Junghyun Lee ^a, Seongjin Hong ^b,*, Taewoo Kim ^a, Shin Yeong Park ^a, Jihyun Cha ^b, Youngnam Kim ^b, Jiyun Gwak ^b, Sunggyu Lee ^c, Hyo-Bang Moon ^c, Wenyou Hu ^d, Tieyu Wang ^e, John P. Giesy ^f,g, Jong Seong Khim ^a,*

^a School of Earth and Environmental Sciences & Research Institute of Oceanography, Seoul National University, Seoul 08826, Republic of Korea ^b Department of Marine Environmental Science, Chungnam National University, Daejeon 34134, Republic of Korea ^c Department of Marine Science and Convergence Engineering, Hanyang University, Ansan 15588, Republic of Korea ^d Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China ^e Institute of Marine Sciences, Shantou University, Shantou 515063, China ^f Department of Veterinary Biomedical Sciences & Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N5B3, Canada ^g Department of Environmental Science, Baylor University, Waco, TX 76798-7266, United States

^*Corresponding authors.

Novel aryl hydrocarbon receptor (AhR) agonists were identified in coastal sediments in the Yellow and Bohai Seas by use of a combination of effect-directed analysis (EDA) and in silico prediction. A total of 125 sediments were screened for AhR-mediated potencies using H4IIE-luc bioassay. Great potencies were observed in organic extracts, mid-polar fraction (F2), and subfractions of F2 (F2.6–F2.9) of sediments collected from Nantong, Qinhuangdao, and Yancheng. Less than 15% AhR potencies could be explained by detected dioxin-like PAHs. Full-scan screening analysis was conducted for the more potent fractions using GC-QTOFMS to investigate the presence of unmonitored AhR agonists. A five-step prioritization strategy was applied; 92 candidate compounds satisfied all criteria. Among these chemicals, thirteen were evaluated for AhR efficacy. Six compounds; benz[b]anthracene, 6-methylchrysene, 2-methylbenz[a]anthracene, 1-methylbenz[a]anthracene, 1,12-dimethylbenzo[c]phenanthrene, and indeno[1,2,3-cd]fluoranthene, exhibited significant AhR-mediated efficacies. 1,12-dimethylbenzo[c]phenanthrene and indeno[1,2,3-cd]fluoranthene were identified as novel AhR agonists. Potency balance analysis showed that the six newly identified AhR agonists explained 0.4–100% of the total AhR-mediated potencies determined. Overall, combining EDA and in silico prediction applied in this study demonstrated the benefits of assessing the potential toxic effects of previously unidentified AhR agonists in sediments from the coasts of China and Korea.