Urinary Fluoride Concentration Research Articles

A Bayesian benchmark concentration analysis for urinary fluoride and intelligence in adults in Guizhou, China

Environmental fluoride exposure has been linked to numerous cases of fluorosis worldwide. Previous studies have indicated that long-term exposure to fluoride can result in intellectual damage among children. However, a comprehensive health risk assessment of fluorosis-induced intellectual damage is still pending. In this research, we utilized the Bayesian Benchmark Dose Analysis System (BBMD) to investigate the dose-response relationship between urinary fluoride (U-F) concentration and Raven scores in adults from Nayong, Guizhou, China. Our research findings indecate a dose-response relationship between the concentration of U-F and intelligence scores in adults. As the benchmark response (BMR) increased, both the benchmark concentration (BMCs) and the lower bound of the credible interval (BMCLs) increased. Specifically, BMCs for the association between U-F and IQ score were determined to be 0.18 mg/L (BMCL1 = 0.08 mg/L), 0.91 mg/L (BMCL5 = 0.40 mg/L), 1.83 mg/L (BMCL10 = 0.83 mg/L) when using BMRs of 1 %, 5 %, and 10 %. These results indicate that U-F can serve as an effective biomarker for monitoring the loss of IQ in population. We propose three interim targets for public policy in preventing interllectual harm from fluoride exposure.

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, β-CrossLaps (β-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 β-CTX and UF levels in adults. In addition, significant correlations were observed between UF–age and serum Ca2+, β-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and β- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while β-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

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

BackgroundFluoride 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. ObjectivesWe examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. MethodsWe 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. ResultsA 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. DiscussionFluoride 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.

Association between urinary fluoride concentrations and the prevalence of metabolic syndrome in adult individuals from the Central Region of Mexico

ABSTRACT Emerging scientific studies have supported the hypothesis that exposure to environmental chemicals increases the incidence of diverse human metabolic disorders. Therefore, this study aimed to evaluate the association between fluoride exposure and metabolic syndrome (MetS) prevalence in people from the Central Region of Mexico. This research included 575 adult individuals. Urinary fluoride concentrations were determined using a potentiometric method. Anthropometric measurements and blood pressure were also acquired. Serum fasting glucose and lipid levels were quantified. For the MetS screening, we used the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The mean urinary fluoride levels were 3.50 ± 2.50 mg/L. The prevalence of MetS was approximately 27 and 25% according to NCEP ATP III and IDF criteria, respectively. A multivariate logistic regression analysis showed significant associations (p < 0.05) between urinary fluoride concentrations and MetS occurrence using NCEP ATP III criteria (OR = 1.60; 95% CI 1.05–2.10) and IDF criteria (OR = 1.35; 95% CI 0.95–1.45). These findings emphasize the need to discover the underlying mechanisms that fluoride exposure has on MetS pathogenesis.

Chronic Fluoride Exposure Induces Ovarian Dysfunction and Potential Association with Premature Ovarian Failure in Female Rats.

Chronic fluorosis has been widely investigated for its adverse effects on skeletal and neurological health; however, its impact on reproductive health, especially in females, remains underexplored. In this study, female Sprague-Dawley rats were exposed to different fluoride concentrations (0.75, 50, and 100mg/L) in their drinking water for six months. Dental fluorosis and increased urinary fluoride content were observed in fluoride-exposed rats, reflecting fluoride accumulation and exposure levels. Chronic fluorosis resulted in reduced ovary organ coefficient, indicating harmful effects on ovarian tissue. Additionally, the number of ovarian primordial and primary/secondary follicles decreased, while the number of atresia follicles increased. Furthermore, chronic fluorosis led to disrupted estrous cycles. Hormonal analysis revealed altered secretion of estrogen, progesterone, anti-Müllerian hormone, luteinizing hormone, follicular stimulating hormone, and inhibin B in response to fluoride exposure. Ultrastructural observation of ovarian granulosa cells showed evidence of apoptosis, which was further confirmed by flow cytometry. Caspase-3 activity was increased, and ATP levels were decreased, suggesting mitochondrial impairment and apoptosis induction. The mRNA and protein expression of BMP15 and GDF9, essential regulators of ovarian function, significantly decreased with increasing fluoride concentration. Furthermore, gene expression analysis identified a panel of premature ovarian failure-related genes that were downregulated in fluoride-exposed rat ovaries. These findings suggest that chronic fluoride exposure may contribute to ovarian dysfunction and possibly the pathogenesis of premature ovarian failure. Understanding the toxicological effects of chronic fluoride exposure on ovarian function is essential for identifying potential environmental risk factors affecting female reproductive health.

Association between ADAMTS14_rs4747096 gene polymorphism and bone mineral density of Chinese Han population residing in fluorine exposed areas in ShanXi Province, China.

This study aimed to investigate the effects of fluorine and ADAMTS14_rs4747096 on bone mineral density (BMD). The survey was explored in a cross-sectional case-control study conducted in Shanxi, China. The BMD was measured by an ultrasonic bone mineral density instrument. The urine fluoride concentration was detected using the fluoride ion electrode. ADAMTS14_rs4747096 polymorphism was examined by multiplex polymerase chain reaction (PCR) and sequencing. The multinomial logistic regressions found that the urine fluoride was a risk factor for osteopenia (OR = 1.379, 95% CI: 1.127-1.687, P = 0.0018), osteoporosis (OR = 1.480, 95% CI: 1.1138-1.926, P = 0.0035), and rs4747096 AG + GG genotype increased the risk of osteoporosis (OR = 2.017, 95% CI: 1.208-3.369, P = 0.0073). In addition, the interaction between urine fluoride and rs4747096 polymorphism on the risk of decreased BMD also was observed. The study suggests that fluoride exposure and mutation G allele in ADAMTS14_rs4747096 may be risk factors for the decrease of BMD. And there is an interaction between the two influencing factors.

Association of Dental Fluorosis and Urinary Fluoride with Intelligence among Schoolchildren.

Fluoride is present naturally in water and has been used worldwide for the prevention of caries. Several studies conducted in high water fluoride or endemic fluorosis areas reported that fluoride adversely affected children's cognitive function, but some studies had negative findings. This study aimed to assess the relationship between urinary fluoride, dental fluorosis, and intelligence among schoolchildren living in communities with non-fluoridated drinking water. This cross-sectional study was conducted on 562 children aged 6-12 years in Taichung, Taiwan. Each child's urinary fluoride level was determined by a fluoride-ion-selective electrode, and the dental fluorosis condition was evaluated according to the criteria of Dean's Index. The Raven's Colored Progressive Matrices-Parallel and Standard Progressive Matrices-Parallel were used to assess children's intelligence. The results showed that the mean (±standard deviation) urinary fluoride concentrations were 0.40 ± 0.27 mg/L (0.43 ± 0.23 mg/g creatinine) among participants. The prevalence of dental fluorosis was 23.67%. After extensive evaluation of potential confounders, dental fluorosis and urinary fluoride were not associated with intelligence quotient (IQ) scores or grades in the regression models. In conclusion, dental fluorosis and urinary fluoride levels were not significantly related to the IQ of schoolchildren living in areas with low drinking water fluoride.

Association between polymorphism and haplotype of ATP2B1 gene and skeletal fluorosis in Han population

ABSTRACT To evaluate the association between ATP2B1 gene polymorphisms and skeletal fluorosis, a cross-sectional study was conducted. In China, 962 individuals were recruited, including 342 cases of skeletal fluorosis. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analysed. The results suggested that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling confounders, the protective effect of GG genotype in rs17249754 was apparent in individuals over 45 years old, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L or serum phosphorus between 1.1 and 1.3. Heterozygote TC in rs7136259 increased the risk of skeletal fluorosis in subjects who are elderly, female, with urinary fluoride more than 1.6 mg/L, serum calcium more than 2.25 mmol/L and blood phosphorus between 1.1 and 1.3 mmol/L. Four loci were found to be tightly related by linkage disequilibrium analysis, and the frequency of distribution of haplotype GCGT was lower in the skeletal fluorosis group.

Factors influencing the spatial distribution and individual variation in urinary fluoride levels in Tibet, China

Nowadays, fluorosis is the most prevalent endemic disease in Tibet and one of the most concerned public health problems in China; urinary fluoride is a common diagnostic indicator of endemic fluorosis. However, the spatial distribution and influencing factors of urinary fluoride content in Tibet remain unclear. This study aims to bridge this gap by geographically weighted regression (GWR), analyses of variance (ANOVAs), Geodetector, and stepwise multiple linear regression (MLR). To achieve this goal, this study first investigated fluoride levels in the fasting urine among 637 Tibetan residents from 73 counties in Tibet, the urinary fluoride level was chosen as an indicator of fluorosis, which can reflect the health impairment. Then we identified the potential factors that could influence the spatial distribution and individual variation of urinary fluoride levels from physical environmental and socioeconomic perspective, respectively. The results showed that urinary fluoride levels in Tibet were slightly exceeding the average value for adult urinary fluoride in China, and that residents with high urinary fluoride were mainly found in the west and east; those with low urinary fluoride were mainly found in the central-southern regions. And the urinary fluoride levels had a significantly positive correlation with water fluoride and a significantly negative correlation with average annual temperature. Urinary fluoride levels increased until age 60 and followed an inverted “U”-shaped trajectory according to annual household income (80,000 renminbi (RMB) was the inflection point); pastoralists had greater exposure to fluoride than farmers. Furthermore, the Geodetector and MLR showed that the urinary fluoride level was influenced by both physical environmental and socioeconomic factors. The socioeconomic factors such as age, annual household income and occupation had a greater impact than the physical environment on urinary fluoride concentration. These findings can provide scientific basis for preventing and controlling endemic fluorosis in the Tibetan Plateau and adjacent areas.

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.

Association between dental fluorosis prevalence and inflammation levels in school-aged children with low-to-moderate fluoride exposure

Inflammation mediates the neurological deficits caused by fluoride. Thus, whether inflammation is the underlying mechanism of dental fluorosis (DF) in school-aged children is worth exploring. A cross-sectional study was conducted to investigate the association between inflammation and the prevalence and severity of DF with low-to-moderate fluoride exposure. Fasting morning urine and venous blood samples were collected from 593 children aged 7–14 years. The fluoride content in the water and urine samples was measured using a fluoride ion-selective electrode assay. The levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were detected using an enzyme-linked immunosorbent assay. The Dean's index was used when performing dental examinations. Regression, stratified, and mediation analyses were performed to analyze the association between fluoride exposure, inflammation, and DF prevalence. In the adjusted regression models, the prevalence of mild DF was 1.723-fold (95% confidence interval [CI]:1.612, 1.841) and 1.594-fold (1.479, 1.717) greater than that of normal DF for each 1 mg/L increase in water and urinary fluoride content, respectively. The prevalence of mild DF increased by 3.3% for each 1 pg/mL increase in the IL-1β level and by 26.0% for each 1 mg/L increase in the CRP level. Stratified analysis indicated a weaker association between fluoride concentration and DF prevalence in boys than in girls, and susceptibility in the boys was reflected by the association of IL-1β with very mild and moderate DF prevalence. For every 1 mg/L increase in water and urinary fluoride levels, the proportion of IL-1β-mediated effects on the prevalence of mild DF was 10.0% (6.1%, 15.8%) and 8.7% (4.8%, 15.2%), respectively, and the proportion of CRP-mediated effects was 9.2% (5.5%, 14.9%) and 6.1% (3.3%, 11.0%), respectively. This study indicates that the DF prevalence may be sex-specific. Inflammatory factors may partially mediate the increased prevalence of mild DF in school-aged children with low-to-moderate fluoride exposure.

Estimation of fluoride ion concentration in urine after application of silver diamine fluoride in patients with severe early childhood caries.

Despite the University of California San Francisco, the American Academy of Pediatric Dentistry (AAPD), and the Food and Drug Administration having approved the use of silver diamine fluoride (SDF) in arresting dentinal caries, literature available on its systemic absorption is limited. This study aimed to assess any systemic absorption of fluoride ion following the topical application of SDF in young children. Children aged between 3 and 6 years who were diagnosed with severe early childhood caries and required rehabilitation were recruited for the study. Before the onset of treatment for the arrest and control of caries, a baseline urine sample as a control was collected from the patient. In accordance with the manufacturer's instructions and AAPD guidelines, SDF was topically applied on a minimum of five carious teeth, following which additional urine samples were collected after 2 h and after 24 h, respectively, of application of SDF. The urine samples were stored at -20°C, and the estimation of fluoride ion concentrations in urine was then ascertained using a fluoride ion selective electrode. The results revealed that the fluoride concentration in urine before application of SDF was 0.66 mg/L ± 0.25 mg/L, and following 2 h of application, it was 1.13 mg/L ± 0.23. However, 24 h postapplication, the urinary fluoride concentration was reduced to 0.63 mg/L ± 0.20, which is close to the baseline value of the control sample. There was no significant systemic absorption of fluoride following the application of SDF, and it could be adopted as an effective and safe agent in the armamentarium for managing caries in young children.

Biological Monitoring of Urinary Fluoride Among Phosphate Fertiliser Production Industrial Workers

Objectives: Fluoride pollution at the workplace environment arises mostly due to anthropogenic activities. The workers working in phosphate fertilizer industry might have chronic exposure to excessive fluoride which can cause adverse health effects. Therefore, the present study was designed to assess urinary fluoride levels in occupationally exposed workers. Methods: In this study, pre and post-shift urinary samples were collected from phosphate fertilizer industry male workers (n=53). Fluoride levels in urine samples were analysed using an Ion Selective Electrode (ISE). Findings: The mean concentration of pre-shift and post-shift urinary fluoride levels were 2.141.35 and 2.422.02 mg/g of urinary creatinine respectively. Workers’ pre-shift mean urine fluoride levels were categorised according to their working departments. Workers from the manufacture plat of Single Super Phosphate (SSP), Granular Single Super Phosphate (GSSP), maintenance, and administration had fluoride levels of 2.871.88, 2.431.01, 2.161.30, and 0.920.601 mg/g of urine creatinine, respectively. Similarly, the post-shift urinary fluoride levels were 3.683.00, 2.641.85, 2.241.78 and 1.140.53 mg/g of urinary creatinine in these departments respectively. One-way analysis of variance shown significant difference in urine fluoride concentrations between pre-shift (ANOVA, df=3, F=4.717; p=0.006) and post-shift samples (ANOVA, df=3, F=2.895; p=0.044). About 22.64 % of subjects in the pre-shift and 3.77% of subjects in the post-shift had exceeded the urinary fluoride limits prescribed by various statutory agencies. Novelty: Based on pre-shift and post-shift work exposure assessments, this study adds new knowledge to scientific research on the fluoride exposure among phosphate fertiliser sector workers. While there is sporadic information on fluoride levels among various other occupational groups, very few reports reported the fluoride levels in fertilizer industryworkers. Outcomes of this study will help to identify the source of fluoride and extent of fluoride exposure so as to suggest the mitigation measure to control fluoride exposure at occupational settings. Keywords: Biological monitoring; Fluoride exposure; Urinary fluoride; Occupational fluoride exposure; Fertilizer industry workers

Assessment of Fluoride Content in Water and Its Impact on the Intelligence Quotient of School Children Aged 12–13 Years

The preliminary study was undertaken with the aim to assess the effect of fluoride content in water on the Intelligence Quotient (IQ) of school children aged 12-13 years residing in areas that differ with respect to fluoride levels. The IQ was measured using Raven's Colored Progressive Matrices in 90 children, who were life-long residents in three villages (30 children each) of similar population size but differing in the level of fluoride in drinking water. Urinary fluoride concentration was measured using the selective ion electrode technique. One-way ANOVA was used for the statistical analysis of the data. Results: Children who lived in locations with fluoride levels of 1.60, 6.70, or 2.80 parts per million in their drinking water had urinary fluoride concentrations of 1.60, 6.82, or 2.69 parts per million, and IQ scores of 16.77 + 8.24, 19.36 + 9.98, or 21.87 + 7.47, respectively. The results indicated that there was a positive correlation between excess fluoride in drinking water and IQ.

Fluoride Concentration in Urine after Supplementation with Quelites in a Population of Adolescents.

Wild plants have detoxifying and protective properties. They reduce or neutralize the toxic effects caused by chemical agents and pollutants and have beneficial effects on the nutritional and health status. This research was conducted to complement a previous clinical intervention in which participants were exposed to high concentrations of arsenic and fluoride in drinking water to discover similarities or differences in the pattern of fluoride (F−) excretion after supplementation with partial areas of purslane and quelite cenizo (SP-Q). The study was 4 weeks long, and it was carried out on a sample of 27 adolescents in an age range of 11–12 years. Anthropometric and dietary evaluations were performed, and the concentrations of fluoride (F−) in urine and drinking water were quantified using the potentiometric method with an ion-selective electrode. The treated group increased urinary F− excretion after the first week (Baseline: 9.23 mg/g creatinine; Week 2: 0.73 mg/g creatinine), together with significant mobilization of F− and a recovery process at the end of the intervention (Week 4: 0.52 mg/g creatinine). The supplement may act by increasing the excretion of F− and the nutritional dietary conditions that contribute to mitigation and recovery in participants exposed to the contaminant while also managing access to drinking water.

Waterborne arsenic and fluoride exposure in Mexico: risk assessment and epidemiological research on their health effects

Many aquifers in Mexico contain toxic levels of arsenic and fluoride; still, 39% of the population relies on groundwater for drinking. Our objectives were to evaluate the health risks of fluoride and arsenic in drinking water in central [Cuenca Alta del Río Laja (CARL)] and northern [Comarca Lagunera (CL)] Mexico, and to compare economic and health trade-offs of different aquifer pumping scenarios. In two CARL studies, we measured arsenic and fluoride in drinking water and fluoride in children’s urine; health risks were estimated through hazard quotients (HQ). In 2018 we assessed dental fluorosis (n=39) and in 2019, we measured intelligence quotient (IQ) (n=74). Another study modeled the revenues, costs, health, and income outcomes from increasing, decreasing, or maintaining the aquifer pumping rates over 100 years. The fourth study assessed cancer and non-cancer risks in CL according to arsenic levels in 91 wells. In CARL, children who drank groundwater had an increased fluoride risk of health effects (HQ= 1.5); 82% presented dental fluorosis, and their urine fluoride concentrations increased 0.96 mg/L per 1 mg/L increase in water fluoride (p &amp;#x3c; 0.001). Urine fluoride was negatively associated with IQ (β= -1.12, CI 95% -4.1, 1.8). Assuming increasing aquifer pumping rates in the next 100 years, arsenic and fluoride concentrations would increase to 40 &amp;#x3bc;g/L and 2.1 mg/L, respectively, potentially diminishing IQ by 6 and 7 points, respectively. In CL, 90% of the sampled wells exceeded the WHO’s arsenic drinking water guidelines; the carcinogenic risk ranged from 2.6×10-⁵ to 6.1×10-³. Children in CARL and CL are drinking groundwater with toxic fluoride and arsenic concentrations that increase their cancer and non-cancer health risks to unacceptable levels. The health and economic benefits of mitigating exposure to arsenic and fluoride greatly exceed the benefits of increasing pumping for more agricultural production. Keywords: arsenic, fluoride, water, Mexico

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

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

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort

BackgroundObservational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. ObjectivesTo evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. MethodsWe studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. ResultsMedian urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31–1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. DiscussionGestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.

Effect of Sodium Fluoride on Reproductive Function Through Regulating Reproductive Hormone Level and Circulating SIRT1 in Female Rats.

Fluorosis causes female reproductive dysfunction with reduced fertility without established pathogenesis. To clarify the mechanism, Sprague-Dawley female rats were selected with drinking water containing 0, 50 (low), 100 (moderate), and 150mg/L (high) sodium fluoride (NaF) for a short (2months), medium (4months), and long term (6months). The water consumption and body weight of female rats were recorded daily. The effect of NaF on the estrous cycle was examined by vaginal smears and recorded in different term treatments. Female and male rats were mated in a 2:1 ratio for 1week at 2-, 4-, and 6-month treatment time for mating performance and fertility rate. Selected female rats were executed for tissue and blood collection at different treatment terms. Twenty-four-hour urine sample from each female rat was collected using the metabolic cage. The levels of steroid hormones and silent information regulator 2 homolog 1 (SIRT1) in serum were measured by appropriate ELISA kits. Body weight of the high NaF group was significantly less during short-term treatment than that of other treatment groups or control group. Urinary fluoride concentration was increased linearly with treatment time. Treatment of NaF significantly decreased steroid hormone level while increased SIRT1 level in the serum. In addition, NaF treatment significantly decreased pregnancy rate. It is concluded that NaF inhibits the secretion of hormone and estradiol (E2) release from the ovary, thereby reducing the rate of pregnant. SIRT1 may be involved in this NaF-induced reproductive dysfunction in female rats through regulating reproductive hormone, FSH, and LH secretion.

The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure

Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.