Selective retention of toxic polychlorinated dibenzo-p-dioxins and dibenzofurans in the liver of the rat after intravenous administration of a mixture.
A mixture of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), purified from fly ash from a municipal incinerator, was administered as a single intravenous dose to male rats. Livers were analyzed after 5 h, 1, 2, 4, 7 and 9 days for PCDD and PCDF content. Starting from t = 5 h 2,3,7,8-substituted congeners were the predominant PCDDs and PCDFs retained. 2,3,4,6,7-PnCDF was the only congener without 4 lateral chlorine atoms retained in the liver. For most of the 2,3,7,8-substituted congeners reliable half-lives could not be calculated due to the short experimental period. For only three 2,3,7,8-substituted congeners was a complete elimination from the liver found, within this time period. These congeners were 2,3,7,8-TCDF, 1,2,3,7,8- and 2,3,4,6,7-PnCDF with half-lives of less than 1, 2.1 and 1.6 days, respectively. The other PCDDs and PCDFs, without 4 lateral chlorine atoms, were not detected in the liver from 5 h to 9 days after i.v. administration. Based on the congeneric distribution patterns, it is suggested that besides metabolism, structural specific binding to the Ah-receptor and cytochrome P-450 complex might also be responsible for this selective liver retention.
van den Berg
M
M
Laboratory of Environmental and Toxicological Chemistry, University of Amsterdam, The Netherlands.
van Wijnen
J
J
Wever
H
H
Seinen
W
W
D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004147:Dioxins / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D008099:Liver / Q000032:analysis / Q000378:metabolism*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D013329:Structure-Activity Relationship
D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C016068:polychlorodibenzofuran; D003577:Cytochrome P-450 Enzyme System