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

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

Moderating Role of TSHR and PTPN22 Gene Polymorphisms in Effects of Excessive Fluoride on Thyroid: a School-Based Cross-Sectional Study.

We aimed to investigate the relationship between the effects excessive of fluoride on thyroid health in children and the moderating role of thyroid stimulating hormone receptor (TSHR) or protein tyrosine phosphatase nonreceptor-22 (PTPN22) gene polymorphisms. Four hundred thirteen children (141 with dental fluorosis and 198 boys) were enrolled from both historical endemic and non-endemic areas of fluorosis in Tianjin, China. The fluoride exposure levels, thyroid health indicators, and TSHR (rs2268458) and PTPN22 (rs3765598) polymorphisms were examined. Multiple logistic models were applied to evaluate the relationship between dental fluorosis and thyroid abnormalities. Children over 9 year old with dental fluorosis have lower FT4 and TGAb levels and thyroid volume and higher TPOAb levels (all P < 0.05). In overall participants, children with dental fluorosis were more likely to have thyroid antibody single positive issues (adjusted P = 0.039) and less likely to have a goiter according to age or body surface area (age or BSA) (adjusted P = 0.003); In the TSHR (rs2268458) SNP = CC/CT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may cause thyroid antibody single positive (adjusted P = 0.036; adjusted P = 0.002); in the TSHR (rs2268458) SNP = TT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may protect children from goiter (age or BSA) (adjusted P = 0.018; adjusted P = 0.013). Excessive fluoride may induce thyroid antibody single positive and reduce goiter in children. Heterogeneity exists in the relationship between excessive fluoride and thyroid antibody single positive or goiter issues across children carrying different TSHR (rs2268458) or PTPN22 (rs3765598) genotypes.

Spatial distribution of fluoride in drinking water and health risk assessment of children in typical fluorosis areas in north China.

China has been suffering from endemic fluorosis for the past 30 years. This study investigated fluoride concentrations in 10 districts of Tianjin, China, to illustrate their spatial distribution characteristics and potential human health risks. The results showed fluoride concentration of 0.01-6.30 mg L-1 with a mean value of 0.99 mg L-1, and 78.82% of water fluoride reaches the standard for drinking water (1.5 mg L-1). Higher fluoride levels were recorded in deep well pumps supply zones, and more potential changes in fluoride occurred was positively correlated with pH in groundwater. Mean value of fluoride in drinking water in 10 districts followed the order of WQ > BC > JZ > NH > BD > BH > JN > JH > DL > XQ. Estimations of non-carcinogenic risk for drinking water indicated that mean hazard quotient values of fluoride for combined pathways (i.e., oral ingestion and dermal absorption) were >1.0 for all age groups of WQ and BC. The results also showed that the estimated risk primarily came from the ingestion pathway. Risk levels for children varied obviously, generally in the order of 1-4y > 4-7y > 7-9y (years old). In the central tendency center and reasonable maximum exposure conditions, estimated risks were 1.25, 1.12, 0.771 and 3.66, 3.29, 2.27, respectively. The results supply material information for health authorities in fluorosis areas to put forward more efficient policies to control the endemic diseases. Attention should be paid to the formulation of health promotion strategies and measures to reduce fluoride intake in order to protect the health of residents.

Threshold effects of moderately excessive fluoride exposure on children's health: A potential association between dental fluorosis and loss of excellent intelligence.

BACKGROUND: Excessive fluoride exposure is associated with adverse health outcomes, but little is known of the effects of moderately chronic fluoride exposure on children's health. OBJECTIVES: We conducted a cross-sectional study to explore the health impact of moderately excessive fluoride in drinking water. METHODS: We recruited 2886 resident children, aged 7 to 13 years, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. The fluoride levels in drinking water and urine were measured using the national standardized ion selective electrode method. We examined the dose-response effects of low-to-moderate fluoride exposure on dental fluorosis (DF) and intelligence quotient (IQ), and evaluated the potential relationships between DF grades and intelligence levels using piecewise linear regression and multiple logistic regression, respectively. RESULTS: The adjusted odds ratios (ORs) of DF were 2.24 (95% confidence interval [CI]: 2.02 to 2.48) for every 0.1 mg/L increment in the water fluoride concentration in the range of 0.80 to 1.50 mg/L, and 2.61 (95% CI: 2.32 to 2.93) for every 0.5 mg/L increment in the urinary fluoride level up to 1.80 mg/L. Every 0.5 mg/L increment in the water fluoride level was associated with a reduction of 4.29 in the IQ score (95% CI: -8.09 to -0.48) in the range of 3.40 to 3.90 mg/L, and a decreased probability of developing excellent intelligence (IQ ≥ 130, OR = 0.60, 95% CI: 0.47 to 0.77) in the range of 0.20-1.40 mg/L, respectively. Every 0.5 mg/L increment in the urinary fluoride level was related to a decrease of 2.67 in the IQ scores (95% CI: -4.67 to -0.68) between 1.60 mg/L to 2.50 mg/L. Excellent intelligence decreased by 51% in children with higher urinary fluoride, and by 30% with each degree increment of DF. CONCLUSIONS: Our study suggests threshold and saturation effects of moderately excessive fluoride exposure on DF and intelligence loss in children, and a potential association between DF and the loss of excellent intelligence.

Role of endoplasmic reticulum stress-induced apoptosis in rat thyroid toxicity caused by excess fluoride and/or iodide.

Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements.

The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity.

In many regions, excessive fluoride and excessive iodide coexist in groundwater, which may lead to biphasic hazards to human thyroid. To explore fluoride-induced thyroid cytotoxicity and the mechanism underlying the effects of excessive iodide on fluoride-induced cytotoxicity, a thyroid cell line (Nthy-ori 3-1) was exposed to excessive fluoride and/or excessive iodide. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, apoptosis, and the expression levels of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. Fluoride and/or iodide decreased cell viability and increased LDH leakage and apoptosis. ROS, the expression levels of glucose-regulated protein 78 (GRP78), IRE1, C/EBP homologous protein (CHOP), and spliced X-box-binding protein-1 (sXBP-1) were enhanced by fluoride or the combination of the two elements. Collectively, excessive fluoride and excessive iodide have detrimental influences on human thyroid cells. Furthermore, an antagonistic interaction between fluoride and excessive iodide exists, and cytotoxicity may be related to IRE1 pathway-induced apoptosis.