Fluoride Metabolism Research Articles

Influence of Coffee on Fluoride Metabolism in Rats

Concomitant intragastric administration of sodium fluoride and coffee resulted in a significantly higher (P less than 0.01) plasma fluoride level than intake of the same amount of fluoride with water. The same result was obtained when coffee was substituted with an equivalent amount of caffeine. Comparison of plasma fluoride levels by total area under the curve of plasma fluoride concentration versus time indicated an almost 2-fold difference. Although the mechanism(s) is not known, it appears that caffeine is responsible for the present observation. This finding could help explain the variations in the incidence of dental fluorosis among people living in optimally fluoridated communities.

Gary M. Whitford The metabolism and toxicology of fluoride, Vol. 13 in monographs in oral science Karger, Basel, 1989; 160 pp., $98.00

Gary M. Whitford The metabolism and toxicology of fluoride, Vol. 13 in monographs in oral science Karger, Basel, 1989; 160 pp., $98.00

High Fluoride Exposure in Hemodialysis Patients

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.

The Physiological and Toxicological Characteristics of Fluoride

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 nondietary sources of fluoride, mainly fluoride-containing dental products, are a major source of ingested fluoride. The article concludes with 12 recommendations for future research.

Summary of Session I: Metabolism of Fluoride

Summary of Session I: Metabolism of Fluoride

Discussion of Session I: Metabolism of Fluoride

Discussion of Session I: Metabolism of Fluoride

Subchronic Inhalation Study with Vinyl Fluoride: Effects on Hepatic Cell Proliferation and Urinary Fluoride Excretion

Subchronic Inhalation Study with Vinyl Fluoride: Effects on Hepatic Cell Proliferation and Urinary Fluoride Excretion. BOGDANFFY, M. S., KEE, C. R., KELLY, D. P., CARAKOSTAS, M. C, AND SYKES, G. P. (1990). Fundam Appl Toxicol. 15, 394/406. Vinyl fluoride is used widely in the manufacture of fluoropolymers. Based in part on the structural similarity of vinyl fluoride to the hepatocarcinogens vinyl chloride and vinyl bromide, a TSCA Section 4 test rule mandated the testing of vinyl fluoride for oncogenicity. This report presents the results of a 90-day inhalation study in rats and mice with vinyl fluoride designed to set test concentrations for a subsequent oncogenicity study. Groups of 15 male and female rats and mice were exposed 6 hr per day, 5 days per week for approximately 90 days to target concentrations of 0, 200, 2000, or 20,000 ppm vinyl fluoride. Clinical chemical, hematological, and urine analyses were performed on rats after 45 and 90 days of exposure. A hematological evaluation was performed on mice following 45 and 90 days of exposure. A complete gross and microscopic evaluation was conducted at the end of the study. After 93 days on test, groups of five rats and five mice per sex were implanted with osmotic minipumps containing [3H]thymidine and were exposed for an additional 5 days to measure cell proliferation in liver, kidney, lung, and nasal cavity tissues. Results of the histopathological, clinical chemical, and hematological evaluations showed no significant effects of vinyl fluoride exposure at any concentration following either 45 or 90 days of exposure. A concentration-related increase in fluoride ion in urine was observed in rats at 45 and 90 days of exposure. A plateau in urinary fluoride excretion was observed at approximately 2000 ppm, suggesting saturation of vinyl fluoride metabolism. Vinyl fluoride-related cell proliferation effects were largely restricted to liver. Hepatic cell proliferation in male and female rats and mice was elevated at all concentrations. The response was similar at concentrations of either 2000 or 20,000 ppm and was consistent with concentration-response relationships for other haloethylenes. Taken together, the urinary fluoride excretion and hepatic cell proliferation data suggest a mechanistic link between the two effects. On the basis of these findings and experience with other haloethylenes, concentrations of vinyl fluoride to be tested for oncogenicity should be chosen such that the full linear range of the concentration-response curve is evaluated. The present study demonstrates through example the value of incorporating cell proliferation studies in standard testing protocols

各種市販実験動物用飼料の組成とそのフッ素含有量

The content of fluorides in experimental animal diets has been discussed and reported by several researchers. In studies on the metabolism of fluoride and dental caries experiments, low fluoride diets have been used with specially prepared formulas. However, data on fluoride content in commercially available diets for animals have not been reported with accurate analysis for total fluoride.The purpose of this study was to examine fluoride contents in various experimental animal diets commercially available and also to ascertain fluoride analysis for the diets, especially for total fluoride in the sample. This information will be useful for designing animal experiments and evaluating the results.Samples of 9 experimental animal diets obtained from 3 manufacturers for fluoride analysis were the diets for mice, hamsters and rats (CA-1, MF and CE-2); the diet for rabbits and guinea pigs (Labo RG-RO and RC-4); the diets for rabbits (CR-3); the diet for dogs (CD-5); the diet for cats (CFE-2); and the cariogenic diet for rats and hamsters (Diet #2000). Each sample was powdered and Ca (OH) 2 (F free) added as a fixative for fluoride during ashing at 550°C. The distillate of fluoride from samples with perchloric acid (F free) was obtained approximately 200mlfrom each sample and also the distillate was analyzed by ion-specific fluoride electrode.Samples were classified by fluoride contents as follows: (1) low-fluoride diet (4-5ppm F-; sample codes: RC-4, CR-3 and Diet #2000); (2) medium-fluoride diet (approx. 20ppm F-; sample codes: Labo RG-RO, CD-5 and CFE-2), and (3) high-fluoride diet (40-80ppm F-; sample codes: CE-2, MF and CA-1). From these results, we found that high-fluoride diets contained fish-meal and low-fluoride diets contained soybean-meal as the major protein source. In order to ascertain analysis procedure for total fluoride in the sample, the distillation rate of fluoride and the ashing time for decomposition of powdered sample included organic and inorganic substances were analyzed statistically by two-way layout of the experimental design. Statistical findings suggested that more than 10 hours of ashing is advisable for each of the distillation rates (30ml/10min, 50ml/10min and 100ml/10min) and also the results obtained in this study revealed relatively high fluoride content in the commercially available diets for experimental animal.We suggest the establishment of guideline for fluoride content in diets for experimental animals, such as AIN-76TMproposed by American Institute of Nutrition Ad Hoc committee for experimental animal diets.

The effect of clodronate (dichloromethylene diphosphonate) on the mineral concentration of dental enamel and bone of the miniature swine.

Diphosphonates are compounds which prevent the crystallisation of calcium phosphates from solution. Our aim was to study the effects of clodronate (dichloromethylene diphosphonate), one of the diphosphonates, on the mineral concentrations of dental enamel and bone. In a subchronic experiment the effects of this compound were investigated. The drug was administered orally in three doses (100, 300, 1000 mg/kg) per day to 32 Göttingen miniature swines for six months. From the acid etch biopsy of enamel the amount of dissolved hydroxyapatite and the concentrations of fluoride and magnesium were measured. The calcium, phosphorus, fluoride, magnesium, carbonate and citrate concentrations were determined from the cancellous bone sample. All values were calculated for dry bone. Calcium/phosphorus and calcium/magnesium ratios were calculated for both enamel and bone. In tooth enamel the magnesium concentration showed a significant dose dependent decrease and calcium/magnesium ratio a significant dose dependent rise. Calcium phosphorus/ratio exhibited a dose dependent increase in surface enamel. Bone fluoride concentration showed a highly significant and calcium/magnesium ratio a significant dose dependent rise. Clodronate seems to interfere with the remineralization process of tooth enamel, through its effect on magnesium. Incorporation of the drug also appears to exhibit a marked action on the fluoride metabolism of bone. This may require attention in certain long term treatment situations with clodronate in high fluoride areas.

Fluoride Metabolism in Chronic Renal Failure

Fluoride Metabolism in Chronic Renal Failure

Fluoride Metabolism in Paget's Disease of Bone

Fluoride Metabolism in Paget's Disease of Bone

Fluoride Therapy for the Pediatric Patient

This article reviews current concepts regarding the mode of action of fluoride, describes the metabolism of fluoride in the child, brings attention to recent changes in protocol for prescribing fluoride supplements, and describes intensive fluoride regimens for patients with special problems.

The Nonlinear Tissue-Binding Character of Fluoride Kinetics in Normal and Anephric Subjects

A study has been made of the fluoride kinetics in man, with a series of 5 healthy subjects and 4 patients with renal insufficiency. The fluoride metabolism was found to conform to nonlinear tissue-binding kinetics. Reanalysis of findings on the rabbit reported in the literature yielded equivalent results. The tissue-binding constants elicited - probably associated with the fluoride metabolism of bone - presented no differences between healthy subjects and uremics. Uremics had a clearly lower fractional fluoride elimination rate (K) compared with the healthy controls. A significant correlation of creatinine clearance on the K value was noted.

Fluoride balances in pregnant and nonpregnant women.

In planning health protection for pregnant as well as nonpregnant women exposed to fluorides, information about their fluoride metabolism is essential. The authors determined fluoride balances in small groups of young women maintained on two different low-fluoride diets for one or two 21-day periods in a metabolic unit. One diet contained an average of 0.41 mg F/day, and the other contained an average of 0.27 mg F/day. Excretion of fluoride in pooled three-day collections for each subject was about 80% in the urine and 20% in the feces. Pregnant (last half of term) and nonpregnant women demonstrated small negative fluoride balances; the averages were about -0.32 mg F/day and -0.15 mg F/day, respectively. Similar values have been found for young males in other studies. Pregnancy in these subjects did not markedly alter normal fluoride metabolism.

Studies of fluoride metabolism in man: A review and report of original data

The dietary intake of fluoride and the fluoride excretions in urine and stool were determined under controlled conditions in man. Fluoride balance studies have shown that the urinary fluoride corresponds to 50–60% of the intake, the fecal fluoride was very low, corresponding to 6% of the intake, and approximately 1 mg fluoride was retained per day during an average fluoride intake of 4.3 mg/day. The fluoride intake depended on the amount of fluoridated water consumed. The dietary fluoride content ranged from 1.2 to 1.5 mg/day. During the intake of supplemental fluoride the fluroide excretions increased but the ratio of the urinary/fecal fluoride was similar. Added fluoride is well retained. Following its discontinuation, very small amounts of the retained fluoride are excreted for several days. Inorganic elements, such as calcium, phosphorus, and magnesium, which have been shown to decrease the intestinal absorption of fluoride in animals were ineffective in man, while aluminum, given as aluminum-containing antacids, markedly decreased the intestinal absorption of fluoride and thereby decreased the retention of fluoride.

Effect of aluminum hydroxide on fluoride metabolism.

Aluminum inhibits intestinal absorption of fluoride in animals but little information is available about man. To determine whether and to what extent aluminum affects fluoride absorption in man, effects of aluminum hydroxide on fluoride metabolism were studied under controlled dietary conditions. Relatively small amounts of aluminum hydroxide were used (30 ml three times daily, containing a total of 1.8 gm aluminum, were given for several weeks). Fluoride balances were determined in control studies and during the intake of aluminum hydroxide. The fluoride intake was the fluoride content of the diet and the drinking water. Two studies were also carried out on a high-fluoride intake. The use of aluminum hydroxide was associated with an increase in fecal fluoride excretion and a decrease in net absorption of fluoride regardless of the intake fluoride, calcium, phosphorus, or magnesium. Urinary fluoride decreased during aluminum hydroxide ingestion. Our studies show that relatively small amounts of aluminum hydroxide inhibit intestinal absorption of fluoride in man.

Fluoride Metabolism in Patients With Chronic Renal Failure

Studies of fluoride metabolism were carried out in patients with chronic renal failure by determining fluoride balances for several weeks. The fluoride intake was due to the analyzed fluoride content of the diet and of the drinking water. The effect of aluminum hydroxide on fluoride metabolism was investigated because this antacid is commonly used therapeutically for these patients. Studies have shown that urinary fluoride excretion in patients with chronic renal failure was significantly lower than that in patients with normal renal function, resulting in a signicantly higher retention of fluoride. Although the fecal fluoride excretion in patients with chronic renal failure was slightly but significantly increased, this change did not compensate for the decrease of the urinary fluoride excretion. The intake of aluminum hydroxide resulted in a significant increase of fecal fluoride excretion and in a significant decrease of net absorption and retention of fluoride in patients with chronic renal failure.

Fluoride metabolism in patients with chronic renal failure

Fluoride metabolism in patients with chronic renal failure

Fluoride and energy metabolism in LS cells.

Six mM fluoride had no effect on lactate production in LS cells incubated in Eagle's minimum essential medium. In Krebs-Ringer phosphate buffer with 10 mM glucose inhibition was found with 3mM fluoride. The fluoride effect was similar in aerobic and anaerobic conditions. Twelve mM fluoride had no inhibitory effect on ATP levels in LS cells.

Magnesium-fluoride interrelationships in man II. Effect of magnesium on fluoride metabolism.

The effect of magnesium on the fluoride balance was investigated in man by determining metabolic balances of fluoride and magnesium in control studies and during magnesium supplementation. The magnesium intake averaged 264 mg/day in the control studies and 825 in the experimental studies. The studies were carried out during four calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes ranging from 800 to 2,000 mg/day. The studies were carried out during a fluoride intake of about 4 mg/day that was due to the dietary fluoride content and the intake of water and during a high fluoride intake of 25 mg/day that was due to the addition of sodium fluoride. During the high magnesium intake, both the urinary and fecal magnesium excretions increased and the magnesium balances became more positive. These changes were not associated with any significant changes of either the urinary or fecal fluoride excretions or of the fluoride balances during the different intakes of calcium phosphorus, or fluoride.