Abstract
The intensive development of medical science has led to an increase in the availability and use of pharmaceutical products. However, nowadays, most of scientific attention has been paid to the native forms of pharmaceuticals, while the transformation products (TPs) of these substances, understood herein as metabolites, degradation products, and selected enantiomers, remain largely unexplored in terms of their characterization, presence, fate and effects within the natural environment. Therefore, the main aim of this study was to evaluate the toxicity of seven native compounds belonging to different therapeutic groups (non-steroidal anti-inflammatory drugs, opioid analgesics, beta-blockers, antibacterial and anti-epileptic drugs), along with the toxicity of their 13 most important TPs. For this purpose, an ecotoxicological test battery, consisting of five organisms of different biological organization was used. The obtained data shows that, in general, the toxicity of TPs to the tested organisms was similar or lower compared to their parent compounds. However, for example, significantly higher toxicity of the R form of ibuprofen to algae and duckweed, as well as a higher toxicity of the R form of naproxen to luminescent bacteria, was observed, proving that the risk associated with the presence of drug TPs in the environment should not be neglected.
Highlights
The intensive development of medical science has led to an increase in the availability and use of pharmaceutical products (Jjemba 2006; Bu et al 2016)
Nowadays, most of scientific attention has been paid to the native forms of pharmaceuticals, while the transformation products (TPs) of these substances, understood as metabolites excreted from the organisms as well as their degradation products resulting from hydrolysis, photolysis, and biodegradation, remain largely unexplored in terms of their characterization, presence, fate, and effects that include an impact on the natural environment and human health (Mompelat et al 2009; Fatta-Kassinos et al 2011; Wilkinson et al 2017; Bottoni and Caroli 2018; Brown and Wong 2018)
In order to explain the possible reasons for the observed differences in the toxicity towards selected organisms, species-specific sensitivity should be considered when dealing with chiral compounds (Nilos et al 2011). At this stage of our knowledge, it is not possible to indicate the exact reasons for the observed differences in toxicity of enantiomers, new ecotoxicological data presented in this study proves that chirality cannot be neglected in the ecotoxicological studies and determination of the risk posed by the pharmaceuticals and their TPs
Summary
The intensive development of medical science has led to an increase in the availability and use of pharmaceutical products (Jjemba 2006; Bu et al 2016). In the case of antibacterial drugs, studies on sulfonamides confirm the abovementioned concerns, reporting lower biological activity of TPs in most cases, with some exceptions, e.g. TP of sulfanilamide was found to elicit similar toxicity towards algae and aquatic plants as its parent compounds (Isidori et al 2005a; Kim et al 2007; García-Galán et al 2008; Białk-Bielińska et al 2017). The occurrence of pharmaceutical TPs in the environment and their potential biological activity indicate the need to extend the environmental risk assessment with ecotoxicological tests for these substances (Han and Lee 2017)
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