Investigations on the liver toxicity of a blend of HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-124 (2-chloro-1,1,1,2-tetrafluoroethane) inguinea-pigs

2,2-Dichloro-1,1,1-tiifluoroethane (HCFC-123) has been developed as a subst itute for ozone-depleting chlorofluorocarbons (CFCs). It is a structural an alogue of halothane and similarities in the metabolic pathways and liver to xicity of both compounds have been described. The present study was initiat ed after an accidental outbreak of hepatitis in an industrial setting to ex amine whether concomitant exposure to 2-chloro-1,1,1,2-tetrafluoroethane (H CFC-124), which is not hepatotoxic, could enhance the liver toxicity of HCF C-123. Male Hartley guinea-pigs were exposed for 4 h to 5000 ppm HCFC-123 a lone or blended with 5000 ppm HCFC-124, either once (single exposure) or on 5 consecutive days (repeated exposure). The animals were killed either 24 or 48 h after the last exposure. A transient cytolytic action of HCFC-123 w as evident by increased mean serum levels of alanine aminotransferase at 24 h and isocitrate dehydrogenase at 24 and 48 h, both after a single or repe ated exposure. The liver toxicity of HCFC-123 was confirmed by pathological examination of liver tissue, which showed mild (foci of necrotic hepatocyt es) to moderate (multifocal random degeneration and necrosis) damage. Steat osis was also observed and was more pronounced after repeated exposure than after single. One animal out of 6 that were repeatedly exposed to the blen d and sacrificed at 24 h showed liver lesions similar to halothane hepatiti s. Although a few other animals responded markedly in the blend-treated gro up, on average, no significant difference in the biochemical or pathologica l lesions was found between the groups treated with HCFC-123 alone or with the blend. Urinary excretion of trifluoroacetic acid and chlorodifluoroacet ic acid increased dose-dependently upon exposure to HCFC-123 and indicated accumulation after repeated exposure. No difference in metabolite excretion was found between animals treated with HCFC-123 alone or blended with HCFC -124, Treatment with HCFC-123 depleted hepatic glutathione levels by about 40 and 25% after single and repeated exposure, respectively; the amplitude of this reduction was not modified by co-exposure to HCFC-124. In conclusio n, this study confirmed the hepatotoxicity of HCFC-123, based on biochemica l, histopathological and metabolite studies, and found only very limited in dication of a potentiation by HCFC-124 of this hepatotoxic effect.