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Today it is generally accepted that a separate quantitative structure activity relationship (QSAR) can be developed for each mechanism of toxic action. This idea has rekindled an interest in modes of action, especially in aquatic systems. One of the first toxic mechanisms to be identified was simple or nonpolar narcosis, a common mechanism observed with most industrial organic chemicals. It is reversible and physical in nature. Within limits, it is independent of molecular structure, being associated with most nonionic, nonpolar, nonreactive chemicals that are either not metabolized or metabolized very slowly. For these reasons it is considered baseline toxicity. Nonpolar narcosis shows equal activity resulting from equal concentration at the site of action. Since this phenomenon is related to hydrophobicity, narcotic potency correlates well with lipid partitioning. The specific site of action is unknown at this time. However, two likely sites are the bimolecular layer of cell membranes and hydrophobic regions of membrane-bound proteins. A threshold volume is believed to be important. Nonpolar narcosis can be defined by a series of specific in vivo behavioral and/or respiratory-cardiovascular responses with fish and is modeled by QSAR in several test systems.
aquatic toxicity, mode of action, nonpolar narcosis, quantitative structure-activity relationship, fish acute toxicity syndrome
Associate professor, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN