Toxicity of carbon disulfide in developing rats: LD50 values and effects on the hepatic mixed-function oxidase enzyme system

Abstract

The 24-hr LD50 values of carbon disulfide (CS 2) were estimated in 1-, 5-, 10-, 20-, 30-, and 40-day-old rats. CS 2 was least toxic to 20-day-old rats (LD50 1545 mg/kg, ip) and most toxic to 1-day-old rats (LD50 583 mg/kg, ip). Twenty-four hours after administration of CS 2 (375 mg/kg, ip) to 1-, 5-, 10-, 20-, 30-, and 40-day-old rats, significant inhibition of cytochrome P-450 and aniline hydroxylation was observed in rats of all ages studied except the 1-day-old rats. Following incubation of hepatic microsomes isolated from 1-, 5-, 10-, 20-, 30-, and 40-day-old rats with CS 2, decreases in activity of the hepatic mixed-function oxidase enzyme system and/or concentration of cytochrome P-450 were observed when an NADPH-generating system was present during incubation. When hepatic microsomes isolated from rats of all ages studied were incubated with C 35S 2, 35S was covalently bound to microsomal protein in the presence of an NADPH-generating system. Also, more 35S than 14C was covalently bound to microsomal membranes after incubation of microsomes isolated from rats of all ages studied with C 35S 2 or 14CS 2 in the presence of an NADPH-generating system. The results of this research demonstrated the LD50 of CS 2, the effects of CS 2 on the hepatic mixed-function oxidase enzyme system, and that the conversion of CS 2 to a covalently binding sulfer-containing biotransformation product varied with age in developing rats.