Integrating Biological Activity with the Fish Plasma Model to Prioritize Antidepressants of Concern in Wastewater: A...

Antidepressants have been widely detected in aquatic environments, raising concerns about their potential adverse effects on the aquatic species. To date, their environmental risks have been primarily assessed by using the risk quotient approach and the classical fish plasma model. However, these methods do not consider the mode of action of antidepressants or interspecies variability in toxicokinetic parameters. In this study, wastewater effluent concentrations of 18 antidepressants and four metabolites in China were predicted based on consumption and used to estimate internal exposure in zebrafish using an adjusted fish plasma model. The pH-dependent octanol-water partition coefficient (Dow) and fathead minnow (Pimephales promelas) parameters were adopted to predict fish steady-state plasma concentrations (FssPCs). Antidepressants more strongly inhibited the zebrafish serotonin transporter (zSERT) than they did against the human transporter (hSERT). The inhibitory potencies of antidepressants against zSERT and hSERT were compared to derive fish therapeutic plasma concentrations (FTPCs), which were used as effect thresholds for risk assessment. The ratios of FssPCs to FTPCs were calculated to assess the environmental risks of antidepressants in China, England, and Japan. Uncertainty analysis was conducted to evaluate the model performance. Overall, the fish plasma model using Dow, fathead minnow parameters, and FTPCs provides an improved framework for predicting environmental risks of pharmaceuticals.