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, or 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 received only air. All animals were sacrificed 48 hr postexposure. Gross and histopathologic examination of the liver, heart, and kidney and routine hematology and clinical chemistry analyses [including isocitrate dehydrogenase (ICDH)] were done on all guinea pigs. Lesions related to HCFC-123 and halothane exposure were limited to the liver and included centrolobular vacuolar (fatty) change, multifocal random degeneration and necrosis, and centrolobular degeneration and necrosis. These lesions were observed in 90-100% of the exposed animals and were absent in the air-only controls. There was significant individual animal variation 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 aminotransferase, 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-induced hepatitis may be susceptible to HCFC-123 by a common mechanism of toxicity.