Tag Archives: fluoride

Skeletal fluorosis, Sri Lanka

Hewavithana PB, Jayawardhane WM, Gamage R, Goonaratna C. Skeletal fluorosis in Vavuniya District: an observational study. The Ceylon medical journal. 2018 Sep 30;63(3):139-142.

BACKGROUND: The WHO recommended safe upper limit for fluoride in drinking water is 1.5 mg/l. Groundwater sources in many parts of Sri Lanka often exceed this limit. The high fluoride content of groundwater and high environmental temperatures in Vavuniya District predispose to pre-skeletal fluorosis and skeletal fluorosis in adults.

OBJECTIVES: To identify residents of Vavuniya District with clinical features of pre-skeletal and skeletal fluorosis; to describe their clinical, biochemical and radiographic features; to determine the fluoride content of blood and urine in individuals with established diagnoses, and of their drinking water.

METHODS: In 98 volunteers we detected 60 with clinical features of pre-skeletal and skeletal fluorosis. Clinical examination, biochemical and radiographic investigations were performed. Forty four with confounding factors were excluded. The balance 16 had radiographic investigation for fluoride bone disease, and assessment of clinical features for pre-skeletal fluorosis. The radiographic criteria of skeletal fluorosis were trabecular haziness, osteosclerosis, osteophytes, cortical thickening and ligamentous or muscle attachment ossification. All 16 had “spot” samples of 15 ml of venous blood taken for biochemical tests and fluoride estimation; and 30 ml of urine, and water from 16 dug wells for fluoride.

RESULTS: The 16 selected (11 males) had BMI between 20.6 and 31.9 kg/m2, and were between 22 and 84 years (x̅ = 59.9 + 20.4). They used water from domestic dug wells for drinking. All had adequate renal function. All serum and urine samples had raised fluoride levels way above the reference ranges for serum (0.02 – 0.18 mg/l) and urine (0.6 – 2.0 mg/l). The 16 water samples showed a mean fluoride content of 2.90 +0.93 mg/l.

INTERPRETATION: In a cohort of 60 individuals in Vavuniya with symptoms suggestive of skeletal fluoride toxicity, 6 had skeletal fluorosis, 10 had pre-skeletal fluorosis, and groundwater sources had fluoride levels much higher than WHO recommended upper limit for drinking water. Residents in Vavuniya are predisposed to pre-skeletal and skeletal fluorosis. All 16 had been misdiagnosed as various types of arthritis.

Toxic effects of fluoride on organisms

Huan Zuo, Liang Chen, Ming Kong, Lipeng Qiu, Peng Lü, Peng Wu, Yanhua Yang, Keping Chen. Toxic effects of fluoride on organisms. Life Sciences
Volume 198, 1 April 2018, Pages 18-24

Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead  to  mitochondrial  damage,  endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity.

Fluoride induced genetic alterations, skeletal fluorosis

Daiwile AP, Tarale P, Sivanesan S, Naoghare PK, Bafana A, Parmar D, Kannan K. Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis. Ecotoxicology and environmental safety. 2018 Nov 20;169:410-417. doi: 10.1016/j.ecoenv.2018.11.035.

Fluoride is an essential trace element required for proper bone and tooth development. Systemic high exposure to fluoride through environmental exposure (drinking water and food) may result in toxicity causing a disorder called fluorosis. In the present study, we investigated the alteration in DNA methylation profile with chronic exposure (30 days) to fluoride (8 mg/l) and its relevance in the development of fluorosis. Whole genome bisulfite sequencing (WGBS) was carried out in human osteosarcoma cells (HOS) exposed to fluoride. Whole genome bisulfite sequencing (WGBS) and functional annotation of differentially methylated genes indicate alterations in methylation status of genes involved in biological processes associated with bone development pathways. Combined analysis of promoter DNA hyper methylation, STRING: functional protein association networks and gene expression analysis revealed epigenetic alterations in BMP1, METAP2, MMP11 and BACH1 genes, which plays a role in the extracellular matrix disassembly, collagen catabolic/organization process, skeletal morphogenesis/development, ossification and osteoblast development. The present study shows that fluoride causes promoter DNA hypermethylation in BMP1, METAP2, MMP11 and BACH1 genes with subsequent down-regulation in their expression level (RNA level). The results implies that fluoride induced DNA hypermethylation of these genes may hamper extracellular matrix deposition, cartilage formation, angiogenesis, vascular system development and porosity of bone, thus promote skeletal fluorosis.

Fluoride exposure for pregnant women, Canada

Till C, Green R, Grundy JG, Hornung R, Neufeld R, Martinez-Mier EA, Ayotte P, Muckle G, Lanphear B. Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada. Environmental health perspectives. 2018 Oct;126(10):107001. doi: 10.1289/EHP3546.

BACKGROUND: Fluoride exposures have not been established for pregnant women who live in regions with and without community water fluoridation.

OBJECTIVE: Our aim was to measure urinary fluoride levels during pregnancy. We also assessed the contribution of drinking-water and tea consumption habits to maternal urinary fluoride (MUF) concentrations and evaluated the impact of various dilution correction standards, including adjustment for urinary creatinine and specific gravity (SG).

METHODS: We measured MUF concentrations in spot samples collected in each trimester of pregnancy from 1,566 pregnant women in the Maternal-Infant Research on Environmental Chemicals cohort. We calculated intraclass correlation coefficients (ICCs) to assess variability in MUF concentrations across pregnancy. We used regression analyses to estimate associations between MUF levels, tea consumption, and water fluoride concentrations as measured by water treatment plants.

RESULTS: Creatinine-adjusted MUF values  were almost two times higher for pregnant women living in fluoridated regions  compared with nonfluoridated regions. MUF values tended to increase over the course of pregnancy using both unadjusted values and adjusted values. Reproducibility of the unadjusted and adjusted MUF values was modest . The municipal water fluoride level was positively associated with creatinine-adjusted MUF, accounting for 24% of the variance after controlling for covariates. Higher MUF concentrations correlated with numbers of cups of black but not green tea. Urinary creatinine and SG correction methods were highly correlated and were interchangeable in models examining predictors of MUF.

CONCLUSION: Community water fluoridation is a major source of fluoride exposure for pregnant women living in Canada. Urinary dilution correction with creatinine and SG were shown to be interchangeable for our sample of pregnant women.

Fluoride toxicity to bone and soft tissue

Wei Q, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L.  A mini review of fluoride-induced apoptotic pathways. Environ Sci Pollut Res Int. 2018 Oct 18. doi: 10.1007/s11356-018-3406-z.

Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity.

Neurotoxicity of fluoride in rats

Jiang P, Li G, Zhou X, Wang C, Qiao Y, Liao D, Shi D. Chronic fluoride exposure induces neuronal apoptosis and impairs neurogenesis and synaptic plasticity: Role of GSK-3β/β-catenin pathway. Chemosphere. 2018 Sep 17;214:430-435. doi: 10.1016/j.chemosphere.2018.09.095.

Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3β (GSK-3β)/β-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3β/β-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3β activity, with decreased inactive phosphorylated GSK-3β levels and increased GSK-3β, the active form of the kinase. Correspondingly, downstream β-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus β-catenin status and the higher dose of NaF also reduced cytoplasmic β-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3β/β-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3β/β-catenin signaling in the fluoride-induced neurotoxicity.

Dental fluorosis prevalence high in Turkey village fluoride study

I’m somewhat surprised that this study has no control group or that the findings were not compared to a town of similar size with no fluoride. Comparing results to national statistics is not very informative. In a limited study such as this observing health effects other than dental fluorosis is unlikely.

Sezgin BI, Onur ŞG, Menteş A, Okutan AE, Haznedaroğlu E, Vieira AR. Two-fold excess of fluoride in the drinking water has no obvious health effects other than dental fluorosis. J Trace Elem Med Biol. 2018 Dec;50:216-222. doi: 10.1016/j.jtemb.2018.07.004. Epub 2018 Jul 11.

BACKGROUND: There is concern that fluorides in the drinking water is hazardous to health.

METHODS: We conducted an observational study in the village of Hanliyenice (population 280), Turkey, which has 2.5 times higher than optimal levels of fluoride in the drinking water and evaluated all children 7-13 years of age (N = 30). We collected information on dental decay, fluorosis, daily water consumption and diet, child history and her family history of cancer, cardiovascular risks/diseases, and asthma, and obtained a blood sample for extraction of genomic DNA. We genotyped ten single nucleotide polymorphisms in aquaporins.

RESULTS: As expected, a high number of children were dental caries free (19 out of 30) and had fluorosis (25 out of 30). Family history of cancer, cardiovascular events, and asthma was not different from the expected figures based on Turkey. One variant just upstream of AQP5 was associated with being fluorosis free. (G allele of AQP5 rs296763, p = 6.0E-6).

CONCLUSIONS: Exposure to levels of fluoride twice as high than the optimum in the drinking water increases the prevalence of fluorosis, dramatically decreases dental caries, and does not increase the risk of cancer, cardiovascular events, and asthma.