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

Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is mea sured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous inj ection 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 eval uated by a nonlinear least-squares method for fitting data to polyexponenti al equations and calculation of relevant pharmacokinetic parameters. Result s indicated that a two-compartment model could describe the elimination of F from plasma. The beta rate constant, total plasma clearance (Cl) and firs t-order rate constants (K-21, K-el) decreased, and the half-time of the bet a-phase (t(1/2 beta)) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high dos es of F damages renal tissue and causes renal dysfunction. The Cl of F is m ainly dependent on renal F excretion. Since severe kidney damage markedly a ffected the toxicokinetics of F and decreased its elimination, other nephro toxic indicators and measurement of plasma F concentration are necessary fo r monitoring high-dose F exposure.