title: General baseline toxicity QSAR for nonpolar, polar and ionisable chemicals and their mixtures in the bioluminescence inhibition assay with Aliivibrio fischeri.
abstract: The Microtox assay, a bioluminescence inhibition assay with the marine bacterium Aliivibrio fischeri, is one of the most popular bioassays for assessing the cytotoxicity of organic chemicals, mixtures and environmental samples. Most environmental chemicals act as baseline toxicants in this short-term screening assay, which is typically run with only 30 min of exposure duration. Numerous Quantitative Structure-Activity Relationships (QSARs) exist for the Microtox assay for nonpolar and polar narcosis. However, typical water pollutants, which have highly diverse structures covering a wide range of hydrophobicity and speciation from neutral to anionic and cationic, are often outside the applicability domain of these QSARs. To include all types of environmentally relevant organic pollutants we developed a general baseline toxicity QSAR using liposome-water distribution ratios as descriptors. Previous limitations in availability of experimental liposome-water partition constants were overcome by reliable prediction models based on polyparameter linear free energy relationships for neutral chemicals and the COSMOmic model for charged chemicals. With this QSAR and targeted mixture experiments we could demonstrate that ionisable chemicals fall in the applicability domain. Most investigated water pollutants acted as baseline toxicants in this bioassay, with the few outliers identified as uncouplers or reactive toxicants. The main limitation of the Microtox assay is that chemicals with a high melting point and/or high hydrophobicity were outside of the applicability domain because of their low water solubility. We quantitatively derived a solubility cut-off but also demonstrated with mixture experiments that chemicals inactive on their own can contribute to mixture toxicity, which is highly relevant for complex environmental mixtures, where these chemicals may be present at concentrations below the solubility cut-off.
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de and Eberhard Karls University Tübingen, Environmental Toxicology, Center for Applied Geosciences, 72074 Tübingen, Germany.
authors.forename: Beate I
authors.identifier: http://orcid.org/0000-0002-5304-706X
authors.initials: BI
authors.lastname: Escher
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de and Department of Clinical Pharmacy, Leipzig University, Eilenburger Str. 15a, 04317 Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumer
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Bittermann
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de.
authors.forename: Luise
authors.initials: L
authors.lastname: Henneberger
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de.
authors.forename: Maria
authors.initials: M
authors.lastname: König
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de.
authors.forename: Christin
authors.initials: C
authors.lastname: Kühnert
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, DE-04318 Leipzig, Germany. beate.escher@ufz.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Klüver
mesh_terms: D048908:Aliivibrio fischeri / Q000187:drug effects*; D001681:Biological Assay / Q000379:methods; D015386:Hazardous Substances / Q000737:chemistry / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D008163:Luminescent Measurements; D008962:Models, Theoretical; D009930:Organic Chemicals / Q000737:chemistry / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D014867:Water; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*
chemical_list: D015386:Hazardous Substances; D009930:Organic Chemicals; D014874:Water Pollutants, Chemical; D014867:Water