1. Introduction

More than 500 million people live in endemic fluorosis areas with an elevated level of fluoride in drinking water and biosphere with public health problems^[1][2]. The fluorosis symptoms span from mild effects on teeth enamel, headaches, dizziness, loss of appetite, to severe pathological disturbances. These include dental and skeletal fluorosis, hypothyroidism, sleep disorders, inflammations, IQ deficits, and suspected autism^[3][4][5][6].

In 1931, H. Trendley Dean, head of the Dental Hygiene Unit at the National Institute of Health (NIH), began investigating the epidemiology of fluorosis in the USA. Dean and his staff determined the fluoride levels in drinking water causing fluorosis. They discovered that fluoride levels of up to one milligram fluoride per liter of drinking water (one ppm) did not cause dental fluorosis in most people. Dean’s reports formed the foundation of the concept that the ingestion of fluoride will augment the teeth enamel and make it less susceptible to dental caries^[7]. Dean suggested adding fluoride to water sources deficient in fluoride to bring its concentration up to the optimal value. After trials in the USA, the World Health Organization (WHO) recommended community water fluoridation (CWF), and many countries implemented this program^[8][9][10]. The CWF recommendation has been followed for over 70 years in developed countries, such as the USA, Canada, Australia, New Zealand, Ireland, and some parts of the United Kingdom (UK)^[9].

CWF started an era of increased income from fluoride as never before in human history. Recently, 370 million people from 27 countries have a supply of fluoridated drinking water^[9]. The number of fluoride sources has further expanded since fluoride is used for the improvement of food, beverages, hygiene, and medical products including fluorinated drugs.

The fluorine atom does not exist in nature in a free and unmixed state. The mineral fluorite (CaF₂) is the main source of fluorine for commercial use. Fluorine readily reacts with other elements to form fluoride compounds, within which it always adopts an oxidation state of −1. Inorganic compounds are formed with hydrogen, metals, and non-metals. Therefore, fluoride refers to the negatively charged ion of the fluorine atom. In general, soil fluoride is not available to plants. There are exceptions such as tea plants that are natural accumulators of fluoride from fertilizers^[1][2][4]. Fruits such as blueberry and grape concentrate fluoride from soil and it might appear in commercial juices. Fluorine excess had been found to be detrimental also to plants. Injury to plants is common all around industries making aluminum, fertilizers, or glass. Special plants might produce the toxic organofluorine compound fluoroacetate, which is used as a defense against grazing by herbivores.

Conflicting views occur in debates addressing whether fluorine is an essential element for humans. The researchers of the Panel of the European Food Safety Authority (EFSA) state that fluoride has no known essential function in human physiology and development^[11]. On the other hand, the WHO and the Centers for Disease Control and Prevention (CDC) consider fluoride to be an important dietary element for humans because of “resistance to dental caries is a physiologically important function"^[12].

2. The Implication of Fluoride Toxicity on Human Health

Early reports about fluoride toxicity in humans appeared in the journal Physiological Reviews already in 1933. Aluminum smelter workers and persons living near the factory where fluoride was in high concentration in the atmosphere suffered with psychiatric and neurological disturbances. Endemic fluorosis is caused by persistent fluoride exposure through ingestion or inhalation, and most commonly, as a result of high fluoride levels in drinking water and beverages^[13][14]. The WHO’s drinking water quality Guideline Value for fluoride is 1.5 mg/L ^[14].

Dental fluorosis results after excess fluoride ingestion, most commonly in drinking water, during tooth formation. For example, dental fluorosis appears in 43–63% of schoolchildren in endemic areas of China with total fluoride intake 2.7–19.8 mg/day^[5]. The rate of dental fluorosis also increases in countries with CWF. In the 2010–2012 survey, dental fluorosis was reported among adolescents aged 12–15 years in the USA with a surprisingly high rate of 65%^[15]. Dental fluorosis might be used as a sensitive indicator of excessive fluoride exposure^[16].

Skeletal fluorosis impacts millions of people in regions with high natural levels of fluoride, like India, China, Pakistan, Iran, and the Gulf region, to name a few ^[13]. The U.S. Environmental Protection Agency (USEPA) sets a maximum contaminant level of 4.0 mg/L to protect against skeletal fluorosis. WHO indicates a clear risk of skeletal fluorosis for a total intake of 14 mg fluoride per day. Nevertheless, the recent findings revealed that consumption of fluoride at even 10 times lower concentrations of 1.5 mg/L caused its high incidence in India^[17]. The chemical analyses show that 80% of water sources in rural areas exceed the WHO fluoride permissible limits and residents are affected by skeletal fluorosis.

Waldbott et al. examined about 500 people affected by chronic fluoride intake from CWF^[18]. These authors observed chronic fatigue, headaches, loss of the ability to concentrate, depression, gastrointestinal symptoms, and deterioration of muscular coordination.