Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems
Environmental Science & Technology, vol. 55, pp. 447–457
Abstract
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 (Cfree) and embryos (Cint;aq) based on nominal effect concentrations (Cnom). 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 7
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Sebastian Lungu-Mitea corresponding
Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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Affiliation as printed
RWTH Aachen , , Worringerweg 1 , ,
Institute for Environmental Research, RWTH Aachen, Worringerweg 1, D-52074 Aachen, Germany
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Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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Swedish University of Agricultural Sciences
Affiliation as printed
Swedish University of Agricultural Sciences , , Box 7028, ,
Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden
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