*2.5. SSRIs*

This therapeutic group has the peculiarity that the phylogenetically ancient and highly conserved neurotransmitter and neurohormone serotonin has been found in invertebrates and vertebrates, although its specific physiological role and mode of action is unknown for many species [158]. Many biological functions within invertebrates, such as reproduction, metabolism, molting and behavior, are under the control of serotonin [159]. Therefore, the pharmaceuticals in this therapeutic group could have tremendous e ffects on these and other organisms [160]. These facts are in agreemen<sup>t</sup> with those found in acute toxicity data found, since for all trophic levels this group had globally the lowest concentrations, which promoted toxic e ffects, being some of these on reproduction, survival and behavior [161].

When observing these data, the most sensitive trophic level was the invertebrates (0.1 μg <sup>L</sup>−1), followed by algae (12.1 μg <sup>L</sup>−1) and fish (72.0 μg <sup>L</sup>−1) [33,57,92]. In invertebrates, the pharmaceuticals with higher toxicity were FLU (100 ng <sup>L</sup>−1) and its metabolite Nor-FLU (300 μg <sup>L</sup>−1) and SER (100 μg <sup>L</sup>−1). On the other side, PAR was the one with lower toxicity [33,36,57,69]. In algae, the pharmaceutical with highest toxicity was SER, however, in invertebrates, FLU surpassed SER toxicity.

The only metabolite referred in the literature concerning toxicity studies was Nor-FLU, with data for algae and invertebrates. When comparing with FLU (algae and invertebrates), it is clear that the median concentrations inducing toxicity were always lower [162].

Studies performed on SER and FLU demonstrated the influence of pH on toxicity, since the uncharged drug can pass easier through the membrane and act inside the cells, showing a tenfold increased toxicity when shifting the pH closest to their pKa, increasing the nonionized form, from 6.5 to 8.5 and from 7.8 to 9, respectively [17,89,92].
