Bacterial toxicity of Acetaminophen and Edaravone, and their binary mixtures: experimental and predicted values using traditional and novel Van Laar-based models.

In recent years, the presence of Pharmaceutical Active Compounds (PhACs) in ecosystems has become a serious environmental problem due to their capacity to induce harmful effects at extremely low concentrations in both humans and wildlife. Water treatment plants have not been designed to remove these types of compounds efficiently. Thus, the detection of these pollutants is essential to evaluate their negative impacts and is one of the emerging issues in environmental chemistry. The main objective of this study is to determine the bacterial toxicity of two PhACs (both individually and as a mixture) through the quantification of bioluminescence inhibition in the marine bacteria Aliivibrio fischeri, a commonly used method in short-term toxicity tests. In this work, Acetaminophen and Edaravone, two drugs approved by the Food and Drug Administration, have been studied. The acute toxicity of these PhACs has been tested at two exposure times (5 and 15 min) and different concentrations, by estimation of the median effective concentration (EC₅₀) for each individual compound or in combination at different concentrations. Moreover, the EC₅₀ of the binary mixtures Acetaminophen/Edaravone have been forecast using two traditional predictive models, Concentration Addition and Independent Action. The results show that toxicity decreases with exposure time and depends on the concentration tested. Furthermore, a novel semi-empirical Van Laar-based model has been proposed and validated with the experimental data from this study and literature data, obtaining satisfactory estimations of the EC₅₀ for binary mixtures. Highlights: The bacterial toxicity of Acetaminophen and Edaravone, as well as their binary mixtures, was evaluated using an Aliivibrio fischeri bioluminescence assay. The predictive power of Concentration Addition and Independent Action models was evaluated for combined bacterial toxicity of PhACs. A new semi-empirical Van Laar-based model was developed and validated to predict the bacterial toxicity of binary mixtures of Acetaminophen and Edaravone, providing accurate estimations with limited experimentation. [ABSTRACT FROM AUTHOR]