Ethylene glycol (EG) is a synthetic chemical that is colorless, odorless, and has a deceptively sweet taste, which contributes to the risk of accidental or intentional ingestion. This compound is widely accessible as a primary ingredient in common household and industrial products. EG is most often found in automotive antifreeze, coolants, and various de-icing fluids, with concentrations frequently reaching up to 95%. Its presence in these readily available products makes it a significant public health concern due to the high potential for poisoning.
Understanding the Lethal Dose
Determining a single “lethal dose” for ethylene glycol is difficult because toxicity varies significantly between individuals. The severity of poisoning depends on a person’s body weight, age, pre-existing health conditions, and the time elapsed before medical treatment begins. For adults, the estimated minimum lethal dose of pure ethylene glycol is often cited around 1.4 milliliters per kilogram (mL/kg) of body weight. This translates to roughly 80 to 120 milliliters (approximately 3 to 4 fluid ounces) for an average adult, which is a relatively small amount.
Children are particularly vulnerable due to their smaller size, meaning a much lower total volume of the substance can be fatal. Any ingestion, regardless of the amount, must be considered a medical emergency requiring immediate attention. The toxicity of the metabolic byproducts means that even doses below the estimated lethal amount can cause severe organ damage. Early intervention is the primary factor that increases the chance of a good outcome and prevents long-term complications.
How Ethylene Glycol Metabolizes into Toxin
The initial ingestion of ethylene glycol causes early symptoms but is not the primary source of severe toxicity. The compound becomes poisonous when processed by the liver enzyme alcohol dehydrogenase (ADH). This metabolic pathway converts ethylene glycol into a series of increasingly toxic byproducts. This breakdown process results in the formation of toxic metabolites.
The first step in the pathway produces glycolaldehyde, which is rapidly converted into glycolic acid. Glycolic acid is the main culprit behind the development of severe metabolic acidosis, a dangerous build-up of acid in the bloodstream. The glycolic acid is further metabolized into glyoxylic acid, which is finally converted into oxalic acid. Oxalic acid is responsible for the devastating effects on the kidneys and other organs. Oxalic acid combines with circulating calcium to form insoluble calcium oxalate crystals. These crystals deposit within the renal tubules of the kidneys, causing acute tubular necrosis and ultimately leading to acute kidney failure.
Stages of Ethylene Glycol Poisoning
Ethylene glycol poisoning progresses through three distinct stages, making initial recognition challenging because symptoms change over time. The first stage, the neurological phase, occurs from 30 minutes to 12 hours after ingestion. During this time, unmetabolized ethylene glycol acts as a central nervous system depressant. This produces symptoms that closely resemble alcohol intoxication, such as slurred speech, dizziness, nausea, and confusion, which can lead to misdiagnosis.
The second phase, the cardiopulmonary stage, manifests between 12 and 24 hours post-ingestion. As toxic glycolic acid accumulates, metabolic acidosis develops, prompting the body to compensate. This compensation results in hyperventilation, or rapid, deep breathing, alongside an elevated heart rate and high blood pressure. Most fatalities, if left untreated, occur during this stage due to cardiopulmonary collapse caused by the acid-base derangement.
The final stage, the renal phase, begins 24 to 72 hours after the initial exposure. This stage is defined by acute kidney injury caused by the deposition of calcium oxalate crystals in the kidneys. Symptoms include flank pain, decreased urine output, or complete absence of urine (anuria). If the patient survives the initial cardiorespiratory failure, the long-term outcome is often chronic kidney failure.
Emergency Response and Medical Treatment
Immediate action is paramount following any suspected ingestion of ethylene glycol, and emergency services or a poison control center must be contacted at once. Medical treatment focuses on two simultaneous objectives: blocking the further metabolism of ethylene glycol and correcting the dangerous metabolic acidosis. The primary strategy is to inhibit the ADH enzyme, which stops the production of the toxic metabolites.
The preferred antidote in the United States is Fomepizole (4-methylpyrazole), which works by binding to and inactivating the ADH enzyme. This action halts the toxic breakdown process and allows the unmetabolized ethylene glycol to be safely excreted. Intravenous ethanol is sometimes used as an alternative antidote if Fomepizole is unavailable, as it competitively saturates the ADH enzyme.
In cases of severe poisoning, established kidney failure, or metabolic acidosis, hemodialysis is often necessary. Dialysis directly removes both the ethylene glycol and its toxic metabolites from the bloodstream, significantly reducing the time the toxins remain in the body. Supportive care, including sodium bicarbonate, is also used to help neutralize the acid buildup caused by the glycolic acid.