Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent

• Published in: The Science of the total environment 2018-04, Vol.621, p.782-790
• Main Authors: David, Arthur, Lange, Anke, Tyler, Charles R., Hill, Elizabeth M.
• Format: Article
• Language: English
• Subjects: Animals; Antidepressants; Antipsychotics; Brain - drug effects; Cyprinidae - blood; Environmental Exposure - adverse effects; Fish; Life Sciences; Neurotransmitter Agents - blood; Neurotransmitter Agents - pharmacology; Neurotransmitters; Santé publique et épidémiologie; SSRIs; Waste Water; Wastewater effluents; Water Pollutants, Chemical - blood; Water Pollutants, Chemical - pharmacology
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2017.11.265

•A complex mixture of neuroactive pharmaceuticals accumulated in the brain and plasma of effluent-exposed roach.•Bioconcentration factors of the pharmaceuticals were 3-40 fold higher in brain compared with blood plasma•Fish plasma concentrations of pharmaceuticals were 33-5714 fold below human therapeutic plasma concentrations•Disruption in neurotransmitter concentrations were observed in brain regions of effluent-exposed fish. [Display omitted] Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were between 3–40 fold higher in brain compared with blood plasma, showing these neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for the potential for any adverse ecotoxicological effects, the effect ratio was calculated from human therapeutic plasma concentrations (HtPCs) and the measured or predicted fish plasma concentrations of pharmaceuticals. After accounting for a safety factor of 1000, the effect ratios indicated that fluoxetine, norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk assessment studies. Furthermore, although plasma concentrations of all the pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in serotonin, glutamate, acetylcholine and tryptophan concentrations were observed in different brain regions of effluent-exposed fish. This study highlights the importance of determining the potential health effects arising from the concentration of complex environmental mixtures in risk assessment studies.