Abstract

Manifestations of hepatic toxicity due to carbon disulfide (CS₂) poisoning were studied in vivo in mice and rats and in the isolated perfused rat liver. Time response studies demonstrated that CS₂ administered i.v., p.o. or as vapor in air impaired sulfobromophthalein sodium (BSP) disappearance from plasma from ½ to 4 hours after treatment and that this effect resolved by 12 hours after treatment. Studies of exogenous bilirubin excretion indicated CS₂ impairment of bilirubin uptake. Pretreatment of mice with phenobarbital, 60 mg/kg i.p., 24 hours before exposure to CS₂ vapor, 110 ppm, significantly reduced CS₂-induced BSP retention. Measurement of serum glutamate pyruvate transaminase and alkaline phosphatase activity after CS₂ treatment did not reveal any evidence of hepatocellular damage acutely or after five days of treatment. In the isolated rat liver, CS₂ produced impaired BSP clearance together with decreased hepatic blood flow and bile flow. Comparison of the effects of CS₂ and α-naphthylisothiocyanate on hepatic function demonstrated similar changes in BSP and bilirubin excretion and impairment of bile flow, whereas elevation of serum glutamate pyruvate transaminase and alkaline phosphatase activity and phenobarbital potentiation seen with α-naphthylisothiocyanate intoxication were not elicited with CS₂.