In silico screening of chemicals for genetic toxicity using MDL-QSAR, nonparametric discriminant analysis, E-state, connectivity, and molecular property descriptors

Toxicology Mechanisms and Methods

Volumn 18, Issue 2-3, 2008, Pages 207-216

  Contrera, Joseph F ^a,b   Matthews, Edwin J ^a   Kruhlak, Naomi L ^a   Benz, R Daniel ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^b Box 1565 ^*  (United States)

Author keywords

Clastogenicity; DNA Damage; Drug Development; E State Indices; Electrotopological; Genetic Toxicity; Genotoxic; In Silico Screening; MC4PC; Mutagenicity; Predictive Toxicology; QSAR

Indexed keywords

CLASTOGEN;

ARTICLE; CHROMOSOME ABERRATION; COMPUTER MODEL; COMPUTER PROGRAM; DECISION MAKING; DISCRIMINANT ANALYSIS; DNA DAMAGE; DNA SYNTHESIS; DRUG INDUSTRY; GENE MUTATION; GENOTOXICITY; IN VIVO STUDY; INTERMETHOD COMPARISON; LYMPHOMA; MUTAGENICITY; NONHUMAN; PREDICTION; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; SCREENING TEST; SENSITIVITY AND SPECIFICITY; VALIDATION PROCESS;

ESCHERICHIA COLI; SALMONELLA TYPHIMURIUM;

EID: 40949150720     PISSN: 15376516     EISSN: 15376524     Source Type: Journal    
DOI: 10.1080/15376510701857106     Document Type: Article

References (45)

1. Anderson, T. W. 1984. An Introduction to Multivariate Statistical Analysis, Second Edition, John Wiley & Sons, New York.
2. Ashby, J., and Tennant, R. W. 1991. Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res. 257:229-306.
3. Benigni, R. 2005. Structure activity relationship studies of chemical mutagens and carcinogens: mechanistic investigations and prediction approaches. Chem. Rev. 105:1767-1800.
4. Cash, G. H. 2001. Prediction of the genotoxicity of aromatic and heteroaromatic amines using electrotopological state indices. Mutat. Res. 491:31-37.
5. Cimino, M. C., and Auletta, A. E. 1993. Availability of the GENE-TOX database on the National Library of Medicine TOXNET system. Mutagen. 8:163-164.
6. Contrera, J. F., Hall, L. H., Kier, L. B., and MacLaughlin, P. 2005a. QSAR modeling of carcinogenic risk using discriminant analysis and topological molecular descriptors. Curr. Drug Discov. Technol. 2:55-67.
7. Contrera, J. F., Kruhlak, N. L., and Benz, R. D. 2007. Comparison of MC4PC and MDL-QSAR rodent carcinogenicity predictions and the enhancement of predictive performance by combining QSAR models. Regul. Toxicol. Pharmacol. 49:172-182.
8. Contrera, J. F., Matthews, E. J., and Benz, R. D. 2003. Predicting the carcinogenic potential of pharmaceuticals in rodents using molecular structural similarity and E-state indices. Regul. Toxicol. Pharmacol. 38:243-259.
9. Contrera, J. F., Matthews, E. J., Kruhlak, N. L., and Benz, R. D. 2005b. In silico screening of chemicals for bacterial mutagenicity using electrotopological E-state indices and MDL-QSAR software. Regul. Toxicol. Pharmacol. 43:313-323.
10. Cooper, J. A., Saracci, R., and Cole, P. 1979. Describing the validity of carcinogen screening tests. Br. J. Cancer 39:87-89.
11. Dearden, J. 2003. In silico prediction of drug toxicity. J. Comput. Aided Mol. Des. 17:119-127.
12. Dearfield, K. D., Auletta, A. E., Cimino, M. C., and Moore, M. M. 1991. Considerations in the U. S. Drug Information Association. Regulation and Control of Genotoxic Impurities. Bethesda, MD, November 17-18, 2005.
13. Environmental Protection Agency's testing approach for mutagenicity. Mutat. Res. 258:259-283.
14. Eriksson, L., Jaworska, J. S., Worth, A. P., Cronin, M. T., McDowell, R. M., and Gramatica, P. 2003. Methods for reliability, uncertainty assessment, and applicability evaluations of classification and regression based QSARs. Environ. Health Perspect. 111:1361-1375.
15. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). 2004. Guideline on the Limits of Genotoxic Impurities. CHMP/SWP/5199/02. http://www.emea.eu.int/pdfs/human/swp/519902en.pdf.
16. Golbraikh, A., and Tropsha, A. 2002. Beware of q2!. J. Molec. Graph. Model. 20:269-276.
17. Hall, L. H. 2004. A structure-information approach to prediction of biological activities and properties. Chem. Biodiversity 1:183-201.
18. Hall, L. H., and Kier, L. B. 1995. Electrotopological state indices for atom types: a novel combination of electronic, topological and valence state information. J. Chem. Inf. Comput. Sci. 35:1039-1045.
19. Hall, L. H., and Kier, L. B. 2001. Issues in the representation of molecular structure: the development of molecular connectivity. J. Molec. Model. Graphics 20:4-18.
20. Hanley, J. A. 1989. Receiver operating characteristic (ROC) methodology: the state of the art. Crit. Rev. Diagn. Imaging 29:307-335.
21. ICH S2A. 1995. Genetic toxicity studies: guidance on specific aspects of regulatory tests for pharmaceuticals. www.ich.org.
22. ICH S2B. 1997. Genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals. www.ich.org.
23. Jacobson-Kram, D., and Contrera, J. F. 2007. Genetic toxicity assessment: employing the best science for human safety evaluation part I: early screening for potential human mutagens. Toxicol. Sci. 96:16-20.
24. Kendall, M. G., Stuart, A., Ord, J. K., 1983. The advanced theory of statistics, Vol. 3, 4th ed. New York: Macmillan Publishing Co.
25. Kier, L. B., and Hall, L. H. 1999. Molecular Structure Description: The Electrotopological State, Academic Press, San Diego.
26. Kier, L. B., and Hall, L. H. 2001. Database organization and similarity searching with E-state indices, SAR. QSAR Environ. Res. 12:55-74.
27. Kirkland, D., Aardema, M., Henderson, L., and Müller, L. 2005. Evaluation of the ability of a battery of three in vitro tests to discriminate rodent carcinogens and non-carcinogens. I. Sensitivity, specificity, and relative predictivity. Mutat. Res. 584:1-256.
28. Kruhlak, N. L., Contrera, J. F., Benz, R. D., and Matthews, E. J. 2007. Progress in QSAR toxicity screening of pharmaceutical impurities and other FDA regulated products. Advan. Drug Deliv. 59:43-55.
29. Lusted, L. B. 1971. Signal detectability and medical decision-making. Science. 171:1217-1219.
30. Matthews, E. J., and Contrera, J. F. 1998. A new highly specific method for predicting the carcinogenic potential of pharmaceuticals in rodents using enhanced MCASE QSAR-ES software. Regul. Toxicol. Pharmacol. 28:242-264.
31. Matthews, E. J., Kruhlak, N. L., Cimino, M. C., Benz, R. D., and Contrera, J. F. 2006a. An analysis of genetic toxicity, reproductive and developmental toxicity and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol. 44:83-96.
32. Matthews, E. J., Kruhlak, N. L., Cimino, M. C., Benz, R. D., and Contrera, J. F. 2006b. An analysis of genetic toxicity, reproductive and developmental toxicity and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods. Regul. Toxicol. Pharmacol. 44:97-110.
33. McGee, P. 2005. Modeling success with in silico tools. Drug Discov. Develop. 8:24-28.
34. McGovern, T., and Jacobson-Kram, D. 2006. Regulation of genotoxic and carcinogenic impurities in drug substances and products. Trends Analy. Chem. 25:790-795.
35. National Institutes of Health, National Library of Medicine. 2005. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances - GENE-TOX Agent Registry. Online computer database - TOXNET file. U.S. Dept. Health and Human Services, Bethesda MD 20894.
36. Organisation for Economic Cooperation and Development (OECD). 2004. 2004 Regulatory Application of (Q)SARs: A U.S. EPA Case Study. ENV/JM/TG(2004)25/ REV2, 14.
37. Perkins, R., Fang, H., Tong, W., and Welsh, W. J. 2003. Quantitative structure-activity relationship methods: Perspectives on drug discovery and toxicology. Environ. Toxicol. Chem. 22:1666-1679.
38. PhRMA Genotoxic Impurity Task Force. 2004. Draft white paper: Establishment of Allowable Concentration of genotoxic Impurities in Drug Substances and Products.
39. Provost, F., and Fawcett, T. 2001. Robust classification for imprecise environments. Mach. Learn. J. 42:203-231.
40. Snyder, D. R., Pearl, G. S., Mandakas, G., Choy, W. N., Goodsaid, F., and Rosenblum, I. Y. 2004. Assessment of the sensitivity of the computational programs DEREK, TOPKAT and MCASE in the prediction of the genotoxicity of pharmaceutical molecules. Environ. Mol. Mutagen. 43:143-158.
41. Tunkel, J., Mayo, K., Austin, C., Hickerson, A., and Howard, P. 2005. Practical considerations on the use of predictive models for regulatory purposes. Environ. Sci. Technol. 39:2188-2199.
42. U. S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Food Additive Safety. 2004. Toxicological Principles for the Safety Assessment of Food Ingredients. http://www.cfsan.fda.gov/ ~redbook/red-toca.html.
43. Votano, J. R., Parham, M., Hall, L. H., Kier, L. B., Oloff, S., and Tropsha, A. 2004. Three new consensus QSAR models for the prediction of Ames genotoxicity. Mutagen. 19:365-377.
44. Wagner, P. M., Nabholz, J. V., and Kent, R. J. 1995. The new chemicals process at the Environmental Protection Agency (EPA): structure-activity relationships for hazard identification and risk assessment. Toxicol. Lett. 79:67-73.
45. Wilson, A. G., White, A. C., and Mueller, R. A. 2003. Role of predictive metabolism and toxicity modeling in drug discovery: a summary of some recent advancements. Curr. Opin. Drug Discov. Devel. 6:123-128.