The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans

Authors

  • Bas J. Blaauboer Institute for Risk Assessment Sciences, Division of Toxicology, Utrecht University, Utrecht, The Netherlands
  • Kim Boekelheide Department of Pathology and Laboratory Medicine, Brown University, Providence, USA
  • Harvey J. Clewell The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
  • Mardas Daneshian Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany
  • Milou M. L. Dingemans Institute for Risk Assessment Sciences, Division of Toxicology, Utrecht University, Utrecht, The Netherlands
  • Alan M. Goldberg Center for Alternatives to Animal Testing, Johns Hopkins University, Baltimore, USA
  • Marjoke Heneweer Shell International B.V., The Hague, The Netherlands
  • Joanna Jaworska Procter & Gamble, Central Product Safety, Strombeek-Bever, Belgium
  • Nynke I. Kramer Institute for Risk Assessment Sciences, Division of Toxicology, Utrecht University, Utrecht, The Netherlands
  • Marcel Leist Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany; Doerenkamp-Zbinden Chair for in vitro toxicology and biomedicine, Faculty of Sciences and Mathematics, University of Konstanz, Konstanz, Germany
  • Hasso Seibert Institute for Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Kiel, Germany
  • Emanuela Testai Istituto Superiore di Sanità, Environment and Primary Prevention Department, Mechanism of Toxicity Unit, Rome, Italy
  • Rob J. Vandebriel Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  • James D. Yager Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA
  • Joanne Zurlo Center for Alternatives to Animal Testing, Johns Hopkins University, Baltimore, USA; Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA

DOI:

https://doi.org/10.14573/altex.2012.4.411

Keywords:

biomarker of toxicity, integrated testing strategies, quantitative in vitro-in vivo extrapolations

Abstract

The role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process. The selection of BoT takes into account that they need to distinguish adverse and adaptive changes in cells. The framework defines the place of in vitro systems in the context of data on exposure, structural and physico-chemical properties, and toxicodynamic and biokinetic modeling. It outlines the determination of a proper point-of-departure (PoD) for in vitro-in vivo extrapolation, allowing implementation in risk assessment procedures. A BoT will need to take into account both the dynamics and the kinetics of the compound in the in vitro systems. For the implementation of the proposed framework it will be necessary to collect and collate data from existing literature and new in vitro test systems, as well as to categorize biomarkers of toxicity and their relation to pathways-of-toxicity. Moreover, data selection and integration need to be driven by their usefulness in a quantitative in vitro-in vivo extrapolation (QIVIVE).

BERJAYA

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Published

2012-11-01

Issue

Vol. 29 No. 4 (2012)

Section

Articles

License

Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s).

How to Cite

Blaauboer, B. J., Boekelheide, K., Clewell, H. J., Daneshian, M., Dingemans, M. M. L., Goldberg, A. M., Heneweer, M., Jaworska, J., Kramer, N. I., Leist, M., Seibert, H., Testai, E., Vandebriel, R. J., Yager, J. D., & Zurlo, J. (2012). The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans. ALTEX - Alternatives to Animal Experimentation, 29(4), 411-425. https://doi.org/10.14573/altex.2012.4.411

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