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

• Published in: Environmental health perspectives Vol. 87; pp. 207 - 211
• Main Authors: Veith, Gilman D., Broderius, Steven J.
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.07.1990
• Subjects: 560300 - Chemicals Metabolism & Toxicology; Acute toxicity; AMIDES; AMINES; Animals; AQUATIC ORGANISMS; AROMATICS; Cell Membrane - drug effects; Chemical hazards; Chemical Phenomena; Chemistry, Physical; Cyprinidae; Drug Synergism; Enzyme Inhibitors - toxicity; Esters; Esters - toxicity; Fish Diseases - chemically induced; Hazardous Substances - classification; Hazardous Substances - pharmacology; Hazardous Substances - toxicity; Humans; Hydrogen Bonding - drug effects; HYDROXY COMPOUNDS; Narcosis; Narcotics; Octanols; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PHENOLS; Phenols - pharmacology; Phenols - toxicity; POLLUTION; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; SENSITIVITY; Sleep Stages - drug effects; Solubility; Structure-Activity Relationship; STRUCTURE-ACTIVITY RELATIONSHIPS; Symposium on Structural Properties for Determining Mechanisms of Toxic Action. October 18-20, 1988. Duluth, Minnesota; SYNERGISM; Toxicants; TOXICITY; Unconsciousness - chemically induced; Water Pollutants, Chemical - classification; Water Pollutants, Chemical - pharmacology; Water Pollutants, Chemical - toxicity; WATER POLLUTION
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.9087207

Narcosis is a nonspecific 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, 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 strictly additive with phenol 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. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.