Biotransformation of bisphenol F by human and rat liver subcellular fractions.
Bisphenol F [4,4'-dihydroxydiphenyl-methane] (BPF) has a broad range of applications in industry (liners lacquers, adhesives, plastics, coating of drinks and food cans). Free monomers of this bisphenol can be released into the environment and enter the food chain, very likely resulting in the exposure of humans to low doses of BPF. This synthetic compound has been reported to be estrogenic. A study of BPF distribution and metabolism in rats has demonstrated the formation of many metabolites, with multiple biotransformation pathways. In the present work we investigated the in vitro biotransformation of radio-labelled BPF using rat and human liver subcellular fractions. BPF metabolites were separated, isolated by high-performance liquid chromatography (HPLC), and analysed by mass spectrometry (MS), MS(n), and nuclear magnetic resonance (NMR). Many of these metabolites were characterized for the first time in mammals and in humans. BPF is metabolised into the corresponding glucuronide and sulfate (liver S9 fractions). In addition to these phase II biotransformation products, various hydroxylated metabolites are formed, as well as structurally related apolar metabolites. These phase I metabolic pathways are dominant for incubations carried out with liver microsomes and also present for incubations carried out with liver S9 fractions. The formation of the main metabolites, namely meta-hydroxylated BPF and ortho-hydroxylated BPF (catechol BPF) is P450 dependent, as is the formation of the less polar metabolites characterized as BPF dimers. Both the formation of a catechol and of dimeric metabolites correspond to biotransformation pathways shared by BPF, other bisphenols and estradiol.
Cabaton
Nicolas
N
ENSBANA, UMR 1229 FLAVIC, F-21000 Dijon, France.
Zalko
Daniel
D
Rathahao
Estelle
E
Canlet
Cécile
C
Delous
Georges
G
Chagnon
Marie-Christine
MC
Cravedi
Jean-Pierre
JP
Perdu
Elisabeth
E
D000818:Animals; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000098833:Bisphenol F Compounds
D001559:Benzhydryl Compounds; D003577:Cytochrome P-450 Enzyme System; C008745:4,4'-bisphenol F; D000098833:Bisphenol F Compounds