Does ketoprofen or diclofenac pose the lowest risk to fish?
Ketoprofen and diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs) often used for similar indications, and both are frequently found in surface waters. Diclofenac affects organ histology and gene expression in fish at around 1 μg/L. Here, we exposed rainbow trout to ketoprofen (1, 10 and 100 μg/L) to investigate if this alternative causes less risk for pharmacological responses in fish. The bioconcentration factor from water to fish blood plasma was <0.05 (4 for diclofenac based on previous studies). Ketoprofen only reached up to 0.6 ‰ of the human therapeutic plasma concentration, thus the probability of target-related effects was estimated to be fairly low. Accordingly, a comprehensive analysis of hepatic gene expression revealed no consistent responses. In some contrast, trout exposed to undiluted, treated sewage effluents bioconcentrated ketoprofen and other NSAIDs much more efficiently, according to a meta-analysis of recent studies. Neither of the setups is however an ideal representation of the field situation. If a controlled exposure system with a single chemical in pure water is a reasonable representation of the environment, then the use of ketoprofen is likely to pose a lower risk for wild fish than diclofenac, but if bioconcentration factors from effluent-exposed fish are applied, the risks may be more similar.
Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. filip.cuklev@neuro.gu.se
Filip
F
Cuklev
Jerker
J
Fick
Marija
M
Cvijovic
Erik
E
Kristiansson
Lars
L
Förlin
D G Joakim
DG
Larsson
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004008:Diclofenac / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007660:Ketoprofen / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D017686:Oncorhynchus mykiss; D014874:Water Pollutants, Chemical / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D014874:Water Pollutants, Chemical; D004008:Diclofenac; D007660:Ketoprofen