CARBON-DISULFIDE NEUROTOXICITY IN RATS - II - TOXICOKINETICS

Carbon disulfide (CS2) is an important industrial chemical widely used in the production of rayon, cellophane, fungicides and biocides. The uptake and elimination kinetics of CS2 was characterized for a single iv dose and for a single inhalation exposure. The uptake of CS2 into t he blood was rapid with hall times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minu tes. The plateau CS2 blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predi cted by linear dose proportionality compared to the 500 ppm and 800 pp m treatments. The CS2 blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment ap parent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated f rom a single 50 mg/kg iv dose. The concentration of CS2 in blood resul ting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 5 00, and 800 ppm CS2 for 2, 4, 8, or 13 weeks. The concentration of CS2 in the blood of male rats remained relatively constant throughout stu dy. However the female 500 and 800 ppm groups showed a marked decrease over the course of the 13 week study. The concentration of CS2 in the blood from the 500 and 800 ppm groups of both sexes at all time point s was higher compared to the 50 ppm group, than would be predicted by linear dose proportionality. The concentration of 2-thiothiazolidine-4 -carboxylic acid in urine collected from the same animals lacked dose proportionality between the treatment groups at all time points. CS2 e xposure caused dose-related decreases in body weight gain in both male and female rats. (C) Intox Press, Inc. 1998.