In Silico Prediction of Physicochemical Properties
John C. Dearden, Andrew Paul Worth · 2007
This report provides a critical review of computational models, and in particular (quantitative) structure-property relationship (QSPR) models, that are available for the prediction of physicochemical properties. The emphasis of the review is on the usefulness of the models for the regulatory assessment of chemicals, particularly for the purposes of the new European legislation for the Registration, Evaluation, Authorisation and Restriction of CHemicals (REACH), which entered into force in the European Union (EU) on 1 June 2007. It is estimated that some 30,000 chemicals will need to be further assessed under REACH. Clearly, the cost of determining the toxicological and ecotoxicological effects, the distribution and fate of 30,000 chemicals would be enormous. However, the legislation makes it clear that testing need not be carried out if adequate data can be obtained through information exchange between manufacturers, from in vitro testing, and from in silico predictions. The effects of a chemical on a living organism or on its distribution in the environment is controlled by the physicochemical properties of the chemical. Important physicochemical properties in this respect are, for example, partition coefficient, aqueous solubility, vapour pressure and dissociation constant. Whilst all of these properties can be measured, it is much quicker and cheaper, and in many cases just as accurate, to calculate them by using dedicated software packages or by using (QSPRs). These in silico approaches are critically reviewed in this report. LIST OF ABBREVIATIONS AIT Auto-ignition temperature ANN Artifical Neural Network Dow Octanol-water distribution coefficient EC European Commission ECB European Chemicals Bureau ECETOC European Centre for Ecotoxicology and Toxicology of Chemicals EPA Environmental Protection Agency F Fugacity ratio or Fischer Statistic GSE General Solubility Equation Ka Acid Dissociation Constant (often as pKa) Koc Organic carbon coefficient – measure of soil sorption Kom Organic matter coefficient – measure of soil sorption Kow Octanol-water partition coefficient MAE Mean absolute error MP Melting point MW Molecular Weight OECD Organisation for Economic Cooperation and Development Q 2 Cross-validated R 2 measure of predictive ability QSAR Quantitative Structure-Activity Relationship QSPR Quantitative Structure-Property Relationship R 2 Coefficient of determination – measure of goodness-of-fit REACH Registration Evaluation and Authorisation of Chemicals RMS Root mean square s Standard error of the estimate Saq Aqueous solubility SMILES Simplified Molecular Line Entry system Tb Boiling point TF Flash point Tm Melting point VP Vapour pressure