Ionic Fluoride Research Articles

Fluoride tissue distribution: intracellular fluoride concentrations.

AbstractThe distribution of fluoride and chloride in muscle, liver, and tendon was studied in groups of 6-15 rats sacrificed at 80-240 min after intraperitoneal injections containing radiofluoride (18F) and radiochloride (36Cl). Liver exhibited a constant 18F(tissue water):18F(plasma water) ratio over 120-220 min and this ratio was constant in muscle over 80-120 min. The 18Ftw/18Fpw ratios for muscle were lower than those of liver. The ratios of 18F distribution for both liver and muscle declined significantly at the longest time periods probably as a result of reductions of intracellular pH and/or increases of extracellular pH. Chloride space volumes were determined from chloride analyses of the tissues and plasma and confirmed by the 36Cl(tissue water):36Cl(plasma water) ratios. The fluid space volumes and the 18F(tissue water):18F(plasma water) ratios were used to indicate that the average intracellular ionic fluoride concentrations of liver and muscle are, respectively, 79 and 38% that of plasma water...

Metabolic Handling of perfluorooctanoic acid in rats.

SummaryThe metabolic fate of perfluorooctanoic acid administered by stomach intubation to female rats was investigated. The nonionic fluorine level in the serum was increased 200-fold after administration of the dose but returned to baseline levels by 52.5 hr. Although perfluorooctanoic acid is rapidly absorbed and bound to nonultrafilterable components in the serum, the entire dose of nonionic fluorine was recovered in the urine and feces after 96 hr. Neither the ionic fluoride level in the serum nor the rate of ionic fluoride excretion in the urine was significantly altered by the administration of perfluorooctanoic acid. Although perfluorooctanoic acid has not been identified in the urine, the available data suggest that it has been excreted intact or in possibly conjugated form.

Detection of Fluorinated Anesthetic Metabolites by Sodium Fusion

A method is reported which utilizes a sodium fusion reaction to decompose organofluorine compounds and yield ionic fluoride which may then be quantified with a specific ion electrode. The method is simple, quick, sensitive, and applicable to fluorinated anesthetic metabolities.

Inorganic and organic fluoride concentrations in tissues after the oral administration of sodium monofluoroacetate (compound 1080) to rats

Male rats were used to study the inorganinc (ionic) and organic fluoride concentration in plasma, liver, kidneys and stomach content after oral doses of 0, 2.2, 3.5, 4.0, 5.0 and 7.0 mg sodium monofluoroacetate (SMFA, Compound 1080)/kg body weight. Tissue and plasma ionic fluoride concentrations were observed to be higher in all rats given SMFA as compared to rats in the control group. This observation suggests in vivo defluorination of SMFA. Homogenates of liver obtained from SMFA poisoned rats showed significant increases in ionic fluoride concentration during a 6-day storage period at +4°C, with the total fluoride concentration (ionic and organic) remaining constant. The average percentages of distribution of SMFA (organic fluoride) in plasma, liver, and kidneys were 7.05, 5.07 and 1.68, respectively. Plasma and tissue SMFA concentrations were generally lower than the corresponding stomach fluid SMFA concentrations for all dosage groups. Lethal concentration of SMFA in the liquid stomach content was in the range 84.9–189 μg/ml, corresponding to total (ionic and organic) fluoride concentrations in the range of 16.1–36 μg/ml.

Serum inorganic fluoride levels in obese patients during and after enflurane anesthesia.

Serum ionic fluoride levels in 24 markedly obese patients (127.6 +/- 6.0 kg) and seven nonobese control subjects (67.3 +/- 1.2 kg) were compared during and following enflurane anesthesia (less than 2.0 MAC hr). Peak serum fluoride levels were higher (28.0 +/- 1.9 vs 17.3 +/- 1.3 micrometers/L, p less than 0.01) and the rate at which fluoride levels increased was more rapid (slope 5.6 vs 2.5 micrometers/L/hr) in obese patients than in control patients. No clinical evidence of nephrotoxicity was found in either group. Vasopressin resistance tests were not performed, and thus it is inknown whether subclinical nephrotoxicity occurred in either study group. Possible reasons for increased enflurane metabolism in obesity are discussed. These possibilities include differences in fluoride ion kinetics, hepatic delivery and penetration of volatile anesthetics, and altered hepatic microsomal enzyme activity. Obesity rather than weight is an important determinant of anesthetic biotransformation.

Concentrations of ionic, total, and bound fluoride in plasma.

We found no significant difference between the means for ionic, bound, and total fluoride concentrations in the plasma of male and female subjects of the same age, living in a community with fluoridated water. When results for the 264 fasting subjects were therefore combined according to age, they indicated that persons over 60 years of age have a significantly higher mean ionic (3.89 mumol/L) and total (6.58 mumol/L) fluoride concentration in plasma than do younger age groups. For younger age groups, means ranged from 2.74 to 3.05 mumol/L for ionic fluoride and from 4.74 to 5.58 mumol/L for total. The bound fluoride concentration was lower in individuals 21 to 30 years of age (1.89 mumol/L) than in older age groups (for whom means ranged from 2.42 to 2.68 mumol/L), but was not significantly different from that of individuals who were younger (2.21 mumol/L). A tendency for the mean ionic fluoride concentration to increase with age was noted, but the concentration was significantly higher than the preceding decade group only in those persons over 60 years of age.

A laboratory evaluation of fluoride dentifrices used in Greece

A laboratory investigation of the fluoride dentifrices commonly used in Greece was done in order to evaluate their caries-preventive potential. The evaluation was based on the determination of the free ionic fluoride and the total soluble fluoride present by a potentiometric fluoride electrode technique. Dentifrices containing MFP, NaF and AlF3 were analyzed. The measured total soluble and free ionic fluoride content were discussed in conjunction with the various dentifrice components. Most of the examined dentifrices were MFP type and the free ionic fluoride was found to vary from 130 to 180 parts/10(6) F-.

Defluorination of fluoroacetate in vitro by rat liver subcellular fractions

An earlier report showing enhanced accumulation of ionic fluoride in bones of rats given fluoroacetate (FAc) suggested an in vivo defluorination of fluoroacetate. Rat liver an organ which shows minimal pathological and biochemical effects in FAc intoxication was found to possess defluorination activity in vitro. Subcellular fractionation of livers from male Sprague-Dawley rats was performed in 0.25 m sucrose and yielded the following fractions: whole homogenate, nuclear, mitochondrial, microsomal and 105,000 g supernatant. Defluorination activity was measured by incubating subcellular fractions and their boiled controls with FAc (1 hr, 37°C, pH 7.4, in 0.1 m Tris-HCl or 0.1% Triton X-100) and comparing the difference in ionic fluoride content at the end of the incubation. Defluorination activity based on protein content was consistently the highest in the 105,000 g supernatant fraction, the only fraction showing an activity increase over the original homogenate. The microsomal fraction had minimal activity. Defluorination activity in the 105,000 g supernatant as a function of time after fraction isolation at 4°C revealed a time-dependent reduction in activity. After 24 hr at 4°C, activity was almost completely lost. The time-dependent loss of activity at 4°C could be regained when glutathione (GSH) was added to this fraction at a final concentration of 5 m m. Furthermore, GSH significantly increased the defluorination activity in all subcellular fractions. A study of the optimum pH for defluorination activity in the 105,000 g supernatant fraction was performed in 0.1 m Tris-maleate buffer. Surprisingly, a complete loss of activity with this buffer resulted throughout the pH range studied (pH 5.6–8.0). Furthermore, defluorination activity of all subcellular rat liver fractions was completely inhibited by maleate and stimulated by glutathione. These results are consistent with the involvement of a sulfhydryl group in the defluorination of FAc in rat liver.

Calcium Fluoride and Fluoridated Hydroxyapatite Formation in Relation to the Acid Dissolution Rate of Enamel Mineral

Hydroxyapatite (HA) discs were treated for 1 min with fluoride solutions of varying concentrations and pH. The calcium fluoride and fluoridated hydroxyapatite (FHA) formed were analysed independently of each other following their separation in molar potassium hydroxide. Only the more intimately associated FHA was found to affect the rate of acid dissolution of HA and its level of formation and the reduction in acid dissolution rate of HA were both found to be linearly related to the logarithm of the ionic fluoride level in the treatment solution following 1 min. pretreatment. The benefit of using acidulated fluoride treatment of enamel is questioned as neutral fluoride treatments of enamel mineral resulted in equivalent protection.

Fluoride uptake by Streptococcus mutans 6715.

The short-term kinetics of fluoride uptake by cells from 20- to 22-h cultures of Streptococcus mutans strain 6715 were studied using rapid filtration and centrifugation techniques. Saline-suspended organisms were diluted with fluoride-containing solutions buffered at four different pH values (2.0, 4.0, 5.5, and 8.2). Fluoride disappearance from the medium was inversely related to pH and to the duration of the exposure at any given pH. The uptake was rapid and extensive at the lower pH values and decreased as the pH increased. Media fluoride concentrations subsequently increased; i.e., fluoride was released from the cells. The presence of glucose, cyanide, or iodoacetate did not influence the results. However, preincubation of the cells in fluoride-free buffers, followed by the addition of fluoride, reduced fluoride uptake markedly. Cell-to-media pH gradients were determined by the distribution of 14C-labeled 5,5-dimethyl-2,4-oxazolidinedione. Fluoride uptake was found to be a function of the magnitude of the pH gradient (P less than 0.001). It is hypothesized that fluoride uptake occurs by the diffusion of hydrogen fluoride and the subsequent trapping of ionic fluoride.

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 in treated sewage and in rain and snow.

The liquid effluent of a sewage treatment plan contained 1.21 ppm ionic and total fluoride, which was higher than 1.0 ppm fluoride in the fluoridated public water supply. The discharge of the effluent into a river did not greatly raise the fluoride content of the river water because of dilution and other factors. The semisolid waste of sewage treatment also contained fluoride, but very little was volatilized on burning. Rain and snow were found to contain detectable quantities of fluoride, and the fluoride content of snow increased markedly during exposure to an urban environment.

Serum ionic fluoride: normal range and relationship to age and sex.

We used the Orion fluoride electrode system to determine the normal range of serum ionic fluoride concentrations and to investigate its relationship to sex and age (A). 87 normal men, aged 18-92 years (mean, 46 years), and 49 normal women, age 19-64 years (mean, 38 years), participated in the study. At the 95% confidence limits, males less than 45 years old had a normal range of 0.29 to 1.52 mumol/litre and males greater than or equal to 45 years old 0.29 + 0.0101 (A-45) to 1.52 + 0.0101 (A-45) mumol/litre. Females, however, had a normal range of 0.022A - 0.32 to 0.022A + 1.07 mumol/litre. A group of 51 men 18-44 years old was compared with a group of 36 men 46-92 years old. The mean serum F- of the older group was shown to be significantly greater (P less than 0.01) than that of the younger group. Factors related to serum ionic fluoride values are (a) tea as an important source of dietary F-, (b) the lack of significant variation during daytime hours, and (c) the lack of significant difference in concentration between serum and plsma F-.

Methoxyflurane biotransformation and renal function following methoxyflurane administration for vaginal delivery or cesarean section.

Methoxyflurane (MOF) administration for conscious analgesia during vaginal delivery (range 5 to 70 min, mean 23 min) or for anesthesia following delivery of the infant at cesarean section (range 25 to 70 min, mean 44 min) was studied in 18 healthy parturients. Serum ionic fluoride increased significantly in both groups 2 hours after discontinuing MOF with peak concentrations of 11.2 and 14.1 mumol/L in the vaginal delivery and cesarean section groups, respectively. Individual peak serum ionic fluoride levels in the 2 groups of 21 and 25 mumol/L were well below reported levels for subclinical toxicity. Significant ionic fluoride elevations in fetal umbilical venous blood (mean 5.3 mumol/L) were measured in the vaginal-delivery group. Maternal urinary ionic fluoride and oxalate were elevated 24 and 48 hours postpartum. BUN, creatinine, urine volume, and urine osmolality remained within normal range. These data indicate that hazardous elevations of serum ionic fluoride with subsequent renal dysfunction are unlikely following low-dose MOF administration for vaginal delivery or cesarean section.

Surface Analysis of Plasma-Polymerized Fluorocarbon Films by X-Ray Photoelectron Spectrometry

Abstract The surface of films deposited from hexafluoroethane and tetrafluoroethylene on plastic and wool textile substrates was analyzed by x-ray photoelectron spectroscopy. The carbon Is spectra obtained from the fluorocarbon surfaces could be resolved into five lines. The three highest binding energy lines were assigned to carbons containing one, two, and three fluorine atoms, respectively. Surface oxidization was detected by the presence of two oxygen Is lines on the surface of the films. Two fluorine Is electron lines were observed on the surface of the films formed from hexafluoroethane on wool. These lines were assigned to fluorine covalently bound to carbon and ionic fluoride. The surface oxygen-fluorine atom ratio was found to vary considerably among the various surfaces analyzed. Fluorocarbon films obtained from plasma polymerization of tetrafluoroethylene contained a significant amount of trifluoromethyl and fluoro-methyl groups on the surface, indicating extensive monomer breakdown in the plas...

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.

Fallacies in the determination of total fluorine and nonionic fluorine in the diffusates of unashed sera and ultrafiltrates

The fluorine values obtained by the spectrophotometric determination of fluoride in the diffusates of acidified unashed body fluids are often higher than the ionic fluoride values. The former higher values, so far believed to represent total fluorine content (ionic fluoride plus nonionic fluorine) of the body fluids, are in fact a consequence of lack of specificity of the colorimetric reagents for fluoride determination under the experimental conditions used. The values so obtained reflect ionic fluoride plus interfering substances, the latter masquerading as nonionic fluorine. Fluorine in representative fluoro-organic compounds now tested and in the nonionic fluorine concentrates prepared from human sera is not readily available for diffusion. The continued use of the diffusion colorimetric procedures for the determination of total F and nonionic F in unashed body fluids would yield more misleading information; and this practice should be discontinued.

Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia.

Anesthetic biotransformation and renal function were studied in obese adult patients (148 plus or minus 8 kg; mean plus or minus SE) anesthetized for three hours with 60 per cent nitrous oxide plus either methoxyflurane or halothane for elective jejunoileal small-bowel-bypass operations. There was no evidence of persistent renal dysfunction in any patient postoperatively, but serum osmolality was elevated 72 hours after methoxyflurane anesthesia. Urine concentrating ability was not determined. Peak serum ionic fluoride concentration was 55.8 plus or minus 5.8 muM/1 two hours after discontinuation of methoxyflurane. Urinary ionic fluoride and oxalate excretions increased postoperatively. Compared with previously reported data from nonobese patients, serum ionic fluoride concentrations in obese patients increased more rapidly during methoxyflurane anesthesia and peaked higher and sooner after discontinuation of methoxyflurane. The peak serum ionic fluoride concentration was 10.4 plus or minus 1.5 muM/1 at the conclusion of halothane anesthesia, significantly more than the corresponding value in nonobese patients. Intraoperative liver biopsies from 23 of 27 patients showed moderate to severe fatty metamorphosis. Fatty liver infiltration may have increased hepatic anesthetic uptake and exposed more methoxyflurane or halothane to hepatic microsomal enzymes. The more rapid elevation and higher peak levels of serum ionic fluoride following methoxyflurane, and to a lesser extent following halothane, may reflect increased anesthetic biotransformation in obese compared with nonobese patients. To avoid excessive serum ionic fluoride elevations the authors recommended limiting low-dose methoxyflurane anesthesia delivered to obese patients with potential fatty liver infiltration to no more than three hours.

A micro method for direct determination of ionic fluoride in body fluids with the hanging drop fluoride electrode

A simple method for direct determination of ionic fluoride in 5 μl samples of body fluids with the hanging drop fluoride electrode, using sodium acetate buffer (pH 4.8) is described. The hanging drop electrode should prove useful in experimental investigations employing small laboratory animals and in clinical laboratories.

Methoxyflurane anesthesia in pediatric patients: evaluation of anesthetic metabolism and renal function.

Serum ionic fluoride concentrations during and following low-dose (6.0 mg/100 ml, 3 hours) methoxyflurane anesthesia and elective operation were measured in 13 pediatric patients (mean age 10.2 years; mean weight 34.5 kg). Peak measured serum ionic fluoride concentration was 21.6 plus or minus 3.3 mumol/1 24 hours after anesthesia. In a previously reported study of adult patients (47.5 years; 71.9 kg), the peak measured serum ionic fluoride concentration was 43.9 plus or minus 5.7 mumol/1 24 hours after low-does (6.8 mg/100 ml,3 hours) methoxyflurane anesthesia. Possible explanations for lower serum ionic fluoride concentrations in pediatric patients comared with adults include 1) slower metabolism of nethoxyflurand; 2) increased renal clearance of ionic fluoride from the blood; 3) greater sorage of ionic fluride in bone; 4) more rapid methoxyflurane elimiantion in the postoperative period. Serum uric acid increased (4.4 to 6.4 mg/100 ml, not significant) 24 hours after anesthesia and operation, while blood urea nitrogen and serum creatinine and osmolality were unchanged postoperatively.