What is the poisonous dose of ethylene glycol?

Poisonous Dose of Ethylene Glycol

The minimum lethal dose of ethylene glycol is approximately 100 mL (or 1.6 g/kg body weight) for a 70-kg adult, though toxicity can occur at much lower doses, and survival has been documented even after massive ingestions exceeding 1 liter. 1, 2

Dose-Response Framework

The toxic threshold and clinical outcomes depend on several critical factors:

Volume-Based Toxicity Thresholds

• Potentially fatal dose: ~100 mL in adults (1.6 g/kg) 2
• Median ingested dose in poisoning cases: 250 mL (range 150-500 mL) 1
• Documented survivable massive ingestions: >1 liter with appropriate treatment 1

For children: Any amount beyond a witnessed taste or lick requires immediate emergency evaluation 3

For adults: A "swallow" (10-30 mL) warrants immediate emergency department referral 3

Concentration-Based Toxicity

The relationship between serum ethylene glycol levels and toxicity:

• Threshold of systemic toxicity: 3.2 mmol/L (20 mg/dL) 2
• Median peak concentration in poisoning cases: 17.6 mmol/L (range 6.9-41.9 mmol/L) 1
• Extreme survivable concentrations: >200 mmol/L (>1240 mg/dL) with aggressive treatment 1

Critical Metabolite Thresholds (More Important Than Parent Compound)

The toxic metabolite glycolate is the primary determinant of outcomes, not ethylene glycol itself. 1

Glycolate Concentration and Mortality Risk

• Low mortality risk: Glycolate ≤12 mmol/L (mortality 3.6%) 1
• High mortality risk: Glycolate >12 mmol/L (mortality 20.4%) 1
• No renal injury threshold: Glycolate concentrations up to 10.1 mmol/L (76.7 mg/dL) 2

Anion Gap as Surrogate Marker

When glycolate levels are unavailable:

• Low risk: Anion gap ≤28 mmol/L (with potassium) 1
• High risk: Anion gap >28 mmol/L (mortality 20.4%) 1

Clinical Pitfalls and Critical Caveats

The absence of symptoms shortly after ingestion does NOT exclude a potentially toxic dose and should never be used as a triage criterion. 3 Patients can remain relatively asymptomatic for up to 24 hours before developing severe metabolic acidosis and organ failure. 4

Time-Dependent Toxicity

The latent period before metabolic acidosis appears is approximately 3-6 hours after ingestion, with progressive toxicity developing over 12-72 hours. 1 The median time from ingestion to hospital admission in poisoning cases is 10 hours (range 4-18 hours). 1

Factors Modifying Toxicity

Ethanol co-ingestion (present in 55% of cases) can delay metabolism and extend the therapeutic window, but does not eliminate toxicity risk. 1 The half-life of ethylene glycol increases from 2-5 hours without treatment to 8.5-14 hours with ethanol. 1

Treatment Thresholds Based on Dose

The EXTRIP 2023 guidelines provide specific treatment algorithms 1:

With fomepizole available:

• Suggest extracorporeal treatment if EG concentration >50 mmol/L OR osmol gap >50

With ethanol only:

• Recommend extracorporeal treatment if EG concentration >50 mmol/L OR osmol gap >50
• If no antidote available: Recommend extracorporeal treatment if EG concentration >10 mmol/L (>62 mg/dL)

Regardless of dose, recommend immediate extracorporeal treatment if:

• Glycolate >12 mmol/L or anion gap >27 mmol/L
• Severe clinical features present (coma, seizures, or acute kidney injury stage 2-3)

Practical Clinical Application

For emergency triage, any adult who ingests more than a "swallow" (10-30 mL) or any child who ingests more than a taste/lick requires immediate emergency department evaluation, regardless of symptoms. 3 Dilute solutions (<20% concentration) have proportionally larger toxic volumes that can be calculated based on concentration. 3

The overall mortality in ethylene glycol poisoning cases is 18.7%, with median time to death of 96 hours post-ingestion. 1 However, with early recognition and aggressive treatment including antidotes and hemodialysis, survival is possible even after extreme exposures.