MechoA+: A Chemical Structure Profiler Raising the Bar for the Prediction of Mechanisms of Toxic Action for Chemical Safety Assessment

Levet, G, Bauer, FJ, Thomas, PC, Cronin, MTD ORCID: 0000-0002-6207-4158, Roberts, J, Gutsell, S, Campos, B, Hodges, G and Firman, J ORCID: 0000-0003-0319-1407 (2026) MechoA+: A Chemical Structure Profiler Raising the Bar for the Prediction of Mechanisms of Toxic Action for Chemical Safety Assessment. Environmental Science & Technology. ISSN 0013-936X

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Abstract

With stakeholders in chemical regulation increasingly advocating for nonanimal testing methodologies, there is a need for reliable in silico tools with wide applicability domains to predict both environmental and human hazards. In this context, the in silico structure-based MechoA+ scheme has been developed to predict molecular initiating events, appropriate for both mammalian and ecotoxicity by merging and refining two previous classification models, MechoA and Sapounidou–Firman schemes. The resulting model is a new decision tree composed of 152 structural alerts able to classify a wide range of substances within 6 mechanistic classes and 27 subclasses and two rules excluding substances out of the scope of the scheme. Analysis of MechoA+ scheme predictions shows a higher percentage of valid predictions (92% predicted positive value on the training set) and wider structural, mechanistic, and taxonomic domains than the previous models on a data set of more than 70,000 substances (covering cosmetics, pesticides, etc.), achieving predictions for 80% of substances. Since MechoA+ is implemented within readily available software tools, its widespread adoption will facilitate more accurate hazard assessments, QSAR building, read-across, and grouping, strengthen regulatory decision-making, and support safer chemical design in early-stage research and development.

Item Type:	Article
Uncontrolled Keywords:	Environmental Sciences
Subjects:	Q Science > QD Chemistry
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	American Chemical Society
Date of acceptance:	26 May 2026
Date of first compliant Open Access:	8 June 2026
Date Deposited:	08 Jun 2026 11:02
Last Modified:	08 Jun 2026 11:02
DOI or ID number:	10.1021/acs.est.5c18657
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28770

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