title: Applying mixture toxicity modelling to predict bacterial bioluminescence inhibition by non-specifically acting pharmaceuticals and specifically acting antibiotics.
abstract: Pharmaceuticals and antibiotics co-occur in the aquatic environment but mixture studies to date have mainly focused on pharmaceuticals alone or antibiotics alone, although differences in mode of action may lead to different effects in mixtures. In this study we used the Bacterial Luminescence Toxicity Screen (BLT-Screen) after acute (0.5 h) and chronic (16 h) exposure to evaluate how non-specifically acting pharmaceuticals and specifically acting antibiotics act together in mixtures. Three models were applied to predict mixture toxicity including concentration addition, independent action and the two-step prediction (TSP) model, which groups similarly acting chemicals together using concentration addition, followed by independent action to combine the two groups. All non-antibiotic pharmaceuticals had similar EC50values at both 0.5 and 16 h, indicating together with a QSAR (Quantitative Structure-Activity Relationship) analysis that they act as baseline toxicants. In contrast, the antibiotics' EC50values decreased by up to three orders of magnitude after 16 h, which can be explained by their specific effect on bacteria. Equipotent mixtures of non-antibiotic pharmaceuticals only, antibiotics only and both non-antibiotic pharmaceuticals and antibiotics were prepared based on the single chemical results. The mixture toxicity models were all in close agreement with the experimental results, with predicted EC50values within a factor of two of the experimental results. This suggests that concentration addition can be applied to bacterial assays to model the mixture effects of environmental samples containing both specifically and non-specifically acting chemicals.
authors.affiliation: Australian Rivers Institute, Griffith School of Environment, Griffith University, Southport, QLD 4222, Australia; The University of Queensland, National Research Centre for Environmental Toxicology (Entox), Brisbane, QLD 4108, Australia.
authors.forename: Peta A
authors.initials: PA
authors.lastname: Neale
authors.affiliation: Australian Rivers Institute, Griffith School of Environment, Griffith University, Southport, QLD 4222, Australia. Electronic address: f.leusch@griffith.edu.au.
authors.forename: Frederic D L
authors.initials: FDL
authors.lastname: Leusch
authors.affiliation: The University of Queensland, National Research Centre for Environmental Toxicology (Entox), Brisbane, QLD 4108, Australia; UFZ - Helmholtz Centre for Environmental Research, Cell Toxicology, 04318 Leipzig, Germany; Eberhard Karls University Tübingen, Environmental Toxicology, Center for Applied Geoscience, 72074 Tübingen, Germany.
authors.forename: Beate I
authors.initials: BI
authors.lastname: Escher
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D049449:Luminescence; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004364:Pharmaceutical Preparations
keywords: Antibiotics; Bacterial toxicity; Concentration addition; Independent action; Pharmaceuticals