Metabolic interactions

Carbon disulphide inhibits the cytochrome P450 redox enzyme complex and affects the metabolism of all compounds dependent on that system for their detoxification, toxicity, or therapeutic action (Cox et al., 1998).

Carbon disulphide has been shown to inhibit the activity of the enzyme aldehyde dehydrogenase; thus concurrent exposure to carbon disulphide and ethanol can increase blood acetaldehyde concentrations (Freundt et al, 1976). It is thought that workers exposed to carbon disulphide may experience a disulfiram-like reaction when subsequently exposed to ethanol (Rainey, 1977).

• Carbon tetrachloride (CCl4)

Exposure to carbon disulphide decreases the toxicity of carbon tetrachloride, which is metabolised by cytochrome P450 to toxic intermediates. Rats dosed simultaneously with carbon disulphide and carbon tetrachloride displayed hepatic effects resembling those due to carbon disulphide alone (ATSDR, 1994). This is thought to be due to destruction of the hepatic P450 metabolic system by carbon disulphide, such that activation of the carbon tetrachloride to toxic metabolites was much reduced. Similar results have been reported in workers exposed to an 80:20 mixture of carbon tetrachloride and carbon disulphide used to fumigate grain (Peters et al., 1987). The neurological effects observed in these individuals resembled those caused by carbon disulphide alone, and there was no evidence of carbon tetrachloride-induced hepatotoxicity (Peters et al., 1987; ATSDR, 1994).

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