Ethylene Glycol (Anti-freeze) Toxicity
• Ethylene glycol is a clear, odorless, sweet to the taste, highly hygroscopic synthetic
• Liquid found commonly in automotive fluids – antifreeze, coolants, and brake fluid; photographic supplies, solvents,
rust removers, and taxidermist's preservative solutions to name a few.
• Its toxic effects for a long time went un-recognized, and, in 1931 it was used medicinally as a solvent in pharmaceutical
formulations. It was implicated in 1937 as the cause of seven-six deaths in human when used as a solvent in sulfanilamide
• It is the most toxic of similarly used alcohols (ethyl alcohol, butylene glycol and propylene glycol). Its concentration
in automotive radiator fluid is high (95%), a source to which pets (dogs and cats) have easy access. Whereas all animal species
are susceptible, to ethylene glycol toxicity, cats remain more susceptible.
The gastrointestinal tract is the primary route of exposure. Ethylene glycol is a small molecule (62 dalton) which undergoes
rapid absorption from the gastrointestinal tract, distributes to the liver where it is rapidly metabolized by the hepatic
alcohol dehydrogenase pathway to toxic metabolites (glycoaldehyde, glycolic acid, glyoxlic acid, oxalic acid, and formic acid),
and is excreted in the urine. These metabolic intermediates (organic acids) induce severe metabolic acidosis, kidney failure
and subsequent death, in exposed animals and humans. Calcium – oxalic acid interaction produces calcium oxalate crystals which
are widely deposited in tubular cells and lumen. Since the metabolites rather than parent compound (ethylene glycol), are
the primary toxins, toxicity is best characterized as lethal synthesis.
Reported toxic dose (exposure by ingestion)
Cats: 1.5 ml/kg
Dogs: 6.6 ml/kg (other reports suggest less)
Man: 1.4 ml/kg
Clinical signs are characterized as triphasic: (Phase 1 Gastrointestinal and CNS: The first 12 hours post ingestion; Phase
11 – Cardio-pulmonary: 12-24 hours post ingestion; and Phase 111 - Renal: 24 hours and beyond), post ingestion of a toxic
dose. Clinical signs are always acute and dose related, and are attributable to both the chemical and physical characteristics of the parent compound and its metabolites. Initial clinical
signs (vomiting, ataxia, weakness, CNS depression, dehydrated, and muscle fasciculation) develop within minutes of ingestion,
becoming progressively worse over the next 12 hours post ingestion of a toxic dose. These clinical signs impact primarily
the gastrointestinal and central nervous systems and are attributable to high blood levels of ethylene glycol and its aldehyde
Affected animals appear transiently improved, becoming worse with time. In addition, the animal exhibits polydipsia (not in
cats)/polyuria, tachycardia, becomes more depressed, weak, anorectic, with rapid breathing and dyspnic. This phase impacts
the cardio-pulmonary systems due to severe metabolic acidosis resulting from metabolite interactions. Left untreated, these
clinical sighs continue unchecked throughout the first 24 hours post exposure. Beyond this point, and the condition remains
untreated, renal failure develops resulting in a oliguric/anuric state, followed by death 72 hours post ethylene glycol ingestion
• Ethylene glycol (mildly toxic) on ingestion is rapidly absorbed and undergoes liver metabolism via the alcohol dehydrogenase
pathway. Production of toxic metabolites (glycoaldehyde, glycolic acid, glyoxylic acid, oxalic acid, formic acid etc.) follow.
Aldehyde metabolites lead to cytotoxicity, calcium oxalate crystal deposition and secondary cerebral edema.
• The presence of these metabolites induces severe metabolic acidosis leading to metabolic changes – increased ionic
gap, osmolarity, osmotic diuresis, polydipsia/polyuria, dehydration leading to calcium oxalate crystal formation. Calcium
oxalic acid reaction forming soluble complexes which are filtered through the glomeruli, and re-crystallize within tubular
lumen. where they are deposited and excreted in urine. Metabolites are cytotoxic to proximal tubular cells, resulting in the
deposition of these calcium oxalate crystals (monohydrate) within the lumen of kidney tubules, thereby causing interstitial
edema and their subsequent urinary excretion.