Novel polar AhR-active chemicals detected in sediments of an industrial area using effect-directed analysis based on in vitro bioassays with full-scan high resolution mass spectrometric screening

Studies investigating aryl hydrocarbon receptor (AhR)-active compounds in the environment typically focus on non- and mid-polar substances, such as PAHs; while, information on polar AhR agonists remains limited. Here, we identified polar AhR agonists in sediments collected from the inland creeks of an industrialized area (Lake Sihwa, Korea) using effect-directed analysis combined with full-scan screening analysis (FSA; using LC-QTOFMS). Strong AhR-mediated potencies were observed for the polar and latter fractions of RP-HPLC (F3.5-F3.8) from sediment organic extracts in the H4IIE-luc in vitro bioassays. FSA was performed on the corresponding fractions. Twenty-eight tentative AhR agonists were chosen using a five-step process. Toxicological confirmation using bioassay revealed that canrenone, rutaecarpine, ciprofloxacin, mepanipyrim, genistein, protopine, hydrocortisone, and medroxyprogesterone were significantly active. The relative potencies of these AhR-active compounds compared to that of benzo[a]pyrene ranged from 0.00002 to 2.0. Potency balance analysis showed that polar AhR agonists explained, on average, ~6% of total AhR-mediated potencies in samples. Some novel polar AhR agonists also exhibited endocrine-disrupting potentials capable of binding to estrogen and glucocorticoid receptors, as identified by QSAR modeling. In conclusion, the focused studies on distributions, sources, fate, and ecotoxicological effects of novel polar AhR agonists in the environment are necessary.