An exploratory study of the use of multivariate techniques to determine mechanisms of toxic action.

The most successful quantitative structure-activity relationships have been developed by separating compounds by their mechanisms of toxic action (MOAs). However, to correctly determine the MOA of a compound is often not easy. We investigated the usefulness of discriminant analysis and logistic regression in determining MOAs. The discriminating variables used were the logarithm of octanol-water partition coefficients (logKow) and the experimental toxicity data obtained from Pimephales promelas and Tetrahymena pyriformis assays. Small total error rates were obtained when separating nonpolar narcotic compounds from other compounds, however, relatively high total error rates were obtained when separating less reactive compounds (polar, ester, and amine narcotics) from more reactive compounds (electrophiles, proelectrophiles, and nucleophiles).

[1]  M. D. Kahl,et al.  Acute toxicity of organic chemical mixtures to the fathead minnow , 1985 .

[2]  Wayne G. Landis,et al.  Environmental toxicology and risk assessment , 1993 .

[3]  R. Lipnick,et al.  Structural properties for determining mechanisms of toxic action , 1989 .

[4]  Gerrit Schüürmann,et al.  Quantitative structure-activity relationships in environmental sciences, VII , 1997 .

[5]  R. L. Lipnick.  Base-line toxicity predicted by quantitative structure-activity relationships as a probe for molecular mechanism of toxicity , 1989 .

[6]  G. Veith,et al.  Relationships between descriptors for hydrophobicity and soft electrophilicity in predicting toxicity. , 1993, SAR and QSAR in environmental research.

[7]  Gerald J. Niemi,et al.  Use of respiratory‐cardiovascular responses of rainbow trout (Salmo gairdneri) in identifying acute toxicity syndromes in fish: Part 1. pentachlorophenol, 2,4‐dinitrophenol, tricaine methanesulfonate and 1‐octanol , 1987 .

[8]  G. Veith,et al.  Rules for distinguishing toxicants that cause type I and type II narcosis syndromes. , 1990, Environmental health perspectives.

[9]  T W Schultz,et al.  Relationships of quantitative structure-activity to comparative toxicity of selected phenols in the Pimephales promelas and Tetrahymena pyriformis test systems. , 1986, Ecotoxicology and environmental safety.

[10]  C. Russom,et al.  Predicting modes of toxic action from chemical structure: Acute toxicity in the fathead minnow (Pimephales promelas) , 1997 .

[11]  Michael H. Abraham,et al.  Solubility properties in polymers and biological media. 8. An analysis of the factors that influence toxicities of organic nonelectrolytes to the golden orfe fish (Leuciscus idus melanotus) , 1987 .

[12]  Toshio Fujita,et al.  Classical and Three-Dimensional QSAR in Agrochemistry , 1995 .

[13]  T W Schultz,et al.  Structure-toxicity relationships for alkanones and alkenones. , 1995, SAR and QSAR in environmental research.

[14]  J. Dodge,et al.  Structure/activity relationships , 1998 .

[15]  B. Hansen,et al.  Priority setting for existing chemicals: European Union risk ranking method , 1999 .

[16]  R. Milne,et al.  The Control and Monitoring of Discharges by Biological Techniques , 1992 .

[17]  S. Bradbury,et al.  Predicting modes of toxic action from chemical structure: an overview. , 1994, SAR and QSAR in environmental research.

[18]  T W Schultz,et al.  Quantitative relationships of structure-activity and volume fraction for selected nonpolar and polar narcotic chemicals. , 1993, SAR and QSAR in environmental research.

[19]  J. Nabholz,et al.  Quantitative Structure-Activity Predictions for Amine Toxicity to Algae and Daphnids , 1993 .

[20]  T. Wayne Schultz,et al.  Structure‐activity relationships for Pimephales and Tetrahymena: A mechanism of action approach , 1997 .

[21]  S. Bradbury,et al.  Quantitative structure-activity relationships and ecological risk assessment: an overview of predictive aquatic toxicology research. , 1995, Toxicology letters.

[22]  Gerald J. Niemi,et al.  A comparative study of molecular similarity, statistical, and neural methods for predicting toxic modes of action , 1998 .

[23]  N. Nirmalakhandan,et al.  QSAR Parameters for Toxicity of Organic Chemicals to Nitrobacter , 1992 .

[24]  J. Hermens,et al.  Classifying environmental pollutants , 1992 .

[25]  T W Schultz,et al.  Structure-toxicity relationships for benzenes evaluated with Tetrahymena pyriformis. , 1999, Chemical research in toxicology.

[26]  S. Bradbury,et al.  Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment. , 1987, Environmental health perspectives.

[27]  Gerald J. Niemi,et al.  Use of respiratory‐cardiovascular responses of rainbow trout (Salmo gairdneri) in identifying acute toxicity syndromes in fish: Part 2. malathion, carbaryl, acrolein and benzaldehyde , 1987 .

[28]  J. Hermens,et al.  QSARs in Environmental Toxicology and Chemistry: Recent Developments , 1995 .