An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods
This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 1...
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| Veröffentlicht in: | Regulatory toxicology and pharmacology 2006-03, Vol.44 (2), p.97-110 |
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| creator | Matthews, Edwin J. Kruhlak, Naomi L. Cimino, Michael C. Benz, R. Daniel Contrera, Joseph F. |
| description | This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the
MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had ∼70% in silico data pooled with ∼30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5–88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with carcinogenicity results (CI values |
| doi_str_mv | 10.1016/j.yrtph.2005.10.004 |
| format | Article |
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| ispartof | Regulatory toxicology and pharmacology, 2006-03, Vol.44 (2), p.97-110 |
| issn | 0273-2300 1096-0295 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Carcinogenicity Carcinogenicity Tests Carcinogens - classification Carcinogens - toxicity Computational toxicology Computer Simulation Evaluation Studies as Topic Genetic toxicity Genetox MC4PC Models, Biological Mutagenicity Tests Predictive modeling Predictive Value of Tests Quantitative Structure-Activity Relationship Quantitative structure–activity relationships Reproduction - drug effects Reproductive and developmental toxicity Reprotox Rodent carcinogenicity bioassay Salmonella Sensitivity and Specificity Software Surrogate Toxicity Tests, Chronic |
| title | An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods |
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