The effect of pretreatment on the biliary excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 3,3',4,4'-tetrachlorobiphenyl in the rat.
The laterally halogenated chemicals 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 3,3',4,4'-tetrachlorobiphenyl (TCB) exhibit the same spectrum of toxic effects as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototype and most toxic member of the halogenated aromatic hydrocarbon family. Metabolism of all three compounds appears to be the rate-limiting step for excretion, which is primarily via the bile into the feces. Therefore, the biliary elimination of TCDF, TCDD, and TCB was examined as an indirect measure of metabolism. Male F344 rats were anesthetized with pentobarbital, the bile duct was cannulated, and 0.1 mumol [3H]TCDD, [14C]TCDF, or [14C]TCB/kg body wt was administered iv. Bile was collected for 0-8 hr while the animals were kept under anesthesia. To determine if TCDF was able to induce its own metabolism in vivo, a single dose of 1.0 mumol TCDF/kg was administered to rats by oral gavage 3 days prior to iv injection of 0.1 or 0.3 mumol [14C]TCDF/kg. Biliary excretion and hepatic concentrations of [14C]TCDF were significantly increased in the pretreated animals. These results suggest an autoinduction of TCDF metabolism. Essentially all biliary [14C]TCDF radioactivity was attributable to metabolites. High-pressure liquid chromatography profiles of biliary radioactivity from 0 to 4 hr were qualitatively different between naive and pretreated rats. To determine if pretreatment with TCDD altered the metabolism of TCDF and vice versa, a single dose of 1.0 mumol TCDF/kg or 0.1 mumol TCDD/kg was administered by oral gavage 3 days prior to iv injection of 0.1 mumol [3H]TCDD or [14C]TCDF/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
McKinley
M K
MK
ManTech Environmental, Inc., Research Triangle Park, North Carolina 27711.
Kedderis
L B
LB
Birnbaum
L S
LS
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000494:pharmacology; D001646:Bile / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D004790:Enzyme Induction / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D008297:Male; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D001140:Aroclors; D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; C014211:2,3,7,8-tetrachlorodibenzofuran; C028451:3,4,3',4'-tetrachlorobiphenyl