Ethylene Glycol

Image found here

Source (1,2)

Ethylene Glycol, also called 1,2-dihydroxyethane, is most well known for its use in antifreeze, deicers, hydraulic fluids and more. Ethylene glycol is usually a clear, syrupy liquid but it often gets its yellowish-green tint from a fluorescent dye used in antifreeze. There is a sweet taste associated with ethylene glycol and it has been regularly misused in the form of accidental ingestion and suicide attempts.

Biotransformation (1)

Once absorbed, ethylene glycol is metabolized to glycolaldehyde and then oxidized to glycolic acid as shown below. Ethylene glycol is not expected to bioaccumulate, but glycolic acid and oxalic acid can, resulting in damage to the kidneys in the form of hypocalcemia. This hypocalcemia is brought about by the chelation of calcium which forms oxalate monohydrate crystals (COM).

image

Image source found here

Toxicokinetics (1,7)

Ethylene Glycol is rapidly absorbed by humans and laboratory mammals through the gastrointestinal tract, but slowly absorbed through the skin. Ethylene glycol is distributed throughout the body and is metabolized in to oxalic acid, carbon dioxide, formate, glycine and malate. The half-life for ethylene glycol is 2.5-8.4 hours and is excreted through exhaled carbon dioxide or urine.

Carcinogenicity (4,5)

The EPA, IARC and DHHS have not classified ethylene glycol as human carcinogen.

Studies in humans and various animal models have shown ethylene glycol to have no carcinogenic properties

A study in mice showed that ethylene glycol was not carcinogenic, but did cause lesions in the liver and kidney.

Signs/Symptoms/Areas of Target (2,3)

Ethylene glycol has several routes of exposure which are listed below, but ingestion is the primary route. Ethylene glycol ingestion resembles that of ethanol intoxication and follows three distinct stages, the neurological stage, cardiopulmonary stage and renal stage.

Image found here

Ocular Exposure: General irritation in the from of swelling of the eyelid and cornea, inflammation of the conjunctiva and iris, and conjunctiva and cornea injury.

Inhalation Exposure: Irritation to mucous membranes and the upper respiratory tract with exposure above 80 ppm resulting in intolerable respiratory discomfort.

Dermal Exposure: General skin irritant

Ingestion Exposure: Ingestion can result in a varying level of of symptoms ranging from mild to severe and are typically ranked accordingly.

  • Stage 1 (mild/moderate)- dizziness, headache, emesis, drowsiness, irritation, restlessness.
  • Stage 2 (mild/moderate)- tachycardia, dysrhythmia, hypertension, hyperventilation.
  • Stage 3 (mild/moderate)- effects unusual
  • Stage 1 (severe)- seizures, loss of consciousness, coma.
  • Stage 2 (severe)- congestive heart failure, pulmonary edema, multi-system organ failure, death.
  • Stage 3 (severe)- acute kidney failure, limited to no excretion of urine, build up of toxic chemicals in bloodstream, death.

Treatments/Biomarkers (6,7)

Ethylene glycol can be diagnosed by conducting urinalysis for oxalic acid or by serum detection in the blood. If levels indicate a potential poisoning, treatment should be sought immediately. GI decontamination using gastric lavage, gastric aspiration and activated charcoal is ineffective due to the rapid absorption of ethylene glycol. There are several options to help counteract ethylene positioning including…

  • Sodium bicarbonate
    • Helps to temporarily correct acidosis
  • Fomepizole or Ethanol Therapy
    • Helps to competitively inhibit toxic metabolites of ethylene glycol
  • Hemodialysis
    • Removes ethylene glycol and glycolic acid

 

References

  1. Chapter 24: Toxic Effects of Solvents and Vapors. Toxic Effects of Solvents and Vapors | Casarett and Doull’s Toxicology: The Basic Science of Poisons, 8e | AccessPharmacy | McGraw Hill Medical (ohio-state.edu)
  2. Ethylene Glycol: Systemic Agent. CDC. CDC – The Emergency Response Safety and Health Database: Systemic Agent: ETHYLENE GLYCOL – NIOSH
  3. Ehylene Glycol. ethylene-glycol.pdf (epa.gov)
  4. National Toxicology Program. 1993. NTP Toxicology and Carcinogenesis Studies of Ethylene Glycol (CAS No. 107-21-1) in B6C3F1 Mice (Feed Studies). 413: 1-177. NTP Toxicology and Carcinogenesis Studies of Ethylene Glycol (CAS No. 107-21-1) in B6C3F1 Mice (Feed Studies) – PubMed (nih.gov)
  5. Ethylene Glycol-ToxFAQs. Ethylene Glycol – ToxFAQs™. (cdc.gov)
  6. How Should Patients Exposed to Ethylene Glycol Be Treated and Managed? How Should Patients Exposed to Ethylene Glycol Be Treated and Managed? (cdc.gov)
  7. ToxGuide for Ethylene Glycol. ToxGuide for Ethylene Glycol (cdc.gov)