Metabolism-based category formation for the prioritisation of genotoxicity hazard assessment for plant protection product residues (Part 5): Acetyl CoA carboxylase inhibitors.

Enoch, SJ ORCID: 0000-0001-9111-5783, Hasarova, Z, Cronin, MTD ORCID: 0000-0002-6207-4158, Bridgwood, K, Rao, S, Hueser, A, Kluxen, FM and Frericks, M (2026) Metabolism-based category formation for the prioritisation of genotoxicity hazard assessment for plant protection product residues (Part 5): Acetyl CoA carboxylase inhibitors. Regulatory toxicology and pharmacology. ISSN 0273-2300

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Abstract

In dietary risk assessment of plant protection products, residues of active ingredients and their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. A dataset of 58 inhibition of acetyl CoA carboxylase herbicides for which either Ames, chromosomal aberration or micronucleus test results were identified from publicly available regulatory submission dossiers. A set of structural space alerts were defined from this dataset, each linked to a key metabolic transformation present in the metabolic space, covering both the cyclohexadiones and aryloxphenoxypropionates classes. A hypothetical case study chemical was used to demonstrate the ability of the structural space alerts to identify metabolically related analogues with which to predict genotoxicity, including the in vivo micronucleus test, via read-across. In addition, the structural space alerts defined were compared to the metabolic simulators in the OECD QSAR Toolbox. The results showed the importance of expert driven methods for defining metabolic similarity for read-across for plant protection products. As with previous work in this area, the key challenge being the need for metabolism data for the development of the structural space alerts.

Item Type:	Article
Uncontrolled Keywords:	genotoxicity; hazard assessment; pesticide residues; read-across; structural alerts; 3214 Pharmacology and Pharmaceutical Sciences; 32 Biomedical and Clinical Sciences; Nutrition; 1115 Pharmacology and Pharmaceutical Sciences; Toxicology; 3214 Pharmacology and pharmaceutical sciences
Subjects:	R Medicine > RA Public aspects of medicine > RA1190 Toxicology. Poisions R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Elsevier BV
Date of acceptance:	1 March 2026
Date of first compliant Open Access:	16 March 2026
Date Deposited:	16 Mar 2026 14:40
Last Modified:	16 Mar 2026 14:40
DOI or ID number:	10.1016/j.yrtph.2026.106079
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28252

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