Maternal hepatic effects of 1,2,4,5-tetrachlorobenzene in the rat.
1,2,4,5-Tetrachlorobenzene (TCB) is an industrial intermediate used in the production of 2,4,5-trichlorophenoxyacetic acid. This herbicide contains trace quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Because of possible maternal hepatic or reproductive effects of this uncharged, low-molecular weight, lipophilic chlorinated benzene 0, 30, 100, 300, and 1000 mg/kg/day of TCB was orally administered to rats on Days 9, 10, 11, 12, and 13 of gestation and the animals were sacrificed on Day 14 of pregnancy. No maternal deaths were recorded and body weight gain was significantly decreased only in the 1000 mg/kg/day group. Maternal liver weight, liver to body weight ratio, and hepatic microsomal protein content were unaffected by TCB treatment. Although Day 14 NADPH-cytochrome c reductase activity was not affected, the maternal hepatic microsomal cytochrome P-450 content was significantly increased by administration of 1000 mg/kg/day of TCB. Microsomal N-demethylation of aminopyrine was slightly increased from 2.4 to 3.4 and 3.5 nmole/mg protein/min at doses of 300 and 1000 mg/kg TCB. However, maternal hepatic microsomal ethoxyresorufin O-deethylase activity was greatly increased from 14 to 30, 40, 50, and 49 pmole/mg protein/min in pregnant rats administered 0, 30, 100, 300, and 1000 mg/kg/day TCB. The microsomal rates of p-nitrophenol and phenolphthalein glucuronidation in vitro were not increased by TCB administration. The maternal hepatic microsomal enzyme induction observed after TCB administration to pregnant rats suggests the presence both cytochrome P-450 and P-448 inducers in the sample of 1,2,4,5-tetrachlorobenzene used.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D002722:Chlorobenzenes / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D011919:Rats, Inbred Strains
D002722:Chlorobenzenes; C018673:1,2,4,5-tetrachlorobenzene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase