**3. Molecular mechanism of fluoride toxicity**

F is redily absorbed by the stomach, lumen, and small intestine, and approximately 75–90% of ingested F is absorbed from the gastrointestinal tract. Fluoride

**Figure 2.** *Molecular mechanism of fluoride-induced toxicity.*

#### *Sources of Human Overexposure to Fluoride, Its Toxicities, and Their Amelioration Using… DOI: http://dx.doi.org/10.5772/intechopen.103714*

transport through biological membranes occurs primarily through the non-ionic diffusion of hydrogen fluoride (HF). The small neutral molecule of HF penetrates cell membranes much faster than the dissociated fluoride ion, resulting in a more pronounced intracellular intake [13]. After ingestion, fluoride is rapidly and virtually absorbed into the blood stream. The ingested fluoride appears in the plasma within 30–60 min after uptake, and it is distributed from the plasma to all tissues and organs within 24 h. The element is taken up into all the tissues of the body, but it is retained and accumulated only in the teeth and other skeletal tissues resulting in dental and skeletal fluorosis when the elements water threshold levels of 1.5–20 mg/L are exceeded, respectively. In general, approximately 50% of absorbed F is retained by uptake in calcified tissues.

F is excreted primarily via urine. Urinary F clearance inceases with urine pH due to a decrease in the concentration of HF. The rate of F removal from plasma, which in healthy adults is approximately 75 mL/min, is approximately equal to the amount of the renal and calcified tissues clearances. For healthy young or middle-aged adults, only 50% of absorbed fluoride that is not assimilated into calcified tissues is excreted in the urine.

The intermediate interaction of fluoride with body systems between its absorption in the gut and its assimilation into skeletal tissue or renal clearance from the body results in a series of toxic effects to the body. These toxicities symptoms are generally referred to as non-skeletal fluorosis. It has been suggested that oxidative stress can be a possible mechanism through which fluoride induces damage to the various tissues. This F toxic mechanism can be summarized as in **Figure 2**.
