LogD-based modelling and ΔlogD as a proxy for pH-dependent action of ionizable chemicals reveal the relevance of both neutral and ionic species for fish embryotoxicity and possess great potential for practical application in the regulation of chemicals.

Autor: Köhler HR; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany. Electronic address: heinz-r.koehler@uni-tuebingen.de., Gräff T; Federal Environment Agency, Wörlitzer Platz 1, Dessau-Roßlau D-06844, Germany., Schweizer M; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Blumhardt J; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Burkhardt J; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Ehmann L; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Hebel J; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Heid C; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Kundy L; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Kuttler J; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Malusova M; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Moroff FM; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Schlösinger AF; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Schulze-Berge P; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany., Panagopoulou EI; Department of Chemistry, Laboratory of Analytical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens GR-15771, Greece., Damalas DE; Department of Chemistry, Laboratory of Analytical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens GR-15771, Greece., Thomaidis NS; Department of Chemistry, Laboratory of Analytical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens GR-15771, Greece., Triebskorn R; Animal Physiological Ecology, Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, Tübingen D-72076, Germany; Steinbeis-Transfer Center Ecotoxicology and Ecophysiology, Blumenstrasse 13, Rottenburg D-72108, Germany., Maletzki D; Federal Environment Agency, Schichauweg 58, Berlin D-12307, Germany., Kühnen U; Federal Environment Agency, Wörlitzer Platz 1, Dessau-Roßlau D-06844, Germany., von der Ohe PC; Federal Environment Agency, Wörlitzer Platz 1, Dessau-Roßlau D-06844, Germany. Electronic address: peter.vonderohe@uba.de.
Jazyk: angličtina
Zdroj: Water research [Water Res] 2023 May 15; Vol. 235, pp. 119864. Date of Electronic Publication: 2023 Mar 14.
DOI: 10.1016/j.watres.2023.119864
Abstrakt: Depending on the ambient pH, ionizable substances are present in varying proportions in their neutral or charged form. The extent to which these two chemical species contribute to the pH-dependant toxicity of ionizable chemicals and whether intracellular ion trapping has a decisive influence in this context is controversially discussed. Against this background, we determined the acute toxicity of 24 ionizable substances at up to 4 different pH values on the embryonic development of the zebrafish, Danio rerio, and supplemented this dataset with additional data from the literature. The LC 50 for some substances (diclofenac, propranolol, fluoxetine) differed by a factor of even >10 3 between pH5 and pH9. To simulate the toxicity of 12 acids and 12 bases, six models to calculate a pH-dependant logD value as a proxy for the uptake of potentially toxic molecules were created based on different premises for the trans-membrane passage and toxic action of neutral and ionic species, and their abilities to explain the real LC 50 data set were assessed. Using this approach, we were able to show that both neutral and charged species are almost certainly taken up into cells according to their logD-based distribution, and that both species exert toxicity. Since two of the models that assume all intracellular molecules to be neutral overestimated the real toxicity, it must be concluded, that the toxic effect of a single charged intracellularly present molecule is, on the average, lower than that of a single neutral molecule. Furthermore, it was possible to attribute differences in toxicity at different pH values for these 24 ionizable substances to the respective deltas in logD at these pH levels with high accuracy, enabling particularly a full logD-based model on the basis of logP ow as a membrane passage descriptor to be used for predicting potential toxicities in worst-case scenarios from existing experimental studies, as stipulated in the process of registration of chemicals and the definition of Environmental Quality Standards (EQS).
Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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