*2.6. Anti-Inflammatories*

Most anti-inflammatories induce the nonspecific inhibition of prostaglandins. This, in turn, means that there is the potential for e ffects on any of the normal physiological functions mediated by prostaglandins. In fish, for instance, prostaglandins influence mechanisms of behavior and reproduction and, therefore, they can act as endocrine disruptors or modulators, because they can exert their e ffects by mimicking or antagonizing the e ffects of hormones, alter their pattern of synthesis and metabolism and modify hormone receptor levels, leading to possible adverse e ffects [7,163–165]. However, di fferent and unexpected toxicity e ffects were also observed. One of the first was reported in Pakistan, where a catastrophic decline in the Oriental White-backed Vulture population (95%) originated from the exposure to DIC contaminated live-stock carcasses, which promoted fatal renal disease [98,138].

Overall, excepting anxiolytics, anti-inflammatories were less toxic than the other therapeutic groups. Regarding the lowest concentrations that produced acute toxicity in the three trophic levels, invertebrates had the lowest value (10 ng <sup>L</sup>−1), followed by algae (10 μg <sup>L</sup>−1) and fish (90 μg <sup>L</sup>−1), however, when using median values, the di fferences become less clear [37,44,57,96]. As for chronic data, higher toxicity was observed in fish (500 ng <sup>L</sup>−1) and invertebrates (200 μg <sup>L</sup>−1), when compared with algae (4.01 mg <sup>L</sup>−1), which is in line with the already referred anti-inflammatories mode of action [70,95].

Data for each anti-inflammatory showed no clear pattern, nonetheless, except for invertebrates, NAP and PARA seemed to have lower toxicity than DIC and IBU. When performing a comparison between DIC and its metabolite (4-OH-DIC) in invertebrates and fish, one could observe that they have similar toxicities. Conversely, PARA transformation product (4-PARA) presented higher toxicity than the parent molecule in all three trophic levels.
