Diclofenac: New data on chronic toxicity and bioconcentration in fish

Abstract

Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug that is regularly detected in surface waters. To support a robust aquatic risk assessment, two early life stage (ELS) tests, compliant with the Organisation for Economic Co-operation and Development (OECD) test guideline 210, were conducted in rainbow trout and in zebrafish. Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined. The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305. The bioconcentration factor (BCF) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish. In the rainbow trout ELS test, the no observed effect concentration (NOEC) including histopathology was 320 µg/L. The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 µg/L. However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 µg/L not a repeatable, treatment-related effect of DCF. This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 µg/L. This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng/L to low µg/L. Environ. Toxicol. Chem. 2013;32:442–452. © 2013 SETAC

Rapid analysis of diclofenac in freshwater and wastewater by a monoclonal antibody-based highly sensitive ELISA

“…In Germany, for example, the yearly consumption exceeds 80 tons [8]. Depending on the efficiency of the WWTP, the parent drug and metabolites enter the environment, followed by bioaccumulation and impairment of aquatic wildlife like mussels and fish, possibly [9][10][11][12][13][14][15]. The most spectacular observation has been reported from South Asia that veterinary use of DCF is the main cause of catastrophic population decline of three species of Gyps vultures since the mid-1990s [16][17][18].…”

“…In surface water, DCF was found at concentrations up to 0.6 μg/L. One subject of current research is whether environmental exposure to DCF at relevant concentration in freshwater can affect certain species, e.g., fish [9][10][11][12][13][14][15]. Recently, DCF and the major human metabolites 4'OH-DCF, 5-OH-DCF, and DCF-1-O-acyl glucuronide (DCF-GLU) were quantified in WWTP influents and effluents [22].…”

Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish

“…Diclofenac also affected gene expression in rainbow trout at 1 µg/L (Cuklev et al, 2011), and it activated VTG and CYP1A expression at 1 µg/L (Hong et al, 2007) and changed feeding behavior at 1000 µg/L (Nassef et al, 2010) in Japanese medaka. Contrary to these investigations, no observed effects were seen at concentrations of 320 µg/L in rainbow trout after 95 days' exposure (Memmert et al, 2013). The NSAIDs ibuprofen and mefenamic acid increased 17β-estradiol, testosterone and transcription of CYP19A gene levels in zebrafish (Ji et al, 2013), indicating that these compounds havebehaviours of endocrine disrupter.…”

“…Previous studies indicate that NSAIDs have effects on fish at environmentally relevant concentrations (Saravanan and Ramesh, 2013) and caused adverse histopathological changes in various tissues of many species (Hoeger et al, 2005;Mehinto et al, 2010;Memmert et al, 2013;Schwaiger et al, 2004) at higher concentrations. Metabolites of naproxen and ibuprofen have been identified in bile as well as in gill and hepatic S9 fractions, respectively, of rainbow trout (Brozinski et al, 2011;Gomez et al, 2011).…”

Inhibition of immune responses and related proteins in Rhamdia quelen exposed to diclofenac

“…That observation caught the attention of the global scientific community [7,8]. Bioconcentration factors for diclofenac in fish from laboratory bioassays are often lower than 500 [11,12], whereas bioaccumulation factors for field-captured fish and aquatic life ranged from 46 to 956 [13,14]. Bioconcentration factors for diclofenac in fish from laboratory bioassays are often lower than 500 [11,12], whereas bioaccumulation factors for field-captured fish and aquatic life ranged from 46 to 956 [13,14].…”