Abnormalities in cadmium fluoride kinetics in serum, bile, and urine after single intravenous administration of toxic doses to rats.
Cadmium fluoride (CdF2, CdF for short) is the most lethal and hepatotoxic of all Cd-containing compounds. The toxic effects of CdF appear to depend on its detoxification and elimination. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of cadmium and fluoride were investigated in the blood, bile, and urine of rats as a model of accidental occupational exposure to CdF. The serum concentration-time profiles measured after intravenous CdF (1.34, 2.67 or 4.01 mg/ per kg body weight) administration were analyzed by compartmental modeling using the WinNonlin program. Bile and urine were collected for 300 min after the administration. The kinetic profiles indicate that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups, leading to a persistently high serum Cd level. The mean total biliary excretions of Cd in the 2.67 and 4.01 mg/kg groups were significantly higher than that in the 1.34 mg/kg group. The abnormal kinetics of Cd was attributable to severe hepatic injury that diminished the capacity for Cd accumulation. The elimination of serum F was delayed in the 4.01 mg/kg group. The mean urinary F excretion amount was not significantly higher in the 4.01 mg/kg group than in the 2.67 mg/kg group. The abnormal kinetics of F was attributable to nephrotoxicity that diminished its elimination from the kidney.
Dote
Tomotaro
T
Department of Hygiene and Public Health, Osaka Medical College, Takatsuki City, Japan.
Adachi
Kazuya
K
Yamadori
Emi
E
Imanishi
Masafumi
M
Tsuji
Hiroshi
H
Tanida
Eri
E
Kono
Koichi
K
D000818:Animals; D001646:Bile / Q000737:chemistry; D019187:Cadmium Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002105:Cadmium Poisoning / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D019187:Cadmium Compounds; C532475:cadmium fluoride; D005459:Fluorides