title: A retrospective evaluation of COMPACT predictions of the outcome of NTP rodent carcinogenicity testing.
abstract: The carcinogenic potentials of 40 National Toxicology Program chemicals previously predicted by Computer Optimised Molecular Parametric Analysis for Chemical Toxicity (COMPACT), based on the identification of potential substrates of cytochromes P4501A and 2E (CYP1A and CYP2E), have been compared with new rodent carcinogenicity results. The COMPACT predictions have also been compared with published Ames mutagenicity data and with our own Hazardexpert predictions for carcinogenicity. Concordance evaluations between rodent carcinogenicity (1/4 segments positive) and predictions by COMPACT or Hazardexpert were 64% for COMPACT (CYP1A only), 72% for COMPACT (CYP1A plus CYP2E), 70% for Hazardexpert alone, and 86% for COMPACT (CYP1A plus CYP2E) plus Hazardexpert. Sensitivities of the predictions were for COMPACT, 75%; Hazardexpert, 60%; and Ames, 54%. Positive predictivities were for COMPACT, 75%; Hazardexpert, 78%; and Ames 81%. Negative predictivites were for COMPACT, 62%; Hazardexpert, 52%; and Ames, 42%.
authors.affiliation: Molecular Toxicology Group School of Biological Sciences, University of Surrey, Guildford, UK.
authors.forename: D F
authors.initials: DF
authors.lastname: Lewis
authors.forename: C
authors.initials: C
authors.lastname: Ioannides
authors.forename: D V
authors.initials: DV
authors.lastname: Parke
mesh_terms: D000818:Animals; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity; D003198:Computer Simulation; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System; D016002:Discriminant Analysis; D005069:Evaluation Studies as Topic; D005260:Female; D008297:Male; D010088:Oxidoreductases; D010089:Oxidoreductases, N-Demethylating; D016016:Proportional Hazards Models; D051381:Rats; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D010089:Oxidoreductases, N-Demethylating