Characterization of biliary metabolites of 4-n-nonylphenol in rainbow trout (Oncorhynchus mykiss).
1. [R-2,6-3H]-4-n-nonylphenol was synthesized and a single dose (5 mg, 1850 KBq) orally administered to rainbow trout. After 48 h, the radioactivity present in the bile amounted 5.5%. More than ten biliary metabolites were separated by hplc and collected for subsequent mass spectrometry analysis. The metabolic profile was totally modified by beta-glucuronidase hydrolysis, showing that most of the metabolites were glucuronic acid conjugates. 2. Conjugated metabolites were identified by lc-ms analysis and their aglycones were analysed by gc-ms analysis as TMS and acetyl derivatives. 3. The major metabolite accounted for 52+/-11% of the biliary radioactivity and was identified as nonylphenol-glucuronide. 4. Nonylphenol was hydroxylated at both omega and omega-1 positions of the alkyl chain, giving 9-hydroxynonylphenol and 8-hydroxynonylphenol. 5. 9-Hydroxynonylphenol was oxidized to the corresponding acid, and subsequently beta-oxidized, yielding 7-(4-hydroxyphenyl)heptanoic acid, 5-(4-hydroxyphenyl)pentanoic acid, 3-(4-hydroxyphenyl)propionic acid and 3-(4-hydroxyphenyl)-2-propenoic acid.
Thibaut
R
R
Laboratoire des Xénobiotiques, INRA, Toulouse, France.
Debrauwer
L
L
Rao
D
D
Cravedi
J P
JP
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism*; D001711:Biotransformation; D008401:Gas Chromatography-Mass Spectrometry; D005966:Glucuronidase / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism*; D014873:Water Pollutants / Q000378:metabolism
D010636:Phenols; D014873:Water Pollutants; C025256:nonylphenol; D005966:Glucuronidase