Practice Essentials
Fluoride toxicity is characterized by a variety of signs and symptoms. [1] In the United States, poisoning most commonly follows ingestion (accidental or intentional) of fluoride-containing products.
However, in many parts of the world (eg, regions of India and China), elevated levels of fluoride in groundwater result in chronic fluoride toxicity (fluorosis). [2, 3] In southwestern China, fluorosis has also been linked to the burning of coal with high fluoride levels—in particular, indoor burning, including as a cooking fuel. [4] Potentially toxic levels of fluoride have also been found in well water in the US. [5]
Fluoride is found in many common household products, including the following:
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Toothpaste (eg, sodium monofluorophosphate)
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Vitamins
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Dietary supplements (eg, sodium fluoride)
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Glass-etching or chrome-cleaning agents (eg, ammonium bifluoride)
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Insecticides and rodenticides (eg, sodium fluoroacetate)
Historically, most cases of serious acute fluoride toxicity have followed accidental ingestion of insecticides or rodenticides.
Symptom onset usually occurs within minutes of exposure, but may be delayed. Manifestations of fluoride toxicity are predominantly gastrointestinal (GI), but neurologic and cardiovascular effects also occur (see Presentation). Long-term exposure to fluoride through elevated levels in drinking water leads to skeletal and dental fluorosis. [2, 5] At its most severe, skeletal fluorosis may result in muscle weakness, tiredness, anemia, dyspepsia, male infertility, and decrease in intelligence quotient. [6]
Tests for measuring fluoride levels are not available in the emergency department. Assessment of patients with suspected fluoride toxicity is directed toward the consequences of the toxicity, and may include the following:
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Electrocardiogram
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Electrolyte levels
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Fingerstick glucose assay
No antidote for fluoride toxicity exists, and fluoride does not adsorb to activated charcoal. Treatment includes gastric aspiration and lavage, and correction of electrolyte abnormalities. (See Treatment and Medication.)
For patient education information, see Poisoning and Poison Proofing Your Home.
Pathophysiology
Fluoride has several mechanisms of toxicity. Upon ingestion, the GI tract is the earliest and most commonly affected organ system. Ingested fluoride can form hydrofluoric acid in the stomach, which leads to GI irritation or corrosive effects.
Once absorbed, fluoride binds calcium ions and may lead to hypocalcemia. Fluoride also has direct cytotoxic effects and interferes with a number of enzyme systems: it disrupts oxidative phosphorylation, glycolysis, coagulation, and neurotransmission (by binding calcium).
Fluoride inhibits Na+/K+-ATPase, which may lead to hyperkalemia by extracellular release of potassium. Fluoride inhibits acetylcholinesterase, which may be partly responsible for hypersalivation, vomiting, and diarrhea (cholinergic signs). Seizures may result from both hypomagnesemia and hypocalcemia.
Severe fluoride toxicity will result in multiorgan failure. Central vasomotor depression as well as direct cardiotoxicity also may occur. Death usually results from respiratory paralysis, dysrhythmia, or cardiac failure.
Long-term exposure to fluoride in drinking water stimulates osteoblastic bone formation, particularly in cancellous bone, and at low levels (1.00-1.06 ppm), this decreases the risk of overall fractures. At higher levels, however (≥4.32 ppm), fluoride can decrease cortical bone mineral density and increase skeletal fragility, leading to increased fracture risk. [7] In addition to effects on bone, a decrease in insulin sensitivity and insulin signaling has been reported in an animal model of chronic fluoride toxicity. [8]
Etiology
The most common type of exposure is ingestion of products that contain fluoride. To obtain the exact name of the product and how much was ingested is extremely important.
Toothpaste contains 1 mg/g of fluoride as sodium monofluorophosphate. This fluoride formulation has low solubility and is generally nontoxic. The toxic effects following large ingestions of the following products usually are limited to GI discomfort:
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Toothpaste
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Oral hygiene products
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Insecticides
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Rodenticides
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Dietary supplements
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Automobile wheel-cleaning products
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Glass-etching products
The use of sodium fluoroacetate as a rodenticide was greatly curtailed in the United States by 1990, because of its toxicity to other mammals, and it is currently licensed only for use against coyotes. Its toxicity stems from the similarity of fluoroacetate to acetate; the available evidence suggests that the fluoride component does not contribute. [9]
Epidemiology
In 2022, the American Association of Poison Control Centers (AAPCC) reported 802 single case exposures to fluoride, with an additional 9059 single case exposures to toothpaste with fluoride and 3981 single cases exposures to mouthwash with fluoride. Overall, children younger than 6 years of age accounted for 75% of cases reported. Only 312 cases were treated in a healthcare facility. Moderate effects were seen in 23 cases and major effects in 1 case, but no deaths were reported. [10]
The AAPCC also reported cases involving the following fluoride compounds [10] :
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Hydrofluoric acid: 493 single exposures, 415 of them in people age 20 years or older, 370 treated in a health care facility, and 5 deaths
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Sulfuryl fluoride fumigant: 159 single case exposures, with 23 cases treated in health care facilities and no major effects or deaths
In infants and children, exposures are usually accidental. Adults usually have intentional exposures. Even in areas of high fluoride exposure, the prevalence of dental fluorosis in deciduous teeth is low, possibly because despite high levels in maternal blood, fluoride is effectively blocked from crossing the placenta and only limited transfer into breast milk occurs. [11]
Fluorosis is endemic in China, mainly due to high fluoride content in groundwater, with an estimated 100 million people affected. [6]
Prognosis
The typical toxic dose for fluoride ingestion has been estimated at 5-10 mg/kg, but symptoms may appear with 3-5 mg/kg. The estimated lethal dose is 5-10 g (32-64 mg/kg) in adults and 500 mg in small children, but death may result from ingestion of as little as 2 g of fluoride in an adult and 16 mg/kg in children. The American Association of Poison Control Centers reported no deaths from exposure to fluoride-containing toothpaste or mouthwash in 2022, but one death from hydrofluoric acid exposure. [10]
A number of studies have reported cognitive deficits in children with higher exposures to fluoride during pregnancy and early development. [12, 13, 14]
