Effect of 18 HR fast and glutathione depletion on 1,1-dichloroethylene-induced hepatotoxicity and lethality in rats.
Jaeger-RJ; Conolly-RB; Murphy-SD
Exp Mol Pathol 1974 Apr; 20(2):187-198
The toxic effects of 1,1-dichloroethylene (75354) (1,1-DCE) were studied in rats. Male Holtzman-rats were exposed for approximately 4 hours in a 30 liter dynamic flow chamber to an air flow of 15 to 20 liters per minute. Concentrations of 1,1-DCE varied from 50 to 20,000 parts per million (ppm). Concentrations of 1,1-DCE in the exposure chamber were determined by gas chromatography. Some animals were fasted 18 hours before exposure. After exposure, rats were sacrificed and their livers were removed. The isolated, perfused liver system as described by Ruderman was used to determine alanine-alpha-ketoglutarate-transaminase (AKT). The estimated 24 hour median lethal concentration (LC50) was 15,000ppm 1,1-DCE for fed rats and 600ppm for fasted rats. The minimum lethal concentration was 200ppm for fasted rats and 10,000ppm for fed rats. AKT elevation occurred at 150ppm in fasted rats, and 2,000ppm in fed rats. Elevated AKT preceded hepatic necrosis and death. The authors conclude that protection against hepatic injury is not restored by feeding fasted animals again nor does preferential uptake of 1,1-DCE by livers from fasted rats account for the enhancement of toxicity. The enhancement of 1,1-DCE toxicity by overnight fasting is of importance because it may suggest that rotating shift work in factories involving 1,1-DCE exposure may enhance risk of liver injury.
NIOSH-Publication; NIOSH-Grant; Organic-solvents; Chemical-properties; Animal-studies; Toxicology; Exposure-levels; Pathogenesis; Physiological-response; Liver-damage; Biological-factors
Physiology Harvard University 665 Huntington Ave Boston, Mass 02115
Experimental and Molecular Pathology
Harvard University, Boston, Massachusetts