No Clear Evidence of Histopathological Effects Linked to NSAIDs in the Kidney or Liver of Fish Exposed to Treated Municipal Wastewaters

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause histopathological changes in the kidney and liver of fish. Still, it is unclear whether exposure to treated municipal wastewater that contains NSAID residues causes similar effects. We therefore conducted a comprehensive, critical review on claimed histopathological changes in fish exposed either to NSAIDs or to treated municipal wastewater in the laboratory or downstream from treatment plants. A detailed scrutinization questioned the basis for several findings. Hepatocellular necrosis, hepatocellular vacuolation, and an increase of developing nephrons/basophilic clusters (DNs/BCs) were overlapping findings, but the lowest observed effect concentrations (LOEC) for the hepatic endpoints were well above concentrations frequently encountered in treated effluents. An increase of DNs/BCs were reported at lower NSAID concentrations, but with some concerns regarding reliability. Hence, there is no clear documentation that histopathological effects caused by NSAIDs are present in fish exposed to municipal effluents. Study design, including the species studied, exposure regimes, endpoints analyzed, and applied methodology varied widely between studies, all of which could make overlapping effects difficult to detect. In addition, limitations in both experimental design and reporting standards in fish histopathology studies prevent any firm conclusions. More comparable study designs in future studies would facilitate comparisons.