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As described above see also Table 1 ; . Identification of the optimal break-points to define each subset of chemicals was critical for the generation of well-defined clusters of highand low-toxicity structural alerts in each of the modules. After processing the 1309 chemicals, the modules contained a fragment library of 903, 274 210 atom fragments. In the A95 module, a small subset of 181 fragments Table 5 ; were correlated with low MRTD values in humans and were subsequently identified as structural alerts. By applying our human expert rules, 56 were identified as decision alerts and a further 25 were identified as possible decision alerts. In the A97 module, 273 fragments that were correlated with high MRTD values in humans were identified as structural alerts. 78 of these structural alerts were identified as decision alerts and a further 37 were identified as possible decision alerts. The decision alerts were the primary basis of MRTD NOEL predictions in this investigation. Decision Alerts in Structurally Similar Chemicals We examined the types of chemicals in the training data set that had specific decision alerts in the A95 high toxicity training data set and the A97 low toxicity data set. We discovered that these decision alerts were often derived from clusters of chemicals that were structurally similar, and that many of the chemicals within a cluster had similar profiles of toxic effects. Five examples of decision alerts identified using the A95 module are presented in Table 6; each of these alerts was derived from a cluster of almost exclusively active chemicals. Furthermore, the chemicals contained in each cluster are the only examples in the training data set which contain the specific alert with an identical number of hydrogens on each atom. The decision alert "CH2CHNHCH" was identified in a cluster of 11 active chemicals, 8 of which were inhibitors of the angiotensinconverting enzyme ACE inhibitors ; and are used to treat + hypertension. The alert "N CH" was found in a larger cluster of 20 active chemicals, 18 of which are either antimuscarinics or muscle relaxants. Another large cluster of 19 chemicals, 17 of which are active, was identified to contain the decision alert "CH2-CH-c 2-OH ", where the hydroxyl substituent is bonded to the second atom of the fragment. 15 of the 19 compounds in this cluster were categorized as sympathomimetics. The decision alert "n cCH-" was found in 8 active chemicals, 6 of which were identified as sedating antihistamines; and finally the decision alert "n cc. 2NH2 " was identified in 13 chemicals, where 5 of the 11 active compounds are antineoplastics and a further 3 are used to treat hypertension. Figure 4 illustrates and augmentin. 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