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 i.v. dose and for a single inhalation exposure. The uptake of CS2 into the blood was rapid with half times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minutes. The plateau CS2 blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predicted by linear dose proportionality compared to the 500 ppm and 800 ppm treatments. The CS2 blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment apparent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated from a single 50 mg/kg i.v. dose. The concentration of CS2 in blood resulting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 500, 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 study. 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 points 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 exposure caused dose-related decreases in body weight gain in both male and female rats.
Moorman
M P
MP
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Sills
R C
RC
Collins
B J
BJ
Morgan
D L
DL
D000280:Administration, Inhalation; D000818:Animals; D002246:Carbon Disulfide / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013844:Thiazoles / Q000652:urine; D053778:Thiazolidines
D013844:Thiazoles; D053778:Thiazolidines; C031677:2-thioxo-4-thiazolidinecarboxylic acid; D002246:Carbon Disulfide