1. Introduction
The presence of pharmaceuticals in the aquatic environment, and their real and potential effects on living organisms, have become major research topics. One important issue to resolve is how best to prioritize pharmaceuticals, so that research is focused on those that present the greatest risk to living organisms. Various strategies have been proposed (Roos et al., 2012). One strategy is to base the ranking of pharmaceuticals on how close the plasma concentrations of wildlife, such as fish, are to the effective drug concentrations in humans, provided that the molecular drug target (i.e. receptor or enzyme) has been conserved: this is the basis of the read-across hypothesis (Huggett et al., 2003, Rand-Weaver et al., 2013 and Tanoue et al., 2015). Currently, little information is available to support the use of the read-across hypothesis to predict the environmental (e.g. river) concentrations of pharmaceuticals that will cause effects to fish. A recent publication (Margiotta-Casaluci et al., 2014) has shown that the anti-depressant fluoxetine affects behavior of fish only when their plasma concentration is within the human therapeutic range. However, the range of fluoxetine concentrations reported to affect various species of aquatic organisms is very wide (Sumpter et al., 2014), suggesting that the read-across hypothesis may not be universally applicable. To assess the robustness of the read-across hypothesis, we investigated the uptake of the human pharmaceutical ibuprofen by fish and the internal (blood plasma) concentrations required to elicit a mode-of-action related effect.