Effect-directed identification of novel aryl hydrocarbon receptor-active aromatic compounds in coastal sediments collected from a highly industrialized area

Self Cite

Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins (Delphinus capensis) and one fin whale (Balaenoptera physalus) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE-luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log K OA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

Section: Methodsmentioning

confidence: 99%

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening

Cha,

Hong,

Lee

et al. 2023

Self Cite

“…AhR-, AR-, GR-, and ER-mediated potencies of REs and RP-HPLC fractions were measured using H4IIE- luc , , MDA-kb2, , and T47D-kb luc , bioassays following the methods of previous studies. The cell culture and experimental conditions are shown in Table S2.…”

Section: Methodsmentioning

confidence: 99%

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening

Gwak

Lee

Cha

et al. 2022

Self Cite

Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log K OW 2.5–3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3–25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17β-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

“…48 Mixture toxic effects are suspected when the BEQ chem is significantly greater than the BEQ bio (Figure 2, Case 1). 6,10 When the BEQ chem and BEQ bio are similar, the analyzed compounds account for most of the responses (Figure 2, Case 2). 11,30 For most environmental samples, the BEQ chem is much smaller than the BEQ bio (Figure 2, Case 3), indicating the presence of unknown toxic substances.…”

Section: Step 2 Selection Of Toxicantmentioning

confidence: 99%

“…In recent years, the identification of novel toxic substances has been enabled due to the development of high-resolution mass spectrometry (HRMS) . Nontarget screening (NTS) aims to detect and identify all substances present in a sample and can be usefully applied in EDA to identify causative toxic substances in highly potent fractions. − The combined use of EDA and NTS addresses the limitations of performing only NTS, which lacks information on the potential toxicity of compounds in environmental samples. − ,− EDA combined with NTS has been applied successfully for the identification of unmonitored toxicants in sediment, wastewater, biota, etc. ,, This approach will help to expand the scope of analysis to include unknown substances, moving away from existing methods that rely solely on target chemical monitoring. , Furthermore, it is expected to facilitate the efficient incorporation of effect-based monitoring (EBM) into environmental monitoring programs. , The purpose of this paper is to describe the current status and limitations of EDA combined with NTS, with case studies of its successful application. In addition, we provide suggestions for the integration of EDA into future environmental monitoring programs and management policies.…”

Section: Effect-directed Analysis Combined With Nontarget Screeningmentioning

confidence: 99%

“…6 Chemical confirmation involves the comparison of retention times of compounds on gas chromatography (GC) or liquid chromatography (LC) using standard materials and the examination of the masses of fragment ions utilizing Full MS/ ddMS 2 . 4,10 When these analyses confirm that the substance matches the compound detected in the sample, quantitative analysis is performed. Toxicological confirmation is conducted with bioassays using diluted standards.…”

Section: Step 2 Selection Of Toxicantmentioning

confidence: 99%

See 1 more Smart Citation

Effect-Directed Analysis Combined with Nontarget Screening to Identify Unmonitored Toxic Substances in the Environment

Hong,

Lee,

Cha

et al. 2023

Self Cite

Effect-directed analysis (EDA) combined with nontarget screening (NTS) has established a valuable tool for the identification of unmonitored toxic substances in environmental samples. It consists of three main steps: (1) highly potent fraction identification, (2) toxicant candidate selection, and (3) major toxicant identification. Here, we discuss the methodology, current status, limitations, and future challenges of EDA combined with NTS. This method has been applied successfully to various environmental samples, such as sediments, wastewater treatment plant effluents, and biota. We present several case studies and highlight key results. EDA has undergone significant technological advancements in the past 20 years, with the establishment of its key components: target chemical analysis, bioassays, fractionation, NTS, and data processing. However, it has not been incorporated widely into environmental monitoring programs. We provide suggestions for the application of EDA combined with NTS in environmental monitoring programs and management, with the identification of further research needs.