Predicting modes of toxic action from chemical structure: an overview.
In the field of environmental toxicology, and especially aquatic toxicology, quantitative structure activity relationships (QSARs) have developed as scientifically-credible tools for predicting the toxicity of chemicals when little or no empirical data are available. A basic and fundamental understanding of toxicological principles has been considered crucial to the continued acceptance and application of these techniques as biologically relevant. As a consequence, there has been an evolution of QSAR development and application from that of a chemical-class perspective to one that is more consistent with assumptions regarding modes of toxic action. The assessment of a compound's likely mode of toxic action is critical for a correct QSAR selection; incorrect mode of action-based QSAR selections can result in 10- to 1000-fold errors in toxicity predictions. The establishment of toxicologically-credible techniques to assess mode of toxic action from chemical structure requires toxicodynamic knowledge bases that are clearly defined with regard to exposure regimes and biological models/endpoints and based on compounds that adequately span the diversity of chemicals anticipated for future applications. With such knowledge bases classification systems, including rule-based experts systems, have been established for use in predictive aquatic toxicology applications.
Bradbury
S P
SP
U.S. Environmental Protection Agency, Environmental Research Laboratory, Duluth, MN 55804, USA.
D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D005399:Fishes; D008954:Models, Biological; D016571:Neural Networks, Computer; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
D010575:Pesticides; D014874:Water Pollutants, Chemical; D015262:Xenobiotics