2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) has been developed as a substitute for
ozone-depleting
chlorofluorocarbons (CFCs). It is a structural analogue of
halothane and similarities in the metabolic pathways and liver toxicity of both compounds have been described. The present study was initiated after an accidental outbreak of
hepatitis in an industrial setting to examine whether concomitant exposure to 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), which is not hepatotoxic, could enhance the liver toxicity of
HCFC-123. Male Hartley guinea-pigs were exposed for 4 h to 5,000 ppm
HCFC-123 alone or blended with 5,000 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 was 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 repeated exposure. The liver toxicity of
HCFC-123 was confirmed by pathological examination of liver tissue, which showed mild (foci of necrotic hepatocytes) to moderate (multifocal random degeneration and
necrosis) damage. Steatosis was also observed and was more pronounced after repeated exposure than after single. One animal out of 6 that were repeatedly exposed to the blend and sacrificed at 24 h showed liver lesions similar to
halothane hepatitis. Although a few other animals responded markedly in the blend-treated group, on average, no significant difference in the biochemical or pathological lesions was found between the groups treated with
HCFC-123 alone or with the blend. Urinary excretion of
trifluoroacetic acid and
chlorodifluoroacetic 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 conclusion, this study confirmed the hepatotoxicity of
HCFC-123, based on biochemical, histopathological and metabolite studies, and found only very limited indication of a potentiation by
HCFC-124 of this hepatotoxic effect.