between MK-8507 dose and estimated mean daily fluoride released at steady-state, data interpolation suggests that the US Environmental Protection Agency reference dose for fluoride would not be exceeded in most patients when administering MK-8507 at doses currently under clinical investigation (≤400 mg once weekly).

Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children.

BACKGROUND: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW). METHOD: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McCarthy Scales (age of 4). Multiple linear regression analyses were carried out adjusting for a wide range of covariates related to the child, mother, family context and other potential neurotoxicants. RESULTS: No association was found between MUFcr levels and Bayley Mental Development Index score. Nevertheless, regarding the McCarthy scales, it was found that per unit (mg/g) of MUFcr across the whole pregnancy, scores in boys were greater for the verbal, performance, numeric and memory domains (ß = 13.86, CI 95%: 3.91, 23.82), (ß = 5.86, CI 95%: 0.32, 11.39), (ß = 6.22, CI 95%: 0.65, 11.79) and (ß = 11.63, CI 95%: 2.62, 20.63) respectively and for General Cognitive Index (ß = 15.4, CI 95%: 6.32, 24.48). For girls there was not any cognitive score significantly associated with MUFcr, being the sex-F interactions significant (P interaction <0.05). Including other toxicants levels, quality of family context or deprivation index did not substantially change the results. CONCLUSIONS: In boys, positive associations were observed between MUFcr and scores in cognitive domains at the age of 4. These findings are inconsistent with those from some previous studies and indicate the need for other population-based studies to confirm or overturn these results at low levels of F in CDW.

Fractional urinary fluoride excretion and nail fluoride concentrations in normal, wasted and stunted 4-5 year-old children in Nepal.

INTRODUCTION: It has been suggested that undernourished children are more likely to develop dental fluorosis. We investigated the effects of nutritional status on systemic fluoride metabolism including the proportion of ingested fluoride excreted through urine (i.e. fractional urinary fluoride excretion - FUFE) and fluoride concentration in nail clippings in children, aged 4-5 years, in Nepal. METHODS: Nutritional status was evaluated using weight-for-age (wasting) and height-for-age (stunting) indices. Total daily fluoride intake (TDFI) was estimated from diet and toothpaste ingestion and 24 -h urine collected to assess daily urinary fluoride excretion (DUFE). FUFE was calculated by dividing DUFE by TDFI. Nail clippings (finger and toe) were collected and analysed for fluoride concentration. RESULTS: Of the 100 children who participated, 89 provided information to assess FUFE and 51 children provided nail samples. Overall, 86.5 % of the 89 children were wasted and 39.3 % were stunted. When the samples were pooled into binary (affected and non-affected) categories, mean TDFI and mean DUFE were statistically significantly higher in the 77 wasted children (57.7 and 29.7 µg/kgbw/d, respectively) than the 12 non-wasted children (39.4 and 17.0 µg/kgbw/d, respectively). TDFI and DUFE were also statistically significantly higher in the 35 stunted children (65.1 and 34.5 µg/kgbw/d, respectively) than in the 54 non-stunted children (48.8 and 23.7 µg/kgbw/d, respectively). However, mean FUFE was similar in all groups. There were no statistically significant differences in fluoride concentration of either fingernails or toenails among the different categories of wasting, while mean fingernail fluoride concentration was statistically significantly higher in stunted (5.4 µg/g) than in non-stunted children (3.5 µg/g). CONCLUSION: Our study found no significant effect of nutritional status on the proportion of ingested fluoride excreted in urine (and consequently the proportion retained in the body). These findings suggest that nutritional status may be less likely to be a main risk factor for the development of dental fluorosis than children's dietary habits or total fluoride intake.

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children's IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.

Public-health risks from tea drinking: Fluoride exposure.

AIMS: Due to new evidence on fluoride neurotoxicity during early life, this study examined maternal exposure to fluoride through tea consumption in a low-fluoride region and measured fluoride releases from commercially available teas (tea bags and loose teas) to determine the need to limit fluoride exposure. METHODS: Maternal urine fluoride (MUF) concentrations were measured in spot urine samples (N=118) from first-trimester pregnant women and in prepared tea infusions made with deionised water from 33 brand teas and 57 loose-tea products, as determined by the direct method of using a fluoride-selective electrode. RESULTS: The fluoride concentration in the local drinking water supplies ranged from 0.10 to 0.18 mg/L, and the creatinine-adjusted MUF ranged from 0.09 to 1.57 mg/L. Seventeen per cent of the women were daily tea drinkers, and their MUFs were higher than those with no consumption (p=0.002). The fluoride concentration from tea bags ranged from 0.34 to 2.67 mg/L, while loose teas showed 0.72-4.50 mg/L (black), 0.56-1.58 mg/L (oolong), 1.28-1.50 mg/L (green), and 0.33-1.17 mg/L (white tea). CONCLUSIONS: Fluoride exposure among pregnant women increases with tea consumption, with likely risks of developmental neurotoxicity to their children. As the fluoride release from tea varies widely, the fluoride concentration should be indicated on tea packages in order to allow consumers to make informed decisions on minimising their fluoride exposure.

Urinary minerals excretion among primary schoolchildren in Dubai-United Arab Emirates.

INTRODUCTION: Urinary excretion of calcium (Ca), magnesium (Mg), phosphorus (P), iodine and fluoride is used to assess their statuses and/or the existence of metabolic abnormalities. In the United Arab Emirates (UAE), the urinary concentration of these minerals among children have not been documented. MATERIALS AND METHODS: A cross-sectional study, including 593 subjects (232 boys and 361 girls), was conducted among healthy 6 to 11-year-old Emirati children living in Dubai. Non-fasting morning urine samples and anthropometrical measurements were collected and analyzed. Results were expressed as per mg of creatinine (Cr). RESULTS: On average, estimated Cr excretion was 17.88±3.12 mg/kg/d. Mean urinary Ca/Cr, Mg/Cr and P/Cr excretions were 0.08±0.07 mg/mg, 0.09±0.04 mg/mg, and 0.57±0.26 mg/mg respectively. Urinary excretion of Ca, Mg and P were found to decrease as age increased. Urinary excretion and predicted intake of fluoride were lower than 0.05 mg/kg body weight per day. Surprisingly, more than 50% of the children were found to have urinary iodine excretion level above adequate. CONCLUSION: The Emirati schoolchildren had comparable levels of urinary Ca, Mg and P excretion to other countries. The 95% percentile allows the use of the current data as a reference value for the detection of mineral abnormalities. Fluoride excretion implies that Emirati children are at low risk of fluorosis. The level of urinary iodine excretion is slightly higher than recommended and requires close monitoring of the process of salt iodization to avoid the harmful impact of iodine overconsumption.

Efficacy of Calcium-Containing Eggshell Powder Supplementation on Urinary Fluoride and Fluorosis Symptoms in Women in the Ethiopian Rift Valley.

Dietary calcium binds Fluoride (F), thus preventing excess F absorption. We aimed to assess the efficacy of supplementing calcium-containing Eggshell Powder (ESP) on F absorption using urine F excretion and on fluorosis symptoms. In total, 82 women (41 Intervention Group, IG; 41 Control Group, CG) were recruited; overall, 39 in each group completed the trial. Morning spot urine was collected before (baseline, BL) and after (endline, EL) the intervention that was 6-months daily supplementation with 2.4 g ESP (providing ~1000 mg of calcium). Dental, skeletal, and non-skeletal fluorosis assessments was carried out at BL and, except for dental, at EL. Relative risk (RR) and linear generalized estimating equation were used to compare outcomes between groups. At BL, urinary F excretion in the IG and CG groups was similar, ~10 mg/L. At EL, urinary F excretion in IG women was six-fold lower (ß = -6.1 (95% CI: -7.1, -5.1)) compared to CG. The risk of developing skeletal and non-skeletal fluorosis were significantly (p < 0.001) reduced in the intervention group. A significant reduction in urinary F excretion and reduction in many fluorosis symptoms were observed among women supplemented with calcium-containing ESP, thus providing evidence for using this dietary calcium source for mitigation of fluorosis. Clinical trials registration: NCT03355222.