Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac

Johanna Näslund,Noomi Asker,Jerker Fick,D.G Joakim Larsson,Leif Norrgren

doi:10.1016/j.aquatox.2020.105583

Johanna Näslund, Noomi Asker + Show 3 more

Open Access

https://doi.org/10.1016/j.aquatox.2020.105583

Copy DOI

Abstract

The presence of diclofenac in the aquatic environment and the risks for aquatic wildlife, especially fish, have been raised in several studies. One way to manage risks without enforcing improved wastewater treatment would be to substitute diclofenac (when suitable from a clinical perspective) with another non-steroidal anti-inflammatory drug (NSAID) associated with less environmental risk. While there are many ecotoxicity-studies of different NSAIDs, they vary extensively in set-up, species studied, endpoints and reporting format, making direct comparisons difficult. We previously published a comprehensive study on the effects of diclofenac in the three-spined stickleback (Gasterosteus aculeatus). Our present aim was to generate relevant effect data for another NSAID (naproxen) using a very similar setup, which also allowed direct comparisons with diclofenac regarding hazards and risks. Sticklebacks were therefore exposed to naproxen in flow-through systems for 27 days. Triplicate aquaria with 20 fish per aquarium were used for each concentration (0, 18, 70, 299 or 1232 μg/L). We investigated bioconcentration, hepatic gene expression, jaw lesions, kidney and liver histology. On day 21, mortalities in the highest exposure concentration group unexpectedly reached ≥ 25 % in all three replicate aquaria, leading us to terminate and sample that group the same day. On the last day (day 27), the mortality was also significantly increased in the second highest exposure concentration group. Increased renal hematopoietic hyperplasia was observed in fish exposed to 299 and 1232 μg/L. This represents considerably higher concentrations than those expected in surface waters as a result of naproxen use. Such effects were observed already at 4.6 μg/L in the experiment with diclofenac (lowest tested concentration). Similar to the responses to diclofenac, a concentration-dependent increase in both relative hepatic gene expression of c7 (complement component 7) and jaw lesions were observed, again at concentrations considerably higher than expected in surface waters. Naproxen bioconcentrated less than diclofenac, in line with the observed effect data. An analysis of recent sales data and reported concentrations in treated sewage effluent in Sweden suggest that despite higher dosages used for naproxen, a complete substitution would only be expected to double naproxen emissions. In summary, naproxen and diclofenac produce highly similar effects in fish but the environmental hazards and risks are clearly lower for naproxen. Hence, if there are concerns for environmental risks to fish with diclofenac, a substitution would be advisable when naproxen presents an adequate alternative from a clinical point-of-view.

Highlights

In the last decades, there has been an increasing concern about pharmaceuticals in the environment and the effects they can have on non-target organisms
We show here that naproxen affects kidney histology and hepatic gene expression, and induces jaw lesions in fish in a similar way as diclofenac does
It is possible that the effects on e.g. mortality and condition factor is a reflection of additional mechanisms of actions that become relevant only at higher exposure concentrations which are less plausible for fish to encounter

Summary

Introduction

There has been an increasing concern about pharmaceuticals in the environment and the effects they can have on non-target organisms. Diclofenac concentrations in treated sewage effluents are gen erally below (Loos et al, 2013) or around 1 μg/L (Brown et al, 2007; Fick et al, 2010a; Meyer et al, 2016) and similar concentrations have been reported in surface water (Lacina et al, 2013; Marsik et al, 2017). Together, these findings have led to concerns for effects on wild fish and the inclusion of diclofenac as one of the first pharmaceuticals on the watch list of priority substances within the European Water Framework Directive (EU, 2013). If an Environmental Quality Standard is set for diclofenac, large investments may be required to reduce emis sions from wastewater treatment plants (WWTPs)

Objectives

Methods

Results

Conclusion