SummaryIn acute inhalational exposure even low doses of carbon disulphide (C 5 2 ) inhibit the oxidative drug metabolism: This inhibition, studied by the example from the side-chain oxidation of hexobarbital, increases steadily in adult female rats during exposure to 100 ppm over 8 hrs, as shown by the prolonged hypnotic-narcotic effect; it is completely reversible within 24 hrs so that repeated identical doses of C 5 2 do not give rise to a cumulative effect The cause of this phenomenon is an inhibition of the microsomal oxydative enzyme system in the liver, as could be demonstrated in purified enzyme preparations from liver homogenates of rats exposed to 50 ppm C 5 2 over 2-8 hrs This inhibitory effect is intimately linked with the presence of C 5 2 in the organism, as seen from its pharmacokinetic behaviour In the course of an 8-hr inhalation ( 400 ppm C 5 2 ) the rate of saturation in the blood and liver is most rapid during the first few hours After the termination of the exposure C 52 is distributed in the blood and liver at a ratio of 3:2.Approximately one third of the C 5 2 that has passed into the liver is found in the isolated microsomes where it is detectable for several hours.Elimination of the inhaled C 5 2 from the blood and liver occurs at a halflife of 35 min and 65 min, respectively The preferred route of elimination is by exhalation, approximately 10 % of the 1 4 C 52 activity being recovered within 4 hrs following subcutaneous injection of 1 4 C 5 2 Significant oxidation of C 5 2 to urinary sulphate has not been found to occur after inhalation Since the inhibition of the microsomal mixed-function oxygenases due to inhaled C 5 2 occurs primarily during its retention in the organism, it is concluded that initially C 5 2 itself acts as the inhibitor, but it appears probable that C 5 2 metabolites (for example, thiurams) are also implicated.

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