ABSTRACT
A large toxicity data set containing the toxicities of 250 phenols and 252 aliphatic compounds to Tetrahymena pyriformis was classified into different groups based on the structure and substituted functional groups. QSAR analysis was performed between the toxicity and calculated descriptors, expressed as hydrophobicity, polarity and ionization. Through an analysis of these class-based compounds, significant relationships were developed between the toxicity and hydrophobicity for non-polar and polar narcotic compounds. A single model for both non-polar and polar narcotics was developed by inclusion of a polar descriptor as well as the hydrophobic parameter logP. The highly hydrophobic polar narcotics can be treated as non-polar narcotics because their polar functional group(s) makes a relatively small contribution as compared to their hydrophobicity. A cut-off to classify the polar narcotics is difficult because polarity of a chemical not only depends on one or two functional groups (i.e. amino- or hydroxyl-) substituted on the compound, but also on the overall hydrophobicity of the compound. The toxicity increases with increasing the ionization by increasing the interaction between ionisable compounds and macromolecules at the target sites. However, the toxicity decreases with increasing the ionization by decreasing the bio-uptake for extremely ionisable compounds. A significant QSAR equation has been developed between the toxicity to T. pyriformis and the descriptors of hydrophobic, polarity/polarizability and ionization parameters for 457 compounds (R(2)=0.87). These compounds contain non-polar, polar and reactive compounds, and some of them are extremely ionisable. The models developed are simple, interpretable and transparent, using a small number of descriptors.
