Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats.
Cadmium nitrate Cd(NO(3))(2) (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-beta-D-glucosaminidase/creatinine, beta(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.
Dote
Emi
E
Department of Hygiene and Public Health, Osaka Medical College, Takatsuki City, Osaka, Japan. hyg025@art.osaka-med.ac.jp
Dote
Tomotaro
T
Shimizu
Hiroyasu
H
Shimbo
Yukari
Y
Fujihara
Michiko
M
Kono
Koichi
K
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D019187:Cadmium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D006947:Hyperkalemia / Q000139:chemically induced*; D008658:Inactivation, Metabolic; D007262:Infusions, Intravenous; D007678:Kidney Glomerulus / Q000293:injuries / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000293:injuries / Q000503:physiopathology; D007928:Lethal Dose 50; D008297:Male; D009566:Nitrates / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019187:Cadmium Compounds; D009566:Nitrates; C035196:cadmium nitrate