Fluoride toxicity is characterized by a variety of signs and symptoms. 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).[1, 2] 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.[3] Potentially toxic levels of fluoride have also been found in well water in the US.[4]
Fluoride is found in many common household products, including the following:
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.[1, 4]
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:
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 the First Aid and Injuries Center, as well as Poisoning and Poison Proofing Your Home.
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.[5] 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.[6]
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:
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.[7]
In 2015, the American Association of Poison Control Centers (AAPCC) reported 18,119 single exposures involving toothpaste with fluoride, 15,886 of them in children younger than 6 years of age.[8] Only 330 cases were treated in a healthcare facility. Moderate effects were seen in 33 cases, and major effects were seen in 2 cases. As with the prior year, no deaths were reported.[8]
In 2015, th AAPCC reported 569 single exposures to hydrofluoric acid, with 482 of those cases being in people age 20 years or olderr. There were 452 cases treated in a health care facility with only 2 reported deaths.[8]
In 2015, the AAPCC reported two single exposures to sodium monofluoroacetate rodenticides. No deaths were reported.[8]
In infants and children, exposures are usually accidental. Adults usually have intentional exposures.
Death may result from ingesting as little as 2 g of fluoride in an adult and 16 mg/kg in children. Symptoms may appear with 3-5 mg/kg of fluoride. Estimated toxic dose for fluoride ingestion is 5-10 mg/kg. The estimated lethal dose is 5-10 g (32-64 mg/kg) in adults and 500 mg in small children. The American Association of Poison Control Centers reported no deaths from exposure to fluoride-containing toothpaste in 2014, but one death from sodium monofluoroacetate rodenticide exposure.[9]
Determine the exact nature, amount, and time of exposure or ingestion. Query the patient, bystanders, paramedics, and family members regarding specifics of exposure or ingestion, including possible co-ingestants. The presentation may vary in subtle ways depending on the route of exposure, which may be by inhalation, skin contact, or ingestion.
Hydrogen fluoride is a colorless, fuming liquid or gas with an irritating odor. Patients exposed to hydrogen fluoride gas directly or from fumes emanating from concentrated hydrofluoric acid have rapid onset of eye, nose, and throat irritation.
Cutaneous contact with aqueous hydrogen fluoride leads to rapid, deep tissue penetration that can cause both local cellular destruction and systemic toxicity. Patients may complain of significant cutaneous pain, hemorrhage, or muscular spasm at the site of contact.
Ingestion of hydrogen fluoride can lead to gastrointestinal symptoms, which may include: nausea, vomiting, and/or gastric pain. However, gastrointestinal symptoms may occur with exposure via any route.
Delayed clinical presentation is quite common. Symptoms may not arise for several days, especially in the case of exposure to dilute solutions of hydrogen fluoride (less than 20%). Consequently, asymptomatic patients should be monitored in the emergency department for 6 hours before possible discharge. Patients may be discharged if asymptomatic and ingestion was less than 3 mg/kg by reliable history. Patients who present with persistent signs and symptoms should be admitted to a monitored bed.
Gastrointestinal signs and symptoms, as follows, predominate:
Neurologic effects are as follows:
Cardiovascular effects are as follows:
Measurement of serum electrolytes may be indicated in patients with suspected fluoride toxicity to investigate for the following abnormalities:
Measure fingerstick on all patients with seizure and altered mental status because of the risk for hypoglycemia with systemic fluoride toxicity. Serum and urine fluoride levels are not available for emergency department evaluation.
Electrocardiogram and cardiac monitoring may be indicated for suspected fluoride toxicity. Abnormalities found may reflect the effects of electrolyte imbalances, as follows:
For prehospital care, emergency medical services personnel should place patients with a known significant ingestion of fluoride on a cardiac monitor and establish intravenous (IV) access. IV calcium should be administered to patients with cardiac dysrhythmias.
In general, victims who have been exposed to hydrogen fluoride gas or vapor do not pose a substantial risk of contamination to prehospital providers. The exception is when a victim's clothing or skin has come in contact with a significant amount of hydrogen fluoride liquid, solution, or condensed vapor.
In the emergency department, rapid decontamination is critical. Any cutaneous exposure should be treated with calcium-containing gels.
The patient should be placed on a cardiac monitor and an electrocardiogram should be obtained. Correct electrolyte abnormalities, especially hyperkalemia, hypocalcemia, and hypomagnesemia. Correct calcium deficiencies with IV calcium chloride or calcium gluconate. Cardiac arrhythmias from fluoride toxicity are difficult to treat because they do not respond to lidocaine, cardioversion, or defibrillation.
Perform gastric aspiration and lavage. Small-bore nasogastric tube aspiration, followed by lavage, is recommended because of the potential severity of this ingestion and the ineffective adsorption of fluoride to activated charcoal. Although fluoride does not bind to activated charcoal, use of activated charcoal is still recommended for patients with intentional ingestions when a polysubstance overdose is possible.
Lavage with milk or a solution containing calcium carbonate or magnesium hydroxide (eg, milk of magnesia) is theoretically attractive but has not been proven beneficial. Lavage with 1%-5% calcium chloride solution has been recommended, to bind fluoride in the stomach. Gastric aspiration and lavage are most effective when instituted within 1 hour of ingestion. Hemodialysis is used for critically ill patients whose condition is refractory to all other forms of treatment.
Consult a toxicologist or poison control center for current acute management recommendations. For intentional ingestions, consider psychiatric consultation after medical clearance.
The goals of therapy in patients with fluoride toxicity are to reduce toxicity and prevent complications. No antidote for fluoride toxicity exists, and activated charcoal does not adsorb fluoride. Electrolytes may be used to correct imbalances resulting from fluoride toxicity.
Clinical Context: Calcium chloride is used to manage the underlying hypocalcemic effects caused by fluoride poisoning.
Clinical Context: Calcium gluconate moderates nerve and muscle performance and facilitates normal cardiac function. For systemic hypocalcemia, the agent can be given intravenously initially, and then calcium levels can be maintained with a high-calcium diet. Some patients require oral calcium supplementation.
Calcium chloride is administered to correct hypocalcemia that may result from fluoride poisoning. Calcium chloride provides 3 times more calcium than calcium gluconate on an equal-volume basis and is preferred (despite greater tissue toxicity if extravasation occurs).