Prediction of Acute Mammalian Toxicity Using QSAR Methods A Case Study of Sulfur Mustard and Its Breakdown Products 英文参考文献.docVIP

Molecules 2012, 17, 8982-9001; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Prediction of Acute Mammalian Toxicity Using QSAR Methods: A Case Study of Sulfur Mustard and Its Breakdown Products Patricia Ruiz 1,*, Gino Begluitti 2, Terry Tincher 2, John Wheeler 1 and Moiz Mumtaz 1 1 Computational Toxicology and Methods Development Lab, Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry, Atlanta, GA 30333, USA 2 Environmental Public Health Readiness Branch, National Center for Environmental Health, Atlanta, GA 30333, USA * Author to whom correspondence should be addressed; E-Mail: pruiz@; Tel.: +1-770-488-3348; Fax: +1-770-488-3470. Received: 6 June 2012; in revised form: 19 July 2012 / Accepted: 23 July 2012 / Published: 27 July 2012 Abstract: Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD50) for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other kn