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In Vitro-In Vivo Extrapolation to Predict Bioaccumulation and Toxicity of Chemicals in Fish Using Physiologically Based Toxicokinetic Models

  • Julita Stadnicka-MichalakEmail author
  • Kristin Schirmer
Part of the Methods in Pharmacology and Toxicology book series


Out of the >107 million chemicals already registered with the Chemical Abstracts Services, less than 0.5% are being regulated, and even fewer are evaluated for their safety. Consequently, a new paradigm in risk assessment is urgently needed. It should encompass faster and less costly methods and reduce the number of animals needed for testing. One proposal is to combine computational modeling with small-scale bioassay methods. This chapter describes the methods that link in vitro bioassays using fish cells with physiologically based toxicokinetic (PBTK) modeling in order to predict the acute toxicity, bioaccumulation, and impact of chemicals on fish growth. The main focus is on PBTK modeling; thus all the model equations and parameters available for eight fish species as well as suggestions for possible software implementation will be provided. The PBTK model described here can account for respiratory and dietary uptake routes and for chemical biotransformation processes.


PBTK model Fish growth Lethality Integrated testing design Predictive modeling Chemical risk assessment Fish cell lines Toxicokinetics and toxicodynamics 



Two ongoing research projects informed about several details that are presented in this chapter. These projects are the ECO34 project funded by the CEFIC-LRI, “A tiered testing strategy for rapid estimation of bioaccumulation by a combined modeling—in vitro testing approach” (PI: Prof. Kristin Schirmer), and the project funded by the 3R Swiss Foundation, “Combining computational modelling with in vitro cellular responses in order to predict chemical impact on fish growth” (PI: Prof. Kristin Schirmer).


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© Springer Science+Business Media, LLC  2019

Authors and Affiliations

  • Julita Stadnicka-Michalak
    • 1
    • 2
    Email author
  • Kristin Schirmer
    • 1
    • 2
    • 3
  1. 1.EPF Lausanne, School of Architecture, Civil and Environmental EngineeringLausanneSwitzerland
  2. 2.Eawag, Swiss Federal Institute of Aquatic Science and TechnologyDübendorfSwitzerland
  3. 3.ETH Zürich, Institute of Biogeochemistry and Pollutant DynamicsZürichSwitzerland

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