Chronic effects of exposure to a pharmaceutical mixture and municipal wastewater in zebrafish

• Published in: Aquatic toxicology Vol. 132-133; pp. 212 - 222
• Main Authors: Galus, Michal, Jeyaranjaan, Judy, Smith, Emily, Li, Hongxia, Metcalfe, Chris, Wilson, Joanna Y.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.05.2013; Elsevier
• Subjects: abnormal development; Animal, plant and microbial ecology; Animals; apoptosis; Applied ecology; Applied sciences; at-risk population; Biological and medical sciences; Chromatography, High Pressure Liquid; chronic exposure; Danio rerio; Development; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions - pathology; Drug-Related Side Effects and Adverse Reactions - physiopathology; drugs; Ecotoxicology, biological effects of pollution; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - embryology; embryonic mortality; Environmental Exposure; environmental impact; Enzyme-Linked Immunosorbent Assay; Exact sciences and technology; Female; fish; Fundamental and applied biological sciences. Psychology; General aspects; Histology; histopathology; In Situ Nick-End Labeling; kidneys; long term effects; Male; oocytes; personal care products; Pharmaceutical mixture; Pollution; Reproduction; Reproduction - drug effects; reproductive performance; risk; Tandem Mass Spectrometry; Waste Water; wastewater; Wastewater effluent; Wastewaters; Water Pollutants, Chemical - toxicity; Water treatment and pollution; Zebrafish; Zebrafish - growth & development; Zebrafish - physiology; Reproduction; ACE; WWE; Pharmaceutical mixture; Development; Wastewater effluent; Zebrafish; Histology; CBZ; MIX; GEM; VEN; Drug; Ecotoxicology; Toxicity; Waste water; Aquatic environment; Vertebrata; Brachydanio rerio; Chronic; Pollution; Pisces; Urban waste water; Cyprinidae; Effluent; Organic compounds
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2012.12.016

► We exposed zebrafish to a mixture of 4 pharmaceuticals and wastewater effluent. ► Exposures were chronic and environmentally relevant concentrations. ► Both mixtures impacted reproduction and histology of the kidney. ► Both mixtures increased developmental abnormalities. Pharmaceuticals and personal care products (PPCPs) are discharged in municipal wastewater. Effects in aquatic organisms exposed to individual pharmaceuticals in the laboratory have raised concerns regarding the environmental impacts of PPCPs, yet environmental exposures are always to complex mixtures. In this study, adult zebrafish (Danio rerio) showed significantly decreased embryo production after a 6 week exposure to a pharmaceutical mixture (MIX; 0.5 and 10μgL−1) of acetaminophen, carbamazepine, gemfibrozil and venlafaxine and to diluted wastewater effluent (WWE; 5% and 25%). Atretic oocytes and altered ovarian histology were significantly increased in female zebrafish exposed to both concentrations of MIX or WWE, which indicates a direct effect on oocyte development that may account for reduced embryo production. Apoptosis within the thecal and granulosa cell layers was identified in female zebrafish with atresia. Exposures to MIX or WWE at both concentrations severely altered kidney proximal tubule morphology, but no histological impacts on other organs were observed. Exposure of embryos to MIX or WWE at the high concentration significantly increased the incidence of developmental abnormalities. Embryo mortality was elevated with exposure to the high concentration of MIX. These studies indicate that chronic exposure of fish to pharmaceutical mixtures and wastewater impacts reproduction and induces histopathological changes, similar to what we have previously seen with single compound exposures. These data suggest that fish populations exposed to pharmaceuticals discharged in wastewater are at risk of negative impacts to reproductive capacity and health.