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Toxicity, Ethylene Glycol

Author: Daniel C Keyes, MD, MPH, Vice Chair, Academic Affairs, Department of Emergency Medicine, John Peter Smith Health Network; Clinical Associate Professor, Department of Surgery, Division of Emergency Medicine and Toxicology, University of Texas Southwestern School of Medicine
Contributor Information and Disclosures

Updated: Jan 25, 2010

Introduction

Background

Several toxic alcohols are of medical and toxicological importance; the principal ones include ethanol, ethylene glycol (EG), methanol, and isopropanol. This article discusses ethylene glycol, a common component of radiator fluid.

Ethylene glycol is the major ingredient of almost all radiator fluid products in the United States. It is used to increase the boiling point and decrease the freezing point of radiator fluid, which circulates through the automotive radiator. These changes to the boiling and freezing points result from the colligative properties of the solute (ie, they depend on the number of particles in the solution). Hence, ethylene glycol is added to prevent the radiator from overheating or freezing, depending on the season. Fluorescein dye is often added to radiator fluid to help identify the source of a leak. The fluorescein in the fluid fluoresces when viewed under ultraviolet light.

Ethylene glycol tastes sweet, which is why some animals are attracted to it. Many veterinarians are familiar with ethylene glycol toxicity because of the frequent cases that involve dogs or cats who drink radiator fluid.

Pathophysiology

The toxic alcohols mentioned above (see Background) are parent compounds that exert most of their toxicity by conversion to metabolites. Although the parent compound, ethylene glycol, may cause some alteration of mental status, it is a relatively nontoxic compound before it is metabolized. The metabolites cause the distinctive toxicity associated with this compound.

Knowing the pathway of ethanol metabolism is necessary to understand ethylene glycol toxicity properly. Ethanol is metabolized by the enzyme alcohol dehydrogenase (ADH) pathway, which is located in the liver and gastric mucosa, and by the cytochrome P-450 mixed function oxidase (MFO) system in the liver. The mixed function oxidase component is subject to greater inducibility than alcohol dehydrogenase.

As with ethyl alcohol and methanol, ethylene glycol is metabolized by alcohol dehydrogenase to form glycoaldehyde. Through interaction with aldehyde dehydrogenase, ethylene glycol is then metabolized to glycolic acid (GA). A profound acidosis often ensues and is attributable to the glycolic acid in circulation. The patient may develop hyperventilation that results from acidemia. This glycolate is then transformed into glyoxylic acid. At this point, the molecule may be transformed into the highly toxic oxalate or the safer glutamate or a -ketoadipic acid metabolites. The administration of particular vitamins may promote the formation of these safer metabolites.

With the formation of oxalate crystals in the urine, calcium oxalate crystals form and accumulate in blood and other tissues. The precipitation of calcium oxalate in the renal cortex results in decreased glomerular filtration and renal insufficiency. Calcium is consumed in circulation, and hypocalcemia may occur.

The rate-dependent step of ethylene glycol metabolism is the alcohol dehydrogenase–catalyzed step. Ethyl alcohol binds much more easily to alcohol dehydrogenase than ethylene glycol or methanol does. Because ethanol is the preferential substrate for alcohol dehydrogenase, the presence of ethanol may essentially block metabolism of ethylene glycol. In addition, this enzyme is blocked by the administration of fomepizole (4-methylpyrazole [4-MP]), which is discussed below (see Emergency Department Care). This is the basis of one therapy used in the United States.

Frequency

United States

Ethylene glycol is a relatively common cause of overdose in American emergency departments. In 2007, 4966 single exposure cases were reported to the American Association of Poison Control Centers;1 the 2008 incidence data remains much the same, with 4921 single exposures to ethylene glycol reported.2 Rapid intervention often makes an important difference in the outcome of ethylene glycol toxicity.

Mortality/Morbidity

According to the annual report of the American Association of Poison Control Centers' National Poison Data System in 2007, 878 had minor outcomes, 365 had moderate outcomes, 135 had severe outcomes, and 16 deaths were documented.1 Similar data were reported in the 2008 American Association of Poison Control Centers' National Poison Data System annual report: 780 minor outcomes, 358 moderate outcomes, 140 major outcomes, and 7 deaths.2

Age

The annual report of the American Association of Poison Control Centers' National Poison Data System in 2007 documented ethylene glycol exposure in 511 children younger than 6 years, 636 in those aged 6-19 years, and 3132 in those older than 19 years.1 The annual report of the American Association of Poison Control Centers' National Poison Data System documented ethylene glycol exposure in 514 children younger than 6 years, 596 in those aged 6-19 years, and 3170 in those older than 19 years.2

Clinical

History

  • As with all poisonings, ascertain the nature of the oral ingestion by talking with the patient.
  • The timing of ingestion is important.
  • The product involved is important. Try to obtain the original container of the ingested substance to confirm its identity.
  • Determine the timing and quantity of liquor or other ethanol ingestion.

Physical

  • After an adequate airway is ensured, monitor vital signs, including temperature and mental status.
  • A patient breathing deeply and rapidly may be manifesting the Kussmaul respirations, which are indicative of a severe metabolic acidosis.
  • Patients with an altered mental status require rapid assessment and therapy directed at rapidly lethal processes. Ensure and maintain an adequate airway.

Causes

Causes of ethylene glycol poisoning include the following:

  • Suicide attempts
  • Accidental ingestions (mainly observed in children)
  • Workplace beverage-container mix-ups

More on Toxicity, Ethylene Glycol

Overview: Toxicity, Ethylene Glycol
Differential Diagnoses & Workup: Toxicity, Ethylene Glycol
Treatment & Medication: Toxicity, Ethylene Glycol
Follow-up: Toxicity, Ethylene Glycol
References
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References

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  2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). Dec 2009;47(10):911-1084. [Medline]. [Full Text].

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Further Reading

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Keywords

ethylene glycol toxicity, antifreeze poisoning, antifreeze ingestion, radiator fluid, antifreeze, glycolic acid, ethylene glycol poisoning, radiator fluid ingestion, ethylene glycol intoxication, calcium oxalate crystals

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Contributor Information and Disclosures

Author

Daniel C Keyes, MD, MPH, Vice Chair, Academic Affairs, Department of Emergency Medicine, John Peter Smith Health Network; Clinical Associate Professor, Department of Surgery, Division of Emergency Medicine and Toxicology, University of Texas Southwestern School of Medicine
Daniel C Keyes, MD, MPH is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, and American College of Physicians-American Society of Internal Medicine
Disclosure: Nothing to disclose.

Medical Editor

Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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