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Determination of “Fitness-for-Purpose” of Quantitative Structure-Activity Relationship (QSAR) Models to Predict (Eco-)Toxicological Endpoints for Regulatory Use

Belfield, SJ, Enoch, SJ, Firman, JW, Madden, JC, Schultz, TW and Cronin, MTD (2021) Determination of “Fitness-for-Purpose” of Quantitative Structure-Activity Relationship (QSAR) Models to Predict (Eco-)Toxicological Endpoints for Regulatory Use. Regulatory Toxicology and Pharmacology, 123. ISSN 0273-2300

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In silico models are used to predict toxicity and molecular properties in chemical safety assessment, gaining widespread regulatory use under a number of legislations globally. This study has rationalised previously published criteria to evaluate quantitative structure-activity relationships (QSARs) in terms of their uncertainty, variability and potential areas of bias, into ten assessment components, or higher level groupings. The components have been mapped onto specific regulatory uses (i.e. data gap filling for risk assessment, classification and labelling, and screening and prioritisation) identifying different levels of uncertainty that may be acceptable for each. Twelve published QSARs were evaluated using the components, such that their potential use could be identified. High uncertainty was commonly observed with the presentation of data, mechanistic interpretability, incorporation of toxicokinetics and the relevance of the data for regulatory purposes. The assessment components help to guide strategies that can be implemented to improve acceptability of QSARs through the reduction of uncertainties. It is anticipated that model developers could apply the assessment components from the model design phase (e.g. through problem formulation) through to their documentation and use. The application of the components provides the possibility to assess QSARs in a meaningful manner and demonstrate their fitness-for-purpose against pre-defined criteria.

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology and Pharmaceutical Sciences
Subjects: R Medicine > RA Public aspects of medicine > RA1190 Toxicology. Poisions
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 07 May 2021 09:18
Last Modified: 09 May 2022 00:50
DOI or ID number: 10.1016/j.yrtph.2021.104956
URI: https://researchonline.ljmu.ac.uk/id/eprint/14965
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