Annals of Environmental Science and Toxicology
Review Article       Open pjestcess      Peer-Reviewed

Fluoride Sources, Toxicity and Its Amelioration: A Review

Vijay K Bharti*, Arup Giri and Krishna Kumar

Defence Institute of High Altitude Research (DIHAR), DRDO, Leh-Ladakh, Jammu & Kashmir, India
*Corresponding author: Dr. Vijay K Bharti, Scientist - D, Defence Institute of High Altitude Research (DIHAR), DRDO, Ministry of Defence, Leh-Ladakh-194101, India, Tel: +91-9779618799; Fax: +91-172-2638500; E-mail:
Received: 30 December, 2018 | Accepted: 17 January, 2018 | Published: 21 January, 2018
Keywords: Ameliorative measures; Fluoride toxicity; Human Health; Oxidative stress

Cite this as

Bharti VK, Giri A, Kumar K (2017) Fluoride Sources, Toxicity and Its Amelioration: A Review. Ann Environ Sci Toxicol 2(1): 021-032. DOI: 10.17352/pjest.000009

In recent scenario, fluorosis is now going to be a severe problem throughout the globe due to toxic effects of fluoride (F) on both plants and animals. F presents in the halogenated group of the periodic table and has the characteristics of electronegativity. Natural geological sources and increased industrialization have contributed greatly to the increasing incidence of fluoride-induced human and animal health issues. In animals and human beings, it exerts adverse effects mainly through the attenuation of antioxidant defense mechanism and chelation of enzymatic cofactors. Thereafter, it causes metabolic disorders through interacting with various cellular processes such as gene expression, cell cycle, metabolism, ion transport, hormonal secretion, endocytosis, apoptosis, necrosis, and oxidative stress. These effects lead to dental mottling, skeletal dysfunctions including crippling deformities, osteoporosis, and other vital organs dysfunction. It was found that, water is the main source of fluoride intake to plants and animals, which further may go into food chain of human beings through consumption of high fluoride content plant and animal origin food. Several preventive and control measures have been developed to ameliorate the fluoride toxicity, like application of synthetic chemicals, plants bioactive molecules, and plant products like fruit pulp, seed mixture, and plant buckle products. Therefore, this article presents up-to-date information on the fluoride sources, toxicity and different amelioration measures to reduce fluoride level directly from water as well as application of different natural/synthetic products/molecules to ameliorate the toxic effects of fluoride in in-vivo models.


In the halides group of the periodic table, fluoride (F) has great importancy due to its smallest size and most electro negativity. Although the mechanisms of F in biological forms are remains unclear but it has the unique chemical and biochemical properties for the size and reactivity [1-3]. It is ubiquitously present in soil, water, plants and air. In the animal body, F makes its presence through water and food. But, some of the recent studies indicate that, most of the F comes from pharmaceutical drugs (20%) and through agrochemicals (30-40%) [4,5]. The variability and presence of fluoride depends upon the location. It was found that F is present in the soil within the range of 10-1000 parts per million (ppm). However, in water it ranges from 0.5 to 2000 ppm. This incident depends upon the sources of water [6,7]. According to World Health Organization (WHO), F exposure to animals above the 1.5 ppm, set at chronic fluoride toxicity. Through water exposure, this type of toxicity is going to endemic in most of the countries across the world [8]. In USA, the normal level of F in drinking water is 4 mg/L [9]. But, in the European country, it is 0.8 ppm [10]. In India, most of the states are showing the greater level of F in drinking water [11]. Fluoride exerts its effects on plants also [12]. It attenuates all the cells and tissues, impaired the stomatal conductance. Simultaneously, it acts as the metabolic and reproductive inhibitor, impaired photosynthesis and respiration pathways. Ultimately, F caused even to plants death [13-18]. In animals, fluoride intoxication causing skeletal impairment, called as skeletal fluorosis. Recently, high fluoride intake has been associated with dental cancer and tumors of other organs. First clinical symptoms appeared like reduced in food intake and loss of body weight gain. After attenuating the antioxidant defence mechanism, F also affect to the gastrointestinal tract, brain, muscle etc.. [19-22]. To ameliorate these effects, several types of synthetic chemicals, herbal drugs, plant bioactive molecule, and plant natural products have been incorporated in the medicinal documentary. For example, melatonin, pineal proteins (epiphyseal proteins), quercetin, curcumin, ascorbic acid, lipoic acid, flavonoids, polyphenols have been found great role against the F toxicity [23-26]. The present review critically discusses on the fluoride sources, worldwide levels and its toxic effects on plants and animals. Furthermore, the article discusses the recent ameliorative steps developed through synthetic chemicals, plant bioactive molecules, and plant natural products.

Biochemistry of fluoride

In the halides group of the periodic tables (group VII), among all other molecules, fluoride has the great importancy due to it’s smallest size and most electro negativity. Although, the mechanisms of F in biological forms are remains unclear but it has the unique chemical and biochemical properties for the size and reactivity [1-3]. It is 13th most abundant element and distributed widely throughout the earth in soil, water, and food. F, a pale yellow colored gas, has atomic number 9 and atomic weight of 18.9984 at standard temperature and pressure [27]. The brief about the F, have been mentioned in the Figure 1 [28]. It has the tendency to exist in the Free State as diatomic molecules. Due to electromotivity characteristics, these can react with less electromotive elements or chemical groups. Fluoride compounds are formed when the element fluoride combines with other chemical elements. It does not occur in a free state in nature [28]. Fluoride however has many unique chemical properties. These properties had a great impact on the special biochemical physiological effects. For these reason, F can affect the metabolism and mechanisms of action within the living system [29]. In addition to the chemical properties and isotopic nature of fluorine has had an important impact on our understanding of the metabolism, toxicity, and therapeutic effects of fluoride. 19-F is one of the isotopes of F and occurs naturally. This isotope has the extremely short half-life.

Sources of fluoride

Natural and anthropogenic sources are the two main ways through which F entered in the environment [30].

Natural sources

Soil: The normal total fluoride content of soil ranges from 150-400 mg/kg. F level in the clay soil is 1000 mg/kg [31]. F contamination to soil is because of the utilization of phosphorus fertilizers which have total 1-1.5% fluorine [32]. Contaminated soil with F, show it’s toxicity after the inhalation of soil contaminants which have vapourized or through the contaminated ground water after the F leaching from the soil [33-35].

Water: Water containing the F concentration up to 1.0 mg/L is safe. Whereas, the F levels in between 1.1 and 2.5 mg/L are marginally contaminated. However, above 2.6 mg/L F level is determined as the highly contaminated [31]. It was found that the level of F in ground water is higher than the surface water as the F percolates from the soil to ground water through leaching process. There are several factors which are responsible for the presence of F in natural ground water from the soil. Among them, geological factors, consistency of the soil, nature of rocks, pH and temperature of the soil, chelating action of other elements, depth of wells, leakage of shallow groundwater, and chemical and physical characteristics of water [36]. Water is an important source of F exposure to human beings and animals.

Forage, grasses and grains: At the vicinity of industrialized area, it was found that forages and grasses contain the higher level of F than the other area. Some studies also found that, grasses and forages has the higher level of F than the industrialized area. It is due to the fluoride rich dust, ash, raining factors for which plants could be affected far from the industry. Plants contamination depends upon several factors like the amount of F released in to the atmosphere, distance between the F source and contaminated area, type of vegetation, height of plants, atmospheric condition, and seasons etc. [37-39]. It has been established the relationship between the F level in soil and plants of F will be increased by 3 ppm for each 100 ppm increase in soil F up to the 2200 ppm [39].

Volcanic activities: Due to volcanic eruption, animals and plants kingdom have been affected throughout the globe (Table 1). Volcanic ash contains high level of F and contaminations of F to the geochemical cycle are frequent. From the volcanic eruption, F has been released in the form of hydrogen fluoride. Erupted F may covered several places and stay for many years. After decaying and leaching, F caused severe casualty to domestic and wild animals [6,40,41].

Anthropogenic sources

Anthropogenic fluoride contamination happens by human activities like industrialization, motorization, fluoride containing pesticides, fluoridation of drinking water supplies, dental products, refrigerants, and fire extinguishers [46,47]. F contamination due to airborne sources also occurred. The mean F concentration in normal areas (unpolluted/non-industrialized) is generally less than 0.1 μg/m3. The levels may be slightly higher in the vicinity of industries, but should not exceed 2–3 μg/m3 [6]. In many countries, coal burning for household purposes was documented as the main source of F causing endemic fluorosis [48,49]. Industrial release fluoride-rich fumes and effluents into the environment also caused casualty in livestock sector like cattle, buffaloes, sheep, goats, camels etc. [50-55]. There are several reports documenting mineral mixture supplements as a major source of fluoride toxicity in livestock [56]. Moreover, incorporation of modern creation and utilization of chemicals in different sectors like hydrogen fluoride (HF), calcium fluoride (CaF), sodium fluoride (NaF), fluorosilicic corrosive (H SiF), sodium hexafluorosilicate (Na SiF), sulfur hexafluoride (SF), and phosphate manures are the main sources of fluoride.

Global scenario of fluoride levels

Around the globe, twenty three nations are belongs to the critical region regarding the fluoride level. Among them India is also present. Billions of people are affected due to fluoride exposure. In India, twenty million people are severely affected by fluorosis and 40 million people are exposed to risk of endemic fluorosis [57]. Level of fluoride in drinking water throughout the globe has been tabulated in the Table 2.

Fluoride toxicity

In Animals: Chronic exposure to F induces an array of deleterious impacts in livestock animals, experimental animals, as well as humans also [6,97,98]. First symptoms of chronic F toxicity in animals are reduced feed intake and body weight gain (BWG) loss [19,22]. Prolonged exposure to F causes fluorosis, leading to a progressive degenerative disease, dental mottling and several types of skeletal dysfunctions [4]. Main mechanism of these deformities, after exposure of F is mainly the generation of different types of ROS production (Table 3). Experimental evidence (Tables 4,5) has indicated that exposure to fluoride results in oxidative stress both in vitro and in vivo in soft tissues such as liver, kidney, brain, lungs etc. Fluoride inhibits the activities of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and catalase and reduces levels of glutathione. Glutathione reduction leads to overproduction of reactive oxygen species at the mitochondrial level, resulting in damage of cellular components. Besides, production of excessive reactive oxygen species results in oxidation of macromolecules, membrane phospholipid breakdown, lipid peroxidation, mitochondrial membrane depolarization and apoptosis (Tables 4,5). Neurodegeneration also occurred due to the F exposure. Several studies indicated that hippocampus of rat brain can lead to the degenerate due to the imbalance between oxidant– antioxidant balance. F crossed the blood brain barrier (BBB) easily and induces neural cell degeneration [24,99-101]. All the effects of fluoride are summarized in the Tables 4,5.

Amelioration of fluoride toxicity

Recently, various studies have been conducted in various fields like development of different techniques to reduce the fluoride level from the water sources directly, use plant metabolites on the experimental animals, and use of different chemical/molecule (melatonin, pineal protein, quercetin etc.). In case of different techniques, several natural and chemical adsorbents such as red soil, charcoal, brick, Waste tea ash, fly-ash, serpentine, alum, Activated carbon, Al-Fe (hydr) oxides, sulfate-doped Fe3O4/Al2O3 nanoparticles, aluminum salts etc have been used (Table 6). On the other hand, use of leaves, seeds, fruit pulps, plant juices of Azadirachta indica, Ficus religiosa, Acacia catechu, Peltiphyllum peltatum and tamarind seeds etc. are also using to reduce the toxic effects of fluoride and summarized in the Table 7. Additionally, some synthetic chemical molecules like melatonin, pineal protein, lycopene, and quercetin, etc. also have the great role to reduce the fluoride induced toxicity. All are summarized in the Table 8.


Through this review, it is summarized that having the electronegativity, fluoride is ubiquitously present in the environments. In some countries it is within the range, whereas most of the countries which have been reviewed showed more than the permissible level as per guideline recommended by WHO. Among different sources, water is the important source of fluoride exposure. Hence, water purification techniques should be developed for safe and economic method for portable water. High fluoride exposure affects human beings and animals health through oxidative stress, immune suppression, apoptosis, and affecting nutrient utilization. Hence, ameliorative measures are important to prevent their endemicity and disease progress. Meanwhile, plant bioactive molecules, several synthetic molecules, and pineal gland secretions have shown protective effect against fluoride toxicity. However, more extensive studies are required for wide application of these molecules as therapeutics agents.

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