Computer-aided toxicity prediction

A number of approaches are available or under development to predict metabolism, including expert systems such as MetabolExpert (Compudrug), Meteor (Lhasa), MetaFore [42] and the databases Metabolite (MDL) and Metabolism (Synopsys) [43]. Ultimately such programs may be linked to computer-aided toxicity prediction based on quantitative structure-toxicity relationships and expert systems for toxicity evaluation such as DEREK (Lhasa) (see also Chapter 8) [44]. 

There are various definitions of what constitutes a computer-aided toxicity prediction method. It is true to say that all techniques are based upon the relationship of the biological activity of one or more molecules with some aspect of chemical structure. This broadest of definitions normally requires three components for a prediction method ... 

Dearden JC. In silico prediction of drng toxicity. J Comput-Aid Mol Des 2003 17 119-27. 

Cronin, M.T.D. Computer-aided prediction of drug toxicity in high throughput screening. Pharm. Pharmacol. Commun. 1998, 4, 157-163. 

Dearden, J.C. (2003) In silico prediction of drug toxicity. Journal of Computer-Aided Molecular Design, 17 (2-4), 119-127. 

As computers become more pervasive and increasingly powerful, specialized programs and databases are being developed to assist in a wide variety of research efforts. This is true in the search for solvent alternatives, and in this section we review the application of computers to solvent substitution studies and cover computer-aided molecular design of new solvents, methods developed for the prediction of physical properties, methods for predicting less precise chemical characteristics such as toxicity and carcinogenicity, and computer-aided design of alternative synthetic pathways. 

Approximately 100,000 separate chemicals may be released into the environment annually it is frightening to consider that reliable toxicity data exist for only a tiny proportion of these chemicals, probably less than 5%. The percentage of chemicals with a complete set of reliable toxicity data (i.e., across a broad spectrum of environmental and human health effects) is considerably less than 5%. Computer-aided prediction of toxicity has the capability to assist in the prioritisation of chemicals for testing, and for predicting specific toxicities to allow for labeling. Chapter 19 describes these activities in more detail. As the reliability of models for toxicity prediction increases, there will undoubtedly be increased use for the filling of data gaps. 

Ames BN, Durston WE, Yamasaki E, Lee FD (1973) Carcinogens are mutagens a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 70 2281-2285 Cunningham AR, Klopman G, Rosenkranz HS (1998) Identification of structural features and associated mechanisms of action for carcinogens in rats. Mutat Res 405 9-27 Dearden JC (2003) In silico prediction of drug toxicity. J Comput Aided Mol Des 17 119-127... 

INFORMATION SOURCES FOR SOFTWARE FOR COMPUTER-AIDED PREDICTION OF TOXICITY METHODS... 

Hehna C, Kazius J. Artificial intelligence and data mining for toxicity prediction. Curr. Comput.-Aid. Drag Des. 2006 2 1-19. 

Gallegos Saliner A. Mini-review on chemical similarity and prediction of toxicity. Curr Comput Aided Drug Des 2006 2 105-22. 

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