Author
MORCK, A. - STOCKHOLM UNIV | |
Larsen, Gerald | |
KLASSON WEHLER, E. - ASTRAZENECA R&D SWEDEN |
Submitted to: Xenobiotica
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/1/2001 Publication Date: 1/1/2002 Citation: Morck, A., Larsen, G.L., Klasson Wehler, E. 2002. Covalent binding of PCB metabolites to lipids: route of formation and characterization. Xenobiotica 32(7):625-640. Interpretive Summary: After a chlorinated biphenyl [3,3',4,4'-tetrachlorobiphenyl (CB-77)] was given orally to normal rats, rats which were germ-free, and bile-duct cannulated male Sprague-Dawley rats approximately 80% of the dose was excreted in feces and/or bile within 3 days. Fifteen percent was excreted as metabolites chemically bound to fats. These fat-bound metabolites appear to be formed in the liver, excreted in the bile, and are not effected by the gut bacteria. These fat-bound metabolites had chemical and physical properties similar to those of lipids. The chlorinated biphenyl was shown to be oxidized with the addition of an alcohol ( -OH) functional group to molecule to which some of the metabolites were chemically attached to the fat molecule. In one fat bound metabolite the fat was determined to be palmitoate. Approximately 70% of the fat-bound metabolites were present in the phospholipid fat fraction. The formation of fat-bound metabolites in the case of this chlorinated biphenyl seems to be a spontaneous reaction rather than an enzymatically catalysed reaction, because of the large number of difference lipids bound to the metabolites. Technical Abstract: After an oral dose of 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (CB-77), the conventional germ-free and bile-duct cannulated male Sprague-Dawley rat excreted approximately 80% of the dose in faeces and/or bile within 3 days. For the germ-free and conventional rat, 15% of the dose was excreted via the faeces as metabolites covalently bound to lipids. Bile-duct-cannulated rats excreted similar amounts of lipid-bound metabolites in the bile. The lipid-bound metabolites appear to be formed in the liver and excreted via the bile, and the microflora did not seem essential for the formation of lipid-bound metabolites. The novel CB-77 metabolites had chemical and physical properties similar to those of lipids with regard to solubility and polarity, as determined by partition characteristics on various chromatographic systems. In addition to identification of hydroxylated CB-77 metabolites, several fatty acid esters of hydroxy-chlorobiphenyls were indicated and one hydroxy-tetrachlorobiphenylol palmitoate was identified, but fay acid esters were minor metabolites. Approximately 70% of the lipid-bound metabolites were present in the fraction that contained phospholipids. The formation of lipid-bound CB-77 metabolites seems a spontaneous reaction rather than an enzymatically catalysed reaction, as indicated by the large number of difference lipid-bound metabolites. |