ACUTE HARMFUL EFFECTS AFTER SINGLE INTRAVENOUS DOSE OF CADMIUM FLUO RIDE IN RATS (THIRD REPORT): KINETICS OF CADMIUM AND FLUORIDE IN BLOOD

摘要

Our previous study reported the LD (lethal dose) of cadmium fluoride (CdF_2, CdF) for 24 hr after i.v. injection in rats, the dose-effect relationships, and the metabolism of cadmium (Cd) and fluoride (F) in bile and urine for investigating the acute toxicities from the standpoint of occupational health. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of Cd and F were investigated in the blood in rats as a model of accidental occupational exposure to CdF. Rats received a single i.v. injection of saline or CdF (1.34, 2.67, or 4.0I (LD 88) mg/kg), which were the same doses of the previous study. This new study investigated the dose-effect relationships of serum kinetic changes of Cd and F. Blood samples were obtained from each individual animal 0, 5, I0, 30, 60, I20, and 300 min after the CdF administration. The serum concentration-time profiles were analyzed by compartmental modeling using the WinNonlin program. These kinetic profiles indicated that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups. 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 abnormal kinetics of F was attributable to nephrotoxicity that diminished F elimination from the kidney.