Identifying bioaccessible suspect toxicants in sediment using adverse outcome pathway directed analysis

• Published in: Journal of hazardous materials 2020-05, Vol.389, p.121853, Article 121853
• Main Authors: Cheng, Fei, Li, Huizhen, Ma, Huimin, Wu, Fengchang, Fu, Zhiyou, You, Jing
• Format: Article
• Language: English
• Subjects: Adverse outcome pathway; Adverse Outcome Pathways; Benzhydryl Compounds - toxicity; Benzopyrans - toxicity; Bioaccessibility; Biological Assay; Biological Availability; Calcium - metabolism; Cell Line; Cell Survival - drug effects; China; Cities; Effect-directed analysis; Geologic Sediments; Hazardous Substances - toxicity; Humans; Membrane Potential, Mitochondrial; Neurotoxicity; Neurotoxicity Syndromes; Phenols - toxicity; Pyrethrins - toxicity; Reactive Oxygen Species - metabolism; Rivers; Sediment; Tetrahydronaphthalenes - toxicity; Toxicity Tests; Water Pollutants, Chemical - toxicity
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2019.121853

[Display omitted] •Multiple endpoint bioassays were used to link adverse outcome pathway to EDA.•Different sensitivity of cells from different organs guided specific pathway selection.•Bioaccessibility was considered in EDA by using large volume XAD resin extraction.•Cypermethrin and musks were identified as key neruotoxicants in urban sediment.•Including bioaccessibility and AOP improved environmental relevance for EDA. Chemical mixtures are a common occurrence in contaminated sediment and determining causal relationship between sediment contamination and adverse outcomes is challenging. The bioavailability and choice of bioassay endpoints played important roles in elucidating causality. As such, bioaccessibility-based XAD extraction and adverse outcome pathway (AOP) guided bioassays were incorporated into an effect-directed analysis to more effectively determine sediment causality. XAD extracts of sediments from urban waterways in Guangzhou, China were examined using cell viability bioassays with four human tumor cells from lung, liver, breast, and bone marrow. Pronounced effects to SH-SY5Y cells were noted, thus neurotoxicity was subsequently focused in the AOP-guided bioassays. Intracellular calcium influx, mitochondrial membrane potential inhibition, reactive oxygen species generation, and cell viability were utilized as evidence for neurotoxicity AOP-guided analysis. Suspect toxicants were identified in active fractions using GC–MS. Toxicity confirmation was performed by evaluating toxicity contributions of the candidates to the pathway. Cypermethrin, bisphenol A, galaxolide, tonalide, and versalide were found as the major stressors across key events of the studied pathway. Moreover, good correlations among key events validated the feasibility of method to predict in vivo response, suggesting that considering bioavailability and AOP improved environmental relevance for toxicant identification in a complex mixture.