Following publication of the FDA Expanded Decision Tree (EDT), a key question arose as to whether applying the Kroes workflow to the EDT dataset would yield comparable TTC values to those derived from the original Munro dataset. Herein, the EDT dataset was processed through the Kroes workflow from which TTC values were derived via bootstrapping for substances that were Cramer class applicable. The resulting values; 34, 13.7 and 1.54 μg/kg bw/day for Cramer classes I-III respectively were comparable to the existing Munro-derived TTCs. Structural coverage was then compared using ToxPrint chemical fingerprints. Whilst a handful of ToxPrints were significantly enriched in each dataset, effect sizes were modest and the vast majority of features were equally prevalent in both datasets confirming chemical concordance between the EDT Cramer subset and the Munro dataset, and supporting the continued validity of the existing Munro-derived TTC values. Using a dataset of known Cramer class assignments, a concordance analysis between Cramer class and EDT assignments showed 65% agreement, with 23% cases where EDT assignments were more permissive. Inspection of discordant substances highlighted limitations in the Cramer tree itself. Within EDT class I, a subgroup of carbohydrate substances was identified that could form a new “EDT class 0”, yielding a TTC of 1387 μg/kg bw/day. Finally, given the lack of a programmatic interface within Toxtree, a Python implementation of the Cramer scheme was developed to support integration into computational workflows. This was validated against the Munro dataset to verify correspondence with the original Toxtree Cramer module.