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

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Bas J. Blaauboer
Kim Boekelheide
Harvey J. Clewell
Mardas Daneshian
Milou M. L. Dingemans
Alan M. Goldberg
Marjoke Heneweer
Joanna Jaworska
Nynke I. Kramer
Marcel Leist
Hasso Seibert
Emanuela Testai
Rob J. Vandebriel
James D. Yager
Joanne Zurlo


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).

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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. and 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), pp. 411–425. doi: 10.14573/altex.2012.4.411.

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