Methylene dianiline: acute toxicity and effects on biliary function.
Kanz-MF; Kaphalia-L; Kaphalia-BS; Romagnoli-E; Ansari-G
Toxicol Appl Pharmacol 1992 Nov; 117(1):88-97
The acute toxicity of the aromatic diamine 4,4'-methylene-dianiline (101779) (DAPM) to the liver, particularly on secretion of biliary constituents and on biliary epithelial cell gamma-glutamyl- transpeptidase (GGT) activity, was investigated in rats. Biliary cannulas were positioned in male Sprague-Dawley-rats under pentobarbital anesthesia. Each rat was given DAPM at 250mg/kg orally in 35% ethanol or 35% ethanol only. Main bile duct cells were severely damaged 4 hours after DAPM administration with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hours. Biliary protein concentration was increased fourfold by 4 hours while concentrations of biliary bile salt and bilirubin were decreased to about 21 and 50%, respectively, of basal values. Glutathione concentration in bile was increased by 100% during the choleretic period after DAPM treatment; by the 4 hour mark, this concentration had decreased to less than 1% of the basal value. Histochemical staining of main bile duct GGT was absent by 8 hours after DAPM. Bile flow was diminished by 40% at 4 hours. By 8 hours three of five rats had no bile flow and none had any bile flow at 24 hours. The authors concluded that 4,4'- methylene-dianiline is selectively toxic to epithelial cells of the major bile ducts and thus should be classified, like ANIT, as a cholangio destructive agent. DAPM rapidly induced profound biliary dysfunction as evidenced by the striking alterations in bile flow and in biliary bile salt, bilirubin, glutathione, protein, and glucose concentrations.
NIOSH-Publication; NIOSH-Grant; Grants-other; Liver-damage; Hepatotoxicity; Biliary-system; Diamines; Toxic-effects; Laboratory-animals; Acute-toxicity
Human Biol Chem and Genetics University of Texas Med BR Dept of Human Biol Chem&gene Galveston, Tex 77550-2774
Other Occupational Concerns; Grants-other
Toxicology and Applied Pharmacology
University of Texas Medical Branch, Galveston, Texas