2011 Fordyce F M. Fluorine: human health risks. In: Nriagu J O (ed.

)
Encyclopedia of Environmental Health, Volume 2, pp. 776–785
Burlington: Elsevier.

Encyclopedia of Environmental Health, Elsevier

Title: Fluorine – Human Health Risks

Author: Fiona M. Fordyce

British Geological Survey
West Mains Road
Edinburgh
EH9 3LA
UK
fmf@bgs.ac.uk

Keywords: dental caries, dental fluorosis, drinking water, fluoridation, fluoride,

fluorine, knock knees, osteoporosis, skeletal fluorosis, teeth

Internet Synopsis: (200 words)

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.

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Chapter:

Introduction

Fluorine is a naturally occurring chemical element, which exists in the rocks, soils,
waters, air, plants and animals on Earth. It is the 13th most abundant in the Earth’s
crust and the most electronegative and reactive of all the elements. As a result,
elemental fluorine does not occur in nature but is found as the fluoride ionic form and
in minerals. This article focuses on the health impacts of inorganic fluorides. Human
fluoride exposure can occur via inhalation, dermal contact or more commonly through
ingestion of food, beverages, dental products and drinking water. The term fluorosis
(fluoride toxicity) was coined by Christiani and Gautier in 1925 to describe the
impacts on vegetation of emissions from a Swiss aluminum smelter. In the early
1930s, human skeletal fluorosis was reported in France and Denmark related to
exposure in mineral processing and cryolite (Na3AlF6) mines respectively. Skeletal
fluorosis was recognized as an endemic disease in India in the late 1930s and has
since been reported in many parts of the world. The disease, which can cause
crippling bone deformities, is commonly related to high fluoride intakes from
drinking water, tea, foodstuffs and inhalation from coal-based fuels. Recent estimates
suggest that 1.7 million people in China and 1 million people in India suffer from the
disease (WHO, 2006). The detrimental health effects of fluoride in humans were also
noted during the late 1800s and early 1900s in populations in Mexico, Italy and the
USA where black teeth and eroded dental enamel were recorded. However, it was
studies by Smith and co-workers in the 1930s that established fluoride in drinking
water as the cause of this disease known as dental fluorosis. Dental fluorosis has since
been reported from all around the globe and latest estimates suggest that it may affect
70 million people (WHO, 2006). Subsequent epidemiological investigations by Dean
and colleagues in the USA during the 1930s and 1940s confirmed the relationships
between the severity of dental fluorosis and increasing fluoride contents in drinking
water. However, this work also demonstrated the beneficial effect of the element in
the prevention of dental caries (decayed or missing teeth). As a result fluoridation
programs have been implemented in many countries and millions of people around
the world are familiar with fluoride as a constituent of dental-care products. Today the
benefaction of water (and other) fluoridation programs is increasingly questioned in
the context of better oral hygiene in many parts of the world, whereas concerns
remain about the detrimental impacts of the element on the millions of people
exposed to high fluoride intakes, particularly in developing countries. Comprehensive
reviews of the health impacts of fluoride have been carried out recently by the World
Health Organization (WHO) and Agency for Toxic Substances and Disease Registry
(ATSDR) (see the section ‘Further reading’); a summary of the main issues is
presented in this article.

Fluoride Health Effects

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Like several other naturally occurring chemical elements, fluoride has both beneficial
and detrimental effects on human health depending on the levels of exposure.

Once absorbed in the human body, the majority of fluoride (approximately 60-80 %)
is retained in the skeleton and the range of fluoride content of human bones is
typically 300-7000 mg kg-1 dry tissue depending on exposure. In contrast, fluoride
levels in blood are normally very low typically ranging from 0.04 mg L-1 in normal
circumstances to 0.5-0.8 mg L-1 in fluorosed populations. The retention of fluoride in
bones versus excretion via the kidneys (and partly the skin) plays the most important
role in the homeostatic mechanism responsible for maintaining the fluoride
concentration in blood. A certain proportion of fluoride (data from different studies
estimate 15-50 %) remains in an ionic state and the rest forms albumin bonds with
calcium acting as a bond mediator. The lowest fluoride concentrations are found in
body soft tissues, which generally contain 0.5-1.0 mg kg-1. However, concentrations
of 3-50 mg kg-1 are not uncommon in epidermal tissues. Therefore, the main fluoride
health issues are associated with bones and teeth.

Beneficial Health Effects

Scientists are still uncertain whether fluoride is essential to human health but the
element has been used successfully to combat both dental and skeletal health effects.

Fluoride in Dental Caries Prevention

Dental caries is one of the most widespread diseases affecting humankind. It is

estimated that in developed countries, dental caries prevalence is currently 95-98 %
and these rates are rising in all cultures around the world where fluoridation/ oral-
hygiene schemes have not been introduced. Caries is the most common cause of tooth
loss, inhibited mastication and poor digestion. Following the work of Dean in the
1940s, numerous studies carried out in the USA and Europe demonstrated a link
between improved dental health and the introduction of fluoridated drinking water to
local communities. Caries prevalence where the water fluoride content was 1 mg L-1
or more was found to be almost half that of communities where drinking water
contained 0.1-0.3 mg L-1 and many countries adopted successful water fluoridation
programs. Indeed this was one of the major public health initiatives of the 20th
century. An array of fluoridated dental products followed including toothpastes,
mouth rinses, gels, varnishes, solutions and tablets as well as fluoridated milk and salt
the in some countries. Studies have demonstrated that fluoride is most beneficial
when constantly present in small quantities in saliva and dental plaque. Hence,
fluoridated water, toothpaste and salt programs are considered now to be the most
efficacious and easiest to implement in public health, particularly for poorer
communities.

In more recent years, as oral hygiene has improved in the world, the difference in
caries prevalence between fluoridated and non-fluoridated drinking water populations
has significantly decreased. This is particularly true in developed countries due to

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intake of fluoride from other sources, primarily dental products. The WHO estimate
that whereas 210 million people have access to drinking water with optimal levels of
fluoride for caries prevention, more than double that number, that is 500 million
people are exposed to the element via the use of fluoridated toothpaste. As a result, in
parts of the world with good oral hygiene, the need for and added benefits from mass
water/salt fluoridation programs are increasingly called into question.

The mechanisms of dental benefaction of fluoride are thought to be several-fold.

Firstly, teeth are formed from the calcium mineral hydroxylapatite. Fluoride is a
powerful calcium-seeking element, hence, during the pre-eruptive stage (i.e. during
tooth formation in children up to 12 years old) ingested fluoride is thought to
accelerate the mineralization process. It can also enter the mineral lattice forming
fluorapatite, which is stronger (less soluble) than hydroxylapatite but more brittle.
Secondly, fluoride acts as an anti-bacterial agent in the mouth helping to minimize
acid-attack on teeth. More recent evidence suggests that the presence of fluoride in
saliva and dental plaque also enhances remineralization at the surface of erupted teeth
and this is thought now to be the primary caries prevention mechanism

Osteoporosis Treatment

Fluoride has been used in the treatment of age-related osteoporosis in high doses of
20-30 mg day-1 sodium fluoride (NaF) and monofluorophosphate (Na2FPO3) for the
last 40 years. The success of the treatments depends not only on the dose but on the
nutritional status, absorption capacity and renal threshold of the individual; hence the
element is often given in conjunction with calcium and Vitamin D. These treatments
have been shown to increase trabecular (spongy) bone density but not cortical
(compact) bone density and protect against vertebral fractures. However, studies
exploring fluoride-treated osteoporosis patients versus control groups and populations
exposed to high versus low fluoride drinking waters give conflicting evidence of the
benefits in the prevention of other fractures, particularly of the hip. Some results
demonstrate a protective role and others an increase in fracture rates. Side effects of
treatment can include gastrointestinal pains; microfractures of the feet and calcium
deficiency.

Detrimental Health Effects

Fluoride is a known toxin and acute and high-dose exposure to the element
(particularly via inhalation) can result in consequences ranging from soft tissue
impacts to death. However, such outcomes are rare and typically occur in
occupational settings (see the section ‘Occupational exposure’). In terms of general
environmental exposure, the main concerns are endemic dental and skeletal fluorosis
that affect significant populations around the world.

Dental Fluorosis

Following the connection between mottled enamel and excess fluoride in drinking
water established by Smith and co-workers in the 1930s, dental fluorosis was
recognized as an irregular calcification disorder (hypomineralization) of the enamel

4
and dentin due to the incorporation of excessive fluoride in these structures. Fluorosed
enamel is porous, often stained and has brown pits and in its more severe form, is
brittle and prone to erosion and breakage (Figure 1). Subsequently, dental fluorosis
has been reported from many regions, commonly associated with drinking water
contents > 1.5 mg L-1 fluoride. It should be noted, however, that conditions vary and
water is not always the main exposure route.

The severity of the condition is thought to reflect the extent of fluoride exposure
during enamel formation in the pre-eruptive phase of tooth development (usually birth
– 8 years) and can affect both temporary and permanent teeth. At the end of tooth
development and mineralization, the enamel and dentin become less penetrable for
fluoride ions; therefore the rate of inclusion and mobilization of fluoride slows
dramatically. Fluoride is incorporated into dental tissues via blood-cell formation
through pulp and saliva (or water) contact with the upper enamel layers. However, the
staining and pitting of dental enamel are thought to occur post-eruption as a result of
enamel matrix disruption.

The mechanism of change in dental hard tissue due to fluoride excess is still open to
debate. Sodium fluoride (NaF) is known to inhibit protein synthesis, which has lead
most workers to believe that fluoride cell toxicity is due to this mechanism. Fluoride
is thought to affect the enamel secretion cells while the outer layer of the tooth is
under development, disrupting the formation of normal enamel. Collagen is the most
widespread protein in the human body and fluoride induces the formation of active
oxygen metabolites, which disturb collagen biogenesis. Since collagen is one of the
most important foundations of bone formation, interruption of the collagen
metabolism could affect dental development.

Other workers have suggested that dental fluorosis occurs as a result of fluoride
interaction with calcium, magnesium, manganese and other elements in the dental
hard tissues, which destroys the biologic activity of the these elements leading to
enamel injuries. Some studies have shown a possible reduction in calcium content
during tooth mineralization, leading to the destruction of dental tissue structure.
However, there is conflicting evidence as to whether changes in calcium and
phosphorous enamel contents occur as a result of excess fluoride exposure.

It has also been suggested that dental fluorosis is related to the more aggressive
chemical activity of fluoride compared to iodine such that fluoride reduces the amount
of iodine in the thyroid gland resulting in functional disorders. Studies demonstrate
that ingested fluoride is absorbed quickly into the blood and blocks thyroid activity. It
should be noted, however, that even if fluoride is both chemically and biologically
iodine-antagonistic, it does not influence goiter prevalence.

Depending on the severity of fluorosis, dental injuries can manifest as chalk-like lines
(line form) and spots (spot form) in various places over the tooth-crown; spot
pigmentation from light yellow to dark brown; small defects in the enamel on the
background of spots (chalk-like-dot form); more pronounced defects (erosive form)
and the complete destruction of dental enamel and wearing down of teeth (destructive
form). Increased fragility of hard dental tissues during fluorosis leads to the brittle
fracture of crowns. Various schemes to assess the severity of dental fluorosis have

5
been devised, the most common of which is Dean’s Index (Table 1). Milder forms of
the disease are often barley detectable and are considered a cosmetic effect.

Many studies demonstrate that the severity of dental fluorosis depends primarily on
the following factors:

1. Fluoride uptake (particularly in water)

2. Duration of exposure
3. Child nutritional characteristics age 1-2 years
4. Physiological status
5. Sensitivity to fluoride intoxication

Endemic fluorosis regions are often characterized by a reduction in the prevalence and
intensity of dental caries. However, during intake of very high concentrations of
fluoride, the anti-caries effect is lost due to the prevalence of severe fluorosis causing
increased fragility and breaking of enamel. Under these conditions, the dentin
becomes exposed and destructive processes, which closely resemble dental caries, are
observed.

Skeletal Fluorosis in Adults

Fluoride also affects the human skeletal structure. Endemic skeletal fluorosis is a
chronic metabolic bone and joint disease caused by intake of large amounts of
fluoride either through water or less commonly from foods/air in endemic areas.
Although not the only exposure route, skeletal fluorosis has most often been reported
in populations consuming > 3-5 mg L-1 in drinking water.

As in the case of teeth, human bones are composed of hydroxylapatite but this mineral
and fluorapatite are end-members in the apatite solid solution series. Therefore
fluoride exchanges readily with the OH- ion in the apatite structure increasing the
brittleness and decreasing the solubility of the bone mass. Within the bone structure,
fluoride accumulates most effectively in growing cells due to better hydration of the
tissues and richer blood supply. Small apatite crystals on the bone surface also enable
rapid inter-crystal and surface fluoride metabolism. Within the same skeleton, fluoride
contents in different types of bone vary. Most fluoride is found in bones containing
abundant spongy tissue.

Fluoride has a strong attraction for calcium ions in the body and binds calcium in the
bone structure. Hence, calcium excretion from other tissues is increased resulting in
an almost constant negative calcium balance. Fluoride ions increase bone-forming
cell activity and enhance accretion, resorbtion and bone turn-over. Since the bones of
the human body are constantly resorbed and redeposited during a life-time, high
fluoride intakes disrupt the stability of bone mineral metabolism leading to
osteosclerosis (bone hardening). Several studies have shown that skeletal fluorosis
patients retain far more calcium in bone than control groups. The result is a range of
skeletal deformities including fixed spine, kyphosis (curvature of the spine) and genu
valgum (knock knees). Calcification of soft tissues such as ligaments can also occur
(Table 2).

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There is a direct correlation between age and bone fluoride content. Although
ingestion of fluoride may occur over a lifetime, after a number of years bones become
saturated with fluoride (although the human organism can never create pure
fluorapatite) and a dynamic equilibrium is established. Some studies suggest a
fluoride plateau appears after 50-55 years but there are other data that show fluoride
contents in bones in older people continue to increase very slowly. If the fluoride
intake drops, then the concentration in blood is reduced and the body remobilizes
fluoride deposited in bones. Over this time, which lasts about two years, fluoride
secretion reduces exponentially. Reduced metabolic rates in later life are also thought
to increase the resorbtion time of fluoride from bones.

Although approximately 80 % of fluoride entering the body is excreted mainly in the

urine, the remainder is absorbed into body tissues from where it is released very
slowly. Therefore, repeated or continuous exposure to fluoride causes accumulation in
the body. Fluoride is a cumulative toxin and unlike dental fluorosis, skeletal fluorosis
is considered to be an indicator of long-term exposure commonly affecting older
members of the population. However, crippling forms of the disease are also seen
children in endemic areas. Hyperthyroidism is a secondary effect of the condition.

Numerous studies have demonstrated links between high fluoride intake from water
and other sources and bone fluoride composition. However, fluoride contents also
depend upon personal characteristics such as age and health, living conditions, length
of exposure, nutritional status and exposure to ultra-violet light (Vitamin D
generation). Low calcium intake has been shown to exacerbate the effects of fluoride
on bone turnover and can result in rickets and osteomalacia (bone softening).

Skeletal Fluorosis in Children

The pharmacokinetics of fluoride in children are characterized by a positive balance.

Under normal conditions, fluoride mobilization from blood plasma to bone tissue is
greater than between plasma and excretion in the urine. The amount of fluoride
resorbed into plasma from the bone tissue in children is greater than that in adults.
Although, the fluoride balance is normally positive in children, factors such as age,
fluoride content in dinking water, food and air, etc. can result in either positive or
negative balances.

Bone mass accumulation in children is very dependant on age, genetic factors and
gender. As a consequence of the rapid rate of growth and bone tissue metabolism,
children dwelling in territories with increased fluoride contents in drinking
water/foods/air very often exhibit inhibited physical maturity. This is due to exposure
at sensitive bone developmental stages particularly the pre- and postnatal period, the
first year of life and during puberty. Several studies comparing children with identical
social and domestic conditions in endemic fluorosis regions and control groups
demonstrate the greater prevalence of children of below average height in fluorosis
areas.

Indeed, changes in the skeletal structure can be induced by relatively small doses of
fluoride. Therefore, children are more susceptible to fluoride intoxication than adults.
Childhood clinical symptoms include rickets, osteoporosis and disorders of the
calcium steady-state balance. Studies have shown that in children with calcium

7
deficient diets, bone tissue disorders were observed in 90 % of subjects whereas in
children receiving > 800 mgCa day-1 only 25 % developed symptoms of fluoride
intoxication. In areas of calcium deficiency, evidence of skeletal fluorosis has been
found in children drinking water with less than 2.5 mg L-1 fluoride.

Skeletal Fractures

The connection between high fluoride intakes and skeletal fractures has been
investigated in many studies. However, the data are equivocal with several studies
reporting beneficial effects of fluoride against fracture rates and other studies
reporting increased fracture rates in high-fluoride populations. Studies examining total
fluoride exposure, but particularly fluoride in drinking water, versus all fracture rates
in China demonstrated a U-shaped dose-response curve. Higher fracture rates were
associated with drinking water intakes below 0.34 mg L-1 and above 4.32 mg L-1
fluoride, the latter in populations exposed to 14 mgF day-1.

Cancer

Large numbers of studies have been carried out in numerous countries to assess
relationships between high-fluoride environmental exposure and cancer. However,
there is no clear evidence of increased cancer morbidity or mortality associated with
exposure via water/food/air. Increased mortality and prevalence of lung, liver,
bladder, stomach, esophagus, pancreas, lymphatic, prostate and brain cancers have
been reported in occupationally exposed workers in the aluminum and cryolite
industries. However, the results are inconsistent and these health effects are most
likely to result from concurrent exposure to other substances. To date, studies in
laboratory animals have not demonstrated that fluoride is carcinogenic.

Other Health Effects

At very high doses usually associated with acute exposure, fluoride interferes with
carbohydrate, lipid, protein, vitamin, enzyme and mineral metabolisms and can lead
to hemorrhagic gastroenteritis, acute toxic nephritis and damage to the liver and
kidneys. Respiratory irritation, pulmonary edema, cardiac arrests and death have also
been reported. Owing to the inhibition of cholinesterase glycolysis (breakdown of
carbohydrates) and the formation of complex fluoride and calcium compounds in
extracellular fluids; such metabolic disorders are observed as hyperkalemia (high
blood potassium), hypocalcemia (low blood calcium) and hypomagnesemia (low
blood magnesium). Fluorine and hydrogen fluoride are highly reactive chemicals and
direct contact with the body can also result in severe skin and eye damage.

The effects of general environmental fluoride exposure on human soft tissue

homeostasis are equivocal. Long-term occupational exposure to fluoride has been
reported to reduce the iodine accumulation activity of the thyroid resulting in a
reduction in triiodothyronine production, an increase in thyrotropic hormone levels in
blood-serum and irregularities of the androgen status (subclinical hypothyrosis).
There is some evidence that continuous fluoride intoxication provokes hypertension
and chronic ischemic heart disease. Some studies have shown that clinically acute
fluoride intoxication manifests as nausea, sickness, diarrhea, stomach ache and heart
rate disorders at concentrations of 6.5-20 mgF L-l in water. However, there is no

8
conclusive evidence that general fluoride exposure results in respiratory, hepatic,
renal, reproductive or genotoxic effects.

Etiology of Fluoride Health Issues

Humans may be exposed to fluoride in air via inhalation, through dermal contact and
via the ingestion of soil, food, dental products and water. Fluoride is also utilized in a
number of industrial processes that release the element to the environment and can
result in occupational exposure.

The level of toxicity depends on the exposure route and form of fluoride. Fluorine
(F2) and anhydrous hydrogen fluoride (HF) are naturally occurring gases whereas the
aqueous form, hydrofluoric acid (HFaq) is one of the most corrosive substances known
to man. Sodium fluoride (NaF) and calcium fluoride (CaF2) are the most common
mineral salts. Sodium fluoride is more soluble than calcium fluoride and is used in
dental products and water fluoridation as well as fluorosilic acid and sodium
hexafluorosilicate (Table 3). The fluoride ion (F-) is the toxicologically active agent
hence reactive compounds such as oxygen difluoride (OF2) are highly toxic whereas
salts such as sodium and calcium fluoride are less so. In general, the more soluble the
fluoride compound, the more toxic it is as it can be readily absorbed via oral
ingestion. The primary exposure routes for fluorine gas and hydrofluoric acid are
acute occupational dermal contact and inhalation whereas for most fluoride
compounds the main concern is chronic oral exposure in drinking water, food and
dental products.

Acute Exposure

In terms of oral ingestion, some acute intoxication incidents have occurred in

fluoridated water supplies as a result of accidental overdosing resulting in fluoride
concentrations of 30-1000 mg L-1. It is estimated that to produce acute symptoms such
as nausea, vomiting and gastric pain, requires oral intakes of at least 1 mg kg-
bodyweight-1 of sodium fluoride and that 32-64 mg kg-bodyweight-1 is the lethal dose
(Table 4). Via inhalation, acute exposures to relatively low concentrations of
hydrogen fluoride (≥ 0.5 ppm) or fluorine gas (≥10 ppm) result in respiratory tract and
ocular effects in humans. Although no dose-response relationships have been
established for dermal exposure, skin lesions have been reported following contact for
a minimum of an hour with 2 % hydrofluoric acid.

Occupational Exposure

Industrial sources of fluoride compounds include coal combustion; steel, glass, brick,
ceramic and glue manufacture; aluminum, copper, nickel and phosphate processing
and fertilizer and pesticide production and use (Table 3). Occupational exposure to
fluoride via inhalation or dermal contact is most likely to occur in welding operations
and aluminum, steel and phosphate production. Indoor air concentrations ≤ 16 500 µg
m-3 have been reported in these settings which exceed the recommended exposure
levels for fluoride (Table 4). Occupational dermal exposure to hydrofluoric acid has
been reported to result in severe tissue damage, respiratory effects, cardiac arrests and
death. Cardiac effects and death are thought to result from hypocalcemia and
hyperkalemia. Eye, throat, chest irritation and vomiting have also been observed in

9
workers exposed to sulfur hexafluoride. Although increased incidence of cancer,
skeletal and respiratory effects have been reported in industrial settings, the workers
were exposed to a variety of other substances and conclusive evidence for the role of
fluoride in these health effects has yet to be established.

Dental-Product Exposure

Fluoridated dental products generally contain 1000-1500 mg kg-1 fluoride and have
been identified as significant sources of fluoride intake, particularly in children.
Studies estimate intakes of 50 µg per brushing and 2 mg per use with mouthwash.
Swallowing toothpaste is thought to contribute 0.50-0.75 mg day-1 fluoride in
children. As a result, low-fluoride products (250-500 mg kg-1) have been developed
for children and are available now in many countries.

Environmental Exposure

Air

Fluorides are widely distributed in air in both particulate and gaseous form. The
degree of toxicity of different chemical species is in the order F2 > OF2 > HF > H2SiF6
> BF3 whereby gaseous fluorides are more toxic than particulates in air. Fluorides are
derived from natural sources such as marine aerosols, volcanic emissions and
continental dusts as well as industry including the production of phosphate fertilizers,
coal ash and burning fuels. However, in non-industrial areas, concentrations in
ambient outdoor air are typically 0.05-1.90 µg m-3 with average exposures of < 1 µg
m-3, which are insignificant in normal circumstances. In areas where high-fluoride
coal products are burned or phosphatic fertilizers are produced, exposure via
inhalation can cause health problems. Human fluorosis has been reported in parts of
China due to the burning of fluoride-rich coal products resulting in household air
contents ≤ 155 µg m-3 (see the section ‘Foodstuffs, diet and drinking water’).

Rocks, Soils and Waters

In the natural environment, fluorides are released through the weathering and
dissolution of rock and soil minerals; from volcanic emissions and in marine aerosols.

The distribution of fluoride in the natural environment is not uniform but is influenced
by geogenic processes and presence of fluoride-bearing minerals. Fluorides are found
in a number of common rock-forming minerals including fluorspar or fluorite (CaF2);
rock phosphates (e.g. fluorapatite: Ca5(PO4)3F); cryolite (Na3AlF6); micas and
hornblende. Typical concentrations in soil range from 20-1000 mg kg-1 although these
can be higher in mineralized areas or due to fertilizer use and volcanic or industrial
emissions. In solution, the element forms F- ions and concentrations in water are often
limited by the solubility of the mineral fluorite (CaF2). Therefore high-fluoride waters
are commonly associated with calcium-poor conditions and where substitution of
calcium by sodium occurs. High pH thermal waters also tend to be rich in the
element. Concentrations in surface water (< 0.5 mg L-1) and seawater (1.2-1.5 mg L-1)
tend to be lower than those in groundwater (1-10 mg L-1) due to longer residence
times for rock-water interactions. However, concentrations in water are highly
variable depending on local conditions and values of 2800 mg L-1 in sodic lakes and

10
50 mg L-1 in groundwater have been reported in volcanic regions of East Africa.
Indeed high-fluoride environments are typically associated with volcanic rocks,
marine sediments and granite and gneissic rock types and occur in many areas of the
globe including the Mediterranean; southern Europe and Russia, the Middle East, the
East African Rift from Jordan to Tanzania, West and southern Africa, India, Pakistan,
Thailand, China and the southern USA. Human dental and skeletal fluorosis affect
millions of people in many of these areas as a result of exposure to high-fluoride
drinking waters (See WHO (2006); Edmunds and Smedley (2005)).

Foodstuffs, Diet and Drinking Water

Fluoride in soil is generally poorly soluble, hence uptake into crops depends not only
on the concentrations in the soil (uptake via the roots) but on the levels of atmospheric
deposition of the element (uptake via the stomata directly into the plant leaf structure).
Indeed, fluoride is found in higher concentrations in the leaves of plants relative to
other components. Although fluoride is found in fluoroacids and nucleocidine it is not
essential to bacteria, algae, fungi and higher plants. Therefore, many crops
accumulate very little of the element and vegetables and fruits normally contain low
concentrations (< 0.4 mg kg-1). However, different plant species uptake the element to
varying degrees and some cereals such as barley, rice, taro, yams and cassava can
contain higher concentrations (~ 2 mg kg-1). Tea is also relatively enriched in the
element and can contain 400 mg kg-1. Tea is recognized as a significant exposure
route with typical intakes of 0.04-2.70 mg person-1 day-1. Indeed dental fluorosis has
been reported in Tibetan populations due to the consumption of brick tea that is made
from older leaves with higher fluoride contents resulting in intakes of 14 mg day-1.
Some fruit juices contain elevated concentrations as fluoride is used as a pesticide
during crop growth. Similarly wines can also contain relatively high quantities of the
element (≤ 6.34 mg L-1).

Dental and skeletal fluoroses have also been reported in populations consuming crops
such as maize and chilies that are dried over fluoride-bearing coal products in
southern China. In order to conserve resources, pulverized coals are mixed with
locally sourced clays to produce fuel briquettes. The coals contain relatively high
amounts of fluoride (100-300 mg kg-1 compared to 50-100 mg kg-1 in most coals).
However, several more recent studies have shown it is the clays that are highly
enriched in the element (> 1000 mg kg-1). Not only the burning of the resultant
briquettes leads to very high indoor air exposure (see the section ‘Air’), but the drying
of foodstuffs also increases the fluoride content of crops enormously (Table 5). As a
result of this combined inhalation and ingestion exposure, it is estimated that dental
fluorosis affects 10 million and skeletal fluorosis 1.5 million people in this region.
Now that the role of clays in fluoride exposure is understood, this will aid the
development of future mitigation strategies.

Fluoride primarily accumulates in the skeletal tissues of grazing animals, therefore,

levels in meat are generally low (< 1 mg kg-1). Seafood contains marginally higher
amounts with concentrations in fish ranging from 2-5 mg kg-1. Despite the fact that
fish protein may contain up to 370 mg kg-1 fluoride and fluoride accumulates in the
bones of canned fish, which are also eaten; even in mixed diets with relatively high
fish consumption, it is estimated that the average daily fluoride intakes are only about
0.2 mg.

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The fluoride content of cows’ milk (0.02-0.06 mg L-1) and human breast milk (0.005-
0.010 mg L-1) is also generally low; hence these do not contribute significantly to
dietary intake. Evidence suggests that concentrations in infant formulae are higher
(0.1-1.6 mg L-1) and studies carried out in six countries demonstrated that formula
made with distilled water supplied 30 µg day-1 fluoride to 3 month old babies. Some
studies have reported dental mottling in infants receiving 0.5 mg day-1 fluoride from
baby formulas.

Other exposure routes include the use of fluoride-contaminated trona

(Na3H(CO3)2.2H2O) known as magadi salt in the cooking process in Tanzania
resulting in dental fluorosis in the local populations. Comparisons between two
endemic regions with water supplies containing 0.2-0.8 mg L-1 fluoride showed lower
dental fluorosis rates (7-46 %, no severe forms) in coastal communities despite the
fact that they consumed more fish and tea than in inland villages where the magadi
was used (53-100 %, severe forms highly prevalent 18-97 %).

With the exception of tea, magadi salt and the dried foodstuffs in China, exposure to
fluoride in foodstuffs is generally considered less important than water as the fluoride
content of most foods is low (< 10 mg kg-1). Furthermore, more than 90 % of the
fluoride present in water is absorbed in the human body compared to only 30-60 % in
foodstuffs. Even fluoride in liquid products (milk, etc.) is assimilated 10 % less than
in water.

Therefore, the WHO determines that in most situations, drinking water is a major
pathway for fluoride to enter the human body. In response to the potentially harmful
effects of the element, the WHO has set a drinking water quality maximum admissible
concentration (MAC) of 1.5 mg L-1 (Table 4). Numerous clinical and experimental
studies show a variety of influences of fluoride on human health depending upon the
content in drinking water. Research has shown that fluoride concentrations between 0-
0.5 mg L-1 are associated with increased rates of dental caries whereas contents
between 0.5-1.5 mg L-1 have a beneficial effect, reducing caries. Concentrations
between 1.5-5 mg L-1 can result in dental fluorosis. Ingestion of 5-40 mg day-1
fluoride via drinking water can produce skeletal deformities and knock knees (genu
valgum) have been reported in adolescents receiving > 10 mgF day-1 in water from
birth.

It is estimated that more than 260 million people globally consume drinking water
containing > 1.5 mg L-1 fluoride many of which live in tropical countries. As outlined
in the section ‘Rocks, soils and waters’; endemic dental and/or skeletal fluorosis are
associated with many of these regions and approximately 25 million people suffer
from fluorosis in India alone. In poorer parts of the world prevalence rates of these
diseases may be upward of 90 % in affected villages. Populations suffering dental
fluorosis are sometimes culturally ostracized limiting the ability to marry and have
family security. Skeletal fluorosis seriously inhibits the ability of populations to work,
contribute to the economy, produce their own food and support their families to the
major detriment of poor communities. Hence both these diseases have serious impacts
in developing countries in particular. As a result of these concerns, numerous methods
to remove fluoride from drinking water have been implemented with varying degrees
of success depending on their sustainability and appropriateness of technology to
recipient populations. Excellent summaries of these methods exist in the literature.

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However, in several cases alternative low-fluoride waters may be available should the
resources exist to identify and exploit them.

Human exposure from fluoride in drinking water depends not only on the
concentration but on the levels of daily water intake. The WHO guidelines are based
on a daily consumption of 2 L, however, intake varies significantly between temperate
and tropical climates and between individuals depending on levels of exercise, health
and preference. For example, numerous studies have demonstrated the occurrence of
dental fluorosis in populations exposed to < 1.5 mg L-1 in drinking water, and not all
populations exposed to 3 - 5 mg L-1 in water develop skeletal fluorosis. Hence these
limits are a guide only to be modified in different circumstances. Typical estimates of
total adult intake in non-fluoridated water areas in temperate regions are of the order
0.6 mg day-1 although this can rise to 2 mg day-1 in fluoridated zones.

Many studies demonstrate that the prevalence and severity of fluorosis are influenced
by complex interactions between dietary factors and the pH of the stomach contents.
Total fluoride absorption in the human body not only depends upon the concentration
in water but on the proportion of liquid to solid matter (food) consumed and the
composition of the food. In the stomach under acid conditions, up to 40 % of the
ingested fluoride can be absorbed following conversion to hydrogen fluoride (HF).
Fluoride that is not absorbed in the stomach is subsequently ingested in the upper
intestine independent of pH. Dental fluorosis is thought to develop when > 0.10-0.15
mgF kg-bodyweight-1 is absorbed.

Studies have shown that soluble compounds, such as sodium fluoride (NaF),
hydrogen fluoride (HF), fluorosilicic acid (H2SiF6) and sodium monofluorophosphate
(Na2FPO3), release fluoride easily, which is almost completely absorbed. However,
the intake of cations such as calcium, magnesium and aluminum - which form
relatively insoluble compounds with fluoride - has a protective effect against
absorption. In contrast, the presence of phosphate and iron may enhance absorption.
Protein deficiency is thought to enhance the effects of fluorosis as proteins aid the
absorption of calcium in the body. Studies in China and Moldova of communities
with similar fluoride intake but differing nutritional status, demonstrated that
populations with lower calcium and protein diets suffered more fluorosis. In addition
to the influence of proteins, there is some evidence to suggest that high fat diets may
exacerbate the adverse health affects of fluoride. Vitamins C and D have also been
implicated in the pathogenesis of fluorosis. Vitamin C aids the hydroxylation of
proline, one of the most important amino acids of the basic bone building material
collagen. Hence, healthy collagen is required if bones are to be calcified correctly.
Vitamin D is known to aid calcium absorption in the body and deficiency has been
both suggested and disputed as a contributory factor in fluorosis in India. These
complex dietary interactions may in part explain why fluorosis is prevalent in some
populations but not in others consuming similar levels of fluoride.

In summary, although the biologic mechanisms are not yet fully understood, the links
between high environmental fluoride and human dental and skeletal fluorosis and low
environmental fluoride and dental caries have been well established. The severity of
clinical response to high fluoride intakes is determined by a variety of factors such as
general nutritional status, length and timing of exposure and genetic status. In all
these diseases, one of the most important exposure routes is drinking water. No

13
effective cures are available for dental or skeletal fluorosis, however, the diseases are
preventable if fluoride intake is controlled. Hence the need for better understanding of
the complex interactions between dietary, drinking water and inhalation exposure for
caries prevention on the one hand and debilitating fluorosis on the other.

Further Reading

ATSDR (2003). Toxicological Profile for Fluorides, Hydrogen Fluoride, and

Fluorine. Washington: Agency for Toxic Substances and Disease Registry.

Christiani, H. and Gautier R. (1925). Emanations fluorees des usines. Eude

experimental de l'action du fluor sur les vegetaux. Annals Hygiene Publique (Paris) 3
49-64

Dai, S., Li, W., Tang, Y., Zhang , Y. and Feng, P. (2007). The sources, pathway and
preventative measures for fluorosis in Zhijin County, Guizhou, China. Applied
Geochemistry 22, 1017-1124.

Dean, H. T. (1942). The investigation of physiological effects by the epidemiological

method. In Mouton, R. F. (ed.) Fluorine and Dental Health. Washington: American
Association for the Advancement of Science 19, 23-31.

Edmunds, W. M. and Smedley P. M. (2005). Fluoride in natural waters. In Selinus,

O. (ed.) Essentials of Medical Geology. London: Elsevier, 301-330.

Fordyce, F. M., Vrana, K., Zhovinsky, E., Povoroznuk, V., Toth, G., Hope, B. C.,
Iljinsky, U. and Baker, J. (2007) A health risk assessment for fluoride in Central
Europe. Environmental Geochemistry and Health. Special Issue Medical Geology in
Developing Counties 29 (2), 83-102.

Krishnamachari, K. A. (1986). Fluorine. In Mertz, W. (ed.) Trace Elements in Human

and Animal Nutrition 1. pp 365-407. London: Academic Press.

Smith, M., Lantz, E. and Smith, H. (1931). The cause of mottled enamel. Science 74,
244.

Susheela, A. K. (1993). Health Aspects: Prevention and Control of Fluorosis in India.

Delhi: NDHI National Drinking Water Mission.

US-NRC (1993). Health Effects of Ingested Fluoride. Washington: US National

Research Council, National Academy Press.

US-PHS (1991). PHS Review of Fluoride: Benefits and Risks. Washington: US Public
Health Service.

WHO (1994). Fluorides and Oral Health. Technical Report 846. Geneva: World
Health Organization.

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WHO (1996a). Guidelines for Drinking Water Quality. Geneva: World Health
Organization.

WHO (1996b). Trace Elements in Human Nutrition and Health. Geneva: World
Health Organization.

WHO (2002). Fluorides. Environmental Health Criteria Report 227. Geneva: World
Health Organization.

WHO (2006). Fluoride in Drinking Water. London: IWA Publishing.

Web-based Resources

World Health Organization, Geneva, Switzerland. Web: http://www.who.int/en/

International Society for Fluoride Research. Web: http://www.fluorideresearch.org/

Centre for Disease Control (USA) Recommendations For Using Fluoride. Web:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5014a1.htm

Agency for Toxic Substances and Disease Registry (USA) Toxicology Profiles. Web:
http://www.atsdr.cdc.gov/toxprofiles/

15
Table 1. Dean’s index to assess the severity of dental fluorosis

Classification Criteria – Description of Enamel

Normal Smooth, glossy, pale creamy-white translucent surface
Questionable A few white flecks or white spots
Very Mild Small opaque, paper white areas covering less than 25% of the tooth
surface
Mild Opaque white areas covering less than 50% of the tooth surface
Moderate All tooth surfaces affected; marked wear on biting surfaces; brown stain
may be present
Severe All tooth surfaces affected; discrete or confluent pitting; brown stain
present
From: Dean (1942)

Table 2. Clinical Phases of Skeletal Fluorosis

Osteosclerotic Bone Ash F Symptoms

Phase Concentration
mg kg-1
Normal Bone 500 to 1000 Normal
Preclinical Phase 3500 to 5500 Asymptomatic; slight radiographically-
detectable increases in bone mass
Clinical Phase I 6000 to 7000 Sporadic pain; stiffness of joints;
osteosclerosis of pelvis and vertebral spine
Clinical Phase II 7500 to 9000 Chronic joint pain; arthritic symptoms; slight
calcification of ligaments; increased
osteosclerosis and spongy bones;
with/without osteoporosis of long bones
Clinical Phase III: > 10 000 Limitation of joint movement; calcification
Crippling Fluorosis of ligaments of neck vertebral column;
crippling deformities of the spine and major
joints; muscle wasting; neurological
defects/compression of spinal cord
Compiled from: US-PHS (1991) and ATSDR (2003)

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Table 3. Common inorganic fluoride compounds and their industrial uses

Fluoride Compound Industrial Use

Anhydrous Hydrogen Fluoride (HF) Production of synthetic cryolite
Fluorine (F2) gas (Na3AlF6), aluminum fluoride(AlF3),
gasoline alkylates and
chlorofluorocarbons
Hydrofluoric Acid (HFaq) Etching semi-conductors and glass
Cleaning brick, glass and aluminum
Tanning leather
Rust removal
Calcium Fluoride (CaF2) Flux in steel, glass, aluminum and enamel
production
Production of hydrofluoric acid (HFaq)
and anhydrous HF
Sodium Fluoride (NaF) Flux in steel, glass, aluminum and enamel
production
Preservative in glue and wood
Pesticide
Sulfur Hexafluoride (SF6) Electronic components
Magnesium and aluminum production
Sodium Hexaflourosilicate (Na2SiF6) Fluoridation of drinking water
Fluorosilicic Acid (H2SiF6) Fluoridation of drinking water
Fluorapatite Ca5(PO4)3F Phosphates and fertilizer
Sodium Monofluorophosphate (Na2FPO3) Dental products
Stannous Fluoride (SnF2) Dental products
Compiled from: ATSDR (2003) and WHO (2002)

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Table 4. Human exposure indicators for fluoride in various media

Substance Exposure Guideline Reference

Sodium Fluoride Total Intake 32-64 mg kg- Lethal Dose
bodyweight-1
Fluorine Air 200 µg m-3 (TWA) US NIOSH REL
Hydrogen Fluoride Air 2500 µg m-3 (TWA) US NIOSH REL
Sodium Fluoride Air 2500 µg m-3 (TWA) US NIOSH REL
Fluorine Air 20 µg m-3 Acute Inhalation
US MRL
Hydrogen Fluoride Air 20 µg m-3 Acute Inhalation
US MRL
Fluoride Oral Intake 10 – 20 mg day-1 Skeletal fluorosis

Fluoride Oral Intake 0.05 mg kg-1 day-1 US MRL

Fluoride Water 5-10 mg L-1 for 10 Skeletal fluorosis
years
Fluoride Water 0.5 mg L-1 Water guideline
minimum to
prevent dental
cariesa
Fluoride Water 0.5 – 1.5 mg L-1 Water guideline
optimum, no
adverse health
effects and dental
caries decreasesa
Fluoride Water 1.5 mg L-1 Water guideline
MAC to prevent
dental fluorosisa
Fluoride Water 3 mg L-1 Water guideline
level above which
skeletal fluorosis
may occura
TWA = Time Weighted Average
US MRL = United States Minimal Risk Level
US NIOSH REL = United States National Institute for Occupational Safety and Health Recommended Exposure
Level
MAC = Maximum Admissible Concentration
a = World Health Organization Drinking Water Guidelines based on consumption of 2 L per day

Table 5. Effect of drying food over high-fluoride briquette fires in southern China

Coal Clay Briquette Fresh Dried Fresh Dried

Chilies Chilies Maize Maize
F mg kg-1 237 2262 828 0.79 110 1.64 1419
Compiled from: Dai et al. (2007)

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Photo: Prof V Povoroznuk, from: Fordyce et al. (2007)

Figure 1. Severe dental fluorosis caused by intake of drinking water with ≤ 2.43 mgF
L-1.

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