Enantioselective ecotoxicity of venlafaxine in aquatic organisms: Daphnia and zebrafish

Venlafaxine is a chiral antidepressant detected in aquatic compartments. It was recently included in the 3rd Watch List from the European Union. The present study aimed to investigate venlafaxine toxicity effects, targeting possible enantioselective effects, using two aquatic organisms, daphnia (Daphnia magna) and zebrafish (Danio rerio). Specimens were exposed to both racemate, (R,S)-venlafaxine (VEN), and to pure enantiomers. Acute assays with daphnia showed that up to 50 000 mu g/L of the (R,S)-VEN induced no toxicity. Organisms were also exposed to sublethal concentrations (25-400 mu g/L) of (R,S)-, (R)- and (S)-VEN, for 21 days. No significant effects on mortality, age at first reproduction, and size of the first clutch were observed. However, a decrease in fecundity was observed for both enantiomers at the highest concentration. Regarding zebrafish, the effects of venlafaxine on mortality, embryo development, behavior, biochemistry, and melanin pigmentation were investigated after 96 h of exposure to the range of 0.3-3000 mu g/L. (R)-VEN significantly increased the percentage of malformations in comparison with (S)-VEN. Behavior was also enantiomer dependent, with a decrease in the total distance moved and an increase in avoidance behavior observed in organisms exposed to (R)-VEN. Despite the biochemical variations, no changes in redox homeostasis were observed. (R)-VEN also led to an increase in zebrafish pigmentation. The different susceptibility to venlafaxine and enantioselective effects were observed in zebrafish. Our results suggest that at environmental levels (R,S)-VEN and pure enantiomers are not expected to induce harmful effects in both organisms, but (R)-VEN increased malformations in zebrafish larvae, even at reported environmental levels. These results highlight the importance of including enantioselective studies for an accurate risk assessment of chiral pollutants. Environ Toxicol Chem 2022;00:1-14. (c) 2022 SETAC

The present study was supported by the National Funds by FCT-Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 (CITAB/Inov4Agro), the European Regrogramselopment Fund (programes COMPETE2020 and PT2020) project UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR), through national funds provided by FCT and Development Fund (ERDF), through the COMPETE-Programa Operacional Factores de Competitividade (POFC) in the framework of PT202rograms the strategic programes UID/BIA/04050/2019 (CBMA) and also FCT/MCTES (PIDDAC), under the project PTDC/CTA-AMB/6686/2020.