Thyroid Hormone Disrupting Effects Of Tetrabromobisphenol A (TBBPA) And Pentabromophenol (PBP) On Goldfish (Carassius Auratus)

Tetrabromobisphenol-A (TBBPA) is the most widely used brominated flame retardants (BFRs) all over the world, and has been found in environment and biological specimen. TBBPA has strong acute toxicity to aquatic organisms, and could interfere with the binding of thyroid hormones (THs) to transthyretin (TTR) or thyroid hormone receptor (TR) in vitro. However, the results seem to be much different among the previous studies on thyroid hormone disrupting effects of TBBPA in vivo. Furthermore, pentabromophenol (PBP) also binds effectively to TTR in vitro, and its effects on fish in vivo should be detected.In present paper, goldfish (Carassius auratus) were exposed to 0.25 mg·l^-1 TBBPA and 0.05 mg·l^-1 PBP for 6 weeks firstly. TBBPA and PBP increased the height of the follicular epithelium, and induced thyroid epithelial cell hypertrophy and hyperplasia. The effects in TBBPA group were more significant. These results indicated that TBBPA and PBP might change goldfish's histopathology by interfering their thyroid hormone homeostasis.Secondly, goldfish were exposed to 0.5 mg·l^-1 TBBPA and 0.1 mg·l^-1 PBP for 28 days. Plasma TH levels were detected by microparticle enzyme immunoassay and radioimmunoassay. Compared with the control groups, TBBPA significantly resulted in the decrease of TT4 and TT3 levels, and the increase of rT₃ level, FT₄: TT₄, FT₃: TT₃, rT₃:TT₄ and rT₃: TT₃. PBP had weaker effects than TBBPA, and it seemed to have no effects on TT3 levels. These results showed that TBBPA and PBP can interfere THs levels in goldfish, and PBP showed poor effects on T3 levels.Thirdly, in the same exposure condition as the above, liver deiodinases activities were detected by radioimmunoassay. TBBPA significantly resulted in the increase of ID2 and ID3 activity, and the decrease of ID1 activity later. PBP could also lead in the increase of ID3 activity and the decrease ID1 activity, but it seemed to have no effects on ID2 activity. These results indicated that TBBPA and PBP might induce the metabolism and clearance of THs in goldfish.Finally, goldfish were exposed to 0.25, 0.025 mg·l^-1 TBBPA and 0.025, 0.0025 mg·l^-1 PBP for 12 weeks. The observation by transmission electron microscope methods showed that TBBPA and PBP could damage the hepatic ultramicrostructure, and the hepatic metabolism may increase. In addition, the damage of gill filament and liver cell nuclear by PBP were far more obvious than those by TBBPA.In brief, these results indicated that TBBPA and PBP could affect the thyroid system of goldfish. TBBPA showed more obvious thyroid hormone disrupting effects than PBP in goldfish, while it's direct toxicity to fish might be less than PBP. Mode of action analytic process suggested that TBBPA might affect the thyroid system in goldfish through both TTR and TR pathway, while PBP might only bring about this effect through TTR pathway. Based on this study, a cascade index system of thyroid hormone disrupting chemicals discrimination was raised.