Facial reconstruction

Search LJMU Research Online

Browse Repository | Browse E-Theses

Principles and Procedures for Assessment of Acute Toxicity Incorporating In Silico Methods

Zwickl, C and Cronin, MTD (2022) Principles and Procedures for Assessment of Acute Toxicity Incorporating In Silico Methods. Computational Toxicology, 24. ISSN 2468-1113

Principles and Procedures for Assessment of Acute Toxicity Incorporating In Silico Methods.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview


Acute toxicity in silico models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an in silico analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including in silico methods and in vitro or in vivo experiments. In silico methods that can assist the prediction of in vivo outcomes (i.e., LD50) are analyzed concluding that predictions obtained using in silico approaches are now well-suited for reliably supporting assessment of LD50-based acute toxicity for the purpose of the Globally Harmonized System (GHS) classification. A general overview is provided of the endpoints from in vitro studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of in vitro data allow for a shift away from assessments solely based on endpoints such as LD50, to mechanism-based endpoints that can be accurately assessed in vitro or by using in silico prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how in silico approaches support the assessment of acute toxicity.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
SWORD Depositor: A Symplectic
Date Deposited: 25 Jul 2022 08:15
Last Modified: 02 Aug 2023 00:50
DOI or ID number: 10.1016/j.comtox.2022.100237
URI: https://researchonline.ljmu.ac.uk/id/eprint/17239
View Item View Item