Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds: Affinity to the mammalian thyroid hormone receptor, and effect on tadpole metamorphosis

The thyroid hormone-disrupting activity of tetrabromobisphenol A (TBBPA), a flame retardant, and related compounds was examined. TBBPA, tetrachlorobisphenol A (TCBPA), tetramethylbisphenol A (TMBPA) and 3,3′-dimethylbisphenol A (DMBPA) markedly inhibited the binding of triiodothyronine (T3; 1 × 10−10 M) to thyroid hormone receptor in the concentration range of 1 × 10−7-1 × 10−4 M, while bisphenol A and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA and DMBPA did not exhibit thyroid hormonal activity in a thyroid hormone-responsive reporter assay using a Chinese hamster ovary cell line (CHO-K1) transfected with thyroid hormone receptor α1 or β1, but TBBPA and TCBPA showed significant anti-thyroid hormone effects on the activity of T3 (1 × 10−8 M) in the concentration range of 3 × 10−6 - 5 × 10−5 M. The thyroid hormone-disrupting activity of TBBPA was also examined in terms of the effect on amphibian metamorphosis stimulated by thyroid hormone. TBBPA in the concentration range of 1 × 10−8 to 1 × 10−6 M showed suppressive action on T3 (5 × 10−8 M)-enhancement of Rana rugosa tadpole tail shortening. These facts suggest that TBBPA, TCBPA, TMBPA and DMBPA can act as thyroid hormone-disrupting agents.