The Sweet Taste of Danger

Unraveling the Mystery of Diethylene Glycol Poisoning

Toxicology Pharmaceutical Safety Global Health

A Hidden Threat in Everyday Products

Imagine a substance so sweet and harmless-looking that it could be mistaken for a common pharmaceutical ingredient, yet so toxic that a single teaspoon could be fatal.

This is the paradox of diethylene glycol (DEG), a chemical that has been responsible for numerous mass poisoning tragedies across the globe for nearly a century. From contaminated medications to tainted consumer products, DEG continues to pose a significant public health risk, particularly in regions with lax regulatory oversight.

Its sweet taste, colorless appearance, and viscous texture make it a perfect—and deadly—stand-in for safer solvents like glycerin or propylene glycol. This article explores the sinister nature of DEG poisoning through the lens of two documented cases, unraveling the science behind its toxicity and the ongoing efforts to prevent further tragedies.

Sweet Taste

Makes it easily mistaken for safe pharmaceutical ingredients

Global Impact

Mass poisonings across multiple continents over decades

Renal Toxicity

Primary target organ is the kidneys, leading to acute failure

Case Reports: When Treatment Becomes Poison

Case 1: Printer Ink Suicide Attempt

Fatal
50-year-old female 50% DEG concentration
Clinical Presentation:
  • Nausea and abdominal pain after consuming printer ink cartridges
  • Black discoloration of mouth and tongue, slurred speech
  • Rapid deterioration within 24 hours: coma, anuric renal failure
  • Metabolic acidosis with elevated anion gap
  • Bilateral cranial nerve VII paralysis
Outcome:

Despite hemodialysis and aggressive supportive care, the patient died seven days after presentation 1 .

Toxicity Progression:
Day 1: GI Symptoms
Day 2: Renal Failure
Day 7: Death

Case 2: Contaminated Medication

High Mortality
64 patients IV administration
Clinical Context:
  • Patients with pre-existing liver disease receiving armillarisin A
  • Medication contaminated with approximately 30% DEG 3
  • 15 patients developed oliguric acute renal failure
  • Latency period: 2-12 days (mean 5 days)
Outcome:

12 of 15 poisoned patients (80%) died within seven days 3 .

Renal Failure Progression:
Normal Function
Oliguria
Anuria
Mean progression from oliguria to anuria: just 1 day

Comparison of Two DEG Poisoning Cases

Aspect Case 1 (Printer Ink) Case 2 (Contaminated Medication)
Route of Exposure Oral ingestion Intravenous administration
DEG Concentration 50% in printer ink 30% in medication
Primary Symptoms GI distress, renal failure, metabolic acidosis, cranial nerve paralysis Acute renal failure, oliguria/anuria
Time Course Death within 7 days Renal failure 2-12 days post-exposure
Mortality 1 death (100% of case) 12 deaths (80% of poisoned patients)
Treatment Hemodialysis, supportive care Supportive care

The Three Stages of DEG Poisoning

Diethylene glycol poisoning typically manifests in three distinct phases, though symptoms may overlap in some cases 1 2 .

Phase 1: Gastrointestinal

Symptoms:
  • Nausea, vomiting, abdominal pain, diarrhea
  • Patients may appear inebriated
  • Abnormal osmolar gap or anion gap metabolic acidosis
Timing:

Onset is rapid after ingestion but can be delayed by co-ingestants like food or ethanol 1 .

Phase 2: Renal Failure

Symptoms:
  • Acute kidney injury - hallmark of DEG toxicity
  • Mild to moderate hepatotoxicity
  • Pancreatitis and cardiac dysrhythmias
Timing:

1-3 days after initial exposure. If untreated, patients often die within one week after onset of anuria and metabolic acidosis 1 2 .

Phase 3: Neurotoxicity

Symptoms:
  • Peripheral neuropathies
  • Cranial nerve palsies (bilateral facial paralysis)
  • Seizures, quadriplegia, and coma
Timing:

Delayed 1-2 weeks after initial exposure. Correlates with degree of nephrotoxicity 1 . Recovery is variable.

Clinical Progression Timeline

Initial Exposure (Day 0)

Ingestion or administration of DEG-contaminated substance

Phase 1: GI Symptoms (Hours to Day 1)

Nausea, vomiting, abdominal pain, possible inebriated appearance

Phase 2: Renal Failure (Days 1-3)

Acute kidney injury, metabolic acidosis, potential hepatotoxicity

Phase 3: Neurotoxicity (Days 7-14)

Neurological manifestations including cranial nerve palsies, peripheral neuropathies

Outcome (Variable)

Recovery with potential permanent damage, or death typically within 1-2 weeks

The Science of Toxicity: How DEG Attacks the Body

Metabolic Pathways and Nephrotoxicity

DEG is rapidly absorbed through oral ingestion, with dermal absorption also possible through broken or damaged skin 1 . Once in the body, it undergoes metabolism primarily in the liver through the same NAD-dependent pathway as ethanol and other toxic alcohols 1 .

Contrary to initial assumptions, DEG is not broken down into significant amounts of ethylene glycol in humans 1 2 . Instead, alcohol dehydrogenase (ADH) oxidizes DEG to 2-hydroxyethoxyacetaldehyde, which aldehyde dehydrogenase then further metabolizes to 2-hydroxyethoxyacetic acid (HEAA) and diglycolic acid (DGA) 1 2 .

These metabolites, particularly DGA, are now recognized as the primary culprits behind DEG's devastating effects on the kidneys.

Key Discovery

Research has revealed that DGA is transported to proximal tubular cells in the kidneys, where it inhibits succinate dehydrogenase, a key enzyme in the citric acid cycle 2 . This inhibition blocks adenosine triphosphate (ATP) production, essentially starving cells of energy and leading to cell death.

DEG Metabolism and Toxic Effects

Compound Formation Pathway Toxic Mechanism Primary Effects
Diethylene Glycol (Parent Compound) Direct exposure Precursor to toxic metabolites Initial GI symptoms, osmolar gap
2-Hydroxyethoxyacetaldehyde Metabolism by alcohol dehydrogenase Intermediate metabolite Contributes to metabolic acidosis
HEAA Metabolism by aldehyde dehydrogenase Weak acid, contributes to acidosis Metabolic acidosis, organ dysfunction
Diglycolic Acid (DGA) From HEAA Inhibits succinate dehydrogenase Nephrotoxicity, acute renal failure
Renal Damage Mechanism

Marked vacuolization and edema of epithelial cells obstruct the tubular lumen, reducing urine flow and resulting in anuria and uremia 2 .

DEG Metabolic Pathway

Diethylene Glycol
Parent Compound
ADH Enzyme
2-Hydroxyethoxyacetaldehyde
Intermediate Metabolite
ALDH Enzyme
HEAA
Acidic Metabolite
Diglycolic Acid (DGA)
Primary Nephrotoxin
Inhibits Succinate Dehydrogenase

A Global History of Tragedy: DEG Mass Poisonings

The history of DEG poisoning spans nearly a century, with remarkably similar patterns repeating across different continents and decades.

Timeline of Major DEG Mass Poisoning Events

Year Country Contaminated Product Reported Deaths
1937 United States Sulfanilamide elixir >100
1990-1992 Bangladesh Paracetamol syrup 236+ children
1995 Haiti Paracetamol syrup 88 children
1998 India Cough syrup 36 children
2006 Panama Cough syrup Hundreds
2008-2009 Nigeria "My Pikin" teething medication 54 children
2023 Various Multiple syrups Ongoing investigations
The 1937 Sulfanilamide Elixir Disaster

The first recorded mass poisoning occurred in the United States in 1937 when DEG was used as a solvent in an antibiotic elixir of sulfanilamide 1 5 .

Deaths were reported shortly after distribution, ultimately claiming over 100 lives—a third of them children 1 .

This catastrophe directly led to the passage of the 1938 Federal Food, Drug, and Cosmetic Act, which required manufacturers to demonstrate product safety prior to marketing 1 5 .

Recent Incidents

Tragically, DEG poisoning incidents continue to occur. Since September 2022, the World Health Organization has reported seven consecutive contamination episodes across at least nine countries 4 .

A concerning commonality is that at least 14 of the involved products were fixed-dose combinations marketed for symptomatic treatment of common cold or flu, many lacking sufficient evidence for efficacy and safety 4 .

DEG Poisoning Impact Statistics

100+

Deaths in 1937 US incident

236

Child deaths in Bangladesh (1990-1992)

80%

Mortality rate in Case 2 (China 2006)

7

Recent contamination episodes since 2022

Diagnosis and Treatment Challenges

Diagnostic Difficulties

Diagnosing DEG poisoning presents significant challenges. Measurement of serum DEG concentration is the most accurate method, but this test is often unavailable at most hospitals and can take weeks to return results from reference laboratories 1 .

Therefore, diagnosis is primarily clinical, based on patient history, physical examination, and basic laboratory tests 1 .

Laboratory Findings
  • The osmolar gap is less helpful for DEG compared to other toxic alcohols due to DEG's large molecular weight
  • A normal osmolar gap does not exclude poisoning 1
  • As DEG metabolizes into toxic compounds, the anion gap increases along with metabolic acidosis
  • Metabolic acidosis is usually present within 24 hours post-ingestion 1

Treatment Strategies

Current treatment approaches focus on three main areas:

Initial management prioritizes airway maintenance, correction of acid-base status, serum electrolytes, and fluid balance 1 . Gastrointestinal decontamination with activated charcoal is not recommended due to low binding affinity for alcohols 1 .

Animal studies suggest a survival benefit from preventing the formation of toxic metabolites through alcohol dehydrogenase inhibition 1 . Fomepizole is the preferred agent, with a loading dose of 15 mg/kg followed by maintenance dosing 1 . If fomepizole is unavailable, ethanol infusion can be used, targeting a blood alcohol concentration of 100-150 mg/dL 1 .

This should be considered, especially for patients with nephrotoxicity or severe metabolic acidosis 1 . Hemodialysis helps remove DEG and its metabolites while correcting acid-base disturbances 1 . Unfortunately, many severely poisoned patients require hemodialysis due to anuric renal failure 1 .
Despite aggressive treatment incorporating fomepizole and hemodialysis, mortality rates from DEG poisoning remain high 1 .

Treatment Modalities and Their Targets

Supportive Care

Airway management, fluid/electrolyte balance, acid-base correction

ADH Inhibition

Prevents formation of toxic metabolites (Fomepizole or ethanol)

Hemodialysis

Removes DEG and metabolites, corrects acid-base disturbances

Prevention: Learning from History

The repeated pattern of DEG mass poisonings has revealed consistent vulnerabilities in pharmaceutical manufacturing and quality control.

Economically Motivated Adulteration

DEG is frequently substituted for more expensive solvents like glycerin or propylene glycol to cut costs 1 9 .

Supply Chain Complexities

Global pharmaceutical supply chains make tracking and verifying raw materials challenging 5 .

Inadequate Quality Control

Manufacturers may fail to perform proper identity testing on raw materials or finished products 9 .

The Scientist's Toolkit: Preventing DEG Contamination

Tool/Method Function Importance
Gas Chromatography (GC) Precise detection and quantification of DEG/EG impurities Gold standard method for accurate measurement
Thin-Layer Chromatography (TLC) Rapid screening for gross DEG contamination Low-cost ($1/test) method accessible in resource-limited settings
Supplier Qualification Verifying reliability of raw material suppliers Prevents economically motivated adulteration at source
100% Container Testing Identity testing of every container of high-risk ingredients Prevents isolated contamination events
Refractometry Screening purity of glycerol and similar solvents Cheap technology for initial screening
Regulatory agencies worldwide have implemented stricter controls in response to these tragedies. The U.S. FDA now recommends testing glycerol, propylene glycol, and other high-risk ingredients for DEG and ethylene glycol contamination, with acceptance limits generally not exceeding 0.10% 7 .

Conclusion: An Ongoing Battle

Diethylene glycol poisoning represents a frustrating convergence of chemical similarity, economic incentive, and regulatory failure.

From the 1937 sulfanilamide tragedy that sparked modern pharmaceutical regulation in the United States to recent incidents, the pattern has repeated with devastating consequences. The cases presented here—one involving intentional printer ink ingestion and another featuring contaminated medication administered to vulnerable patients—illustrate the diverse pathways through which DEG exposure can occur.

While treatment protocols have advanced with the use of fomepizole and hemodialysis, prevention remains the most effective strategy. Implementation of rigorous quality control measures, thorough supply chain oversight, and simple, inexpensive screening tests could prevent most, if not all, future DEG poisoning events.

As global pharmaceutical supply chains continue to expand and complexify, maintaining vigilance against this preventable threat becomes increasingly critical. The sweet-tasting solvent that has claimed hundreds of lives over nearly a century serves as a sobering reminder that technological progress must be matched by unwavering commitment to quality and safety in medical products.

References