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Fluoride, well established as one of the most toxic elements known to humans when ingested in large doses, is likely among the least understood medicines that primary care practitioners may encounter in terms of its chronic toxicology. In areas of the world where Fluoride is naturally elevated in the drinking water, endemic fluorosis is relatively common. This is a crippling skeletal condition and it is a major public health problem in the areas where Fluoride levels are severely elevated (#Ayoob and Gupta, 2006). Skeletal fluorosis remains an undiagnosed problem in North America but there have been several obvious cases reported (#Whyte, et al, 2005, #Eichmiller, et al, 2005, #Boyle and Chagnon, 1995). Even chronic exposure to relatively low daily doses of Fluoride can lead to joint pain, a symptom of early stage, skeletal fluorosis. While most dentists recognize that over exposure to Fluoride can result in Dental Fluorosis, other health care professionals might be unaware that fluoride is toxic to other parts of the body. Physicians should be able to identify young patients at risk for skeletal fluorosis by quickly examining their teeth. Excess Fluoride intake causes dental fluorosis, a mottling of teeth. Dental Fluorosis has been on the rise in North America because of the widespread exposure to fluorides in fluoridated water, oral care products, pollution and synthetic chemicals including fluorinated drugs. While chronic fluorosis remains largely undetected, acute fluoride poisoning is likely something that a family physician might actually encounter and treat.

Pharmacology of Fluoride

Fluoride ions convert to hydrofluoric acid (HF) at pH 1.0-2.0 in the gut and are rapidly absorbed. Approximately 50% of ingested Fluoride is excreted in the urine (#J. Ekstrand, G. Alván1, O. Boréus1, and A. Norlin). A small amount is excreted in the feces, saliva and sweat. Serum Fluoride levels peak within 1 hour of ingestion and return to normal after approximately 3 to 5 hours. Fluoride accumulates in patients with impaired kidney function and its retention is affected by the acid-base balance: a diet rich in meat protein will produce an acidic renal filtrate and cause more Fluoride to be retained. Nearly all (99%) of retained Fluoride is incorporated into developing bones and teeth in the mineral. Fluoride exchanges with the hydroxyl groups of existing hydroxyapatite crystals in bone to form fluorapatite (FA), which is less soluble in acid. Tooth enamel with more FA is more resistant to acid erosion from dietary acids and the weak acids produced by oral bacteria that cause dental decay. Similarly, FA in bone makes it more resistant to osteoclasts, which use protons to dissolve the mineral. The pharmacokinetics of Fluoride are described in detail by Whitford (#Whitford, 1999).

The Epidemiology of Fluorosis

In Canada most non-fluoridated communities have less than 0.3 mg/L (parts per million or ppm) Fluoride occurring naturally in their drinking water. Fluoride is added to elevate the Fluoride level to 0.8 - 1.0 ppm, a level that was designed to maximize the benefits of Fluoride and minimize Dental Fluorosis (#Brown and Polove, 1963). 7 Many Canadian cities have been adding fluoridated chemicals, primarily silicofluorides, to the drinking water for over 40 years. (Some cities - e.g. Vancouver, Montreal- for many reasons, did not fluoridate.) There has been a steady rise in the prevalence and severity of Dental Fluorosis (#Foman, et al, 2000 and #Rozier, 1999). Overall, levels at or in excess of 12.5% of the population fluoridated communities have disfiguring Dental Fluorosis which is deemed fluorosis that which the majority of dentists would treat as most fluorosis is left unattended. (#Mcdonaugh, 2000 and (#Riordan, 2006).

Etiology and Pathophysiology of fluorosis

Dental Fluorosis: Dental Fluorosis is a defect of tooth development characterized by generalized white spots, brown stains and pitting of the enamel of the permanent teeth (#Table 1). Fluoride, when ingested during the formation and maturation of tooth enamel, interferes with a number of cellular events because it inhibits various enzyme systems (#DenBeston, et al, 2002), the G-protein complex (#Matsuo, et al, 1998), and it removes and replace proteins with enamel crystals (#Aoba and Fejerskev, 2004). The severity of the defect appears to be proportional to the total Fluoride consumed. #Table 1 presents an example of mild-to-moderate Dental Fluorosis, demonstrating that as children affected with fluorosis age, the defective enamel, which is quite weak, tends to erode and the enamel may take on an appearance of pitting or flaking. The condition nearly always occurs with symmetry, that is, teeth that developed at the same time are similarly affected. When fluoride exposure is early in life (age 1-3 years), only the anterior incisors and first molars are affected. When excess exposure occurs later, while the premolars, canines and second molars are developing, then sometimes these teeth are the only ones affected (#Ishii and Suckling, 1991). Excessive fluoride intake from birth results in Dental Fluorosis in all the teeth (see Table 1).

Table 1: Timing of chronic daily fluoride ingestion and the corresponding dental fluorosis pattern that can be expected.

Fluoride Intake (mg/kg/day}

When Exposed

Permanent Teeth Infected

Dental Fluorosis Severity

< 0.5

0-3 years

Incisors, 1st Molars



0-3 years

incisors, 1st molars, and tips of canines & premolars


> 0.15

0-3 years

all teeth


< 0.05

3-6 years

Premolars, canines, 2nd molars



3-6 years

Premolars, canines, 2nd molars


> 0.15

3-6 years

all teeth


< 0.5

0-6 years

all teeth


0.10 - 0.15

0-6 years

all teeth


> 0.15

0-6 years

all teeth


Bone fluorosis: Severe forms of fluorosis, common in India and China, where the Fluoride levels in the underground water supplies that are used for drinking water can vary between 10 and 20 ppm, have not been documented in North America. The stages of bone fluorosis and its symptoms relating to fluoride in bone, are shown in #Table 2. Physicians seldom turn to fluoride as a potential etiological factor for joint pain.

Table 2. Preclinical and Clinical Stages of human skeletal fluorosis and correlation with bone ash fluoride concentrations (adapted from the National Academy of Sciences - see #Department of Health and Human Services).

Osteosclerotic Phase

Ash Concentration (mg F/kg)

Normal Bone


Preclinical Phase -
asymptomatic, slight radiographically -
detectable changes in bone mass


Clinical Phase I
-sporadic pain, stiffness of joints
osteosclerosis of pelvis & vertebral column


Clinical Phase II
-chronic joint pain, arthritic symptoms,
-slight calcification of the ligaments,
-increased osteosclerosis of cancellous bones,
with or without osteoporosis of long bones


Phase III- Crippling Fluorosis
-limitation of joint movement
-calcification of ligaments in the neck, vertebral column
-crippling deformities of the spine and major joints.
-muscle wasting, neurological defects, compression of the
spinal chord



Sources of Excess Systemic Fluoride

Water, beverages, and food
Fluoride is the 17th most abundance element in the earth's crust and occurs naturally in Canada in ocean water (mean 1.3 ppm) groundwater (between 0.86 - 1.4 mg/L) and soil (up to 2000 ppm) (#Warrington, 1990). Due to its ubiquity, it is ingested on a daily basis in varying amounts. Certain foods contain more fluoride than others, and the Fluoride Content in Tea can be very high. Dark tea, for example, is enriched in fluoride (3 - 6 ppm). Artificially fluoridating the drinking water results in a significant increase in Fluoride ingestion on a daily basis since this creates a 'halo' effect; foods and beverages processed in a city served by artificially fluoridated water will contain elevated levels of Fluoride. Accidental fluoridation overfeeds have resulted in entire communities suffering acute fluoride poisoning, one resulting in death (#Gessner, et al, 1994) and there have been accidental exposures of the concentrated fluoridation chemicals that have resulted in severe acute fluoride chemical burns and life-threatening sequelae (#Bjornhagen, et al, 2003).

Fluoride Supplements
Fluoride supplements are no longer considered an important public health measure even where children reside in non-fluoridated communities or drink from private water wells (#Burt, 1999). Because they are a major risk factor in causing Dental Fluorosis (#Ismail and Bandekar, 1999) with very little evidence that they help to reduce dental caries (#Limeback, et al, 1998) the Canadian Dental Association (CDA) modified its recommendations for the use of fluoride supplements in 1998 (#Limeback, et al, 1998) and then again in 2000 (#Swan, 2000). If the current CDA guidelines (total daily fluoride not to exceed 0.05 mg/kg/day) are taken literally, physicians should consider abandoning prescribing fluoride supplements altogether unless they are prepared to estimate the total intake from all sources (i.e. ingestion, imbibition, inhalation and dermal absorption). Fluoride works primarily by means of a topical effect (#Limeback, 1998 and #Featherstone, 2000), so it may provide some benefit in lozenge form in patients at high risk for dental decay. Fluoride therapy should be provided by dentists only.

The fluoride content of infant formulae made with fluoridated tap water ranges from about 0.7 to 1.4 ppm. (#McKnight-Hanes, et al, 1988 and #Silva and Reynolds, 1996. These levels are 100-fold higher than the levels found naturally in breast milk (#Foman and Ekstrand, 1999). A daily dose exceeding 0.05 mg/kg/d can result Dental Fluorosis (#Whitford, 1990). Based on average fluid intakes and body weights, many infants exceed intakes of 0.15 mg fluoride/kg/day (#Erdal and Buchanon, 2005). The long-term medical consequences of this level of fluoride intake have never been studied.

Many common pharmaceuticals used in medicine are fluorinated. The list of fluorinated drugs number in the hundreds but the more common ones include Celebrix, Cipro, Diflucan, Prozac, Dalmane, Lipitor, and nearly all of the halogenated general anesthetics. Depending on the molecular formula, these drugs contain from 3% to 17% fluorine by weight. Some have been shown to lose free fluoride from defluorination by cytochrome p450 enzymes (#Martinez, et al, 1997 and #Pradhan, et al, 1995). Most fluorinated general anesthetics elevate serum Fluoride but some to levels that pose risks to kidney function, at least during the fluoride exposure (#Nishiyama and Hanaoka, 1998).

Increased Fluoride intake can occur from inhaling fluoride-polluted air. In Canada the mean concentration of Fluoride in ambient air is generally low (< 0.05 µg/m3) but samples are were much higher near steel plants in Hamilton (0.2 µg/m3), within 0.5 km of a phosphate fertilizer plant in BC ( 0.5 µg/m3), 1 km from a brick manufacturing plant in Brampton ( 0.7 µg/m3), and on Cornwall Island ( 0.43 µg/m3) 4 km from an aluminum plant (#Government of Canada, 1993). The highest Fluoride levels found in air have been documented in China where coal is burned extensively for industrial power generation. In some areas where dental fluorosis has been documented to be quite severe and skeletal fluorosis has been observed, the concentration of fluoride in ambient air can be as high as 11 µg/m3 (#Feng, et al, 2003).

Can Dental Fluorosis Predict Bone Problems?

The effects of exposure to daily Fluoride doses that cause mild to moderate dental flurososis may foretell a future bone problems. In one region of Mexico, where the Fluoride levels in the water ranged from 1 ppm to 4 ppm, children with increased Dental Fluorosis had a higher incidence of bone fractures(#Alarcon-Herrera, et al, 2001). Chronic exposure to fluoridated water, even as low as 1 ppm, has been shown to increase the risk for bone fractures in the elderly, especially the hips (#Danielson, et al, 1992). This corroborates the clinical trials where high daily doses of Fluoride usually fail to successfully treat osteoporosis(#Riggs, et al, 1987). Despite a mitogenic effect on osteoblasts and a resultant increase in bone mass, Fluoride alters the crystal structure in such a way as to render the bone more susceptible to fracture. The mechanism of fluoride's action on bone cells is believed to be through the activation of the G-protein complex(#Susa, 1999).


Acute Toxicity - clinical signs, diagnosis, treatment
The usual sources of acute fluoride poisoning in children are listed in Table 3. This table can be used for quickly assessing whether the probable toxic dose has been exceeded. The clinical signs and symptoms of acute toxicity are shown in Table 4. Every parent (and health care professional) should be aware of the potential emergency that could result from an ingestion of a sizable amount of fluoride. When the fluoride source is known and severe symptoms develop, emergency care, including a visit to the local hospital, should be considered.

Table 3. Usual Sources of Fluoride Poisoning - Calculating Probably Toxic Dose

Fluoride Source


Amount Usually Used

Amount Containing A Probably Toxic Dose for a 10 kg toddler

Amount Containing A Probably Toxic Dose for a 20 kg toddler

Total mg Fluoride Swallowed

Fluoride Supplements

0.25 mg F

1 tab/day



1/4 x Tabs swallowed

Fluoride Supplements

0.5 mg F

1 tab a day



1/2 x tabs swallowed

Fluoride Supplements

1.0 mg F

1 tab a day



tabs swollowed

Fluoridated Toothpaste

NaF 0.22%

Pea size amount per brushing

50cc (1/5 of tube)

100 cc

1 L

cc swallowed

Fluoridated Toothpaste

MFP 0.76%





Fluoridated Toothpaste

SnF2 0.4%





Accidental Overfeed of Fluoridated Water

e.g. 0.1 mg fluoride/ml (100 ppm)

1 L/day


1 L

0.1 x mL consumed

Fluoridated Mouthrinse

NaF 0.05%


One cup (225 ml)

450 ml

4.5 x ml swallowed

Fluoridated Mouthrinse

NaF 0.2%


Approx. one capful (58 ml)

116 ml

1.16 X ml swallowed

Professional Fluoride Gel

2.2% NaF gel

5 ml every 6 months

5 ml

10 ml

10 X ml swallowed

Professional Fluoride Gel

APF 1.23% F

5 ml every 6 months

4 ml

8 ml

12.3 X ml swallowed

Household Glass etcher/cleaner

3% HF

Accidental ingestion?

1.7 ml

3.4 ml

30 X ml swallowed


Table 4. Symptoms and treatment of acute fluoride poisoning

Acute Symptoms

excess salivation, tremors, weakness, convulsions, shallow breathing, nausa, vomiting, abdominal pain, diarrhea and eventually shock.

emergency home treatment for a probable toxic dose (5 mg fluoride/kg)
-see above for estimates

1. contact Poison Control Center and provide:

    • the patient's age, weight, and condition
    • the name of the product (ingredients and strengths if known)
    • the time it was swallowed
    • the amount swallowed
      2. follow instructions of the hospital emergency department or the poison control center
      3. Give milk every 4 hours

If symtoms worsen, go immediately to hospital emergency -take the product container along.


    • gastric lavage.
    • IV calcium
    • Supportive therapy.


depends on dose: if patients survives 48 hrs., recovery is likely

Chronic Toxicity - clinical signs, diagnosis, treatment of Bone Fluorosis
When patients present with symptoms of severe joint pain, radiographic examination of a fluoride-poisoned person will show osteosclerosis and increased bone density. Blood and urine Fluoride tests can be ordered in most large urban centers. Teaching hospitals occasionally test for Fluoride in urine and serum using an ion selective electrode. These are usually carried out by special order. 24-hour urine Fluoride levels should be compared with creatinine levels3 but normal urine levels are below 0.3 ppm. Normal serum levels are in the 1.0 ?M range (0.02 ppm). Fluoride levels can be elevated where Fluoride in the drinking water is excessive (Health Canada recommends a maximum of 1.5 ppm) and from chronic, daily ingestion of high amounts of Fluoride from other sources2, 3 but can also be high immediately following acute doses from accidental ingestion or from general anesthesia. 38 It was suggested that regular use of safe drinking water may reverse the complexity of fluorosis to the some extent (Susheela and Bhatnagar 2002)

Medical Management of Fluoride Toxicity

While the clinician and most poison control centers may be well prepared for acute fluoride poisoning, chronic fluoride poisoning is more difficult to recognize and manage. When everyone in an entire community appears to have symptoms of nausea and vomiting, a fluoridation overfeed, especially in small communities, should be considered as a potential cause and Public Health should be alerted. Bottle-fed infants that do no tolerate formula may improve with straight formula or formula reconstituted with distilled water or water that has been treated by reverse osmosis (RO). Patients who consume large quantities of water or who have renal problems should avoid fluoridated water altogether. Physicians should at least consider that some joint pain complaints may simply be the result of exposure to too much fluoride and develop a strategy to reduce the fluoride intake. Finally, patients should be reminded to inform their dentists if they avoid fluorides, so that alternative therapies to prevent dental decay can be initiated.


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