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Human & Experimental Toxicology, Vol. 21, No. 3, 115-122 (2002)
DOI: 10.1191/0960327102ht233oa

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

D FV Lewis

Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK; d.lewis{at}surrey.ac.uk

M G Bird

Unit of Carcinogen Identification and Evaluation, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France

M N Jacobs

Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK

The results of computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) and Hazard Expert 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 (EHOMO) 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.

Key Words: COMPACT • Cytochrome P450 • HazardExpert • Human Carcinogens


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