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.
Keywords: Adverse outcome pathway; Bioaccessibility; Effect-directed analysis; Neurotoxicity; Sediment.
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