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The aim of the current study was to understand and develop models to predict the pH-dependent toxicity of ionizable pharmaceuticals in embryos of the zebrafish Danio rerio. We found a higher uptake and toxicity with increasing neutral fraction of acids (diclofenac, genistein, naproxen, torasemide, and warfarin) and bases (metoprolol and propranolol). Simple mass balance models accounting for the partitioning to lipids and proteins in the zebrafish embryo were found to be suitable to predict the bioconcentration after 96 h of exposure if pH values did not differ much from the internal pH of 7.55. For other pH values, a kinetic ion-trap model for the zebrafish embryo explained the pH dependence of biouptake and toxicity. The total internal lethal concentrations killing 50% of the zebrafish embryos (ILC50) were calculated from the measured BCF and LC50. The resulting ILC50 were independent of external pH. Critical membrane concentrations were deduced by an internal mass balance model, and apart from diclofenac, whose specific toxicity in fish had already been established, all pharmaceuticals were confirmed to act as baseline toxicants in zebrafish.

Reported off‐target effects of antihistamines in humans draw interest in ecotoxicity testing of first‐ and second‐generation antihistamines, the latter of which have fewer reported side effects in humans. Because antihistamines are ionizable compounds, the pH influences uptake and toxicity and thus is highly relevant when conducting toxicity experiments. Zebrafish embryo toxicity tests were performed with the 3 first‐generation antihistamines ketotifen, doxylamine, and dimethindene and the 2 second‐generation antihistamines cetirizine and levocabastine at pH 5.5, 7.0, and 8.0. We detected effects on survival, phenotype, swimming activity, and heart rate for 4 antihistamines with the exception of levocabastine, which did not show any lethal or sublethal effects. When compared to lethal concentrations, effect concentrations neither of phenotype malformation nor of swimming activity or heart rate deviated by more than a factor of 10 from lethal concentrations, indicating that all sublethal effects were fairly nonspecific. First‐generation antihistamines are weak bases and showed decreasing external effect concentrations with increasing neutral fraction, accompanied by increased uptake in the fish embryo. As a result, internal effect concentrations were independent from external pH. The pH‐dependent toxicity originates from speciation‐dependent uptake, with neutral species taken up in higher amounts than the corresponding ionic species. Cetirizine, which shifts from a zwitterionic to an anionic state in the measured pH range, did not show any pH‐dependent uptake or toxicity. Environ Toxicol Chem 2019;00:1–11. © 2019 SETAC

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Der Aufsatz von Lisa Bittner begibt sich in das Kiel der unmittelbaren Nachkriegszeit. Bittner beleuchtet in ihrem Beitrag die letztlich erfolglosen Versuche verschiedener Akteurinnen und Akteure, den Kieler Juraprofessor Hans Kurt Paul Brandt aus der jugoslawischen Kriegsgefangenschaft zu befreien. Die Autorin fragt nach den Motivationen einzelner Gruppen, sich für dessen Heimkehr einzusetzen, und reflektiert das starke Engagement der Studierenden, die dieser Thematik einen eigenen Artikel im Kieler Studenten, der ersten Studierendenzeitung der CAU nach dem Zweiten Weltkrieg, widmeten. Gleichfalls legt der Beitrag professorale Netzwerke offen, die während der NS-Zeit geknüpft wurden und noch lange darüber hinaus wirkten. Diesen gelang es nicht nur, die junge Studierendenschaft für ihre Zwecke einzuspannen, sondern auch, sich gegenseitig in der jungen Bundesrepublik zahlreiche Karrierechancen zu ermöglichen.