Estrogenic and thyroid hormone activity of a series of hydroxy-polychlorinated biphenyls

A series of novel synthetic monohydroxy polychlorinated biphenyls (OH-PCBs) (5 trichloro-, 5 tetrachloro- and 5 pentachloro-compounds) have been characterized (H-1 and C-13 NMR and high resolution MS) and their estrogenic and thyroid hormone activities assessed using a yeast two-hybrid assay, both with and without possible metabolic activation by rat liver S9 preparation. Moderate estrogenic activity was found for 2,3,4'-trichlorobiphenyl-4-ol (compound 5) but this was eliminated when exposed to the S9 mix. 2,2',3',4,6-Pentachlorobiphenyl-3-ol (13) and 2',3,3',6-tetrachlorobiphenyl-4-ol (10) both showed weak estrogenicity in the absence of the S9 mix. The estrogenicity of compound (10) was enhanced 10-fold by exposure to S9 metabolic activation but that of compound (13) remained unchanged. 2',4,5',6-Tetrachlorobiphenyl-2-ol (6) showed strong thyroid hormonal activity (5% of that of T4) whereas 3',4,6-trichlorobiphenyl-3-ol (4), compound (10) and 2,3',4,5',6-pentachlorobiphenyl-3-ol (14) showed moderate activity, and 2',3,3', 5-tetrachlorobiphenyl-2-ol (8) and 3,3',5,5',6-pentachlorobiphenyl-2-ol (11) showed weak activity. The activity of (4) was eliminated by S9 metabolic activation whereas those of (6) and (14) were weakened and that of (10) remained unchanged. (C) 2003 Elsevier Science Ltd. All rights reserved.