EPR studies of in vivo radical production by 3,3',5,5'-tetrabromobisphenol A (TBBPA) in the Sprague-Dawley rat.
Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard and it is of interest to determine the mechanism of their toxicity. Of all the BFRs, 3,3',5,5'-tetrabromobisphenol A (TBBPA) is produced in the largest volume. Previous studies by Szymanska et al. (2000) have shown that TBBPA is hepatotoxic in rats. We report here that when TBBPA (100 or 600 mg/kg) dissolved in DMSO and alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) was administered ip to male Sprague-Dawley rats the POBN/CH(3) spin adduct was detected by electron paramagnetic resonance (EPR) in the bile. When (13)C-DMSO was employed the POBN/C(13)H(3) adduct was observed. Also present in the bile was the 2,6-dibromobenzosemiquinone radical derived from 2,6-dibromohydroquinone, a known metabolite of TBBPA. Reaction of the 2,6-dibromobenzosemiquinone radical with oxygen would generate superoxide from which hydrogen peroxide can form by dismutation. The hydroxyl radical generated via the Fenton reaction from hydrogen peroxide reacts in vivo with DMSO to give the methyl radical which is trapped by POBN. These observations suggest that the hepatotoxicity of TBBPA in rats may be due to the in vivo generation of the hydroxyl radical as a result of redox reactions involving the TBBPA metabolite 2,6-dibromohydroquinone and its corresponding semiquinone radical.
Chignell
C F
CF
Laboratory of Pharmacology and Chemistry, NIEHS/NIH, Research Triangle Park, NC 27709, USA. chignell@niehs.nih.gov
Han
S-K
SK
Mouithys-Mickalad
A
A
Sik
R H
RH
Stadler
K
K
Kadiiska
M B
MB
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005411:Flame Retardants / Q000378:metabolism / Q000633:toxicity*; D005609:Free Radicals / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D011075:Polybrominated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D005411:Flame Retardants; D005609:Free Radicals; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A