Metabolism

Carbon disulphide is extensively metabolised, irrespective of the route of administration. Approximately, 70% to 95% of absorbed carbon disulphide is metabolised, the rest is excreted by lung and kidneys (Davidson and Feinleib, 1972).

The metabolism of carbon disulphide occurs by two distinct pathways. In the primary pathway carbon disulphide spontaneously reacts directly with free amine and sulphydryl groups of cellular amino acids and polypeptides. The products of these reactions are dithiocarbamates (from reaction with amine and amino acids), and trithiocarbamates (from the reaction with sulphydryl groups). Both the dithocarbamates and trithiocarbamates are water-soluble and are excreted by the kidney. The second pathway is the microsomal oxidation of carbon disulphide to reactive intermediates, which then covalently bind to cell macromolecules (Bus, 1985).

Some carbon disulphide is metabolised to inorganic sulphides including thiourea, 2-mercapto-2-thiazolin-5-one and 2-thiothiazolidine-4-carboxylic acid (TTCA) (McKee et al., 1943; Baselt, 2000). TTCA is found in the urine of workers exposed to carbon disulphide (Van Doorn et al., 1981; Meuling et al., 1990). The urinary concentration of TTCA is quantitatively related to the uptake of carbon disulphide (Campbell et al., 1985). Campbell et al. (1985) calculated that at a carbon disulphide exposure concentration of 30 mg/m3 (9.6 ppm), less than 6% is metabolised to TTCA.

Inhaled carbon disulphide undergoes significant metabolism to non-volatile compounds and the elimination of these acid-labile metabolites is sufficiently prolonged to suggest their accumulation on repeated exposures (McKenna and DiStefano, 1977).

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