Acute Lethal Toxicity, Hyperkalemia Associated with Renal Injury and Hepatic Damage after Intravenous Administration of Cadmium Nitrate in Rats

Abstract

(CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD 50 of CdN was determined to be 5.5 mg/ kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/ kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-β-D-glucosaminidase/creatinine, β 2 -microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN. (J Occup Health 2007; 49: 17-24)

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

“…The means of AUC 0→300 and AUC 0→∞ of the 4.01 mg/ kg group were significantly higher than those of the 1.34 and 2.67 mg/kg groups. The mean volumes of bile at 2 weighting, where Y is the serum cadmium concentration predicted using the model. AUC was calculated using a noncompartmental modeling method.…”

“…Thus, Cd was gradually eliminated from the serum and distributed widely to the other areas, particularly in the 4.01 mg/kg group. T 1/2β , Vss, MRT, and AUC 0→300 increased and K 10 , K 12 , and K 21 decreased in the 2.67 and 4.01 mg/kg groups to a greater 2 weighting, where Y is the serum cadmium concentration predicted using the model. AUC was calculated using a non-compartment modeling method.…”

“…In our previous study, we reported that urine volume apparently decreased in CdF-treated groups 1) . Additionally, it has been reported that urine volume decreases and BUN and serum creatinine increases 5 h after the intravenous administration of CdN (3 Cd mg/ kg) 2) . It has also been reported that BUN and serum creatinine considerably increase after the intravenous administration of CdCl 2 (CdL)(2.1 Cd mg/kg) 18) .…”

“…The WinNonlin program calculates model predictions using standard equations 8) . The best fits of the Cd and F data were obtained using a twocompartment and a one-compartment model, respectively, ˆ ˆ with a 1/ (Y) 2 iterative weighting scheme, where Y is the serum concentration predicted using the model. The twocompartment parameter estimated from the regression analysis included the half-life of Cd in the α phase (T 1/2α ), the half-life of Cd in the β phase (T 1/2β ), the apparent volume of distribution at the steady state (Vss), the rate constant for Cd transfer from the central to the peripheral compartment (K 12 ), the rate constant for Cd return from the peripheral to the central compartment (K 21 ), the elimination rate constant from the central compartment (K10), and the mean residence time (MRT).…”

“…We reported that the AST and ALT activities measured at 300 min in the 2.67 and 4.01 mg/kg groups were significantly higher than those of rats in the control group 1) . The results showed that CdF is the most lethal 1) and hepatotoxic of all Cd-containing compounds, such as cadmium chloride and cadmium nitrate (Cd(NO 3 ) 2 , CdN for short) 2) . We also concluded a dose of 4.01 mg/kg causes renal dysfunction, and acute renal failure was induced at doses higher than 2.67 mg/ kg 1) .…”