Ellison, C.M.; Cronin, M.T.D.; Madden, J.C.; Schultz, T.W. Definition of the structural domain of the baseline non-polar narcosis model for Tetrahymena pyriformis. SAR QSAR Environ. Res. 2008, 19, 7-8, 751–783.

Abstract

The aim of this work was to develop a high-quality 1-octanol/water partition coefficient-dependent (log P) baseline quantitative structure-activity relationship (QSAR) for the toxicity (log IGC(50)(-1)) of classic non-polar narcotics to Tetrahymena pyriformis, and subsequently use this model to define the domain of applicability for baseline narcosis. The toxicities to T. pyriformis of 514 possible non-polar narcotics were assessed. A QSAR to predict toxicity was created from a training set of 87 classic non-polar narcotics (the saturated alcohols and ketones): log IGC(50)(-1) = 0.78 log P-2.01 (n = 87, r(2) = 0.96). This model was then used to predict the toxicity of the remaining chemicals. The chemicals from the large dataset which were poorly predicted by the model (i.e. the prediction was > +/-0.5 log units from the experimental value) were used to aid the definition of structural categories of chemicals which are not non-polar narcotics. Doing so has enabled the domain for non-polar narcosis to be defined in terms of structural categories. Defining domains of applicability for QSAR models is important if they are to be considered for making predictions of toxicity for regulatory purposes.