The present study used diffusive gradients in thin film (DGT) samplers deployed in situ at a wastewater-impacted site (Clarkboro Ferry) for 20 days to develop a predictive model between time-weighted mean concentrations of seven selected antipsychotic compounds in water and those in resident benthic invertebrates, specifically crayfish (Faxonius virilis). The model was further combined with a model of desorption of antipsychotic compounds to predict kinetics at the sediment-water interface. Antipsychotic compounds were mostly detected in adult crayfish and internal concentrations were similar among targeted compounds, except for lesser concentrations of duloxetine. The model, based on the mass balance of organic chemicals, to predict uptake by organisms exhibited good agreement with measured values (R  = 0.53-0.88), except for venlafaxine (R  = 0.35). At the sediment-water interface, positive fluxes were observed for antipsychotic compounds and the results from DGT-induced fluxes in sediments (DIFS) coupled with equilibrium hydroxyl-β-cyclodextrin extraction further indicated partial resupply of antipsychotic compounds from sediments to the aqueous phase, despite the labile pool being relatively limited. The results of the present study affirm that DGT techniques can be used as a predictive tool for contamination in benthic invertebrates and can simulate the ability of contaminant resupply from sediments. Environ Toxicol Chem 2023;42:1696-1708. © 2023 SETAC.

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