Publikation:

The Use of Biomarkers of Toxicity for Integrating In Vitro Hazard Estimates Into Risk Assessment for Humans

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Blaauboer_256471.pdf
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2012

Autor:innen

Blaauboer, Bas J.
Boekelheide, Kim
Clewell, Harvey J.
Dingemans, Milou M. L.
Goldberg, Alan M.
Heneweer, Marjoke
Jaworska, Joanna
Kramer, Nynke I.

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ALTEX. 2012, 29(4), pp. 411-425. ISSN 1868-596X. Available under: doi: 10.14573/altex.2012.4.411

Zusammenfassung

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).

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

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

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ISO 690BLAAUBOER, Bas J., 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, 2012. The Use of Biomarkers of Toxicity for Integrating In Vitro Hazard Estimates Into Risk Assessment for Humans. In: ALTEX. 2012, 29(4), pp. 411-425. ISSN 1868-596X. Available under: doi: 10.14573/altex.2012.4.411
BibTex
@article{Blaauboer2012Bioma-25647,
  year={2012},
  doi={10.14573/altex.2012.4.411},
  title={The Use of Biomarkers of Toxicity for Integrating In Vitro Hazard Estimates Into Risk Assessment for Humans},
  number={4},
  volume={29},
  issn={1868-596X},
  journal={ALTEX},
  pages={411--425},
  author={Blaauboer, Bas J. and Boekelheide, Kim and Clewell, Harvey J. and Daneshian, Mardas and Dingemans, Milou M. L. and Goldberg, Alan M. and Heneweer, Marjoke and Jaworska, Joanna and Kramer, Nynke I. and Leist, Marcel and Seibert, Hasso and Testai, Emanuela and Vandebriel, Rob J. and Yager, James D. and Zurlo, Joanne}
}
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