PREDICTING MODES OF TOXIC ACTION FROM CHEMICAL-STRUCTURE - ACUTE TOXICITY IN THE FATHEAD MINNOW (PIMEPHALES-PROMELAS)

In the field of aquatic toxicology, quantitative structure-activity re lationships (QSARs) have developed as scientifically credible models f or predicting the toxicity of chemicals when little or no empirical da ta are available. In recent years, 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 to xic action. The objective of this research was to develop procedures t hat relate modes of acute toxic action in the fathead minnow (Pimephal es promelas) to chemical structures and properties. An empirically der ived database for diverse chemical structures of acute toxicity and co rresponding modes of toxic action was developed through joint toxic ac tion studies, the establishment of toxicodynamic profiles, and behavio ral and dose-response interpretation of 96-h LC50 tests. Using the res ults from these efforts, as well as principles in the toxicological li terature, approximately 600 chemicals were classified as narcotics (th ree distinct groups), oxidative phosphorylation uncouplers, respirator y inhibitors, electrophiles/proelectrophiles, acetylcholinesterase inh ibitors, or central nervous system seizure agents. Using this data set , a computer-based expert system has been established whereby chemical structures are associated with likely modes of toxic action and, when available, corresponding QSARs.