Residues of Cardiovascular and Lipid-Lowering Drugs Pose a Risk to the Aquatic Ecosystem despite a High Wastewater Treatment Ratio in the Megacity Shanghai, China

Abstract

The residues of pharmaceuticals in surface waters of megacities and ecotoxicological implications are of particular concern. In this study, we combined field investigations and model simulations to explore the contamination of cardiovascular and lipid-lowering drugs, one group of the most prescribed medications globally, in surface waters of a typical megacity, Shanghai, with a high wastewater treatment ratio (≈96%). Among 26 target substances, 19 drugs were detected with aqueous concentrations ranging from 0.2 (ketanserin) to 715 ng/L (telmisartan). Of them, angiotensin II receptor antagonists, telmisartan and irbesartan, were dominant besides β-blockers. Spatial distribution analysis demonstrated their much higher levels in tributaries compared to the mainstream. The results of model simulations and field investigation revealed relatively low concentrations of cardiovascular and lipidlowering drugs in surface waters of Shanghai compared to other cities in highly developed countries, which is associated with low per capita usage in China. Ecotoxicological studies in zebrafish embryos further revealed developmental effects, including altered hatching success and heart rate, by irbesartan, telmisartan, lidocaine, and their mixtures at ng/L concentrations, which are typical levels in surface waters. Overall, the present results suggest that the high wastewater treatment ratio was not sufficient to protect fish species in the aquatic ecosystem of Shanghai. Exposure to cardiovascular and lipid-lowering drugs and associated risks will further increase in the future due to healthcare improvements and population aging.

Reduced Transcriptome Analysis of Zebrafish Embryos Prioritizes Environmental Compounds with Adverse Cardiovascular Activities

“…Furthermore, there are potential cardiovascular disruptive compounds that are missed in the hit list due to lack of transcriptome profiling, as, for instance, cardiovascular pharmaceuticals that are designed for these purposes and occurring in the environment. 15,50 Despite these limitations, our approach via transcriptome profiling yields positive results and underpins the success in the confirmation of known and the discovery of unknown cardiovascular disruptors as verified by the following experimental data. Verification Experiments.…”

“…Thus, as a limitation of our concept, a few active compounds that lack investigation at different concentrations, or which do not fulfill all criteria, may not be identified due to different exposure times and concentrations and due to the lower number of affected genes. Furthermore, there are potential cardiovascular disruptive compounds that are missed in the hit list due to lack of transcriptome profiling, as, for instance, cardiovascular pharmaceuticals that are designed for these purposes and occurring in the environment. , Despite these limitations, our approach via transcriptome profiling yields positive results and underpins the success in the confirmation of known and the discovery of unknown cardiovascular disruptors as verified by the following experimental data.…”

“…They also lead to large variations among investigations. For example, a 28 °C culture temperature was employed in our fish facility, while 26 or 27 °C culture temperatures can be found in other studies. , Such variations in the experimental procedures may explain the inconsistency between data from the previous transcriptomics and the present verification experiments.…”

Environmental impact of cardiovascular healthcare

“…Two studies examined concentrations of cardiovascular and lipid regulating drugs in effluent water released from municipal wastewater treatment plants, and in surface waters globally. Many cardiovascular drugs (58 of 82 drugs assessed in a systematic review of 322 studies, 13 and 19 of 26 drugs assessed in a recent primary study in Shanghai, China) 14 were detected in both types of waterways, in concentrations of up to several μg/L in wastewater and up to hundreds of ng/L in surface waters. ß-blockers, lipid regulating agents, ACE inhibitors, angiotension II receptor antagonists and diuretics were commonly studied and found in waterways, even after wastewater treatment.…”

Human Apparent Volume of Distribution Predicts Bioaccumulation of Ionizable Organic Chemicals in Zebrafish Embryos

“…A recent study showed that pharmaceuticals present a threat to ecosystems and human beings in more than a quarter of the studied surface waters globally . Although wastewater treatment infrastructure has been continuously advancing, it is still insufficient to remove trace emerging contaminants, including many pharmaceuticals . As such, it is estimated that approximately 80% of pharmaceuticals are IOCs .…”