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Advancing In Vitro–In Vivo Extrapolations of Mechanism-Specific Toxicity Data Through Toxicokinetic Modeling

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In vitro Environmental Toxicology - Concepts, Application and Assessment

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 157))

Abstract

International legislation, such as the European REACH regulation (registration, evaluation, authorization, and restriction of chemicals), mandates the assessment of potential risks of an ever-growing number of chemicals to the environment and human health. Although this legislation is considered one of the most important investments in consumer safety ever, the downside is that the current testing strategies within REACH rely on extensive animal testing. To address the ethical conflicts arising from these increased testing requirements, decision-makers, such as the European Chemicals Agency (ECHA), are committed to Russel and Burch’s 3R principle (i.e., reduction, replacement, refinement) by demanding that animal experiments should be substituted with appropriate alternatives whenever possible. A potential solution of this dilemma might be the application of in vitro bioassays to estimate toxic effects using cells or cellular components instead of whole organisms. Although such assays are particularly useful to assess potential mechanisms of toxic action, scientists require appropriate methods to extrapolate results from the in vitro level to the situation in vivo. Toxicokinetic models are a straightforward means of bridging this gap. The present chapter describes different available options for in vitro-in vivo extrapolation (IVIVE) of mechanism-specific effects focused on fish species and also reviews the implications of confounding factors during the conduction of in vitro bioassays and their influence on the optimal choice of different dose metrics.

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Acknowledgements

The authors acknowledge funding through the project “DioRAMA – Assessment of the dioxin-like activity in sediments and fish for sediment evaluation “that was financed by the German Federal Ministry of Transport, Building and Urban Development, as well as a personal scholarship of the German National Academic Foundation (“Studienstiftung des deutschen Volkes“) which was granted to the first author.

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Author notes

  1. Thomas G. Preuss

    Present address: Chair of Environmental Biology and Chemodynamics, Institute for Environmental Research, Aachen Biology and Biotechnology – ABBt, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany

Authors and Affiliations

  1. Department of Ecosystem Analysis, Institute for Environmental Research, Aachen Biology and Biotechnology – ABBt, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany

    Markus Brinkmann & Henner Hollert

  2. Bayer CropScience AG, Monheim am Rhein, Germany

    Thomas G. Preuss

  3. College of Resources and Environmental Science, Chongqing University, 1 Tiansheng Road Beibei, Chongqing, 400715, China

    Henner Hollert

  4. College of Environmental Science and Engineering and State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, 1239 Siping Road, Shanghai, China

    Henner Hollert

  5. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, China

    Henner Hollert

Authors
  1. Markus Brinkmann
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  2. Thomas G. Preuss
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  3. Henner Hollert
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Corresponding authors

Correspondence to Markus Brinkmann or Henner Hollert .

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Editors and Affiliations

  1. Federal Institute of Hydrology, Koblenz, Germany

    Georg Reifferscheid

  2. Federal Institute of Hydrology, Koblenz, Germany

    Sebastian Buchinger

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Brinkmann, M., Preuss, T.G., Hollert, H. (2016). Advancing In Vitro–In Vivo Extrapolations of Mechanism-Specific Toxicity Data Through Toxicokinetic Modeling. In: Reifferscheid, G., Buchinger, S. (eds) In vitro Environmental Toxicology - Concepts, Application and Assessment. Advances in Biochemical Engineering/Biotechnology, vol 157. Springer, Cham. https://doi.org/10.1007/10_2015_5015

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