Abnormalities in Cadmium Fluoride Kinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats

Abstract

Abnormalities in Cadmium FluorideKinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats: Tomotaro DOTE, et al. Department of Hygiene and Public Health, Osaka Medical College-Cadmium fluoride (CdF 2 , 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. (J Occup Health 2008; 50: 339-347)

Toxicological aspects of cadmium and occupational health activities to prevent workplace exposure in Japan: A narrative review

“…The toxicity of Cd is directly related to the solubility of its salts, which makes Cd 2þ ions readily available. The highly soluble fluoride and nitrate are reported to be among the most toxic of the Cd compounds (Adachi et al, 2007;Dote et al, 2008;Dote et al, 2007). The LD 50 values for different Cd compounds administered to mice by intragastric administration are shown in Table 1 (Friberg et al, 1992).…”

Chronic exposure to Mn inhalation may have lasting effects: A physiologically-based toxicokinetic model in rats

“…Kinetic modeling has been done for other metals such as cadmium (Dote et al 2008), zinc (House and Wastney 1997), mercury (O'Flaherty 1998), nickel (Hack et al 2007), arsenic (Gentry et al 2004) and lead (for review see Rabinowitz 1998) in rats. Toxicokinetic (TK) models for Mn have described whole-body Mn clearance rates (Dorman et al 2002a;Dorman et al 2006;Takeda, Sawashita, and Okada 1995), brain clearance rates (Calonder et al 1999), lung clearance rates (Thompson et al 2006), and biliary uptake and elimination (Teeguarden et al 2007a;Teeguarden et al 2007b).…”