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Toxicology Rounds

Toxicology Rounds

An Automotive Solvent that Is Sweet and Deadly

Gussow, Leon MD

doi: 10.1097/01.EEM.0000695612.15005.4c
    diethylene glycol, toxicity, poisoning

    It's a liquid found in many home garages, often stored in containers that are not childproof. It has a pleasant smell and a sweet taste, making it unusually attractive to toddlers. No one knows precisely the toxic dose, but it may be less than a tablespoon for a 10 kg child.

    It's not ethylene glycol or methanol, not even isopropyl alcohol or gasoline. This poisonous liquid is not a pesticide, herbicide, or any of the other usual suspects that come to mind when we think of toxic substances found in home garages, but it can be just as dangerous.

    I'm talking about diethylene glycol (DEG). This poisonous solvent is found in automotive products, most commonly brake fluid. I've heard about two cases of potential pediatric exposure to DEG over the past several months, both of which involved children who may have taken a sip or two of brake fluid.

    Many clinicians are not exactly clear about what DEG is or the unique challenges involved in managing these exposures, but there are five important things to know about DEG and its toxicity.

    Diethylene glycol is not ethylene glycol. DEG is manufactured by joining two molecules of ethylene glycol through an ether (—O—) bond. It was originally thought the ether bond was broken, releasing ethylene glycol, when DEG was ingested. In fact, this does not happen to any significant extent. The ether bond is quite stable. DEG has toxic metabolites and clinical manifestations that are different from those of ethylene glycol.

    The two primary toxic metabolites of diethylene glycol are HEAA and DGA. DEG is metabolized in the liver through a pathway similar to that of ethanol and other common toxic alcohols. It is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase to 2-hydroxyethoxyacetic acid (HEAA). HEAA is metabolized to diglycolic acid (DGA) in an additional step involving an enzyme not yet well characterized. HEAA and DGA are the real culprits in DEG toxicity.

    DEG toxicity occurs in three stages. The first starts on the day after ingestion, and involves inebriation, nausea, vomiting, and the beginning of metabolic acidosis. A significantly increased osmol gap can support the diagnosis, but a normal one does not rule it out. During the second stage (24-72 hours after ingestion), metabolic acidosis increases dramatically as progressive acute renal failure can lead to anuria and require hemodialysis. The final stage (five days to several weeks after ingestion) involves a wide range of delayed neurological sequelae, including neuropathy of the cranial and peripheral nerves, decreased vision and hearing, paralysis, encephalopathy, coma, and cerebral edema. Patients who don't develop renal failure after ingestion of DEG do not seem to go on to develop manifestations of delayed neurotoxicity.

    A key goal of early therapy is to protect renal function. Significant amounts of DEG and HEAA are eliminated through the kidneys. Unfortunately, DEG is an osmotic diuretic predisposing to volume depletion and prerenal azotemia. Once renal function is impaired, increasing amounts of DEG and HEAA are retained and metabolized to diglycolic acid (DGA), a powerfully nephrotoxic agent that accumulates in the renal cortex and causes proximal tubule necrosis.

    Recent research suggests that HEAA is not primarily responsible for renal damage in DEG poisoning, but instead contributes to metabolic acidosis and possibly neurotoxicity. Once the kidneys fail, the damage is often irreversible, and many patients become dependent on hemodialysis. Early supportive care in these patients before acute kidney injury should include careful attention to volume repletion and urine output. Using bedside ultrasound to visualize the size and collapsibility of the inferior vena cava may help in managing fluid status.

    Diethylene glycol levels are often not readily available. The initial management decision is straightforward when a patient presents after possibly ingesting a significant amount of methanol or ethylene glycol but looks well and does not have metabolic acidosis or renal impairment: Block the metabolism with the alcohol dehydrogenase inhibitor fomepizole and check toxic alcohol levels. Fomepizole will block the first step in DEG metabolism, but it's difficult to know which endpoint to aim for without the ability to measure DEG levels. We would expect some amount of DEG to be excreted unchanged in the urine, but when is it safe to stop the fomepizole?

    An alternative approach in a well-appearing patient with a possible DEG ingestion is careful observation for 12 to 24 hours, with frequent rechecks of renal function and the anion gap. Any evidence of new metabolic acidosis or renal failure would be grounds for starting fomepizole and considering the need for hemodialysis. Significant DEG exposure could essentially be ruled out if the patient looked well and blood chemistries remained unremarkable throughout the observation period.

    These are complex cases with potentially severe consequences that have to be managed with incomplete data. It is advisable to contact the local poison control center about all of these cases. All potential exposures should also be referred for medical evaluation because the toxic and lethal doses of DEG appear to be quite small.

    Most of our experience with severe DEG toxicity comes from episodes of mass poisoning when DEG was substituted illegally as a solvent in pharmaceutical products to replace more expensive nontoxic ingredients such as propylene glycol or glycerine. A total of 105 people died in the United States in 1937 when DEG was used to manufacture the antibiotic Elixir Sulfanilamide. (The Scientist. May 31, 2013; This incident led to the passage of the Federal Food, Drug, and Cosmetics Act of 1938, which remains the basis for the regulatory power of the FDA.

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    Dr. Gussowis a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago, an assistant professor of emergency medicine at Rush Medical College, a consultant to the Illinois Poison Center, and a lecturer in emergency medicine at the University of Illinois Medical Center in Chicago. Follow him on Twitter@poisonreview, and read his past columns at

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