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.