Biotransformation of the flame retardant tetrabromo-bisphenol A by human and rat sub-cellular liver fractions.
The comparative in vitro metabolism of the flame retardant tetrabromo-bisphenol A was studied in rat and human using a [(14)C]-radio-labelled molecule. Tetrabromo-bisphenol A is metabolised into the corresponding glucuronide (liver S9 fractions) and several other metabolites produced by cytochrome P450 dependent pathways (liver microsomes and liver S9 fractions). No major qualitative differences were observed between rat and human, regardless of the selected concentration, within the 20-200 microM range. Tetrabromo-bisphenol A undergoes an oxidative cleavage near the central carbon of the molecule, that leads to the production of hydroxylated dibromo-phenol, hydroxylated dibromo-isopropyl-phenol and glutathione conjugated dibromo-isopropyl-phenol. The main metabolites of tetrabromo-bisphenol A are two molecules of lower polarity than the parent compound, characterised as a hexa-brominated compound with three aromatic rings and a hepta-brominated dimer-like compound, respectively. Both structures, as well as the lower molecular weight metabolites resulting from the breakdown of the molecule, suggest the occurrence of chemically reactive intermediates formed following a first step oxidation of tetrabromo-bisphenol A.
Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1089 Xénobiotiques, 180 chemin de Tournefeuille, BP3, 31931 Toulouse Cédex 9, France.
Daniel
D
Zalko
Caroline
C
Prouillac
Anne
A
Riu
Elisabeth
E
Perdu
Laurence
L
Dolo
Isabelle
I
Jouanin
Cécile
C
Canlet
Laurent
L
Debrauwer
Jean-Pierre
JP
Cravedi
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005411:Flame Retardants / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D011075:Polybrominated Biphenyls / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A