Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals
- Pegasus Technical Services, Inc., 46 E. Hollister St., Cincinnati, OH 45219 (United States)
- National Center for Environmental Assessment, U.S. Environmental Protection Agency, 26 W Martin Luther King Drive, Cincinnati, OH 45268 (United States)
- National Homeland Security Research Center, U.S. Environmental Protection Agency, Region 7, ENSV/IO, 901 N 5th Street, Kansas City, KS 66101 (United States)
Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD{sub 50}]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD{sub 50}) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD{sub 50} and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD{sub 50}s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD{sub 50} for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction.
- OSTI ID:
- 21182707
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 234, Issue 2; Other Information: DOI: 10.1016/j.taap.2008.09.028; PII: S0041-008X(08)00419-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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