Biochemical effects of 1,1-dichloroethylene in rats: comparison with carbon tetrachloride and 1,2-dichloroethylene.
The biochemical effects of 1,1-dichloroethylene (75354) (1,1-DCE), carbon-tetrachloride (56235) (CCl4), and 1,2-dichloroethylene (540590) (1,2-DCE) were compared in rats. Holtzman-rats were administered a single dose per os of either 100 to 500 milligrams per kilogram (mg/kg) 1,1-DCE, 400 or 1500mg/kg of the cis and trans isomers of 1,2-DCE, or 800mg/kg of CCl4. Difference between males and females were examined in rats treated with either 200 or 400mg/kg 1,1-DCE. The effects of pretreatment with intraperitoneal daily injections of 50mg/kg sodium-phenobarbital (57307) 5 days prior to treatment with 1,1-DCE or CCl4 were examined. The median lethal dose (LD50) values of 1,1-DCE and CCl4 were administered in adrenalectomized and sham operated male rats. Liver glucose-6- phosphatase (G-6-Pase), liver alkaline-phosphatase (AP), tyrosine- transaminase (TT), plasma AP, and alanine-transaminase (AT) were determined in homogenized liver by undisclosed biochemical methods. Liver AP activity was increased about 8 fold, and liver TT activity was increased 11 fold at 22 hours after a dose of 500mg/kg 1,1-DCE. Mean liver G-6-Pase was maximally depressed at 46 hours. Plasma AP was elevated 5 fold at AT 19 fold at 46 hours. Time of maximum effect was similar for doses of 100 and 300mg/kg 1,1-DCE. Both 1,1- DCE and CCl4 were more potent along parameters than the cis and trans isomers of 1,2-DCE. The liver AP and TT and plasma TT response to 400mg/kg 1,1-DCE were significantly greater than the response to 800mg/kg CCl4. Phenobarbital pretreatment increased the effect of CCl4 on liver G-6-Pase, liver AP, plasma AP, and plasma AT activities, but did not enhance the effect of 1,1-DCE on any of the parameters studied. Phenobarbital pretreatment significantly reduced the effects of 1,1-DCE on liver AP and TT and plasma AT activities. Female rats were more susceptible to decreased liver G-6-Pase and increased AP activity following 1,1-DCE than males. Adrenalectomized animals were more susceptible than controls to 1,1- DCE and CCl4 in the first 24 hours post administration; however, the 96 hour LD50 for CCl4 was the same in experimental and control animals, while the difference in susceptibility to 1,1-DCE remained unchanged.