Fluoride Kinetics and Metabolism

Abstract

Fluoride, after absorption from the gastrointestinal tract, respiratory tract, or skin and mucous membrane reaches different organs and body tissues through blood circulation. Following oral intake, unabsorbed fluoride is excreted through feces, and 50–70 % of absorbed fluoride is excreted through urine, per-spiration, saliva, milk, and egg (in birds) and rest is retained in the body. Calcified tissues, mainly bone and teeth, act as a natural sink for fluoride and contain about 99 % of the total body fluoride burden. Fluoride accumulation in soft tissues is very low, with kidneys having the highest concentration. The placenta appears to protect the fetus from the toxic effects of fluoride as evident from low transplacen-tal fluoride passage in many animal species. Normal cerebrospinal fluid contains very low fluoride concentration, but it increases marginally during chronic fluoride toxicity. The exoskeleton in invertebrates, skeletal tissues in fish, and hair and fin-gernails in vertebrates also accumulate fluoride and may act as bioindicators of the fluoride burden in animals. Fluoride absorption, distribution, deposition in body tissues, and excretion are governed by many factors, although the basic features remain identical in humans and different species of animals. Figure 3.1 depicts the pathways of fluoride distri-bution, retention, and excretion after its oral intake. 3.1 Absorption Fluoride compounds can be absorbed via different routes including the gastroin-testinal tract, respiratory tract, and through skin and mucous membranes. The gastrointestinal tract is the major route of fluoride uptake, except for animals raised in polluted or industrial environments where fluoride compounds are present in high concentration as vapors, fumes, or dust. In animals, fluoride is absorbed mostly in the stomach (in simple-stomach animals), rumen, abomasum (in rumi-nants), and upper intestine by a passive process, although its excretion into the mucosa of the intestine is by active transport (Parkins 1971). The rate of active transport of fluoride in intestinal mucosa decreases with the increasing age of the animal (USEPA 1980). Permeation of fluoride through the gastric mucosa is pH dependent; the higher acidity of stomach contents increases F absorption. In the stomach under acidic conditions, fluoride ions can reversibly combine with hydro-gen ion to form hydrogen fluoride (HF) or hydrofluoric acid, which is an uncharged molecule and can readily pass through biological membranes. Hydrofluoric acid has pKa 3.45. Hence, any fluoride present at a pH below 3.45 will exist mainly in the undissociated form as HF. At pH above 3.45, as in blood plasma, tissue fluid, and the like, fluoride exists mainly in ionized form. In ruminants, only about 50 % of ingested fluoride is absorbed in the rumen, because the rumen pH is around 5–6, which is not suitable for fluoride absorption (Weinstein and Davison 2004). The rate and extent of F absorption in the gastrointestinal tract is also regulated by several other factors, the most important among them being the chemical nature and solubility of fluoride compounds. In general, inorganic F compounds are more soluble and hence rapidly and extensively absorbed from the gastrointestinal tract. Sodium fluoride has the highest bioavailability, whereas calcium fluoride, magne-sium fluoride, and aluminum fluoride have poor bioavailability. Bioavailability of fluoride from bone and fish meal is nearly 50–60 %. Other factors modulating F absorption include species, sex, and age of the animal and presence of dietary components including minerals (divalent cations), fat, protein, and fiber. In human beings, only 50 % of the fluoride from fish protein concentrate is absorbed because Fluoride ingestion