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

Area of Science:

• Environmental Toxicology
• Chemical Analysis
• Risk Assessment

Background:

• Chemical mixtures in contaminated sediments pose challenges in establishing causality between contamination and adverse outcomes.
• Bioavailability and bioassay endpoint selection are critical for elucidating causal relationships in sediment toxicity.

Purpose of the Study:

• To develop and apply an effect-directed analysis incorporating bioaccessibility and adverse outcome pathways (AOPs) for improved sediment toxicity causality.
• To identify specific toxicants in urban waterway sediments and confirm their contribution to neurotoxicity.

Main Methods:

• Bioaccessibility-based XAD extraction of sediment samples.
• Adverse Outcome Pathway (AOP)-guided bioassays focusing on neurotoxicity endpoints (calcium influx, mitochondrial potential, ROS, viability).
• Gas Chromatography-Mass Spectrometry (GC-MS) for suspect toxicant identification and toxicity confirmation.

Main Results:

• XAD extracts from Guangzhou urban waterways exhibited significant neurotoxicity in SH-SY5Y cells.
• Cypermethrin, bisphenol A, galaxolide, tonalide, and versalide were identified as major contributors to neurotoxicity across key AOP events.
• Strong correlations among AOP key events validated the method's ability to predict in vivo responses.

Conclusions:

• Integrating bioavailability and AOPs enhances the environmental relevance of toxicant identification in complex chemical mixtures.
• The developed effect-directed analysis is a feasible method for predicting in vivo responses from sediment contamination.
• This approach improves the determination of causal relationships between sediment contamination and adverse biological outcomes.