Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures

The results of computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) and HazardExpert evaluations on 14 established human carcinogens are reported. The concordances between COMPACT and carcinogenicity (71%) and between HazardExpert and carcinogenicity (57%) are significantly improved when taken in combination, where all 14 carcinogens are correctly identified by the two systems used in conjunction. However, if a negative energy of the highest occupied molecular orbital (E-HOMO) value is regarded as evidence of electrophilic reactivity likely to give rise to mutagenicity and carcinogenicity, then 13/14 (93%) of the carcinogens are correctly identified by combination with the COMPACT procedure alone. It is possible, therefore, to establish likely carcinogenicity arising from either P450 mediation (CYP1 and CYP2E) or compound electrophilicity via the employment of a straightforward approach to molecular and electronic structure calculation, a process that can be performed in a relatively short time frame (i.e., less than 1 hour per chemical) and at a low cost.