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Title: Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases

2-Butoxyethanol (BE) is a massively produced glycol ether of which more than 230 million pounds was produced in the United States in 1983. It is extensively used in aerosols and cleaning agents intended for household use. This creates a high potential for human exposure during its manufacturing and use. A single exposure of rats to BE causes severe hemolytic anemia accompanied by secondary hemoglobinuria as well as liver and kidney damage. Butoxyacetic acid (BAA) was earlier identified as a urinary metabolite of BE. In addition, we have recently identified two additional urinary metabolites of BE, namely, BE-glucuronide and BE-sulfate conjugates. The current studies were undertaken to investigate the metabolic basis of BE-induced hematotoxicity in male F344 rats. Treatment of rats with pyrazole (alcohol dehydrogenase inhibitor) protected rats against BE-induced hematotoxicity and inhibited BE metabolism to BAA. Pyrazole inhibition of BE metabolism to BAA was accompanied by increased BE metabolism to BE-glucuronide and BE-sulfate as determined by quantitative high-performance liquid chromatography analysis of BE metabolites in urine. There was approximately a 10-fold decrease in the ratio of BAA to BE-glucuronide + BE-sulfate in the urine of rats treated with pyrazole + BE compared to rats treated with BE alone. Pretreatment ofmore » rats with cyanamide (aldehyde dehydrogenase inhibitor) also significantly protected rats against BE-induced hematotoxicity and modified BE metabolism in a manner similar to that caused by pyrazole. Administration of equimolar doses of BE, the metabolic intermediate butoxyacetaldehyde, or the ultimate metabolite BAA caused similar hematotoxic effects. Cyanamide also protected rats against butoxyacetaldehyde-induced hematotoxicity.« less
Authors:
; ;
Publication Date:
OSTI Identifier:
6120412
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Pharmacol. Exp. Ther.; (United States); Journal Volume: 242:1
Research Org:
National Institute of Environmental Health Sciences, Research Triangle Park, NC
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ENZYME INHIBITORS; BIOLOGICAL EFFECTS; GLYCOLS; METABOLISM; TOXICITY; PYRAZOLES; ACETALDEHYDE; ALCOHOL DEHYDROGENASE; ANEMIAS; INHIBITION; KIDNEYS; LIQUID COLUMN CHROMATOGRAPHY; LIVER; METABOLITES; RATS; SULFATES; URINE; ALCOHOLS; ALDEHYDES; ANIMALS; AZOLES; BIOLOGICAL MATERIALS; BIOLOGICAL WASTES; BODY; BODY FLUIDS; CHROMATOGRAPHY; DIGESTIVE SYSTEM; DISEASES; ENZYMES; GLANDS; HEMIACETAL DEHYDROGENASES; HEMIC DISEASES; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; MAMMALS; MATERIALS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; OXIDOREDUCTASES; OXYGEN COMPOUNDS; RODENTS; SEPARATION PROCESSES; SULFUR COMPOUNDS; SYMPTOMS; VERTEBRATES; WASTES 560300* -- Chemicals Metabolism & Toxicology