title: Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures.
abstract: 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.
authors.affiliation: Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK. d.lewis@surrey.ac.uk
authors.forename: D F V
authors.initials: DF
authors.lastname: Lewi
authors.forename: M G
authors.initials: MG
authors.lastname: Bird
authors.forename: M N
authors.initials: MN
authors.lastname: Jacobs
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D002273:Carcinogens / Q000009:adverse effects*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005069:Evaluation Studies as Topic; D015386:Hazardous Substances / Q000009:adverse effects*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D012984:Software / Q000706:statistics & numerical data
chemical_list: D002273:Carcinogens; D015386:Hazardous Substances; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D042926:Cytochrome P-450 CYP4A; D010089:Oxidoreductases, N-Demethylating