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

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 nonspecific 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 organized at three further levels of detail beyond broad domains to separate out the mechanistic group, specific mechanism, and the MIEs responsible. The novelty of 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.

Automated summary

This study developed a new classification scheme to group chemicals based on their toxicological mechanisms, with detailed categorization into three broad domains representing non-specific toxicity, reactive mechanisms, and specific mechanisms. The novelty of this approach lies in its reference to taxonomic diversity, transparency, quality of supporting evidence on molecular initiating events, and its ease of updating.