QSAR modeling of acute toxicity on mammals caused by aromatic compounds: the case study using oral LD50 for rats

J Environ Monit. 2010 May;12(5):1037-44. doi: 10.1039/b919489d.

Abstract

The goal of the study was to predict toxicity in vivo caused by aromatic compounds structured with a single benzene ring and the presence or absence of different substituent groups such as hydroxyl-, nitro-, amino-, methyl-, methoxy-, etc., by using QSAR/QSPR tools. A Genetic Algorithm and multiple regression analysis were applied to select the descriptors and to generate the correlation models. The most predictive model is shown to be the 3-variable model which also has a good ratio of the number of descriptors and their predictive ability to avoid overfitting. The main contributions to the toxicity were shown to be the polarizability weighted MATS2p and the number of certain groups C-026 descriptors. The GA-MLRA approach showed good results in this study, which allows the building of a simple, interpretable and transparent model that can be used for future studies of predicting toxicity of organic compounds to mammals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Algorithms
  • Animals
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / toxicity*
  • Lethal Dose 50
  • Models, Chemical
  • Organic Chemicals / chemistry
  • Organic Chemicals / toxicity*
  • Quantitative Structure-Activity Relationship*
  • Rats
  • Regression Analysis
  • Toxicity Tests, Acute / methods*

Substances

  • Environmental Pollutants
  • Organic Chemicals