The effects of repeated14C halothane exposure in mice

Abstract

THE ANAESTHETIC ADMINISTRATION Of 14C labelled halothane has been shown to cause non-volatile halothane metabolites to accumulate in the liver of mice) These labelled halothane metabolites are bound to liver microsomes in proportion to liver blood flow, hepatic arterial oxygen tension and enzyme induction? Cohen 3 showed that repeated weekly injections of labelled halothane caused non-volatile metabofires to accumulate and increase in the liver suggesting stimulation of enzyme induction. In contrast, Topham and Longshaw 4 showed that repeated daily inhalations of labelled halothane produced no accumulation of non-volatile metabolites using whole body auto-radiography techniques. Stevens and co-workers 5 reported that constant subanaesthetic inhalations of halothane for 35 days caused reproducible dose dependent liver toxicity. This could be related to Sawyer's 6 work which showed optimum halothane metabolism at 1/100 MAC. It was hypothesized that increasing halothane concentrations depressed the necessary enzyme systems for halothane metabolism and that optimum metabolism may only be present in the post-anaesthetic period.In an attempt to clarify the divergent results of other workers, our study measured metabolism of halothane with chronic repeated exposures, determined the specific site of metabolism and assessed possible hepatotoxicity by light and electron microscopy. METHODS

Hepatotoxicity and Halothane Metabolism in an Animal Model with Application for Human Toxicity

“…No, 1, February, 1979 repeated halothane anaesthesia. Alternatively, increased biotransformation due to enzyme induction may be the mechanism for this reported increase in incidence of hepatic necrosis following repeat exposure to halothane, and, accumulation of toxic metabolites in the liver may also play a part (Stoyka and Havasi 1977 ). As yet direct evidence is not available for an increased risk of hepatotoxicity resulting from metabolic changes associated with repeat exposure to halothane.…”