QSAR study of the acute toxicity to fathead minnow based on a large dataset

Abstract

Acute fathead minnow toxicity is an important basis of hazard and risk assessment for compounds in the aquatic environment. In this paper, a large dataset consisting of 963 organic compounds with acute toxicity towards fathead minnow was studied with a QSAR approach. All molecular structures of compounds were optimized by the hybrid density functional theory method. Dragon molecular descriptors and log K_ow were selected to describe molecular information. Genetic algorithm and multiple linear regression analysis were combined to develop models. A global prediction model for compounds without known mode of action and two local models for organic compounds that exhibit narcosis toxicity and excess toxicity were developed, respectively. For all developed models, internal validations were performed by cross-validation and external validations were implemented by the setting of validation set. In addition, applicability domains of models were evaluated using a leverage method and outliers were listed and checked using toxicological knowledge.

Keywords:

• Aquatic organisms
• global model
• local model
• GA-MLR
• QSAR

Acknowledgements

This work is supported by National High Technology Research and Development Program 863 Project (2012AA06A301) and the Research Fund for the Doctoral Program of Higher Education of China (project No. 20130131110058).