Plasma Fluoride Research Articles

Relationship between Fluoride in the Drinking Water and the Plasma Fluoride Concentration in Man

The plasma fluoride concentration in 15 subjects living in three different districts with 9.6, 1.2 and 0.25 ppm fluoride in the drinking water, was followed over 36 h. In the 9.6-ppm-fluoride area the

Influence of variations in fluoride intake on the ionic and bound fractions of plasma and muscle fluoride.

SummaryThe changes occurring in the ionic, bound, and total fluoride contents of plasma and muscle from rats shifted from low fluoride intake to high fluoride intake and back to low fluoride intake were examined. Approximately 10 days were required for the reequilibration of the ionic and total fluoride levels of plasma and muscle following changes in the dietary fluoride intake. Data have been obtained that show the systematic changes produced in the bound fraction of plasma and muscle fluoride by variations in dietary fluoride intake.

Fluoride concentrations in saliva after single oral doses and their relation to plasma fluoride

The saliva and plasma fluoride (F) concentrations following intake of different doses of fluoride tablets were studied in six subjects. There was a close relationship between saliva F and plasma F and the ratio was 0.64 +/- 0.01 (s.e.). The plasma half life of F was 4-16 h. This results indicate that saliva F may be a useful substitute for blood sampling in studies concerning the pharmacokinetics of fluoride.

Plasma fluoride concentrations in rats acutely poisoned with sodium fluoride

Female rats of average body weight 250 g proved to be approximately twice as susceptible to the acute toxic effects of sodium fluoride given po as were female rats weighing on the average 80 or 150 g. The 24-hr oral LD50 values were 31, 54, and 52 mg of F/kg, respectively. Following single doses of 25 mg of F/kg for 250-g rats or 50 mg of F/kg for rats weighing 80 or 150 g, absorption of fluoride from the gastrointestinal tract was approximately 50% complete in less than 90 min for the 250-g rats and in about 2 hr for the 80- and 150-g animals. In treated rats given 50 mg of F/kg, plasma fluoride concentrations (normally 0.3 μg/ml or less) increased to 10 μg/ml or more in 15 min in 80- or 150-g rats. Quantitatively similar increases were noted in 250-g rats given 25 mg of F/kg. Plasma fluoride concentrations of 8–10 μg/ml or higher were often associated with death, regardless of dose or body weight (age), but were achieved more rapidly in the heaviest rats. In surviving rats, plasma fluoride concentrations declined rapidly from maximal values reaching concentrations at 24 hr of 3 and 0.3 μg/ml, respectively, for the 150- and 250-g rats, and of approximately 4 μg/ml at 8 hr for the 80-g rats. Plasma fluoride concentrations after near lethal doses were dose-dependent. The greater resistance of the 80- and 150-g rats to the lethal effects of fluoride may reflect the greater efficiency of the younger skeletons in removing fluoride from the circulation.

Influence of dietary fluoride restriction on regulation of plasma nd soft tissue fluoride contents.

The adjustments in total fluoride concentration in plasma, bones, liver, and muscle were examined when rats were given a diet of very low fluoride content following a dietary regimen of elevated fluoride intake. The animals received a diet containing 34 ppm of fluoride and water with 50 ppm added fluoride in the 28-day initial period and in the depletion period they were given a diet containing only 0.21 ppm of fluoride and distilled water. The findings indicated a 12-fold increase in the fluoride content of the humeri after 28 days of high-flurodie intake with a greater increment by the epiphyses than by the diaphyses. During 21 days of the depletion period the skeletal fluoride was reduced by only 7.7% indicating a marked retention of fluoride during processes of bone remodeling and growth. The plasma, muscle, and liver total fluoride contents were significantly increased at the end of the period of high-fluoride intake, but these concentrations were found to be restored to base-line levels in 3-7 days of the depletion period. By comparison of the distribution of total fluoride with injected radiofluoride between tissue and plasma waters, it was concluded that muscle and liver contain bound fluoride that does not exchange completely with ionic fluoride.

Hypoxia and halothane metabolism in vivo: release of inorganic fluoride and halothane metabolite binding to cellular constituents.

Fluoride release and covalent binding of halothane metabolites were studied in rats pretreated with phenobarbital and anesthestized with halothane in the presence of high (40 per cent) and low (7 per cent) oxygen tensions. The purpose of producing hypoxia was to promote the reductive pathways involved in the metabolism of halothane. Halothane anesthesia under hypoxic conditions caused a significant elevation in the plasma fluoride concentration. There was also a greater than three-fold increase in covalent binding of 14C-halothane metabolites to microsomal lipids in hypoxic rats. The lipid/protein binding ratio in control animals averaged 0.76, while hypoxic animals had a binding ratio of 3.24. The findings demonstrate that defluorination of halothane does occur during hypoxic conditions. It is hypothesized that the products produced by this reductive metabolic pathway are also potentially more hepatotoxic than the oxidative metabolites, based upon the increased covalent binding of halothane metabolites under hypoxic conditions.

Increased serum bromide concentration after halothane anesthesia in man.

Seven healthy male volunteers received 6.6 plus or minus 0.5 (SE) per cent-hours of halothane-oxygen anesthesia without surgery. Serum bromide concentrations increased from 0.6 plus or minus 0.1 before anesthesia to 2.9 plus or minus 0.2 mEq/l on the second day after anesthesia. On the ninth day serum bromide was still elevated to 2.5 plus or minus 0.1 mEq/l. These bromide concentrations represent psychoactive levels and may account for previously recognized prolonged changes in mood and intellectual function after halothane. Plasma and urinary fluoride concentrations did not increase significantly.

Plasma fluoride levels following obstetrical use of methoxyflurane.

Plasma fluoride levels were measured in 106 patients undergoing labour and delivery or Caesarean section. Mean plasma fluoride levels in all groups of patients studied were well below the levels expected to produce renal impairment. In one case with probable excessive methoxyflurane use, plasma fluoride level reached 73.4 μmol/1. Umbilical venous fluoride levels were about one-half the mother’s venous level at delivery.

Relationships of human plasma fluoride and bone fluoride to age.

Fluoride analyses were carried out on blood samples from fasting subjects and on iliac crest biopsies obtained at autopsy, using an ion-selective electrode. Correlation coefficients of 0.53 and 0.67 respectively were determined between plasma fluoride and age, and bone fluoride and age. The proportionate rates of increase of fluoride levels in plasma and bone with age and the similarity of the correlation coefficients suggest that the fasting plasma fluoride concentration is in equilibrium with bone fluoride.

Fluoride secretion in rat bile.

The rate of bile secretion in fasted male rats and corresponding bile and plasma fluoride concentrations were studied to determine if significant quantities of fluoride are secreted into the small intestine from the bile duct during fluoride absorption. The osmolalities and fluoride levels were similar to those of plasma ; this suggests that the rat biliary system does not concentrate fluoride.

Effects of Alternating Periods of High- and Low-Fluoride Ingestion on Dairy Cattle

Two- and five-month old Holstein heifers were exposed to different intake patterns of dietary fluoride for 6 years. They were divided into five lots: Control, no fluoride supplement (I); continuous exposure to 1.5mg F/kg body weight per day (II and IV); alternating exposure to 1.5mg F/kg for 6 months and control for 6 months (III); or 3.0mg F/kg for 4 months and .75mg FAg for 8 months (V). The average yearly exposure of Lot V was equal to Lots II and IV while that of Lot III was equal to half of this intake.None of the fluoride treatments affected growth rate or reproduction. There was no consistent effect on milk production. Plasma fluoride concentrations closely followed current fluoride intake. Urinary fluoride concentrations varied with intake but remained elevated during low intake. Skeletal fluoride retention was directly related to total fluoride intake and not to pattern of intake. The degree of dental fluorosis was related to the amount of fluoride fed and to the plasma fluoride concentration at the time each incisor was developing. The dental lesions observed in Lot III (alternate exposure) were similar to those often seen in field cases of fluoride exposure.The most severe effects of fluoride ingestion were in Lot V (high and low intake). These animals had severely worn molar teeth, extensive osteofluorosis, and they experienced periods of extreme lameness. Short periods of high fluoride intake balanced by periods of lower intake were more damaging to cattle than constant exposure to the same average yearly intake.

Plasma fluoride levels in rabbits acutely poisoned with sodium fluoride.

SummaryFollowing acutely toxic oral doses of sodium fluoride, plasma F levels (normal–0.01 to 0.07 ppm) promptly rose to high values; doses of 100 to 140 mg/kg gave one hour plasma F concentrations of 12 to 41 ppm. One hour plasma F values over 28 ppm were associated with death in 12 hr or less. Rabbits usually survived for at least 24 hr if 1–hr levels were less than 24 ppm.

Fluoride-Induced Diuresis: Plasma Concentrations in the Rat

The rates of urine flow and the plasma fluoride concentrations were measured in anesthetized rats receiving continuous infusions of graded levels of fluoride in isotonic solutions. Infusion of 500 nmoles of fluoride/min produced the maximum diuresis, three times the mean control urine flow rate, and a plasma fluoride concentration of 272 μM. The 100 nmoles/min fluoride infusion rate produced an 80% increase in urine flow rate with a plasma fluoride concentration of 56 μM. These findings are consistent with estimates made for man and with the suggestion that the nephrotoxicity following methoxyflurane anesthesia is at least in part due to metabolism of methoxyflurane to inorganic fluoride.

Roles of kidney and skeleton in regulation of body fluid fluoride concentrations.

SummaryAn acute dose of 2.94 mg of fluoride, given by gastric intubation to mature female rats with or without previous high fluoride intakes, was rapidly absorbed and distributed in the body fluid compartments. Limited excursions of plasma fluoride contents were observed since the mechanisms establishing equilibrium of distribution of fluoride between blood and bone and those of urinary excretion of fluoride functioned rapidly. There was no evidence that animals with initially elevated skeletal fluoride contents were deficient in ability to control elevations of plasma fluoride contents or to dispose of fluoride in the urine. Results from the animals with a previous low fluoride exposure showed that skeletal regulation of the body fluoride was faster and quantitatively larger than excretion of fluoride by the kidney. At least 29% of the fluoride administered was absorbed by these animals in 5 hr. At 50 hr at least 88% of the administered dose was absorbed and 70% of the dose had been deposited in the ske...

Effect of Dietary Fluoride on Food Intake and Plasma Fluoride Concentration in the Rat

The effect of excessive amounts (200–600 ppm) of dietary fluoride on the food intake and plasma fluoride concentration of rats of various ages was investigated. In older animals, the decline in food intake was partially corrected within a week even though the plasma fluoride concentration remained elevated. When the same amounts of fluoride were fed to younger animals, a longer exposure to the diet was required before an improvement in food intake was seen. The ability of the rat to increase its consumption of the high fluoride diet following an initial drop in consumption suggests some type of adaptation to the elevated plasma and soft tissue fluoride concentrations.

Regulation of plasma and tissue fluoride contents by the skeleton.

Regulation of plasma and tissue fluoride contents by the skeleton.

Absorption of fluoride through the oral mucosa of rats

The oral cavity of rats was isolated by means of ligating the oesophagus. Blood was withdrawn from one group of rats via a carotid catheter and the plasma fluoride concentration was determined before and for 2 hr after the application of sodium fluoride or sodium chloride solutions to their oral mucosa. A marked rise in the plasma fluoride level was noted with the maximum concentration reached within 30–60 min. A second group of rats was used for urinary excretion studies. Urine was collected for 24 hr prior to surgery and the application of the test solutions and for 24 hr after. These animals also had their tracheas cannulated. The amount of urinary fluoride for the 24 hr period was 6–7-fold greater in the fluoride-treated rats than that in the saline controls. The study indicated that fluoride ions from sodium fluoride solutions can be absorbed through rat oral mucosa, but probably at a relatively slow rate.

Effect of Method of Fluoride Administration on Plasma Fluoride Concentrations

Two groups of sheep were given 2 mg F/kg either as a single oral dose or as a continuous intrarumenal infusion for a 13-week period, and the response in plasma fluoride was determined. After an oral dose there was a rapid increase in plasma fluoride to a peak at 2 to 3 hours and a slower decline to near the predosage level by 12 hours. A considerable difference in the manner in which individual sheep metabolized fluoride was evident from the daily plasma fluoride curves. When the same amount of fluoride was continuously infused, the plasma fluoride concentration was relatively constant throughout the day, and except for the peak period of about 6 hours, was higher than that from the sheep given an oral dose.

Use of Urine to Serum Fluoride Concentration Ratios to confirm Serum Fluoride Analyses

IN 1966 I published1 results showing that the normal concentration of fluoride in human serum is about one-tenth the generally accepted value—that of Singer and Armstrong. Part of the evidence supporting my results was the “at least five-fold discrepancy” that could be shown in their data2 which is most easily explained by an error in the measurement of the serum fluoride. The discrepancy involves the ratio of urine to plasma fluoride concentrations when determined by fluorine-18 as compared with stable fluoride analyses. Because the concentration of fluoride in urine is well established in contrast to that in serum where analysis is much more difficult, it is reasonable to question the latter when there is a discrepancy. Singer and Armstrong3, however, in their recent rebuttal, think that I came to erroneous conclusions because I .directed attention to only two of their analyses, which they now consider aberrant.

Normal human serum fluoride concentrations.

TAVES1 has indicated that our method2 for estimation of serum fluoride content based on diffusion of hydrogen fluoride gives results which are about ten times too large, but our values3 of human plasma fluoride content, which he quotes, were not obtained by the diffusion method but by an entirely different procedure4 which requires ashing of the sample with magnesium oxide followed by separation of the fluoride by distillation from perchloric acid. The agreement of the results for fluoride analyses of urine, bovine plasma, dentine, liver and muscle obtained by the two procedures1, which are quite different in principle, furnishes mutual support of the reliability and accuracy of both methods. Nevertheless, we have carried out further experiments, some of which are like those reported by Taves, and our evidence is that both of our methods give results for plasma fluoride content which are not markedly in error.