Identification of AhR agonists in sediments of the Bohai and Yellow Seas using advanced effect-directed analysis and in silico prediction

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

“…Because VEGA QSAR is based on compound structures, some models may produce different results. Thus, an integrated evaluation that carefully considers the necessary information and quantifies the mechanisms of toxic expression is required . From the result of investigating the additional toxicity of seven tentative ER agonists through EPA ToxCast, some compounds were confirmed to have AR, GR, and ER activities (Table ).…”

“…Thus, an integrated evaluation that carefully considers the necessary information and quantifies the mechanisms of toxic expression is required. 64 From the result of investigating the additional toxicity of seven tentative ER agonists through EPA ToxCast, some compounds were confirmed to have AR, GR, and ER activities (Table 1). Overall, the newly identified ER agonists were confirmed to have various potential toxicities, such as mutagenicity, carcinogenicity, and developmental toxicity.…”

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

“…Such materials are frequently unavailable , or cannot be purchased due to their high cost or export/import restrictions . In such instances, in silico modeling and toxicity prediction databases can be utilized to predict the toxicological potencies of chemicals, providing insights into their toxicity mechanism, effective concentration (EC), and inhibitory concentration . 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 . , When these analyses confirm that the substance matches the compound detected in the sample, quantitative analysis is performed.…”

“…Effect-directed analysis (EDA) is a valuable method for identifying major toxicants in environmental samples. − It enables the detection of toxic substances in samples with complex matrixes, as “finding a needle in a haystack.” − The principle of EDA is to reduce sample complexity by fractionating samples that exhibit significant toxicity. − Subsequently, bioassays and chemical analyses are conducted repeatedly to identify the major toxic substances in highly potent fractions. − This process is challenging, but the results have far-reaching implications for the identification of toxic substances that have not been monitored previously. − Target chemicals are often called the “tip of the iceberg” because they account for only a small portion of the observed biological effects, indicating that unmonitored toxic substances may be present in environmental samples. In recent years, the identification of novel toxic substances has been enabled due to the development of high-resolution mass spectrometry (HRMS) .…”

“…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.…”