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In silico approaches in organ toxicity hazard assessment: current status and future needs in predicting liver toxicity

Bassan, A, Alves, VM, Amberg, A, Anger, LT, Auerbach, S, Beilke, L, Bender, A, Cronin, MTD, Cross, KP, Hsieh, J-H, Greene, N, Kemper, R, Kim, MT, Mumtaz, M, Noeske, T, Pavan, M, Pletz, J, Russo, DP, Sabnis, Y, Schaefer, M , Szabo, DT, Valentin, J-P, Wichard, J, Williams, D, Woolley, D, Zwickl, C and Myatt, GJ (2021) In silico approaches in organ toxicity hazard assessment: current status and future needs in predicting liver toxicity. Computational Toxicology. ISSN 2468-1113

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Hepatotoxicity is one of the most frequently observed adverse effects resulting from exposure to a xenobiotic, for example, in pharmaceutical research and development it is one of the major reasons for drug withdrawals, clinical failures, and discontinuation of drug candidates. The development of faster and cheaper methods to assess hepatotoxicity that are both more sustainable and more informative is critically needed. The biological mechanisms and processes underpinning hepatotoxicity are summarized and experimental approaches to support the prediction of hepatotoxicity are described, including toxicokinetic considerations. The paper describes the increasingly important role of in silico approaches and highlights challenges to the adoption of these methods including the lack of a commonly agreed upon protocol for performing such an assessment and the need for in silico solutions that take dose into consideration. A proposed framework for the integration of in silico and experimental information is provided along with a case study describing how computational methods have been used to successfully respond to a regulatory question concerning non-genotoxic impurities in chemically synthesized pharmaceuticals.

Item Type: Article
Subjects: R Medicine > RA Public aspects of medicine > RA1190 Toxicology. Poisions
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 13 Sep 2021 11:47
Last Modified: 09 Sep 2022 00:50
DOI or ID number: 10.1016/j.comtox.2021.100187
URI: https://researchonline.ljmu.ac.uk/id/eprint/15480
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