Hepatic fibrosis and cirrhosis after chronic administration of alcohol and "low-dose" carbon tetrachloride vapor in the rat.

Rats were exposed to carbon tetrachloride vapor, 5 days/wk, 6 hr/day, for periods of 5 or 10 wk at a concentration that by itself caused only fatty change with minimal liver cell necrosis and no fibrosis. The same carbon tetrachloride exposure when given in association with chronic alcohol feeding resulted in extensive hepatic fibrosis at 5 wk and established micronodular cirrhosis at 10 wk. The periodicity of the exposure profile was chosen to simulate that of human exposure to environmental toxins, albeit at a higher dose than would be permitted in the workplace. The development of significant liver injury in this animal model raises the possibility that some chronic liver injury in humans may be due to alcohol potentiation of other hepatotoxins present in the environment at subtoxic levels.