Selective serotonin reuptake inhibitors and β-blocker transformation products may not pose a significant risk of toxicity to aquatic organisms in wastewater effluent-dominated receiving waters.

A probabilistic ecological risk assessment was conducted for the transformation products (TPs) of 3 β-blockers (atenolol, metoprolol, and propranolol) and 5 selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) to assess potential threats to aquatic organisms in effluent-dominated surface waters. To this end, the pharmacokinetic literature, the University of Minnesota's Biocatalysis/Biodegradation Database Pathway Prediction System aerobic microbial degradation software, and photolysis literature pertaining to β-blockers and SSRIs were used to determine their most likely TPs formed via human metabolism, aerobic biodegradation, and photolysis, respectively. Monitoring data from North American and European surface waters receiving human wastewater inputs were the basis of the exposure characterizations of the parent compounds and the TPs, where available. In most cases, where monitoring data for TPs did not exist, we assumed a conservative 1:1 parent-to-TP production ratio (i.e., 100% of parent converted). The US Environmental Protection Agency (USEPA)'s EPISuite and ECOSAR v1.11 software were used to estimate acute and chronic toxicities to aquatic organisms. Hazard quotients, which were calculated using the 95(th) percentile of the exposure distributions, ranged from 10(-11) to 10(-3) (i.e., all significantly less than 1). Based on these results, the TPs of interest would be expected to pose little to no environmental risk in surface waters receiving wastewater inputs. Overall, we recommend developing analytical methods that can isolate and quantify human metabolites and TPs at environmentally relevant concentrations to confirm these predictions. Further, we recommend identifying the major species of TPs from classes of pharmaceuticals that could elicit toxic effects via specific modes of action (e.g., norfluoxetine via the serotonin 5-hydroxytryptamine [5-HT]1A receptors) and conducting aquatic toxicity tests to confirm these findings. To our knowledge, this is the first quantitative probabilistic ecotoxicological assessment of all of the predicted and probable TPs of these pharmaceuticals, and our approach provides a framework for future such studies with other compound classes as data become available.