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Classifying environmental pollutants. 2: Separation of class 1 (baseline toxicity) and class 2 (‘polar narcosis’) type compounds based on chemical descriptors
Author(s) -
Verhaar Henk J. M.,
Urrestarazu Ramos Eñaut,
Hermens Joop L. M.
Publication year - 1996
Publication title -
journal of chemometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.47
H-Index - 92
eISSN - 1099-128X
pISSN - 0886-9383
DOI - 10.1002/(sici)1099-128x(199603)10:2<149::aid-cem414>3.0.co;2-f
Subject(s) - quantitative structure–activity relationship , pollutant , chemistry , polar , toxicity , acute toxicity , chemical toxicity , baseline (sea) , applicability domain , biological system , aquatic toxicology , environmental chemistry , stereochemistry , organic chemistry , biology , physics , fishery , astronomy
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.