K. E. Reynolds

Plasma and Developing Enamel Fluoride Concentrations During Chronic Acid-base Disturbances

Mild acid-base disturbances were induced in rats for 30 days. These disturbances did not affect % ash of maxillary incisors or % P of the developing enamel from mandibular incisors. Total fluoride intake (food and water) among groups drinking fluoride-free water was constant. Nevertheless, average plasma and developing enamel fluoride concentrations were highest in the acidotic group and lowest in the alkalotic group. Among groups drinking water containing 50 ppm fluoride, total fluoride intake was highest by the alkalotic group and lowest by the acidotic group. Plasma and enamel fluoride concentrations, however, were highest in the acidotic group. It is concluded that plasma and developing enamel fluoride levels can be independent of, or inversely related to, fluoride intake.

Acute fluoride toxicity: The influence of acid-base status

The influence of preexisting acid-base disturbances on acute fluoride toxicity was studied in anesthetized rats. Metabolic acidosis was induced by the administration of NH4Cl and alkalosis by NaHCO3. Fluoride was infused iv until death occurred. One experiment involved intact animals (n = 18); another study used nephrectomized animals (n = 8). The alkalotic animals survived twice as long, tolerated higher fluoride doses (54.7 vs 29.2 mg/kg, intact; 32.5 vs 25.4 mg/kg, nephrectomized), died with higher plasma fluoride concentrations (2.60 vs 1.79 mm, intact; 3.53 vs 1.77 mm, nephrectomized), and generally had higher systemic blood pressures, heart rates, and glomerular filtration rates at any given plasma fluoride concentration. The renal excretion, renal clearance, and fractional renal clearance (CFGFR) of fluoride were all consistently higher in the alkalotic animals. Tissue-to-plasma fluoride concentration ratios for heart and skeletal muscle were lower in the alkalotic group, which suggested a smaller volume of distribution for fluoride in alkalosis. This was also indicated by consistently higher plasma fluoride concentrations in the alkalotic animals of the study in which all animals were nephrectomized. It is concluded that a preexisting metabolic alkalosis renders the animal less sensitive to the toxic effects of acutely administered fluoride. The mechanism(s) by which alkalosis protects against fluoride toxicity involves an enhanced renal fluoride clearance rate. It may also involve lower intracellular fluoride concentrations at any given extracellular fluoride level.

Acute fluoride toxicity: influence of metabolic alkalosis.

Abstract Acute fluoride toxicity was induced in anesthetized rats by the continuous iv infusion of fluoride at 1.40 μmol/min. This infusion continued until the death of the animals. Early signs of toxicity, which developed in all animals during the first hour of fluoride infusion, included diuresis, falling urinary osmolality, and glomerular filtration rate at plasma fluoride concentrations of 0.4 to 0.5 m m . The animals were then assigned to three groups. Groups 1, 2, and 3 received intravenous infusions of isotonic saline (control), isotonic sodium bicarbonate, and isotonic sodium bicarbonate plus acetazolamide, respectively. Compared to group 1, groups 2 and 3 survived the high fluoride infusion longer (5.93 vs 7.61 and 10.27 hr, respectively) and tolerated more fluoride (47.8 vs 61.9 and 80.7 mg/kg, respectively). At any given time (dose) after starting the high fluoride infusion, plasma fluoride concentrations were lower and mean arterial blood pressures, glomerular filtration rates, fluoride renal excretions, clearances and fractional clearances, and blood and urine pH values were higher in animals from groups 2 and 3 compared to group 1. Further, group 3 was more resistant to fluoride toxicity than group 2. Terminal tissue-to-plasma fluoride concentrations for heart were lowest in groups 2 and 3 while there were no differences among the groups for brain. It is concluded that metabolic alkalosis can favorably influence the course of a developing episode of acute fluoride toxicity and that this maneuver should be an important addition to the currently accepted therapeutic regimen.

Blood and urinary 18F pharmacokinetics following parenteral administration in the rat

Blood and urinary excretion time courses of 18F administered parenterally to rats were monitored for two hours. The intraperitoneal, subcutaneous, and intravenous routes gave kinetically indistinguishable results after ten minutes following the dose. The blood time course during the first hour following intramuscular dosing showed a relative constancy and suggested a delayed absorption time.

Fluoride absorption from subcutaneous sites: influence of volume and concentration.

A recent report described the time courses of blood radiofluoride (18F) concentrations and urinary 18F excretions in rats following parenteral administration (WHITFORD ET AL, J Dent Res 56:858-861, 1977). Variations in either the injected volume or fluoride (F) concentration could influence the absorption rate by altering the local microcirculation and, therefore, the time courses of blood concentrations and urinary excretion. This study was done to determine the influence of these two variables after subcutaneous injection. Eighteen, 213 -+3 gm, female Wistar rats were anesthetized with pentobarbital sodium (35 mg/kg, ip). Urine samples were collected via bladder catheters and blood samples were collected from carotid artery cannulae at timed intervals. Injections were given beneath the skin overlying the abdomen lateral to the midline. In the F concentration study, each rat received 0.20 ml. The F concentrations (as NaF) of the injectates for groups Cl, C2, and C3 were 10.4, 51.1, and 772 mM respectively. Thus, these groups received 0.19, 0.91, and 13.74 mg F/kg. The injectates for groups Cl and C2 were made isotonic with NaCl. The injectate for C3 was already hypertonic and was included because this dose is appropriate to acute F toxicity studies. In the volume study, each rat received 0.87 mg F/kg. The animals in groups Vl, V2, and V3 received 0.10, 0.20, and 0.50 ml, respectively. All injectates contained Evans blue dye