HEPATOTOXICITY IN GUINEA-PIGS FOLLOWING ACUTE INHALATION EXPOSURE TO 1,1-DICHLORO-2,2,2-TRIFLUOROETHANE

Groups of 10 male Hartley guinea pigs were exposed to 3.0, 2.0, 1.0, o r 0.1% (v/v) 1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) or 1.0% (v/ v) halothane by inhalation for 4 hr. A sixth group of 10 guinea pigs r eceived only air. All animals were sacrificed 48 hr postexposure. Gros s and histopathologic examination of the liver, heart, and kidney and routine hematology and clinical chemistry analyses [including isocitra te dehydrogenase (ICDH)] were done on all guinea pigs. Lesions related to HCFC-123 and halothane exposure were limited to the liver and incl uded centrolobular vacuolar (fatty) change, multifocal random degenera tion and necrosis, and centrolobular degeneration and necrosis. These lesions were observed in 90-100% of the exposed animals and were absen t in the air-only controls. There was significant individual animal va riation in susceptibility to both HCFC-123 and halothane, resulting in a spectrum of histologic lesions and clinical chemistry values within each exposure group. Alanine aminotransferase, aspartate aminotransfe rase, and ICDH were the most significant predictors of hepatocellular damage. Similarities in the response between halothane and HCFC-123 in this guinea pig model suggests that humans susceptible to halothane-i nduced hepatitis may be susceptible to HCFC-123 by a common mechanism of toxicity.