A framework is presented that is intended to facilitate the evaluation of potential aquatic ecological risks resulting from discharges of down the drain chemicals. A scenario is presented using representatives of many of the types of chemicals that are treated domestically. Predicted treated effluent chemical concentrations (PECS) are based on reported loading rates and routine removal rates for three types of treatment: trickling filter (TF), activated sludge secondary treatment (AS), and AS plus advanced oxidation process (AOP). In Tier I, PECs were compared with the lowest predicted no effect concentration (PNEC) obtained from the literature using safety factors as needed. A cumulative risk characterization ratio (cumRCR) <1.0 indicates risk is unlikely and no further action is needed. Otherwise, a Tier 2 assessment is used, in which PNECs are based on trophic level. If Tier 2 indicates a possible risk, then a retrospective assessment is recommended. In Tier 1, the cumRCR was > 1.0 for all three treatment types in our scenario, even though no chemical exceeded a hazard quotient of 1.0 in AS or AOP. In Tier 2, AS yielded a lower cumRCR than TF due to higher removal rates and the cumRCR in AOP was <<1.0. Based on the maximum cumulative risk ratio (MCR), more than one third of the predicted risk was accounted for by one chemical and at least 90% was accounted for by three chemicals, indicating that few chemicals influenced the mixture risk in our scenario. We show how a retrospective assessment can test whether certain chemicals hypothesized as potential drivers in the prospective assessment could have, or are having, deleterious effects on aquatic life.