Effects of chronic inhalation of halothane, enflurane or isoflurane in rats

Male Fischer 344 rats were exposed to halothane, enflurane or isoflurane vapour 20 p.p.m., or air, for up to 30 weeks. None of the anaesthetic agents led to hepatocellular necrosis. Exposure to halothane resulted in slight increases in serum alanine aminotransferase activity, an increase in the size of the liver, an increase in hepatic microsomal cytochrome P-450 content and a minimal amount of fatty change in the liver. None of these effects were observed during exposure to enflurane or isoflurane. Urinary fluoride excretion was increased during exposure to either enflurane or isoflurane. Using this increase as an index of anaesthetic biotransformation, we found that the extent of biotransformation of isoflurane was only slightly lower than that of enflurane.