A Brief Review of Bio-Markers for Chronic Fluoride Poisoning in Humans

Shanti Lal Choubisa^{1, 2*}

¹Department of Advanced Science and Technology, National Institute of Medical Science and Research, NIMS University Rajasthan, Jaipur, Rajasthan 303121, India

²Former Department of Zoology, Government Meera Girls College, MLS University, Udaipur, Rajasthan 303002, India

^*Corresponding Author: Shanti Lal Choubisa, Department of Advanced Science and Technology, National Institute of Medical Science and Research, NIMS University Rajasthan, Jaipur, Rajasthan 303121, India

Received: 14 August 2026; Accepted: 18 August 2026; Published: 20 August 2026

Introduction

It is well known that fluoride (F-) is found naturally and/or anthropogenically in varying amounts in almost every environment, such as soil, water, air, food, etc. However, it is most commonly found in groundwater in varying concentrations. In drinking water, the World Health Organization (WHO) recommends a maximum permissible or safe limit of 1.5 mg/L [1]. Approximately 260 million people worldwide live in areas where fluoride concentrations in various drinking water sources exceed 1.5 mg/L [2-5]. Although fluoride is beneficial for the mineralization and strengthening of developing teeth and bones, it becomes toxic and harmful to the human body when ingested in excessive amounts or exposed to it for long periods of time.

Worldwide, approximately 200 million people in more than 25 countries suffer from chronic fluoride poisoning or fluoride-related health problems due to high fluoride levels in drinking water [2-5]. Besides drinking water, industrial fluoride pollution is also a potential source of fluoride poisoning in humans, but it is limited to specific areas around the source [6-10]. Chronic fluoride poisoning in humans is usually detected by appearance of dental and skeletal fluorosis. However, fluoride toxicity can also be detected or estimated by the presence of fluoride in various biological samples such as hair, nails, teeth and bones, milk, blood plasma, urine, etc. These are natural bio-markers that provide accurate and up-to-date information about fluoride exposure and toxicity in a given environment. This article briefly reviews various bio-markers for chronic fluoride poisoning, or fluorosis. These can be used to confirm fluoride toxicity or endemic fluorosis in populations residing in any geographical area.

Fluoride poisoning in humans

When fluoride enters the body, whether through excessive intake or repeated exposure via sources such as fluoridated water, industrial fluoride emissions, or fluoride-containing foods, it is absorbed through the digestive or respiratory tracts and eventually distributed to all parts of the body via the bloodstream. While more than 50% of the absorbed fluoride is excreted from the body through feces, urine, and sweat, the remainder is retained and accumulates in various organs. However, it accumulates most significantly in calcified tissues, such as bones and teeth, compared to non-calcified organs [1,11]. Fluoride also possesses the ability to cross the placental and blood-brain barriers, thereby reaching the developing foetus and the human brain [12-14].

It is well established that the accumulation of fluoride in the body disrupts various physiological and metabolic processes. This leads to fluoride poisoning in people of all ages, resulting in the development of various physical deformities. These toxic or pathological changes induced by fluoride in the body are collectively termed 'fluorosis' [1,11]. The pathological changes affecting the teeth (staining or discoloration) and bones (periosteal exostosis, osteoporosis, and osteophytosis) are permanent and irreversible, and they can be easily identified upon visual inspection [11]. These pathological changes in the teeth and bones are referred to as 'dental fluorosis' and 'skeletal fluorosis,' respectively. However, changes in soft tissues or organs caused by fluoride are mostly reversible; they disappear over time once the source of fluoride exposure is removed and are generally referred to as non-skeletal fluorosis [11]. Fluoride also exerts neurotoxic effects during child development or adversely impacts cognitive abilities, leading to mental impairments such as reduced learning and memory capacity, lower intelligence quotient (IQ), intellectual disability, and dementia. A higher incidence of Attention-Deficit/Hyperactivity Disorder (ADHD) is also observed in children affected by chronic fluoride exposure or fluorosis [15-22]. The precise mechanism underlying these fluoride-induced neurological disturbances or disorders in children is not yet clearly understood.

Dental fluorosis is the earliest visible sign of the toxic effects of prolonged fluoride exposure; it is a sensitive, indexive, and significant indicator found worldwide [11]. Clinically, it is characterized by hypocalcification (calcium deficiency) across the tooth surface. It typically manifests as opaque lines, ranging from light to dark brown, running horizontally or in streaks across the tooth surface (Figure 1).

Figure 1: 'Dental fluorosis' in children, resulting from prolonged exposure to excessive fluoride or chronic fluoride poisoning, is a widely recognized clinical bio-marker of chronic fluoride toxicity.

Skeletal fluorosis is extremely painful and more severe than dental or non-skeletal fluorosis; it impairs mobility at a very early age. The most common bone changes caused by fluoride are periosteal exostosis, osteoporosis, and osteophytosis [23,24]. These skeletal changes manifest as vague pain in the body and joints. Excessive fluoride accumulation in the muscles reduces mobility, leading to the development of disabilities in both children and adults (Figure 2). Individuals severely affected by skeletal fluorosis often walk with a limp. In advanced stages, neurological syndromes such as genu- varum (bow-leggedness) and genu-valgum (knock-knees) develop; this represents the most severe phase of skeletal fluorosis, for which there is no cure, and the condition persists for a lifetime [25-29].

Figure 2: 'Skeletal fluorosis' in old women, resulting from prolonged exposure to excessive fluoride or chronic fluoride poisoning.

Various health issues are also observed during the early stages of chronic fluoride poisoning resulting from prolonged exposure to fluoride. These include gastrointestinal problems (such as occasional diarrhea or constipation, abdominal pain, flatulence, etc.), hives (urticaria), frequent urination (polyuria), excessive thirst (polydipsia), disturbances in endocrine and reproductive functions, adverse effects on foetal development (teratogenic effects), kidney impairment, genotoxic effects, apoptosis, excitotoxicity, asthma, genital itching, lethargy, muscle weakness, bronchitis accompanied by severe coughing, nasal irritation, irregular reproductive cycles, miscarriage, and stillbirth [30-32]. These are the early symptoms of chronic fluoride poisoning. It is not necessary for an individual affected by fluoride poisoning to exhibit all these health issues simultaneously.

Bio-markers for chronic fluoride poisoning

Bio-markers, or biological markers, are defined as naturally occurring indicators that signal events taking place within biological systems. They can be substances, molecules, structures, genes, or biological and pathological processes, the presence of which reflects the state of a living organism. These bio-markers are utilized not merely as diagnostic tests, but as indicators of specific diseases or biological changes. They are frequently measured and analysed to assess normal biological and pathological processes, serving as indicators of biological conditions, physiological processes, or diseases [33,34]. Broadly, bio-markers are classified into three categories: (a) exposure (plasma, bone, teeth, urine, saliva, dental plaque, plaque fluid, hair, nails, etc.), (b) susceptibility (genetic factors, acid-base imbalance, renal issues, bone development, and nutritional status), and (c) effect bio-markers (dental caries, dental fluorosis, and the activity and severity of skeletal fluorosis) [33,34].

According to the World Health Organization, "fluoride bio-markers are primarily useful for detecting and monitoring fluoride deficiency or excess in the body [35]. These fluoride bio-markers can be categorized as follows: contemporary markers or short-term exposure indicators (urine, plasma, and saliva), recent markers or medium-term exposure indicators (nails and hair), and historical or long-term markers (bone and teeth). These bio-markers can also serve as a tool to assess the impact of water fluoridation on bone quality and other bodily conditions [36-41]."

The presence of fluoride in environmental samples such as fodder and animal feed indicates persistent fluoride pollution in the environment [42,43]. However, beyond morbidity and mortality, fluoride levels in biological sample, such as milk, urine, blood serum, teeth, and bone, serve as superior bio-markers for chronic fluoride poisoning or toxicity in both humans and animals [44-50]. Estimating fluoride levels in blood serum and urine is the most accurate and reliable method for assessing the status of chronic fluoride poisoning in humans and animals [51]. However, among the various bio-markers for long-term fluoride exposure, urinary fluoride concentration is generally considered the best or ideal bio-indicator of fluoride exposure and endemic fluorosis. This is because urine samples can be collected easily and non-invasively, and they reflect the cumulative impact of various sources of fluoride exposure, such as industrial pollution, fluoride-rich drinking water, and dietary intake [49,50]. However, fluoride levels in urine vary among individuals and across regions. This depends on factors such as age, season, climatic conditions (e.g., arid versus humid environments), and the fluoride content in drinking water or other sources of fluoride exposure [51]. There is no doubt that “dental fluorosis is a widely recognized clinical bio-marker of prolonged excessive fluoride exposure (or toxicity) during childhood”.

Conclusion

Chronic fluoride poisoning (manifesting as fluorosis) in humans is most prevalent in regions where drinking water, air, and food are contaminated with fluoride. Globally, approximately 200 million people across more than 25 countries suffer from the effects of chronic fluoride toxicity or fluoride-related health issues due to the consumption of high-fluoride water. In many countries, industrial fluoride pollution is also a potential cause of chronic fluoride toxicity in humans. Fluoride poisoning leads to dental and skeletal deformities, collectively known as fluorosis, which are permanent and irreversible conditions; skeletal deformities, in particular, cause lifelong, mild to severe pain. The prevalence of chronic fluoride poisoning in a population can be readily assessed by measuring fluoride levels in specific biological samples or bio-markers, such as plasma, bone, teeth, urine, saliva, dental plaque, plaque fluid, hair, and nails. These bio-markers serve not only to detect the condition but also act as indicators of fluoride toxicity or fluorosis. However, measuring fluoride levels in blood serum and urine remains the most accurate and reliable method for assessing the status of chronic fluoride toxicity in both humans and animals. Among the various bio-markers for chronic fluoride exposure, urinary fluoride concentration is generally considered the best or ideal bio-indicator for fluoride exposure and endemic fluorosis. Nevertheless, dental fluorosis is a widely recognized clinical bio-marker for chronic, excessive fluoride exposure (or toxicity) during childhood.

<4>Acknowledgements

The author thanks to Professor Darshana Choubisa, Department of Prosthodontics, Geetanjali Dental and Research Institute, Udaipur, Rajasthan 313002, India for her assistance.

Conflicts of Interest

We have no conflict of interest.

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