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Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems

Lungu-Mitea, Sebastian and Vogs, Carolina and Carlsson, Gunnar and Montag, Maximiliane and Frieberg, Kim and Oskarsson, Agneta and Lundqvist, Johan (2021). Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems. Environmental Science and Technology. 55 , 447-457
[Journal article]

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Abstract

Linking cellular toxicity to low-tier animal toxicity and beyond is crucial within the adverse outcome pathway concept and the 3R framework. This study aimed to determine and compare the bioavailable effect concentrations in zebrafish cell lines and embryos. Acute, short-term toxicity (48 h) of eight veterinary pharmaceuticals was measured in two zebrafish cell lines (hepatocytes, fibroblasts) and zebrafish embryos. Seven endpoints of cytotoxicity were recorded. The fish embryo acute toxicity test was modified by adding sublethal endpoints. Chemical distribution modeling (mass balance) was applied to compute the bioavailable compound concentrations in cells (C-free) and embryos (C-int;aq) based on nominal effect concentrations (C-nom). Effect concentration ratios were calculated (cell effects/embryo effects). A low correlation was observed between cytotoxicity and embryo toxicity when nominal concentrations were used. Modeled bioavailable effect concentrations strongly increased correlations and placed regression lines close to the line of unity and axis origin. Cytotoxicity endpoints showed differences in sensitivity and predictability. The hepatocyte cell line depicted closer proximity to the embryo data. Conclusively, the high positive correlation between the cell- and embryo-based test systems emphasizes the appropriate modulation of toxicity when linked to bioavailable concentrations. Furthermore, it highlights the potential of fish cell lines to be utilized in integrated testing strategies.

Authors/Creators:Lungu-Mitea, Sebastian and Vogs, Carolina and Carlsson, Gunnar and Montag, Maximiliane and Frieberg, Kim and Oskarsson, Agneta and Lundqvist, Johan
Title:Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems
Series Name/Journal:Environmental Science and Technology
Year of publishing :2021
Volume:55
Page range:447-457
Number of Pages:11
Publisher:AMER CHEMICAL SOC
ISSN:0013-936X
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Cell Biology
URN:NBN:urn:nbn:se:slu:epsilon-p-110533
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-110533
Additional ID:
Type of IDID
DOI10.1021/acs.est.0c04872
Web of Science (WoS)000606821200045
ID Code:22193
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:12 Feb 2021 10:14
Metadata Last Modified:12 Feb 2021 10:21

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