skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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:
Research Org.:
National Institute of Environmental Health Sciences, Research Triangle Park, NC
OSTI Identifier:
6120412
Alternate Identifier(s):
OSTI ID: 6120412
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Pharmacol. Exp. Ther.; (United States); Journal Volume: 242:1
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

Citation Formats

Ghanayem, B.I., Burka, L.T., and Matthews, H.B. Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases. United States: N. p., 1987. Web.
Ghanayem, B.I., Burka, L.T., & Matthews, H.B. Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases. United States.
Ghanayem, B.I., Burka, L.T., and Matthews, H.B. Wed . "Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases". United States. doi:.
@article{osti_6120412,
title = {Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases},
author = {Ghanayem, B.I. and Burka, L.T. and Matthews, H.B.},
abstractNote = {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 of 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.},
doi = {},
journal = {J. Pharmacol. Exp. Ther.; (United States)},
number = ,
volume = 242:1,
place = {United States},
year = {Wed Jul 01 00:00:00 EDT 1987},
month = {Wed Jul 01 00:00:00 EDT 1987}
}
  • The available information on the acute and subchronic toxicity of ethylene glycol monobutyl ether is reviewed. Data from animal studies have been examined from the standpoint of dose-response relationships and the sensitivity of various animal species (rats, guinea pigs, mice, dogs, rabbits), including man, to the effects of this chemical. In view of recent findings with other chemically related glycol ethers, particular attention has been given to possible adverse effects on blood and testicular tissue. In evaluating the hazard that this chemical may pose to man, consideration has been given to likely routes of exposure and its irritant properties. Itmore » is concluded that the available information continues to support the current ACGIH TWA/sub 8/-TLV of 25 ppm with a STEL of 75 ppm. 24 references, 5 tables.« less
  • The interfacial tension [gamma] of the ternary two-phase system of water-nonane-ethylene glycol monobutyl ether (C[sub 4]E[sub 1]) was measured as a function of the total mole fraction of C[sub 4]E[sub 1] at six temperatures under atmospheric pressure. To analyze the experimental results thermodynamically, it was shown that the y value should be plotted not against the total mole fraction of C[sub 4]E[sub 1] but against the equilibrium mole fraction in the nonane and water phases. It was found that the entropy of adsorption of C[sub 4]E[sub 1] from the nonane phase decreases and that from the water phase increases, comparedmore » to the entropy of the pure nonane/water interface formation, with increasing surface density of C[sub 4]E[sub 1]. Adsorption was discussed on the basis of the thermodynamic quantities of adsorption and transfer of C[sub 4]E[sub 1] molecules.« less
  • The acute toxicity of ethylene glycol monopropyl ether (EGPE) and ethylene-glycol monopropyl ether acetate (EGPEA) was determined in a series of standardized tests. The oral LD/sub 50/ in rats was 3089 and 9456 mg/kg EGPE and EGPEA, respectively. Skin irritation was slight following an occluded single dose application of either compound to the guinea pig abdomen. The dermal LD/sub 50/ for guinea pigs was 1 to 5 mL/kg and greater than 20 mL/kg EGPE and EGPEA, respectively. EGPE produced a very weak positive sensitization response in one of five guinea pigs. EGPE produced transient moderate to severe eye irritation inmore » rabbits while EGPEA produced slight eye irritation. Subchronic toxicity was determined in a series of oral and inhalation studies. Groups of 10 male rats were dosed with 15, 7.5, 3.75 or 1.88 mmole/kg EGPE and 30, 15, or 7.5 mmole/kg EGPEA by gavage 5 days/week for 6 weeks. Hemoglobinuria was seen at least once at all dose levels of both compounds. EGPE had little effect on feed consumption or body weight gain, while body weight gain was reduced in the two high dose groups exposed to EGPEA and feed consumption was reduced at all dose levels. Hematologic changes were seen at all dose levels of both compounds. Absolute and/or relative spleen weights were increased at all but the lowest EGPE dose level and at all EGPEA dose levels. Gross and histopathologic examinations revealed significant effects on the spleen of animals exposed to EGPE and on the spleen, liver, kidney, and testes of animals exposed to EGPEA. Groups of 10 rats (5 M, 5 F) were exposed to 800, 400, 200 or 100 ppm EGPE or EGPEA 6 hr/day, 5 days/week for a total of 11 exposures. Body weight gains in all exposure groups were comparable to controls. 13 references, 13 figures, 9 tables.« less
  • Short-term and subchronic vapor inhalation studies have shown that there are pronounced differences in the toxicological properties of ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME). Overexposure to EGME has resulted in adverse effects on testes, bone marrow and lymphoid tissues in laboratory animals. PGME does not affect these tissues, and instead, overexposure to PGME has been associated with increases in liver weight and central nervous system depression. EGME is primarily oxidized to methoxyacetic acid in male rats, while PGME apparently undergoes O-demethylation to form propylene glycol. Since methoxyacetic acid has been shown to have the samemore » spectrum of toxicity as EGME in male rats, the observed differences in the toxicological properties of EGME and PGME are thought to be due to the fact that the two materials are biotransformed via different routes to different types of metabolites. 6 references, 3 figures, 12 tables.« less
  • Glycol alkyl ethers represent a class of high-production-volume chemicals with widespread industrial applications as solvents and chemical intermediates. Comparative toxicity studies with three glycol ethers, 2-methoxyethanol, 2-ethoxyethanol, and 2-butoxyethanol, were conducted in F344/N rats and B6C3F1 mice in both 2-week and 13-week drinking water studies. Toxicologic endpoints evaluated in animals included histopathology, hematology, clinical chemistry, urinalysis, and reproductive system parameters. Genetic toxicity was also evaluated for each glycol ether in several in vitro and in vivo assays.