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.

Microbial responses to anthropogenic dissolved organic carbon in the Arctic and Antarctic coastal seawaters

“…Our results suggest an overall expression response to ADOC compounds consistent with perturbation of cellular membranes due to the nonspecific accumulation of hydrophobic compounds to the cell surfaces and into the membrane lipids that we explored in detail (see below and Fig. 5) (Cronin et al, 2000;Escher et al, 2017;Joye et al, 2018).…”

“…5; Cronin et al, 2000;Escher et al, 2017), as well as a detoxification mechanism (Wirsen et al, 1987;Fig. 5; Cronin et al, 2000;Escher et al, 2017), as well as a detoxification mechanism (Wirsen et al, 1987;Fig.…”

“…The capacity of marine bacteria to change membrane composition is an adaptive mechanism to the non-specific accumulation of hydrophobic compounds at the cell membranes ( Fig. 5; Cronin et al, 2000;Escher et al, 2017), as well as a detoxification mechanism (Wirsen et al, 1987;Fig. 5).…”

“…They cross cell membranes by passive diffusion and can be absorbed into cytoplasmic structures, become inserted into the membrane phospholipid bilayer (absorption), and/or be adsorbed on the outside of the cell wall (Koelmans, 2014). This uptake of OPs causes a baseline toxicity to the cells by narcosis, the non-specific intercalation of hydrophobic compounds into the phospholipids of the biological membranes, inducing a perturbation of the membrane's permeability, rigidity and efficiency (Van Wezel et al, 1995;Cronin et al, 2000;Escher et al, 2017). Recent studies have shown that hydrophobic OPs have toxicological effects on temperate and polar phytoplankton.…”

pH‐Dependent Uptake and Sublethal Effects of Antihistamines in Zebrafish (Danio rerio) Embryos

“…An increase in neutral fraction led to higher BCF apparent values and higher internal concentrations for ketotifen, doxylamine, and dimethindene. A linkage between neutral fraction and uptake was proposed in previous studies (Escher and Hermens 2004;Neuwoehner and Escher 2011;Boström and Berglund 2015) and experimentally observed for acids and bases (Nakamura et al 2008;Valenti et al 2009;Rendal et al 2011;Escher et al 2017;Khatikarn et al 2018).…”