The metabolism and toxicity of fluoride are discussed with emphasis on new scientific findings. The gastric absorption, tissue distribution, and renal excretion of the ion are all influenced by the magnitude and direction of the pH gradient between adjacent body fluid compartments. This mechanism explains the asymmetric distribution of fluoride across cell membranes, and the manipulation of transmembrane pH gradients has proven efficacious in acute fluoride toxicity. The comparative metabolism and relative toxicities of ionic fluoride and monofluorophosphate are discussed. It is no longer certain that there is a difference between the acute toxic potentials of sodium fluoride and those of MFP. It is concluded that the “probably toxic dose” or PTD of fluoride—the dose which should trigger therapeutic intervention and hospitalization—is 5 mg/kg of body weight. As currently packaged, many dental products contain sufficient fluoride to exceed the PTD for young children. There is a need for additional research into the sources, effects, and fate of strongly bound or organic fluoride compounds. Attention is drawn to the fact that, while the metabolic characteristics and effects of fluoride in young and middle-aged adults have received considerable research attention, there is a paucity of such information for young children and the elderly. The increasing prevalence of dental fluorosis is addressed. It is concluded that non-dietary sources of fluoride, mainly fluoride-containing dental products, are a major source of ingested fluoride. The article concludes with 12 recommendations for future research.
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