Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1021/acs.est.9b02563
Titel (primär) Combined ion-trapping and mass balance models to describe the pH-dependent uptake and toxicity of acidic and basic pharmaceuticals in zebrafish embryos (Danio rerio)
Autor Bittner, L.; Klüver, N.; Henneberger, L.; Mühlenbrink, M.; Zarfl, C.; Escher, B.I.
Quelle Environmental Science & Technology
Erscheinungsjahr 2019
Department BIOTOX; ZELLTOX
Band/Volume 53
Heft 13
Seite von 7877
Seite bis 7886
Sprache englisch
Supplements https://pubs.acs.org/doi/suppl/10.1021/acs.est.9b02563/suppl_file/es9b02563_si_001.pdf
Abstract

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.

dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=22059
Bittner, L., Klüver, N., Henneberger, L., Mühlenbrink, M., Zarfl, C., Escher, B.I. (2019):
Combined ion-trapping and mass balance models to describe the pH-dependent uptake and toxicity of acidic and basic pharmaceuticals in zebrafish embryos (Danio rerio)
Environ. Sci. Technol. 53 (13), 7877 - 7886 10.1021/acs.est.9b02563