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INTRODUCTION

Fluoride-liberating chemicals are found in some automobile wheel cleaners, rust removers, glass-etching solutions, pesticides, agents used in aluminum production, dietary supplements, drugs used to prevent dental caries, and the antifungal voriconazole. It is also found in hydrogen fluoride and hydrofluoric acid, which have additional dermal and inhalational hazards and are discussed separately. By ingestion, soluble fluoride salts are rapidly absorbed and are more acutely toxic than poorly soluble compounds (Table II–27). Most toothpaste contains up to 5 mg of fluoride per teaspoon, and tea can contain 0.3–5.1 mg of fluoride per liter. Although low fluoride concentrations added to public drinking water decreases tooth decay, in some parts of the world high concentrations of fluoride contaminating drinking water causes a number of chronic health problems including skeletal fluorosis.

TABLE II–27.FLUORIDE-CONTAINING COMPOUNDS

MECHANISM OF TOXICITY

  1. In addition to its direct cytotoxic and metabolic effects, fluoride binds avidly to calcium and magnesium, causing hypocalcemia and hypomagnesemia and generates reactive oxygen species. Fluoride toxicity disrupts many intracellular mechanisms, including glycolysis, G-protein–mediated signaling, oxidative phosphorylation, adenosine triphosphate (ATP) production, function of Na+/K+-ATPase, and potassium channels.

  2. Pharmacokinetics. Fluoride is a weak acid (pKa = 3.4) that is passively absorbed from the stomach and small intestine. In an acidic environment, more fluoride is present as hydrogen fluoride (HF), which is absorbed more rapidly than ionized fluoride. Fasting peak absorption occurs in 30–60 minutes. The volume of distribution is 0.5–0.7 L/kg. Fluoride is not protein bound but binds readily to magnesium and calcium in blood and tissues and is deposited in bone. The elimination half-life is 2.4–4.3 hours and is prolonged in patients with renal failure.

TOXIC DOSE

Vomiting and abdominal pain are common with acute ingestions of elemental fluoride of 3–5 mg/kg (see Table II–27); hypocalcemia and muscular symptoms appear with ingestions of 5–10 mg/kg. Death has been reported in a 3-year-old child after ingestion of 16 mg/kg and in adults with doses in excess of 32 mg/kg. Although chronic total fluoride intake above 14 mg per day is associated with a clear excess risk of skeletal adverse effects, a threshold closer to 6 mg per day has been suggested by the World Health Organization, International Programme on Chemical Safety.

CLINICAL PRESENTATION

  1. Acute poisoning. Nausea and vomiting frequently occur within 1 hour of ingestion. Symptoms of serious fluoride intoxication include skeletal muscle weakness, tetanic contractions, respiratory muscle weakness, and respiratory arrest. Hypocalcemia, hypomagnesemia, hyperkalemia, and increased QT interval can occur. Death is due to intractable cardiac dysrhythmias and usually occurs ...

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