Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1002/etc.4934
Lizenz creative commons licence
Titel (primär) Trout and human plasma protein binding of selected pharmaceuticals informs the fish plasma model
Autor Henneberger, L.; Mühlenbrink, M.; Klüver, N.; Escher, B.
Quelle Environmental Toxicology and Chemistry
Erscheinungsjahr 2022
Department BIOTOX; ZELLTOX
Band/Volume 41
Heft 3
Seite von 559
Seite bis 568
Sprache englisch
Topic T9 Healthy Planet
Supplements https://setac.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Fetc.4934&file=etc4934-sup-0001-2020_11_04_SI_Trout_human_plasma.pdf
Keywords Bioaccumulation; Bioavailability; Hazard/Risk assessment; Pharmaceuticals; Predictive toxicology
Abstract Concerns are increasing that pharmaceuticals released into the environment pose a risk to non‐target organism like fish. The fish plasma model (FPM) is a read‐across approach and uses human therapeutic blood plasma concentrations for estimating likely effects in fish. However, the FPM neglects differences in plasma protein binding between fish and humans. Since binding data for fish plasma are scarce, the binding of twelve active pharmaceutical ingredients (APIs, acidic, basic and neutral) to rainbow trout (Oncorhynchus mykiss) and human plasma was measured using solid‐phase microextraction (SPME). The plasma‐water distribution ratios (Dplasma/w) of neutral and basic APIs were similar for trout and human plasma, differing by not more than a factor of 2.7 per API. For the acidic APIs Dplasma/w of trout plasma were much lower than for human plasma, by up to a factor of 71 for naproxen. The lower affinity of the acidic APIs to trout plasma compared to human plasma suggests that the bioavailability of these APIs is higher in trout. Read‐across approaches like the FPM should account for differences in plasma protein binding to avoid over‐ or underestimation of effects in fish. For the acidic APIs, the effect ratio of the FPM would increase by a factor of 5 to 60 if the unbound plasma concentrations were used to calculate the effect ratio. Neutral and basic pharmaceuticals showed similar binding to trout and human blood plasma. Acidic pharmaceuticals (e.g., naproxen) bind to trout plasma with a lower affinity, suggesting a higher bioavailability of these pharmaceuticals in trout than in human plasma.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=23898
Henneberger, L., Mühlenbrink, M., Klüver, N., Escher, B. (2022):
Trout and human plasma protein binding of selected pharmaceuticals informs the fish plasma model
Environ. Toxicol. Chem. 41 (3), 559 - 568 10.1002/etc.4934