Yoshihito Tanaka

Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-dose fluoride exposure

Abstract Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is measured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose–response relationship was recognized between these F doses and renal tissue injury. Blood samples were removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Results indicated that a two–compartment model could describe the elimination of F from plasma. The β rate constant, total plasma clearance (Cl) and first-order rate constants (K21, Kel) decreased, and the half-time of the β-phase (t1/2β) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high doses of F damages renal tissue and causes renal dysfunction. The Cl of F is mainly dependent on renal F excretion. Since severe kidney damage markedly affected the toxicokinetics of F and decreased its elimination, other nephrotoxic indicators and measurement of plasma F concentration are necessary for monitoring high-dose F exposure.