The in vivo biotransformation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat |
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Authors: | J.C. Ramsey J.G. Hefner R.J. Karbowski W.H. Braun P.J. Gehring |
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Affiliation: | Toxicology Research Laboratory 1803 Building Dow Chemical USA Midland, Michigan 48640 USA |
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Abstract: | This study presents evidence for the in vivo biotransformation of TCDD in the rat. Three male rats with indwelling bile loop cannulas were given repeated daily po doses of 15 μg [14C]TCDD/kg body weight. After either two, four, or six doses, the total output of bile from one rat was collected for 24 hr following the last dose. Biliary 14C activity was excreted at a rate similar to the excretion of 14C activity in the feces of normal (noncannulated) rats given po doses of [14C]TCDD. Therefore it is not likely that enterohepatic recycling plays a significant role in the retention of 14C activity following a dose of [14C]TCDD. High-pressure liquid chromatography of the bile from these rats showed the presence of at least eight radioactive peaks and very little, if any, unchanged TCDD. These metabolites were all more polar than TCDD, and the chromatographic profile was altered following incubation of the bile with β-glucuronidase. These data, in conjunction with previous studies, indicate that the metabolic transformation of TCDD in the liver may be the rate-limiting step in the elimination of TCDD from the body. |
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Keywords: | Author to whom reprint requests should be sent. |
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