Abstract
As the knowledge on the joint effects of pharmaceuticals towards different non-target organisms is still limited, the aim of our study was to evaluate the toxicity of mixtures of pharmaceuticals, as well as their baseline toxicity towards three selected organisms, namely the bioluminescent bacteria Aliivibrio fischeri, the crustacean Daphnia magna, and the duckweed Lemna minor. Different mixtures composed of three up to five pharmaceuticals having the same or different mechanisms of action in terms of their therapeutic activity (non-steroidal anti-inflammatory drugs, opioid analgesic, antibacterial and anti-epileptic drugs) were investigated. The observed EC50s were compared with those predicted using the concentration addition (CA) and independent action (IA) models. In general, the EC50 values for mixtures predicted with the CA model were lower than those obtained with the IA model, although, in some cases, test predictions of these two models were almost identical. Most of the experimentally determined EC50 values for the specific mixtures were slightly higher than those predicted with the CA model; hence, a less than additive effect was noted. Based on the obtained results, it might be concluded that the CA model assumes the worst-case scenario and gives overall closer predictions; therefore, it should be recommended also for modeling the mixture toxicity of pharmaceuticals with different modes of action.
Highlights
During the last decades, the problem of the presence of residues of pharmaceuticals in the environment has gained huge scientific attention (Ankley et al 2007; Kümmerer, 2010; Rodriguez-Mozaz et al 2010; aus der Beek et al 2016; Klatte et al 2017; Pereira et al 2020; Vasilachi et al 2021)
The investigated mixtures were composed of pharmaceuticals belonging to the same therapeutic group as well as those with different modes of action in order to evaluate the applicability of the concentration addition (CA) and independent action (IA) models for the prediction of their joint toxic effects
The CA model is suitable to predict the effects of mixtures composed of both and non- acting chemicals towards bacteria (Neale et al 2017)
Summary
The problem of the presence of residues of pharmaceuticals (recognized as emerging pollutants) in the environment has gained huge scientific attention (Ankley et al 2007; Kümmerer, 2010; Rodriguez-Mozaz et al 2010; aus der Beek et al 2016; Klatte et al 2017; Pereira et al 2020; Vasilachi et al 2021). The Environmental Risk Assessment (ERA) of pharmaceuticals is mainly carried out for individual substances (CHMP 2006; CVMP 2008; VICH 2000, 2005) They are present in the environment in different mixtures. In the recently published report of German Environment Agency (Dusi et al 2019) based on the data presented in 504 peer-reviewed articles published in 2010–2016, 771 pharmaceutical substances were detected in 75 countries worldwide. This proves how complex is the problem of the presence of the mixtures of pharmaceuticals in the environment. This proves how complex is the problem of the presence of the mixtures of pharmaceuticals in the environment. Godoy and Kummrov (2017) in
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