Special Issue "The Harmful Effects of Fluoride Exposure"

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Environmental Health".

Deadline for manuscript submissions: closed (31 July 2019).

Special Issue Editors

Dr. Hardy Limeback

Guest Editor
University of Toronto, Faculty of Dentistry, Toronto, Canada
Interests: collagen biochemistry; fluoride exposure
Prof. Dr. William Potter
Website
Guest Editor
University of Tulsa, Department of Chemistry and Biochemistry, Tulsa, United States
Interests: Biochemistry; Clinical Biochemistry; Biochemistry of Nutrition; Biochemistry of Nutraceuticals; Steroid Hormones and Metabolic Products with respect to Mental Health; Effects of Exercise and other Treatment Regimes; Non-invasive Salivary and Hair Diagnostics

Special Issue Information

Dear Colleagues,

Although fluoride is widely used for dental and industrial applications, our understanding of chronic and sub-acute mechanisms for fluoride toxicity are incomplete.  Nevertheless, environmental exposures to fluoride from a wide range of consumer products and industrial sources are still increasing.  New studies support a growing body of evidence that fluoride should be classified as a neurological toxicant and that the interplay between fluoride toxicity depends greatly on other nutritional and immunological factors. Advancing our knowledge of genetic, developmental and comorbidity susceptibilities to fluoride toxicity are needed.  This special issue invites papers to evaluate and monitor the many factors regarding fluoride exposures and mechanisms of toxicity.

Dr. Hardy Limeback
Prof. Dr. William Potter
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2300 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Fluoride exposure from industrial pollution
  • Fluoride exposure from metabolism of fluorinated compounds
  • Acute toxicity of fluoride from accidental or intentional fluoride exposure
  • Chronic daily fluoride exposure from air, drinking water, foods, and drugs
  • Fluoride metabolism
  • Fluoride’s effect on mineralized tissues
  • Fluoride’s effect on soft tissues
  • Risk assessment of fluoride exposure
  • Effect of socioeconomic status (SES) on chronic fluoride exposure
  • Effective means to minimizing fluoride exposure or its effects

Published Papers (7 papers)

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Research

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Open AccessArticle
In Vivo Comparison of the Phenotypic Aspects and Molecular Mechanisms of Two Nephrotoxic Agents, Sodium Fluoride and Uranyl Nitrate
Int. J. Environ. Res. Public Health 2019, 16(7), 1136; https://doi.org/10.3390/ijerph16071136 - 29 Mar 2019
Cited by 1
Abstract
Because of their nephrotoxicity and presence in the environment, uranium (U) and fluoride (F) represent risks to the global population. There is a general lack of knowledge regarding the mechanisms of U and F nephrotoxicity and the underlying molecular pathways. The present study [...] Read more.
Because of their nephrotoxicity and presence in the environment, uranium (U) and fluoride (F) represent risks to the global population. There is a general lack of knowledge regarding the mechanisms of U and F nephrotoxicity and the underlying molecular pathways. The present study aims to compare the threshold of the appearance of renal impairment and to study apoptosis and inflammation as mechanisms of nephrotoxicity. C57BL/6J male mice were intraperitoneally treated with a single dose of U (0, 2, 4 and 5 mg/kg) or F (0, 2, 5, 7.5 and 10 mg/kg) and euthanized 72 h after. Renal phenotypic characteristics and biological mechanisms were evaluated by urine biochemistry, gene/protein expression, enzyme activity, and (immuno)histological analyses. U and F exposures induced nephrotoxicity in a dose-dependent manner, and the highest concentrations induced severe histopathological alterations as well as increased gene expression and urinary excretion of nephrotoxicity biomarkers. KIM-1 gene expression was induced starting at 2 mg/kg U and 7.5 mg/kg F, and this increase in expression was confirmed through in situ detection of this biomarker of nephrotoxicity. Both treatments induced inflammation as evidenced by cell adhesion molecule expression and in situ levels, whereas caspase 3/7-dependent apoptosis was increased only after U treatment. Overall, a single dose of F or U induced histopathologic evidence of nephrotoxicity renal impairment and inflammation in mice with thresholds under 7.5 mg/kg and 4 mg/kg, respectively. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Open AccessArticle
Old and New Threats—Trace Metals and Fluoride Contamination in Soils at Defunct Smithy Sites
Int. J. Environ. Res. Public Health 2019, 16(5), 819; https://doi.org/10.3390/ijerph16050819 - 06 Mar 2019
Cited by 2
Abstract
The aim of this study was to investigate soil contamination with trace elements and fluoride at sites in Szczecin (NW Poland) where economic activity was historically associated with the use of trace metals. As the Polish legislation does not recognize the lasting impact [...] Read more.
The aim of this study was to investigate soil contamination with trace elements and fluoride at sites in Szczecin (NW Poland) where economic activity was historically associated with the use of trace metals. As the Polish legislation does not recognize the lasting impact of historical pollution on soils, land developers are not obliged to determine soil pollution in the new residential areas, including parks and playgrounds for children. Therefore, in this study, at the locations of defunct metalwork enterprises (smithies, foundries, chemical plants, and small metal production plants), which were closed down after World War II, we determined lead (Pb), chromium (Cr), copper (Cu), zinc (Zn), iron (Fe), manganese (Mn), nickel (Ni), mercury (Hg), cadmium (Cd), and cobalt (Co) levels in the soil. In addition, we also determined fluoride (F) levels due to the contemporary fluoride pollution in the area generated by a large chemical plant with a post-production phosphogypsum waste landfill and a power plant complex. Our results show that soil at the sites of now-defunct smithies can still act as a significant source of trace metals. Pb concentration in the surface (0–20 cm) and subsurface (20–40 cm) layers exceeded concentration thresholds for soils with first-degree pollution. The concentrations of Zn and Cu also exceeded their natural background limits. Furthermore, our research indicates an increased concentration of fluoride in surface layers of the soil; however, not exceeding the fluoride content threshold. These observations have important consequences for public health and safety because, presently, the studied sites function as housing estates and other public facilities. Therefore, contaminated soil at these sites may pose a threat to the health of local residents and should be closely monitored for trace metal contamination levels. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Open AccessArticle
Influence of Acetylcholinesterase Inhibitors Used in Alzheimer’s Disease Treatment on the Activity of Antioxidant Enzymes and the Concentration of Glutathione in THP-1 Macrophages under Fluoride-Induced Oxidative Stress
Int. J. Environ. Res. Public Health 2019, 16(1), 10; https://doi.org/10.3390/ijerph16010010 - 20 Dec 2018
Cited by 3
Abstract
It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we [...] Read more.
It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Review

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Open AccessReview
Chronic Fluoride Exposure and the Risk of Autism Spectrum Disorder
Int. J. Environ. Res. Public Health 2019, 16(18), 3431; https://doi.org/10.3390/ijerph16183431 - 16 Sep 2019
Cited by 2
Abstract
The continuous rise of autism spectrum disorder (ASD) prevalent in the past few decades is causing an increase in public health and socioeconomic concern. A consensus suggests the involvement of both genetic and environmental factors in the ASD etiopathogenesis. Fluoride (F) is rarely [...] Read more.
The continuous rise of autism spectrum disorder (ASD) prevalent in the past few decades is causing an increase in public health and socioeconomic concern. A consensus suggests the involvement of both genetic and environmental factors in the ASD etiopathogenesis. Fluoride (F) is rarely recognized among the environmental risk factors of ASD, since the neurotoxic effects of F are not generally accepted. Our review aims to provide evidence of F neurotoxicity. We assess the risk of chronic F exposure in the ASD etiopathology and investigate the role of metabolic and mitochondrial dysfunction, oxidative stress and inflammation, immunoexcitotoxicity, and decreased melatonin levels. These symptoms have been observed both after chronic F exposure as well as in ASD. Moreover, we show that F in synergistic interactions with aluminum’s free metal cation (Al3+) can reinforce the pathological symptoms of ASD. This reinforcement takes place at concentrations several times lower than when acting alone. A high ASD prevalence has been reported from countries with water fluoridation as well as from endemic fluorosis areas. We suggest focusing the ASD prevention on the reduction of the F and Al3+ burdens from daily life. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Open AccessReview
Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health
Int. J. Environ. Res. Public Health 2019, 16(8), 1427; https://doi.org/10.3390/ijerph16081427 - 21 Apr 2019
Cited by 5
Abstract
In this study, several lines of evidence are provided to show that Na+, K+-ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as [...] Read more.
In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Open AccessReview
Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health
Int. J. Environ. Res. Public Health 2019, 16(6), 1086; https://doi.org/10.3390/ijerph16061086 - 26 Mar 2019
Cited by 7
Abstract
The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and [...] Read more.
The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Open AccessReview
The Contribution of Fluoride to the Pathogenesis of Eye Diseases: Molecular Mechanisms and Implications for Public Health
Int. J. Environ. Res. Public Health 2019, 16(5), 856; https://doi.org/10.3390/ijerph16050856 - 08 Mar 2019
Cited by 3
Abstract
This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect [...] Read more.
This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na+, K+-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations. Full article
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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