Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-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 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 beta rate constant, total plasma clearance (C1) and first-order rate constants (K21, Kel) decreased, and the half-time of the beta-phase (t1/2beta) 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 C1 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.
Dote
T
T
Department of Hygiene and Public Health, Osaka Medical College, Takatsuki City, Japan.
Kono
K
K
Usuda
K
K
Nishiura
H
H
Tagawa
T
T
Miyata
K
K
Shimahara
M
M
Hashiguchi
N
N
Senda
J
J
Tanaka
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000097:blood* / Q000139:chemically induced*; D016018:Least-Squares Analysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D005459:Fluorides