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In the first part of a broader study on the effects of individual and multicomponent mixtures of pharmaceutical active compounds, the authors used the Microtox test system to analyze in detail the effects of 10 widely used human and veterinary pharmaceutical active compounds toward the bioluminescent bacterium Aliivibrio fischeri. The experimental results indicated moderate toxicity for the majority of the tested compounds. Comparison between experimental 50% inhibitory concentrations and those predicted from the quantitative structure-activity relationship models indicated that most of the tested pharmaceutical active compounds behave as polar narcotic compounds toward A. fischeri (only the antibiotic chlortetracycline seemed to have a specific mechanism of action). A comparison between the experimental results and a collection of acute toxicity data on other nontarget organisms indicated that in general A. fischeri has a comparable sensitivity to other aquatic species. However, according to the Globally Harmonized System of Classification and Labelling of Chemicals, the majority of the investigated chemicals can be classified as harmful or nontoxic for aquatic ecosystems. Finally, based on comparisons among the 95th percentile of measured environmental concentrations found in European Union water bodies and acute toxicity data on various aquatic organisms, no risk to aquatic life exists when the tested pharmaceutical active compounds are assessed as individual chemicals. Environ Toxicol Chem 2017;36:807-814. © 2016 SETAC.

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The combined toxicities of binary mixtures of veterinary pharmaceutical active compounds were examined using the bioluminescent bacterium Aliivibrio fischeri as a test organism (Microtox® test). Mixtures were prepared at an equitoxic ratio that corresponded to the inhibitory concentration, 10% (IC10) of individual pharmaceutical active compounds. In addition, the toxicity was determined of a multicomponent mixture that contained all of the investigated pharmaceutical active compounds mixed at a ratio corresponding to their individual predicted no-effect concentration (PNEC) values. The experimental results were successively compared with those obtained by applying the 2 most widely used models for predicting mixture toxicity, the concentration addition (CA) and independent action (IA) models. Although the toxicity of the multicomponent mixture tested was well predicted by the CA and IA models, deviations from the model predictions were found for almost all of the binary mixtures. The deviations from the CA and IA models were greater at lower concentrations, particularly when diclofenac sodium and amoxicillin were present in the mixture. Based on these results, another hypothesis was tested, that of toxicological interactions occurring in binary mixtures (in the direction of synergistic or antagonistic effects), by applying the combination index method, which allowed for computerized quantification of synergism, the additive effect and antagonism. The application of this method confirmed, for at least half of the binary combinations, the clear presence of synergistic deviations at the lowest tested concentrations, with a tendency toward antagonism at the higher ones. In 1 case, a relevant antagonistic interaction was observed. Environ Toxicol Chem 2017;36:815-822. © 2016 SETAC.