Rules for Distinguishing Toxicants That Cause Type (I) and Type (II) Narcosis Syndromes

摘要

Narcosis is a non-specific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms and using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals were generally more toxic than predicted by narcosis (I) models and characterized by a different mode of action called narcosis (II) syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis (II) syndrome may result from the presence of a strong hydrogen bonding group on the molecule and narcosis (I) syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes.