A. Human StudiesInhalation is the major route of occupational exposure to carbon disulfide. Investigations in volunteers and occupationally exposed workers suggest that equilibrium between inhaled and exhaled CS2 is generally attained during the first 2 hr of Initially, the fraction of inhaled CS2 absorbed was relatively constant over a wide range of exposure concentrations, with approximately 70 to 80% of the inhaled carbon disulfide a b s~r b e d .~' .~~~~~~~ At equilibrium, retention of inhaled CS2 declined to approximately 15 to 45% of the inhaled vapor.61,2239289 It is interesting to note a report that described retention of inhaled CS2 in individuals not previously exposed to this agent that was greater than in those who were chronically exposed to CS2.289 Although the mechanism of the decreased retention with chronic exposure is not known, this observation does suggest caution in extrapolation of acute human exposure data to the chronic exposure situation.Percutaneous absorption is a second potential source of occupational exposure to CS2. Dutkiewicz and Baranowska" evaluated skin absorption by immersion of the hand in aqueous CS2 solutions (0.33 to 1.67 g/Q) for 1 hr. Absorption of CS2 was quantitated by two methods: indirectly by determining CS;? elimination by the lung; and by measurement of the CS2 concentration in the aqueous solutions before and after immersion of the hand. Absorption rates determined by solution analysis were found to range from 0.232 to 0.789 mg/cm2/ hr and were approximately 10 times higher than rates calculated from lung excretion of CS2. Further calculations indicated that only 3% of cutaneously absorbed CS2 was eliminated by the lung. Using the solution data, these investigators also calculated that immersion of a hand for 1 hr in a viscose rayon washing bath containing 0.1 mg/g CS2 would result in a total dose of 17.5 mg. One potential difficulty with this study, however, was that no precautions were described to prevent loss of CS2 from the solutions due to volatilization. Failure to adequately control for this variable would result in an overestimate of percutaneous absorption.Following inhalation exposure the primary route of excretion for unmetabolized CS2 is exhalation from the lung. In 1943, McKee et a1.'56 estimated that 6 to 10% of exposure. 148,156,250,254,296 Volume 11, Issue 3
CRC Critical Reviews in Toxicologyidentification of metabolite(s) responsible for the hepatotoxic effects of high-dose exposure to CS2, particularly in phenobarbital pretreated rats. The formation of the toxic metabolite(s) is thought to involve activation of CS2 by the microsomal mixed function oxidase system.
Formation of Water-Soluble MetabolitesAn early study by Strittmatter et a1.226 characterized the overall disposition of the radiolabel in guinea pigs after inhalation of 35S-carbon disulfide. A small fraction (8 to 17%) of the total radioactivity recovered during the 48 hr after various inhalation exposures (13.6 ppm for 8 hr; 20.6 ppm for 16 hr, 25.7 ppm for 40 hr) was exhaled as CS2. ...
