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 (1H and 13C 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.