Natural History And Long-Term Impact Of Dental Fluorosis: A Prospective Cohort Study by Loc G Do , Diep H Ha , A John Spencer

The study assessed longitudinal changes in the presentation of dental fluorosis and evaluated the impact of fluorosis on the perception of oral health among young adults.

Link : https://www.mja.com.au/system/files/issues/204_01/10.5694mja15.00703.pdf

Exposure to Fluoride in Drinking Water and Hip Fracture Risk: A Meta-Analysis of Observational Studies By Xin-Hai Yin , Guang-Lei Huang , Du-Ren Lin , Cheng-Cheng Wan , Ya-Dong Wang , Ju- Kun Song , Ping Xu

Many observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk.

Link : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447426/pdf/pone.0126488.pdf

Recommendations For Fluoride Limits In Drinking Water Based On Estimated Daily Fluoride Intake In The Upper East Region, Ghana By Laura Craig , Alexandra Lutz , Kate A. Berry, Wei Yang

Both dental and skeletal fluorosis caused by high fluoride intake are serious public health concerns around the world. Fluorosis is particularly pronounced in developing countries where elevated concentrations of naturally occurring fluoride are present in the drinking water, which is the primary route of exposure. The World Health Organization recommended limit of fluoride in drinking water is 1.5 mg F− L−1, which is also the upper limit for fluoride in drinking water for several other countries such as Canada, China, India, Australia, and the European Union. In the United States the enforceable limit is much higher at 4 mg F− L−1, which is intended to prevent severe skeletal fluorosis but does not protect against dental fluorosis. Many countries, including the United States, also have notably lower unenforced recommended limits to protect against dental fluorosis. One consideration in determining the optimum fluoride concentration in drinking water is daily water intake, which can be high in hot climates such as in northern Ghana. The results of this study show that average water intake is about two times higher in Ghana than in more temperate climates and, as a result, the fluoride intake is higher. The results also indicate that to protect the Ghanaian population against dental fluorosis, the maximum concentration of fluoride in drinking water for children under 6–8 years should be 0.6 mg F− L−1 (and lower in the first two years of life), and the limit for older children and adults should be 1.0 mg F− L−1.

Sodium Fluoride Promotes Apoptosis by Generation of Reactive Oxygen Species in Human Lymphocytes by Manivannan Jothiramajayam, Sonali Sinha, Manosij Ghosh, Anish Naga, Aditi Jana & Anita Mukherjee

Fluoride generated the attention of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and with in vivo experimental models. Interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. This study focused on examining the adverse effects of inorganic fluoride (NaF) on human lymphocyte cells in vitro. Mitochondrial function, oxidative stress, cell cycle progression, and mode of cell death were combined with genotoxic endpoints. Data demonstrated that NaF at lower concentrations, although not significantly cytotoxic and genotoxic, induced oxidative stress leading to apoptotic cell death. The results also suggested that at low concentrations (<1 μg/ml), NaF may affect cell cycle progression. Taken together, our findings confirm earlier reports on mechanisms involved in NaF-induced apoptosis.

Trends On Oxidative Stress And Antioxidant Status In Fluoride Affected Areas In Kolar District, India By Adarsh Manjunath , C. D. Dayanand , C. Muninarayana , Pradeep Kumar Vegi

In the global scenario, twenty three nations have the problem of excess fluoride in  drinking water and resulting endemicity for fluorosis India lies in a  geographical fluoride belt; fluorosis is an endemic condition prevailed in 17 states of India. The highest  endemicity rate has been reported in Andhra Pradesh, Rajasthan, Punjab, Tamilnadu and Karnataka In Karnataka, totally 16 districts are endemic viz Dharwad, Gadag, Bellary, Belgaum, Raichur, Bijapur, Gulbarga, Chitradurga, Tumkur, Chikmagalur, Mandya, Bangalore Rural, Mysore, Mangalore, Shimoga  and Kolar. Fluorosis is a disease state caused by excess intake of Fluoride through  drinking water, food, or inhalation. Acute high level exposure to fluoride is rare and usually  due to accidental contamination of drinking water or due to fires or  explosions. Moderate level & chronic exposure of above 1.5 mg/L of water as per the WHO guideline  value of fluoride in water is more common. Fluoride is  also known to cross the cell membranes and to enter soft tissues.

Link : https://www.researchgate.net/publication/265599980_Trends_on_oxidative_stress_and_antioxidant_status_in_fluoride_affected_areas_in_Kolar_district_India

Health Impact to Different Concentrations of Fluoride in Drinking Water of South India By M. Shanthi , B V Thimma Reddy , Shivani Kohli

Water is our body’s principle chemical component and makes up about 60 percent of body weight. It is essential to good health and lot of functions like regulating body temperature, carrying nutrients to cells, flushes toxins out of vital organs and so on. It is life for all living beings. But nowadays, pure drinking water is available to very few people and others take more or less contaminated water. The contamination may be caused either by natural forces or by industrial effluents, and one such contamination is fluoride.

Link : http://www.ijss-sn.com/uploads/2/0/1/5/20153321/ijss_june-01.pdf

The Effect Of Non-Fluoride Factors On Risk Of Dental Fluorosis: Evidence From Rural Populations Of The Main Ethiopian Rift By Julia Kravchenko , R. Brittany Merola , Tewodros Rango , Christopher Paul , Igor Akushevich , Erika Weinthal , Behailu Atlaw , Courtney Harrison , Peter G. McCornick , Avner Vengosh , Marc Jeuland

Elevated level of fluoride (F−) in drinking water is a well-recognized risk factor of dental fluorosis (DF). While considering optimization of region-specific standards for F−, it is reasonable, however, to consider how local diet, water sourcing practices, and non-F− elements in water may be related to health outcomes. In this study, we hypothesized that non-F− elements in groundwater and lifestyle and demographic characteristics may be independent predictors or modifiers of the effects of F− on teeth. Dental examinations were conducted among 1094 inhabitants from 399 randomly-selected households of 20 rural communities of the Ziway–Shala lake basin of the Main Ethiopian Rift. DF severity was evaluated using the Thylstrup-Fejerskov Index (TFI). Household surveys were performed and water samples were collected from community water sources. To consider interrelations between the teeth within individual (in terms of DF severity) and between F− and non-F− elements in groundwater, the statistical methods of regression analysis, mixed models, and principal component analysis were used. About 90% of study participants consumed water from wells with F− levels above the WHO recommended standard of 1.5 mg/l. More than 62% of the study population had DF. F− levels were a major factor associated with DF. Age, sex, and milk consumption (both cow's and breastfed) were also statistically significantly (p b 0.05) associated with DF severity; these associations appear both independently and as modifiers of those identified between F− concentration and DF severity. Among 35 examined elements in groundwater, Ca, Al, Cu, and Rb were found to be significantly correlated with dental health outcomes among the residents exposed to water with excessive F− concentrations. Quantitative estimates obtained in our study can be used to explore new water treatment strategies, water safety and quality regulations, and lifestyle recommendations which may be more appropriate for this highly  populated region.

Fluoride, Premature Birth And Impaired Neurodevelopment By John D. MacArthur

Premature or preterm birth is birth prior to 37 weeks (8.5 months) of pregnancy. Not just a temporary
problem dealt with during the first weeks of an infant’s life, premature birth is a leading cause of long- term neurological disabilities in children. Significantly more educational assistance than children who were born at term. The societal economic burden associated with preterm birth in the United States is estimated to be at least $26 billion per year, or more than $50,000 per infant born preterm. Premature birth is the most common pregnancy complication that can seriously compromise the newborn brain’s viability and normal development. Many studies have documented the prevalence of a broad range of central nervous system dysfunctions and neurodevelopmental impairments in people who were born preterm, including mental retardation, ADHD, and major depression. The genesis and wiring of the human brain during fetal development is one of the most remarkable feats in all of biology. During the last trimester, dynamic changes occur in the two brain areas most important to cognitive processes: the cerebellum whose surface area increases 30-fold; and the cerebral cortex whose white matter undergoes striking changes. Preterm infants are more likely to have lower IQs and require

Link : http://www.johndmacarthur.com/reports/FluoridePrematureBirthMacArthurNov2013.pdf

Haematological changes in fluorotic adults and children in fluoride endemic regions of Gaya district, Bihar, India by Shahla Yasmin, Sumeet Ranjan & Doris D’Souza

Groundwater used for drinking and cooking was analysed for fluoride (F), and health surveys were conducted in Bodh Gaya, Amas and Bankebazaar  blocks of the Gaya district, Bihar, India. Amas and
Bankebazaar blocks were F endemic areas with mean F = 2.36 ± 0.23 mg/L (N = 27). Bodh Gaya was
considered as control area with mean F = 0.59 ± 0.03 mg/L (N = 11). Health survey showed that more than 50 % of adults and more than 55 % of children had complaints of gastro-intestinal (GI) disturbances in the F endemic areas, while less than 20 % of adults and less than 10 % of children complained of GI problems in the control areas. Haematological analyses were conducted on age- and sex-matched fluorotic subjects (N = 93) of F endemic areas, and non-fluorotic subjects (N = 52) of control area showed lowered haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration in the fluorotic subjects, suggesting the occurrence of anaemia in the fluorotic subjects.

Factors Affecting the Bioaccessibility of Fluoride From Seafood Products by R.A. Rocha, B. de la Fuente, M.J. Clemente, A. Ruiz, D. Velez, V. Devesa

Fluoride is considered important for health because of its beneficial effect on the prevention of dental caries and on bone development in the child population. However, excessive intake has negative effects. The main pathway for exposure is oral, through consumption of drinking water, and some food products. Therefore its bioaccessibility (quantity of the element solubilized during the digestive process) is a parameter to be considered when estimating the risk/benefit associated with this element. The aim of the present study was to evaluate the influence of the digestion phase, gastrointestinal digestion factors (pH, pepsin and bile salt concentrations) and the presence of cations on the bioaccessibility of fluoride from seafood products. The results show that the solubilization of fluoride takes place entirely during the gastric phase. Its bioaccessibility is strongly influenced by conditions that favor the formation of insoluble complexes of fluoride with other elements present in the matrix. The factors that are most influential in reducing its bioaccessibility are the increase in pH in the gastric phase, the presence of cations, especially in the intestinal phase, and a low concentration of bile salts.

Biopolymer-Reinforced Synthetic Granular Nanocomposites For Affordable Point-Of-Use Water Purification by Mohan Udhaya Sankar , Kamalesh Chaudhari , Thalappil Pradeep , Sahaja Aigal , Shihabudheen M. Maliyekkal , Amrita Chaudhary, Anshup, Avula Anil Kumar

Creation of affordable materials for constant release of silver ions in water is one of the most promising ways to provide microbially safe drinking water for all. Combining the capacity of diverse nano- composites to scavenge toxic species such as arsenic, lead, and other contaminants along with the above capability can result in affordable, all-inclusive drinking water purifiers that can function
without electricity. The critical problem in achieving this is the synthesis of stable materials that can release silver ions continuously in the presence of complex species usually present in drinking water that deposit and cause scaling on nanomaterial surfaces. Here we show that such constant release materials can be synthesized in a simple and effective fashion in water itself without the use of electrical power. The nanocomposite exhibits river sand-like properties, such as higher shear strength in loose and wet forms. These materials have been used to develop an affordable water purifier to deliver clean drinking water at US $2.5/y per family. The ability to prepare nanostructured compositions at near ambient temperature has wide relevance for adsorption-based water purification.

Link : http://www.pnas.org/content/110/21/8459.full.pdf

Excessive Fluoride Consumption Leads to Accelerated Death of Erythrocytes and Anemia in Rats by Natalia Ivanovna Agalakova & Gennadii Petrovich Gusev

The present study was performed to evaluate an overall effect of long-term consumption of excessive
fluoride (F) amounts by rats on their erythrocytes. The animals were administered regular drinking water (0.4 ppm F) or the same water supplemented with 2, 10, and 20 ppm F (as NaF) for 12 months. Chronic exposure of the rats to increasing F doses induced a progressive rise of the plasma F concentration accompanied by a dose-dependent fall of hematocrit and decrease in the mean erythrocyte volume. Consumption of 10 and 20 ppm F resulted in appearance of morphologically abnormal cells (stomatocytes and echinocytes) in the peripheral blood. Rise of the water F concentration to 20 ppm F led to significant increase in the number of phosphatidylserine-exposing erythrocytes, although suppression of cell viability was revealed in all three groups of F-poisoned rats. A compensatory enhanced release of reticulocytes was not sufficient to compensate for erythrocyte loss. Dose-dependent accumulation of free cytosolic Ca2+ appears to be a major pathophysiological process underlying the development of F-induced death processes in rat erythrocytes. In addition, 10 and 20 ppm F induced ATP depletion and generation of peroxides in erythrocytes, whereas superoxide and glutathione levels were not altered. Thus, long-term intoxication of the rats with F triggers premature death of their erythrocytes due to intrinsic death-associated biochemical defects and development of anemia.

Link : https://www.researchgate.net/publication/236836623_Excessive_Fluoride_Consumption_Leads_to_Accelerated_Death_of_Erythrocytes_and_Anemia_in_Rats

A Possible Mechanism For Combined Arsenic And Fluoride Induced Cellular And DNA Damage In Mice by Swaran J. S. Flora, Megha Mittal, Vidhu Pachauri and Nidhi Dwivedi

Arsenic and fluoride are major contaminants of drinking water. Mechanisms of toxicity following individual exposure to arsenic or fluoride are well known. However, it is not explicit how combined exposure to arsenic and fluoride leads to cellular and/or DNA damage. The present study was planned to assess (i) oxidative stress during combined chronic exposure to arsenic and fluoride in drinking water, (ii) correlation of oxidative stress with cellular and DNA damage and (iii) mechanism of cellular damage using IR spectroscopy. Mice were exposed to arsenic and fluoride (50 ppm) either individually or in combination for 28 weeks. Arsenic or fluoride exposure individually led to a significant increase in reactive oxygen species (ROS) generation and associated oxidative stress in blood, liver and brain. Individual exposure to the two toxicants showed significant depletion of blood glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6PD) activity, and single-stranded DNA damage using a comet assay in lymphocytes. We also observed an increase in the activity of ATPase, thiobarbituric acid reactive substance (TBARS) and a decreased, reduced and oxidized glutathione (GSH : GSSG) ratio in the liver and brain. Antioxidant enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were decreased and increased in liver and brain respectively. The changes were more pronounced in liver compared to brain suggesting liver to be more susceptible to the toxic effects of arsenic and fluoride. Interestingly, combined exposure to arsenic and fluoride resulted in less pronounced toxic effects compared to their individual effects based on biochemical variables, IR spectra, DNA damage (TUNEL and comet assays) and histopathological observations. IR spectra suggested that arsenic or fluoride perturbs the strength of protein and amide groups; however, the shifts in peaks were not pronounced during combined exposure. These results thus highlight the role of arsenic- or fluoride-induced oxidative stress, DNA damage and protein interaction as the major determinants of toxicity, along with the differential toxic effects during arsenic–fluoride interaction during co-exposure. The study further corroborates our earlier observations that at the higher concentration co-exposures to these toxicants do not elicit synergistic toxicity.

Link: http://pubs.rsc.org/en/Content/ArticleLanding/2012/MT/C1MT00118C#!divAbstract

Pregnant women living in areas of endemic fluorosis in Senegal and low birth weight newborns: Case–control study by M. Diouf , D. Cisse, C.M.M. Lo, M. Ly, D. Faye, O. Ndiaye

In developing countries, maternal and neonatal mortality rates remain high [1]. Amongst mortality causes during the neonatal period, low birth weight is decisive. It has been defined by the World Health Organization as a birth weight under 2500 g.  According to the EDS III survey (Health and Demographic Survey) [2] in Senegal, 13.5% of women on average give birth to newborn infants weighing less than 2500 g. These newborn babies are a daily concern due to the difficulties related to their care and the frequent negative impact of low weight on their growth. The high burden of infectious and/or inflammatory disease is amongst the most determinant causes of death. To that we can add dental pathologies, enamel defects, congenital or acquired [3]. Just like other chemicals, fluorine and fluorides have both beneficial and toxic effects with significant implications on public health. Even though we have noted that an optimal dose of 1 mg of fluoride per litre in drinking water is beneficial for the prevention of tooth decay, extended exposure to higher concentrations can lead to adverse effects on enamel and bones [4,5]. In fact, a concentration of fluoride higher than 2 mg/l causes enamel deterioration increasing with fluoride intake, and this can occur in conjunction with other conditions or might increase certain risks. In pregnant women, placental transport of fluorides happens as early as the 19th week of pregnancy [6–9]. In some countries, and more specifically  in the United States, several studies have focused on dental fluorosis and low birth weight [3,10,11]. One of the pretexts used to justify water fluoridation is a high prevalence of low birth weight. But fluoridation is beneficial only for newborn infants whose birth weight is greater than or equal to  3400 g [12]. These studies focused on the increase of the prevalence of dental fluorosis due to the fact that a significant proportion of newborns have a low birth weight (under 2500 g).

Link : http://fluoridealert.org/wp-content/uploads/Diouf-2011.translation1.pdf

Fluoride Metabolism By Marilia Afonso Rabelo Buzalaf , Gary Milton Whitford

Knowledge of all aspects of fluoride metabolism is essential for comprehending the biological effects of this ion in humans as well as to drive the prevention (and treatment) of fluoride toxicity. Several aspects of fluoride metabolism – including gastric absorption, distribution and renal excretion – are pH-dependent because the coefficient of permeability of lipid bilayer membranes to hydrogen fluoride (HF) is 1 million times higher than that . This means that fluoride readily crosses cell membranes as HF, in response to a pH gradient between adjacent body fluid compartments. After ingestion, plasma of F– fluoride levels increase rapidly due to the rapid absorption from the stomach, an event that is pH-dependent and distinguishes fluoride from other halogens and most other substances. The majority of fluoride not absorbed from the stomach will be absorbed from the small intestine. In this case, absorption is not pH-dependent. Fluoride not absorbed will be excreted in feces. Peak plasma fluoride concentrations are reached within 20–60 min following ingestion. The levels start declining thereafter due to two main reasons: uptake in calcified tissues and excretion in urine. Plasma fluoride levels are not homeostatically regulated and vary according to the levels of intake, deposition in hard tissues and excretion of fluoride. Many factors can modify the metabolism and effects of fluoride in the organism, such as chronic and acute acid-base disturbances, hematocrit, altitude, physical activity, circadian rhythm and hormones, nutritional status, diet, and genetic predisposition. These will be discussed in detail in this review.

Fluorine – Human Health Risks By Fiona M. Fordyce

Fluorine (fluoride) is beneficial to human health in low concentration but toxic in excess. One of the main exposure routes is via drinking water. It is unproven whether fluoride is essential for health but numerous studies have demonstrated that low concentrations in drinking water (0-0.5 mg L-1) are associated with increased dental caries (tooth decay) rates whereas contents of 0.5-1.5 mg L-1 are protective against the disease. As a result, fluoride is widely used in dental products and water fluoridation programs have been implemented in many countries. However, exposure to higher concentrations via drinking water (> 1.5 mg L-1), some teas and fluoride-contaminated salt and the burning of high-fluoride fuels can cause deformities of the hard tissues, namely dental and skeletal fluorosis. Dental fluorosis is an irregular calcification disorder of the enamel-forming process during childhood leading to pitted, stained and eroded teeth. In contrast, skeletal fluorosis is a crippling disease caused by over-mineralization of the bones and joints as a result of longer term exposure to high fluoride intakes. It is estimated that these diseases affect over 70 million people globally, limiting their ability to work and support their families. Hence the need for better understanding of environmental exposure to help mitigate these health outcomes.

Link : https://www.researchgate.net/publication/281263108_Fluorine_Human_Health_Risks

Influence Of Selenium And Fluoride On Blood Antioxidant Capacity Of Rats by Pei Feng, Jun-ren Wei, Zi-gui Zhang

This study is to explore the effect of selenium and fluoride on blood antioxidant capacity of rats, and try to find out the optimal level of selenium in drinking water against fluorosis. Animals were divided into control group, sodium fluoride treated group (NaF, 50 mg/L) and selenium + NaF treated group (sodium selenite 0.375, 0.75, 1.5 mg/L) in water were respectively administered to male rats, which were decapitated after 6 months. Their blood was collected for GSH-Px activity, plasma SOD activity, T-AOC assay, uric acid assay, sialic acid (SA) content and MDA content, and the fluidity of erythrocyte membrane by electron spin resonance (ESR) was analyzed. The results showed that, compared with the control group, the blood antioxidant capacity of the rats exposed to fluoride was down-regulated significantly (P < 0.05, P < 0.01), MDA content increased significantly (P < 0.05), the fluidity of erythrocyte membrane decreased (P < 0.05, P < 0.01). Meanwhile,the treatments of selenium along with NaF compared with fluorosis group, SOD activity, GSH-Px activity and T-AOC assay increased respectively, MDA content decreased significantly (P < 0.05) in NaF + Se (Se 0.75, 1.5 mg/L) treated groups, uric acid level was up-regulated, but had no statistical significant difference (P > 0.05). The fluidity of erythrocyte membrane showed significant increase (P < 0.05), the content of SA was lower. Fluorosis could induce the decline of blood antioxidant capacity and the fluidity of erythrocyte membrane, as evident in this study, and Se at different levels possess some antagonistic effects on blood induced by fluoride. However, high dose of selenium (1.5 mg/L) is the optimum concentration.

High Prevalence Of Genu Varum/Valgum In European Children With Low Vitamin D Status And Insufficient Dairy Products/Calcium Intakes By A Voloc, L Esterle , T M Nguyen , O Walrant-Debray , A Colofitchi , F Jehan , M Garabedian

The prevalence of lower limb deformities physiologically decreases after 5 years of age. It remains high in some tropical and subtropical regions where it has been associated with severe vitamin D deficiency, low calcium/milk intakes, malnutrition, and/or fluoride overexposure. Very little data is available in apparently healthy Caucasian children and adolescents.  Design: We evaluated the prevalence of genu varum/valgum and other clinical symptoms, and assessed vitamin D status and markers of calcium metabolism in 226 apparently healthy European full-time boarders (7–16 years) seen during winter–spring and fed a cereal-based diet with little access to meat, milk, and dairy products. A cohort of 71  white children and adolescents hospitalized for acute illness served as age-matched controls. Results: Association studies showed a high prevalence of lower limb deformities (36%) and higher alkaline phosphate activities in the 21% of children and adolescent full-time boarders with serum 25-(OH)D levels %30 nmol/l, and low serum calcium in the 74% of boarders with 25-(OH)D levels %50 nmol/l, compared with boarders with higher vitamin D status. No such anomalies were found in the control cohort despite lower serum 25-(OH)D levels. Conclusions: Low 25-(OH)D levels, at least during winter–spring, combined with additional risk factors such as very low calcium/milk intakes and possibly digestive disorders, are associated with an increased risk of genu varum/valgum in European children and adolescents. Thus, dietary fortification, or supplementation with vitamin D, may be recommended, at least during the winter, to European children and adolescents with either none or insufficient calcium/dairy product intakes.

Link : http://www.eje-online.org/content/163/5/811.full.pdf

Molecular Mechanisms Of Fluoride Toxicity By Olivier Barbier , Laura Arreola-Mendoza , Luz Maria Del Razoa

Halfway through the twentieth century, fluoride piqued the interest of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and in in vivo experimental models. Until the 1990s, the toxicity of fluoride was largely ignored due to its “good reputation” for preventing caries via topical application and in dental toothpastes. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. In recent years, several investigations demonstrated that fluoride can induce oxidative stress and modulate intracellular redox homeostasis, lipid peroxidation and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response, metabolic enzymes, the cell cycle, cell–cell communications and signal transduction. The primary purpose of this review is to examine recent findings from our group and others that focus on the molecular mechanisms of the action of inorganic fluoride in several cellular processes with respect to potential physiological and toxicological implications. This review presents an overview of the current research on the molecular aspects of fluoride exposure with emphasis on biological targets and their possible mechanisms of involvement in fluoride cytotoxicity. The goal of this review is to enhance understanding of the mechanisms by which fluoride affects cells, with an emphasis on tissue-specific events in humans.

Link : https://www.researchgate.net/publication/45281342_Molecular_mechanisms_of_fluoride_toxicity_Chem_Biol_Interact

Arsenic And Fluoride Two Major Ground Water Pollutants by Swapnila Chouhan and S J S Flora

Increasing human activities have modified the global cycle of heavy metals, non metals and metalloids. Both arsenic and fluoride are ubiquitous in the environment. Thousands of people are suffering from the toxic effects of arsenicals and fluorides in many countries all over the world. These two elements are recognized worldwide as the most serious inorganic contaminants in drinking water. Many studies have reported as regards to simple fluorosis and arsenicosis, but the knowledge of the joint action of these two elements is lacking and the results derived from previous studies were inconclusive. Contradictory results were reported in experimental studies in which different joint actions such as independent, synergistic and antagonistic effects were observed. This indicates that interaction mechanism of these two elements is considerable complicated and requires extensive studies. When two different types of toxicants are simultaneously going inside a human body they may function independently or can act as synergistic or antagonistic to one another. Thus there is an urge to resolve the question that how arsenic and fluoride act in condition of concomitant exposure. Although there have been reports in literature of individual toxicity of arsenic and fluoride however, there is very little known about the effects following the combined exposure to these toxicants. This review focused on recent developments in the research on the condition of individual exposure to arsenic and fluoride along with the recent updates of their combined exposure to better understand the joint action of these two toxicants.

Link: http://nopr.niscair.res.in/bitstream/123456789/9735/1/IJEB%2048%287%29%20666-678.pdf