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Development of an Enhanced Mechanistically-Driven Mode of Action Classification Scheme for Adverse Effects in Environmental Species

Sapounidou, M, Ebbrell, DJ, Bonnell, M, Campos, B, Firman, J, Gitsell, S and Cronin, MTD Development of an Enhanced Mechanistically-Driven Mode of Action Classification Scheme for Adverse Effects in Environmental Species. Environmental Science and Technology. ISSN 0013-936X (Accepted)

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Abstract

This study developed a novel classification scheme to assign chemicals to a verifiable mechanism of (eco)toxicological action to allow for grouping, read-across and in silico model generation. The new classification scheme unifies and extends existing schemes and has at its heart, direct reference to molecular initiating events (MIEs) promoting adverse outcomes. The scheme is based on three broad domains of toxic action representing non-specific toxicity (e.g. narcosis), reactive mechanisms (e.g. electrophilicity and free radical action) and specific mechanisms (e.g. associated with enzyme inhibition). The scheme is organised at three further levels of detail beyond broad domains to separate out mechanistic group, specific mechanism and the MIEs responsible. Novelty in this approach comes from the reference to taxonomic diversity within the classification, transparency, quality of supporting evidence relating to MIEs and that it can be updated readily.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: ACS American Chemical Society
Date Deposited: 08 Jan 2021 09:51
Last Modified: 08 Jan 2021 10:00
URI: https://researchonline.ljmu.ac.uk/id/eprint/14239

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