The disposition and the liver and thymus gland toxicity of 3,3',4,4'-tetrachlorobiphenyl in the female rat.
3,3',4,4'-Tetrachlorobiphenyl (TCBP) was administered orally to adult female Sprague--Dawley rats in the oral dosage regimen, 5 mg X kg-1 X day-1 for 21 days, followed by a 22-day postdosing period. Control animals received either the corn-oil vehicle (1 mL X kg-1 X day-1) or no treatment. 3,3',4,4'-TCBP distributed preferentially into the adipose tissue and liver, and apparent steady-state xenobiotic concentrations were attained in the adipose tissue (8 micrograms/g) and liver (300 ng/g) prior to the cessation of dosing. The 3,3',4,4'-TCBP concentrations in the serum, brain, kidneys, and thymus gland were lower and more variable than those in the adipose tissue and liver. During the postdosing period, 3,3',4,4'-TCBP was eliminated from the adipose tissue and liver by apparent first-order kinetics with elimination half-life values of 2.5 days and 0.8 day, respectively. The major route of excretion of unmetabolized 3,3',4,4'-TCBP was via the feces, and the amount excreted over 24 h did not exceed 8% of the dose administered on any given day. Throughout the experiment, there were no differences in the body weight or food and water intake for the 3,3',4,4'-TCBP-treated animals compared with the corn-oil-treated and nontreated rats. There was a significant increase in liver weight and a significant decrease in thymus gland weight for the 3,3',4,4'-TCBP-treated rats compared with the corn-oil-treated rats at the cessation of dosing and at 11 days thereafter, but there were no observable histological changes in these organs as assessed by light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006207:Half-Life; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution
D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl