Acute toxicity assessment for binary and tertiary mixtures containing fluoxetine, propranolol and diclofenac to microcrustacean and zebrafish embryos

Abstract

Pharmaceuticals are essential for treatment and prevention of several diseases and for the maintenance of human and animal’s life quality. Due to the increasing use of pharmaceuticals worldwide, many actives substances are currently detected in μg.L-1 and ng.L-1 in different environmentals matrices such as surface water, ground water, soil and sediment. Many of these emerging pollutants are recalcitrant to biological treatment process in WWTPs and they may cause ecotoxicological effects on organisms and also possible to reach the human food chain. Pharmaceuticals are frequently detected as mixtures and may induce toxic effects to aquatic organisms, producing synergistic, additive or antagonistic toxic effects. Fluoxetine hydrochloride (FXT) is a selective serotonin reuptake inhibitor, prescribed as an antidepressant. Propranolol (PRP) is a beta-adrenergic blocker widely prescribed for the treatment of cardiovascular diseases and diclofenac sodium (DIC) is a non-steroidal anti-inflammatory drug, often recognized as the “world’s most popular pain killer”. These compounds are worldwide used for healthy treatment and also often detected in aquatic environments. This work aims to assess the toxicity of three pharmaceutical individually and in a mixture for both Daphnia similis and zebrafish embryos. The results of individual acute toxicity showed that the microcrustacean was more sensitive to FXT (EC50 = 1.08 mg/L), PRP (EC50 = 5.92 mg/L) and DIC (EC50 = 25.0 mg/L), respectively, while for zebrafish embryos, it was only calculated LC50 of 30.5 mg/L for DIC, after 48h exposure. Antagonistic effects of binary mixtures of FLX + PRP (EC50 = 9.38%) and FXT + DIC (EC50 = 24.2%) were observed to D. similis. For Danio rerio embryos, binary mixture of FLX + DIC (LC50 = 82.1%) presented antagonistic effects, while no acute toxicity was observed for the of FXT + PRP mixture. Tertiary mixture of the three compounds showed an antagonist effect (EC50 = 5.57%) for the microcrustacean and additive effect for zebrafish embryos (LC50 = 87.5%). In conclusion, most of the binary mixture resulted in antagonistic effects, in which the response of acute toxicity depended on the organism and type of pharmaceutical mixture. Therefore, it is necessary further studies to assess the toxicity of different mixtures.