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Sub-structure-based category formation for the prioritisation of genotoxicity hazard assessment for pesticide residues (part 2): Triazoles.

Enoch, SJ, Hasarova, Z, Cronin, MTD and Frericks, M Sub-structure-based category formation for the prioritisation of genotoxicity hazard assessment for pesticide residues (part 2): Triazoles. Regulatory Toxicology and Pharmacology. ISSN 0273-2300 (Accepted)

Full text not available from this repository. Please see publisher or open access link below:
Open Access URL: https://doi.org/10.1016/j.yrtph.2022.105237 (Published version)

Abstract

In dietary risk assessment, residues of pesticidal ingredients or 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. To characterise similarity and to identify structural alerts associated with genotoxic concern, a set of chemical sub-structures was derived for an example dataset of 66 triazole agrochemicals for which either Ames, chromosomal aberration or micronucleus test results are publicly available. This analysis resulted in a set of ten structural alerts that define the chemical space, in terms of the common parent and metabolic scaffolds, associated with the triazole chemical class. An analysis of the available profiling schemes for DNA and protein reactivity shows the importance of investigating the predictivity of such schemes within a well-defined area of structural space. Structural space alerts, covalent chemistry profiling and physico-chemistry properties were combined to develop chemical categories suitable for chemical prioritisation. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing. The key challenge in the approach was identified as being the need for pesticide-class specific metabolism data as the basis for structural space alert development.

Item Type: Article
Uncontrolled Keywords: Category formation; Genotoxicity; Hazard assessment; Metabolism; Mutagenicity; Pesticide residues; Read-across; Structural alerts; Triazole; 1115 Pharmacology and Pharmaceutical Sciences; Toxicology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
SWORD Depositor: A Symplectic
Date Deposited: 05 Aug 2022 08:38
Last Modified: 05 Aug 2022 08:38
DOI or Identification number: 10.1016/j.yrtph.2022.105237
URI: https://researchonline.ljmu.ac.uk/id/eprint/17346

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