Biological Mechanism for the Toxicity of Haloacetic Acid Drinking Water Disinfection Byproducts

• Published in: Environmental science & technology Vol. 45; no. 13; pp. 5791 - 5797
• Main Authors: Pals, Justin A, Ang, Justin K, Wagner, Elizabeth D, Plewa, Michael J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-07-2011
• Subjects: Acetates - metabolism; Acetates - toxicity; Acids; Animals; Applied sciences; Biological and medical sciences; By products; CHO Cells; Cricetinae; Cricetulus; Disinfectants - metabolism; Disinfectants - toxicity; Disinfection & disinfectants; DNA Damage; Drinking water; Ecotoxicology and Human Environmental Health; Electrophoresis; Epidemiology. Vaccinations; Exact sciences and technology; General aspects; Glyceraldehyde-3-Phosphate Dehydrogenases - antagonists & inhibitors; Glycolysis - drug effects; Halogenation; Infectious diseases; Kinetics; Medical sciences; Models, Biological; Molecular Structure; Pollution; Toxicity; Toxicity Tests - methods; Water Supply - standards; USA; Human; Drinking water; Carboxylic acid; Toxicity; Haloacetic acid; Disinfection; Secondary pollutant; Mechanism of action; By product; Public health; Organic compounds
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es2008159

The halogenated acetic acids are a major class of drinking water disinfection byproducts (DBPs) with five haloacetic acids regulated by the U.S. EPA. These agents are cytotoxic, genotoxic, mutagenic, and teratogenic. The decreasing toxicity rank order of the monohalogenated acetic acids (monoHAAs) is iodo- > bromo- ≫ chloroacetic acid. We present data that the monoHAAs inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity in a concentration-dependent manner with the same rank order as above. The rate of inhibition of GAPDH and the toxic potency of the monoHAAs are highly correlated with their alkylating potential and the propensity of the halogen leaving group. This strong association between GAPDH inhibition and the monoHAA toxic potency supports a comprehensive mechanism for the adverse biological effects by this widely occurring class of regulated DBPs.