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In Silico Models for Repeated-Dose Toxicity (RDT): Prediction of the No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) for Drugs

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In Silico Methods for Predicting Drug Toxicity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1425))

Abstract

The preclinical stage in drug development requires the determination of repeated-dose toxicity (RDT) in animal models. The main outcome of RDT studies is the determination of the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL). NOAEL is important since it serves to calculate the maximum recommended starting dose (MRSD) which is the safe starting dose for clinical studies in human beings. Since in vivo RDT studies are expensive and time-consuming, in silico approaches could offer a valuable alternative. However, NOAEL and LOAEL modeling suffer some limitations since they do not refer to a single end point but to several different effects and the doses used in experimental studies strongly influence the final results. Few attempts to model NOAEL and LOAEL have been reported. The available database and models for the prediction of NOAEL and LOAEL are reviewed here.

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Acknowledgments

This work was supported by the project HEALTH-F5-2010-267042 ToxBank (supporting integrated data analysis and servicing of alternative testing methods in toxicology) funded by the European Commission and Cosmetics Europe under the Seventh Framework Programme.

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Authors and Affiliations

  1. Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy

    Fabiola Pizzo

  2. Mario Negri Institute for Pharmacological Research, IRCCS, Milano, Italy

    Emilio Benfenati

Authors
  1. Fabiola Pizzo
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  2. Emilio Benfenati
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Correspondence to Fabiola Pizzo .

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Editors and Affiliations

  1. Mario Negri Inst for Pharm Rsrch, IRCCS, Milan, Italy

    Emilio Benfenati

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Pizzo, F., Benfenati, E. (2016). In Silico Models for Repeated-Dose Toxicity (RDT): Prediction of the No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) for Drugs. In: Benfenati, E. (eds) In Silico Methods for Predicting Drug Toxicity. Methods in Molecular Biology, vol 1425. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3609-0_9

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  • DOI: https://doi.org/10.1007/978-1-4939-3609-0_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3607-6

  • Online ISBN: 978-1-4939-3609-0

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