Excretion of fluoride

The major route of fluoride excretion is via the kidney and urine 40-60% of the daily intake is excreted in the urine with an elimination half-life of about 5 h [17,85]. Fluoride excretion is influenced by a number of factors, including glomerular filtration rate, urinary flow and urinary pH. The excretion of fluoride in urine is reduced in individuals with impaired renal function. Urine fluoride excretion is 0.79 mg/day in humans with normal renal function, 0.53 mg/day in those with questionable and 0.27 mg/day in those with impaired renal function [86],... 

Vinylidene fluoride is taken up rapidly via the pulmonary route in rats, but at equilibrium the mean concentration (by volume) in rats was only 23% of that in the gaseous phase. Metabolism proceeded very slowly and was saturable at exposure concentrations of about 260 mg/m Its maximum rate was 1% that of vinyl chloride and less than 20% that of vinyl fluoride there has been a report of an increase in the urinary excretion of fluoride in exposed rats. No alkylating intermediate was demonstrated after passage through a mouse-liver microsomal system. However, vinylidene fluoride inhibits mixed-function oxidase activity in vitro and, like similar halogenated compounds that are transformed to reactive metabolites, it alters rat intermediary metabolism, leading to acetone exhalation (lARC, 1986). 

A. Specific levels. Serum fluoride concentrations are not useful after acute exposure but may be used in evaluating chronic occupational exposure. Normal semm fluoride is less than 20 mcg/L, but varies considerably with dietary and environmental intake. In workers, preshift urine excretion of fluoride should not exceed 3 mg/g of creatinine. 

Many other dietary factors have been reported to affect calcium bioavailability. Phytate, fiber, cellulose, uronic acids, sodium alginate, oxalate, fat (only in the presence of steatorrhea), and alcohol have been reported to decrease calcium bioavailability (15). Lactose and medium chain triglyceride increase it (15). FTuoride also affects calcium retention primarily by stimulating bone formation thereby decreasing calcium excretion (33-38). The effects of fluoride on calcium utilization have been variable (34,38,39). 

Based on limited epidemiologic evidence, fluoride supplements, with or without calcium, estrogen and vitamin D, are used by clinicians for the treatment of osteoporosis. However, knowledge of the effects of fluoride on calcium and phosphorus metabolism in normal animals is limited although Spencer et al. (32) reported that ingestion of fluoride by three osteoporotic men did not affect calcium absorption but caused a decrease in urinary excretion. Moreover, there is a need to determine the long-term effects of fluoride treatment on bone strength and on soft tissues ( ). 

Fluoride concentration in the urine has been used as a biological indicator of fluoride." Most absorbed fluoride is excreted rapidly in the urine. A portion is stored in bone, but a nearly equal amount is mobilized from bone and excreted. Some storage of fluoride occurs from the ingestion of as little as 3 mg/ day. Evidence from several sources indicates that urinary fluoride concentrations not exceeding 5 mg/1 in preshift samples taken after 2 days off work are not associated with detectable osteosclerosis and that such changes are unlikely at urinary levels of 5-8 mg/1." Preshift urinary fluoride concentration is considered to be a measure of the worker s body (skeletal) burden of fluoride, whereas the postshift sample is taken to be representative of exposure conditions during that work shift. 

A commonly used indicator for fluoride exposure is its concentration in urine [85,99]. The urinary excretion rate of fluoride correlates better with its concentration in plasma than in urine [85]. 

Boron elfectively counteracts symptoms of fluoride intoxication in humans (Zhou etal. 1987) and in rabbits poisoned experimentally (Elsair et al. 1980a, 1980b, 1981). Humans suffering from skeletal fluorosis experienced 50 to 80% improvement after drinking solutions containing 300 to IKX) mg of borax per liter daily, 3 weeks a month for 3 months (Zhou et al. 1987). Boron enhances sequestration of fluoride from bone and excretion through kidneys and possibly the intestinal tract (Elsair et al. 1980a, 1981). 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

Drablos PA, Hetland S, Schmidt F et al. 1992. Uptake and Excretion of Aluminum in Workers Exposed to Aluminum Fluoride and Aluminum Oxide. Aluminum Assoc/et al. Aluminum Health 2nd Int Conf, Tampa, FL 157(4) Feb 2-6, 92. 

Ingested uranium is excreted mostly in the feces urinary excretion is generally low. The biological halftimes of soluble uranium compounds (uranium hexafluoride, uranyl fluoride, uranium tetrachloride, uranyl nitrate hexahydrate) are estimated in days or weeks those of the less soluble compounds (uranium tetrafluoride, uranium dioxide, triuranium octaoxide) are estimated in years. No information is currently available on the excretion of dermally absorbed uranium. Transdermally absorbed uranium is expected to behave identically to uranium compounds absorbed through the lungs and the gastrointestinal tract. 

Absorption across the skin is probably slight and methods of pesticide use rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut is efficient and potentially lethal. Excretion is chiefly in the urine renal clearance of fluoride from the blood is rapid. However, large loads of absorbed fluoride poison renal tubule cells. Functional tubular disturbances and sometimes acute renal failure result. 

Fuji K, Morio, M, Kikuchi,. Pharmacokinetic study in excretion of inorganic fluoride, a metabolite of sevoflurane. Hiroshima J Med Sci 1987 36 89-94. 

Fluoride ions are absorbed from both the stomach and the small intestine. The soluble salts are efficiently absorbed, and the peak increase of fluoride in blood plasma is within 1 hour of ingestion. Ions are rapidly cleared from plasma into tissue in exchange with anions, such as hydroxyl, citrate, and carbonate. At least 95% of the 2.6 g of total body fluoride is located in bones and teeth. Almost 90% of excess fluoride is excreted in urine. 

Kedey CE, Cochran JA, Lennon MA, O MuUane DM, Worthington HV. Urinary fluoride excretion of young children exposed to different fluoride regimes. Community Dent Health 2002 19 12-7. 

Fluoride is removed from plasma by urinary excretion [%] and uptake into calcified tissues [97]. Normally each mechanism represents about 50% of the removal [98]. Renal fluoride excretion is characterized by glomerular filtration followed by variable tubular reabsorption. The tubular reabsorption is influenced by tubular fluid flow rate [99] and urinary pH [100, 101]. Manipulation of urinary pH in patients undergoing a standard enflurane anesthetic resulted in plasma levels of fluoride in patients with alkaline urine that was 50% lower than in patients with acidic urine [102]. 

D. Enhancement of Elimination Enhancement of elimination is possible for a number of toxins, including manipulation of urine pH to accelerate renal excretion of weak acids and bases. For example, alkaline diuresis is effective in toxicity due to fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates. Urinary acidiflcation may be useful in toxicity due to weak bases, including amphetamines, nicotine, and phencyclidine, but care must be taken to avoid acidosis and renal failure in rhabdomyolysis. Hemodialysis or hemoperfusion enhances the elimination of many toxic compounds, including acetaminophen, ethylene glycol, formaldehyde, lithium, methanol, procainamide, quinidine, salicylates, and theophylline. Cathartics such as sorbitol (70%) may decrease absorption and hasten removal of toxins from the gastrointestinal tract. 

Isoflurane is more resistant to biotransformation in man than are other volatile halogenated anaesthetics [201,241,245] although there can be metabolic variations in different animal species [245], An average recovery of95 percent has been obtained in exhaled air, while post-operative urinary excretion of ionic and bound organic fluoride accounted for less than 0.2 per cent of the total fluorine dose [201]. In a separate study of 9 surgical patients, serum inorganic fluoride levels were 4.4 0.4 umol dm 6 h after anaesthesia [241 ]. 

Blood contains about 0-1-0-2 mg F per litre but only a small part of this is in ionic form. The level shows only a transient rise after the ingestion of fluoride and the range is not exceeded in subjects consuming up to 4 mg per litre in drinking water. Thus it seems that the plasma fluoride level in Man is effectively regulated. The fluoride content of the soft tissues seem to be of the same order as that of the plasma, although the intracellular concentration of ionic fluoride is probably less. Two mechanisms, namely excretion and deposition in the calcified tissues, operate to keep the fluoride content of the body fluids and soft tissues at a low level. 

Deposition of fluoride in the bones is not completely irreversible and a person who moves from a region where the concentration in the drinking water is high, e.g. 8 mg per litre, to one where it is appreciably lower excretes increased amounts of fluoride in his urine for some time afterwards. Presumably this is due to loss of physicochemically exchangeable fluoride and also to osteoclastic activity. 

That portion of absorbed fluorine which is not taken up by the bones and teeth (50% or more of the fluorine absorbed) is excreted mainly in the urine (although small amounts are excreted in the sweat and the feces), with the result that the level of fluoride in the blood plasma is quite constant. 

Tamarind food supplementation enhances the excretion of excess fluoride and the retention of calcium in children living in fluoride endemic areas."... 

Toxicity. Fluoroborates are excreted mostly in the urine (22). Sodium fluoroborate is absorbed almost completely into the human bloodstream and over a 14-d experiment all of the NaBF ingested was found in the urine. Although the fluoride ion is covalently bound to boron, the rate of absorption of the physiologically inert BF from the gastrointestinal tract of rats exceeds that of the physiologically active simple fluorides (23). 

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