Approaches for externally validated QSAR modelling of Nitrated Polycyclic Aromatic Hydrocarbon mutagenicity†

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8–12 May 2006, Lyon, France.

Abstract

Nitrated Polycyclic Aromatic Hydrocarbons (nitro-PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A set of mutagenicity data (TA100) for 48 nitro-PAHs was modeled by the Quantitative Structure-Activity Relationships (QSAR) regression method, and OECD principles for QSAR model validation were applied. The proposed Multiple Linear Regression (MLR) models are based on two topological molecular descriptors. The models were validated for predictivity by both internal and external validation. For the external validation, three different splitting approaches, D-optimal Experimental Design, Self Organizing Maps (SOM) and Random Selection by activity sampling, were applied to the original data set in order to compare these methodologies and to select the best descriptors able to model each prediction set chemicals independently of the splitting method applied. The applicability domain was verified by the leverage approach.

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8–12 May 2006, Lyon, France.

Keywords:

• Nitro-PAH
• QSAR
• Mutagenicity, 2D-molecular descriptors
• Splittings
• External validation

Acknowledgements

The financial support given by MIUR (PRIN-04 project: SITECOS) is gratefully acknowledged. Thanks are due to Roberto Marotta for the data set preparation.

Notes

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8–12 May 2006, Lyon, France.