CLASSIFYING ENVIRONMENTAL POLLUTANTS. 2: SEPARATION OF CLASS 1 (BASELINE TOXICITY) AND CLASS 2 ('POLAR NARCOSIS') TYPE COMPOUNDS BASED ON CHEMICAL DESCRIPTORS

摘要

A large part of the xenobiotics that are encountered as aquatic pollutants can be regarded as belonging to the so-called class 1 or baseline toxicity compounds. It is generally accepted that these compounds act through or can be considered to act through one and the same mechanism. A second important class of aquatic pollutants is formed by the slightly more toxic class 2 or polar narcosis compounds; this class of compounds is made up of, among others, phenols, anilines and similar slightly polar species and can also be considered to act through a single toxic mechanism. It has been shown that for both groups of chemicals the acute aquatic toxicity can be adequately modelled using a single-parameter quantitative structure-activity relationship (QSAR) equation based on log K_(ow). Furthermore, it has been shown that for compounds with a log K_(ow) above about 2.7 the distinction between the two classes, and hence between the two associated QSARs, breaks down. Apparently, the more specific mode of action, if there indeed is such a separate mechanism, converges to baseline toxicity at high log K_(ow). It therefore remains to be demonstrated whether this so-called 'polar narcosis' really is a distinct mode of action or just a perturbation of the baseline toxicity mechanism due to the more polar nature of the compounds. The chemical domain of class 1 and class 2 type compounds has been defined as a set of (sub)structural rules or structural alerts. In the current paper we constructed a PLS discriminant analysis QSAR model, based on non-empirical molecular descriptors, that is able to distinguish between class 1 and class 2 compounds. We also constructed a PLS regression analysis QSAR model, based upon the same set of molecular descriptors, that is capable of predicting the acute aquatic toxicity to fish for a combined set of class 1 and class 2 chemicals. Interestingly, the prime descriptor for both discrimination of class 1 and class 2 compounds and bringing them together in the toxicity prediction model is Q~-, which is a measure of the hydrogen bond acceptor capacity of a molecule.