Background: Many QSAR studies have been developed to predict acute toxicity
over several biomarkers like Pimephales promelas, Daphnia magna and Tetrahymena pyriformis.
Regardless of the progress made in this field there are still some gaps to be resolved
such as the prediction of aquatic toxicity over the protozoan T. pyriformis still lack a QSAR
study focused in accomplish the OECD principles.
Methods: Atom-based quadratic indices are used to obtain quantitative structure-activity
relationship (QSAR) models for the prediction of aquatic toxicity. Our models agree with
the principles required by the OECD for QSAR models to regulatory purposes. The database
employed consists of 392 substituted benzenes with toxicity values measured in T. pyriformis
(defined endpoint), was divided using cluster analysis in two series (training and test
Results: We obtain (with an unambiguous algorithm) two good multiple linear regression models for non-stochastic
(R2=0.807 and s=0.334) and stochastic (R2=0.817 and s=0.321), quadratic indices. The models were internally validated
using leave-one-out, bootstrapping as well as Y-scrambling experiments. We also perform an external validation using the
test set, achieving values of R2
pred values of 0.754 and 0.760, showing that our models have appropriate measures of goodness-
of-fit, robustness and predictivity. Moreover, we define a domain of applicability for our best models.
Conclusion: The achieved results demonstrated that, the atom-based quadratic indices could provide an attractive
alternative to the experiments currently used for determining toxicity, which are costly and time-consuming.