Elimination

Following inhalation, the primary route of excretion for unmetabolised carbon disulphide is exhalation from the lung. Approximately, 5% to 30% of carbon disulphide is excreted unchanged by the lungs (McKee et al, 1943; Teisinger and Soucek, 1949; Davidson and Feinleib, 1972; Baselt, 2000). Elimination is rapid (Baselt, 2000). Studies indicate that there is a 25% reduction in blood concentrations in one hour and concentrations approach zero at 2 hours (Teisinger and Soucek, 1949). In a volunteer study, elimination of inhaled carbon disulphide was characterised by an initial fast rate giving a half-life of 1.1 minutes, followed by a relatively slow rate with a half-life of 109.7 minutes (Rosier et al., 1987a).

Carbon disulphide is deposited in the body in free and bound forms and its elimination rate is determined by the route of exposure, and the ratio of these two forms in the body (Coppock and Buck, 1981).

Only about 0.05% is excreted unchanged by the kidneys (Teisinger and Soucek, 1949). About two thirds of this is excreted in a bound form, and requires acidification and aeration of urine for its release. Metabolised carbon disulphide appears primarily in the urine as inorganic sulphur-containing metabolites, thiourea, 2-mercapto-2-thiazolin-5-one and 2-thiothiazolidine-4-carboxylic acid (TTCA); the latter two compounds are conjugates with glycine and cysteine, respectively (Baselt, 2000). Urinary TTCA accounts for 1-2% of an absorbed dose of carbon disulphide (Rosier et al., 1987b), but the concentration does not appear to correlate with the environmental concentration of carbon disulphide (Kitamura et al., 1993).

On evaluating the effect of an 8 hour inhalation exposure to 2 mg/l (640 ppm) of carbon disulphide in rats, McKenna and DiStefano (1977) reported that although tissue concentrations of free carbon disulphide reached a plateau within 4-5 hours, tissue concentrations of the acid labile metabolites continued to increase throughout the 8 hour exposure. The study also showed that acid-labile metabolites were eliminated slowly after termination of exposure, which is a significant finding in that it suggests that these metabolites may accumulate in the body after repeated carbon disulphide exposure.

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