**4. Final Remarks**

A literature review was conducted in order to understand the toxicity and ERA of pharmaceuticals in the aquatic environment. In this context, a broad and specialized background was obtained, enabling an overview of the state of the art in these subjects.

Regarding the toxicity data, although the differences observed between different therapeutic groups and within each therapeutic group, all therapeutic groups with the exception of anxiolytics, had at least one toxicity report for concentrations below 1 μg L−1. The trophic level with the lowest concentrations promoting toxic effects was fish, followed by invertebrates and algae, emphasizing that fish, the trophic level closer to humans, are more prone to toxicity effects from the selected pharmaceuticals.

The results also show that pharmaceuticals with higher RQs are not the ones with higher occurrence and that proper toxicity data is important to a correct evaluation of the ERA.

The ERA performed for the pharmaceuticals in the different aquatic compartments revealed, with the exception of anxiolytics, RQs higher than 1, not only for WWIs but also for all aquatic compartments, for all trophic levels and therapeutic groups.

The therapeutic groups with the highest RQs in all aquatic compartments are hormones, antiepileptics, anti-inflammatories and antibiotics and the pharmaceuticals with the highest values are the EE2, CAR, IBU, CIP and AZI in all aquatic compartments. Highlighting threat to all the aquatic organisms exposed, namely on the feminization of fish by EE2 and its impact on aquatic ecosystems. Additionally, two antibiotics are among the pharmaceuticals with higher RQs and the ERA does not evaluate the emergence of bacterial resistance. If this issue was also evaluated it would probably confirm why they are considered the therapeutic group with the highest risk for humans, regarding the residues of medicinal products in the environment.

Unfortunately, the pressure of pharmaceuticals on aquatic bodies will continue to rise, and, therefore, mitigation measures and changes in legislation must be implemented.

**Supplementary Materials:** The following are available online: Table S1: Ecotoxicological data on the selected pharmaceuticals, Table S2: Occurrence data from the different aquatic compartments for environmental risk assessment evaluation.

**Author Contributions:** Conceptualization, A.P. (André Pereira), L.S. and A.P. (Angelina Pena); Methodology, A.P. (André Pereira), L.S. and A.P. (Angelina Pena); Formal analysis, A.P. (André Pereira); Writing—original draft preparation, A.P. (André Pereira); Writing—review and editing, A.P. (André Pereira), L.S. and C.L. (Celia Laranjeiro); Supervision, C.L. (Celeste Lino) and A.P. (Angelina Pena); Project administration, A.P. (Angelina Pena). All authors have read and agreed to the published version of the manuscript.

**Funding:** The work was supported by UIDB/50006/2020 with funding from FCT/MCTES through national funds. **ConflictsofInterest:**Theauthorsdeclarenoconflictof interest.
