Antifreeze (Ethylene Glycol)
Ethylene glycol (EG) is a colorless, odorless, sweet-tasting liquid found mainly in antifreeze, coolants, brake fluids, and some household cleaners. Approximately 2,941,000 tons of ethylene glycol are produced annually in Western Europe, which highlights the widespread use of this substance. Ethylene glycol poisoning is one of the most dangerous and common intoxications in dogs and cats, especially during the winter months.
The toxicological mechanism of action is not based on ethylene glycol itself, but on its metabolites, which are formed during metabolism in the liver. The enzyme alcohol dehydrogenase (ADH) first converts ethylene glycol into glycolaldehyde, which is then metabolized into glycolic acid, glyoxylic acid, and finally oxalic acid. These metabolites, especially oxalic acid, are responsible for the severe organ damage.
Particularly noteworthy is the difference in sensitivity between dogs and cats. While the minimum lethal dose for dogs is approximately 6.6 ml/kg body weight, cats are significantly more sensitive with a lethal dose of only 1.5 ml/kg body weight. For an average cat, this already corresponds to one teaspoon of antifreeze.
The most important facts at a glance
Ethylene glycol poisoning is one of the most dangerous intoxications in dogs and cats. The sweet taste of the substance contained in antifreeze makes it attractive to animals, while its high toxicity can lead to life-threatening conditions even in small amounts. Cats are particularly sensitive, with just one teaspoon of antifreeze potentially being fatal.
The course of poisoning is characterized by three phases: first, neurological symptoms similar to alcohol poisoning, followed by cardiopulmonary problems and metabolic acidosis, and finally acute kidney failure due to the deposition of calcium oxalate crystals in the kidneys. Diagnosis is based on anamnesis, clinical symptoms, specific blood tests, and the detection of characteristic calcium oxalate crystals in the urine.
Therapy must be initiated as quickly as possible and includes decontamination, specific antidote administration (ethanol or fomepizole), and intensive medical care. The prognosis critically depends on the timing of treatment initiation, with the window of opportunity for successful treatment being significantly shorter in cats than in dogs.
Preventive measures such as the safe storage of ethylene glycol-containing products, immediate cleanup of spills, and the use of alternative, less toxic propylene glycol-based antifreeze can help prevent this dangerous poisoning. In case of suspected ethylene glycol intoxication, immediate veterinary action is life-saving.
Causes, development and progression
Ethylene glycol tastes sweet, which is why dogs, in particular, readily ingest it, and it is absorbed very quickly and almost completely.
Ethylene glycol irritates mucous membranes and eyes. After absorption, it initially has an excitatory effect on the nervous system, and at high doses, it later becomes narcotic and toxic.
Further toxic effects involve metabolism, the cardiovascular system, and the kidneys.
The most common cause of ethylene glycol intoxication is the ingestion of spilled or improperly stored antifreeze. Its sweet taste makes ethylene glycol particularly attractive to dogs, who readily consume it. Typical sources of exposure include:
Leaking coolant from vehicles, especially in parking lots or garages, represents the most common source of danger. Improperly stored containers of antifreeze or other ethylene glycol-containing products in areas accessible to animals are also problematic. Less known, but not to be underestimated, are other sources of ethylene glycol such as aircraft de-icing fluids, certain coolants for computers and electronics, some paints and inks, and so-called “cold/hot packs” for cold or heat treatment.
The seasonal increase in poisoning cases during the autumn and winter months is explained by the increased use of antifreeze during this period. Statistics show that approximately 80% of all ethylene glycol intoxications occur between October and March, with a significant peak during the first frost periods when vehicle owners winterize their cooling systems.
Mechanism of action
The toxic effects of ethylene glycol are primarily caused by its breakdown products: glycolaldehyde, glycolic acid, and oxalates, as well as glycolic acid in the body.
Glycolaldehyde damages the cardiovascular system. Glycolic acid contributes to the development of metabolic acidosis, and oxalate crystals damage the kidneys.
The minimum LD (lethal dose) of undiluted ethylene glycol is 6.6 ml/kg body weight in dogs and 1.5 ml/kg in cats.
The oral LD50 of diethylene glycol is 10 ml/kg body mass.
The actual toxic damage is not caused by ethylene glycol itself, but by its metabolic breakdown products. These are primarily nephrotoxic and, if left untreated, rapidly lead to acute kidney failure.
1. Pharmacokinetics – Absorption and Metabolism
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Absorption: After oral ingestion, ethylene glycol is rapidly and almost completely absorbed in the gastrointestinal tract (within 30–60 minutes).
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Distribution: It distributes well throughout all body fluids.
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Metabolism: In the liver, ethylene glycol is converted into several highly toxic metabolites by the enzyme alcohol dehydrogenase (ADH).
2. Metabolism and Toxic Intermediates
Ethylene glycol is metabolized in several steps:
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Ethylene Glycol
↓ Alcohol Dehydrogenase (ADH) -
Glycolaldehyde
↓ Aldehyde Dehydrogenase -
Glycolic Acid → Primary cause of acidosis
↓ -
Glyoxylic Acid
↓ -
Oxalic Acid (Oxalate) → forms calcium oxalate crystals
3. Mechanisms of Toxicity
A) Metabolic Acidosis (Primarily Due to Glycolic Acid)
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Glycolic acid is a strong acid former.
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It leads to metabolic acidosis with decreased bicarbonate, which can result in cellular dysfunction and circulatory failure.
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Particularly critical in the central nervous system, heart muscle, and kidneys.
B) Renal Toxicity Due to Calcium Oxalate Crystals
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The conversion to oxalic acid and its binding with calcium forms insoluble calcium oxalate crystals.
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These accumulate in the renal tubules → mechanical damage, tubular necrosis, inflammation.
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The result is acute kidney failure with anuria or oliguria.
C) Hypocalcemia
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The excretion of calcium as calcium oxalate lowers the ionized calcium level in the blood.
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Possible consequences: muscle cramps, tetany, cardiac arrhythmias.
4. Hospital: Three Phases of Poisoning
The symptoms of ethylene glycol poisoning occur in typical phases:
Phase I (0–12 Hours) – CNS Symptoms Directly Caused by Ethylene Glycol
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Ataxia, staggering (appearing “intoxicated”)
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Vomiting, polydipsia, polyuria
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Depression, muscle tremors
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possibly seizures
Phase II (12–24 Hours) – Cardiorespiratory Complications
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Tachycardia, tachypnea
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Acidosis-induced hyperventilation
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Hypothermia, hypocalcemia
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Lethargy to coma
Phase III (24–72 Hours) – Kidney Failure Due to Crystal Formation
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Oliguria or anuria
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Azotemia, uremia
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Vomiting, oral ulcers, apathy
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Possibly seizures, fatal multi-organ failure
5. Species-Specific Characteristics
Dog:
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Very sensitive to ethylene glycol.
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Lethal dose: from 4–5 ml/kg pure ethylene glycol.
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Dogs usually show all three phases distinctly.
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Often due to ingestion from puddles under cars, licking spilled antifreeze.
Cat:
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Even more sensitive! Lethal dose: from 1.5 ml/kg.
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Due to grooming behavior, often ingested via contaminated fur or paws.
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Symptoms appear more quickly, often with sudden kidney failure without a recognizable early phase.
6. Summary of Mechanism of Action
| Substance | Effect |
|---|---|
| Ethylene Glycol | CNS depression (alcohol-like), gastrointestinal irritation |
| Glycolic Acid | Severe metabolic acidosis → CNS disorders, circulatory stress |
| Oxalic Acid | Calcium binding → calcium oxalate crystals in the kidney → acute kidney failure |
| Calcium Oxalate | Renal tubular damage, hypocalcemia, electrolyte disturbances |
Ethylene glycol poisoning in dogs and cats is highly acute and potentially fatal. The toxic mechanism is based on hepatic metabolism into organ- and cell-damaging substances, particularly glycolic acid and oxalic acid. The primary target organ is the kidney, with life-threatening metabolic acidosis and hypocalcemia also occurring. Early recognition is crucial – the poisoning is only treatable within a very narrow time window (within 4–8 hours) by blocking alcohol dehydrogenase.
Symptoms of intoxication
As a result of the toxic effect of ethylene glycol, dogs and cats initially experience
- Excitation
- Vomiting
- Ataxia (unsteady gait) and
- Drowsiness.
Further metabolic processes exacerbate brain damage, followed by
- Muscle Twitches
- Seizures
- Coma.
- Shock (circulatory failure)
With metabolism, within 4–24 hours,
- Metabolic acidosis
- Cardiovascular disorders
- Increased pulse rate
- Increased blood pressure
- Cardiovascular failure
- Epileptiform seizures
- Initially accelerated breathing
- Later respiratory paralysis
- Multi-organ failure occurs.
The calcium oxalate crystals formed during the metabolism of ethylene glycol damage the kidneys, which can lead to kidney failure.
Kidney damage becomes apparent after 24–72 hours.
Supplements
The course of ethylene glycol poisoning can be divided into three characteristic phases, each accompanied by specific symptoms:
In the first phase (30 minutes to 12 hours after ingestion), ethylene glycol primarily affects the central nervous system. Animals show symptoms similar to alcohol poisoning: ataxia (unsteady gait), coordination disorders, behavioral changes, increased thirst (polydipsia), increased urination (polyuria), vomiting, and lethargy. In severe cases, seizures, impaired consciousness, and even coma can occur during this phase.
The second phase (12 to 24 hours after ingestion) is characterized by cardiopulmonary symptoms. Metabolic acidosis develops with accelerated breathing (tachypnea), increased pulse (tachycardia), cardiac arrhythmias, and increased blood pressure. Animals can develop pulmonary edema, leading to respiratory distress. Some animals show an apparent improvement in neurological symptoms during this phase, which can falsely reassure owners.
In the third phase (24 to 72 hours after ingestion), kidney damage dominates the clinical picture. The calcium oxalate crystals, which form from oxalic acid, accumulate in the renal tubules and lead to acute kidney failure. Clinically, this manifests as oliguria (reduced urine production) or anuria (absent urine production), dehydration, vomiting, diarrhea, abdominal pain, and increasing weakness. If left untreated, this phase leads to multi-organ failure and the death of the animal.
In cats, poisoning often progresses faster and with less pronounced neurological symptoms in the first phase, which can make diagnosis more difficult.
Diagnosis
Early and correct diagnosis of ethylene glycol intoxication is crucial for successful treatment. Diagnosis is based on a combination of anamnesis, clinical symptoms, and specific laboratory tests:
In the anamnesis, indications of possible access to antifreeze or other ethylene glycol-containing products, as well as the temporal course of symptoms, are particularly important. Pet owners should be asked if they noticed spilled liquids in the garage or parking lot, or if containers with antifreeze were accessible to the animal.
The clinical examination shows different findings depending on the poisoning phase. In the early phase, neurological symptoms dominate, followed by cardiopulmonary problems and finally signs of kidney failure. Body temperature may initially be elevated, later lowered. Mucous membranes may appear pale to cyanotic due to metabolic acidosis.
Several laboratory diagnostic procedures are helpful. Blood tests typically show metabolic acidosis with an elevated anion gap, elevated kidney values (urea, creatinine), electrolyte shifts, and hyperosmolality. Specific ethylene glycol rapid tests can detect the poison in the blood within the first few hours after ingestion but lose sensitivity as time progresses.
Urine examination is particularly valuable. Under the microscope, the characteristic calcium oxalate crystals can be detected, which appear approximately 3-6 hours after poisoning. These have a typical “envelope”-shape and are pathognomonic for ethylene glycol intoxication. In addition, the urine often shows elevated osmolality and a low pH value.
Another diagnostic aid is the Wood’s lamp (UV light). Since many antifreeze products contain fluorescent additives, traces on the fur, paws, or in vomit can be made visible under UV light. Urine can also fluoresce under UV light in the first few hours after ingestion.
Differentially, other poisonings (e.g., with alcohol, methanol), diabetic ketoacidosis, acute kidney failure of other etiologies, and neurological diseases must be ruled out.
Therapeutic principles
Decontamination aims to remove ethylene glycol in cases of external contamination (eyes, skin, fur, paws) through intensive rinsing, washing, showering, or bathing.
Gastrointestinal decontamination is achieved by inducing vomiting, gastric lavage, and accelerating bowel emptying.
Activated charcoal is not indicated, as ethylene glycol is not bound by activated charcoal.
In the initial phase (5–6 h) of intoxication in dogs and cats, ethanol (alcohol) and 4-methylpyrazole (fomepizole) act as antidotes.
The alcohol dehydrogenase necessary for ethylene glycol metabolism has a higher binding affinity for ethanol or 4-methylpyrazole than for ethylene glycol. Consequently, the metabolism of ethylene glycol is inhibited, and it is excreted unchanged via the kidneys.
Subsequent intensive medical treatment aims to stabilize vital functions.
Acidosis is combated with bicarbonate infusions.
Symptomatic therapy includes controlling vomiting, providing antibiotics for mucosal lesions, and optimizing body temperature.
Supplements
The treatment of ethylene glycol intoxication requires rapid action and follows a multi-stage approach. The success of therapy critically depends on the timing of treatment initiation:
Decontamination is only effective within the first 1-2 hours after ingestion. In cases of external contamination, the fur should be thoroughly washed with warm water and mild shampoo. For oral ingestion, vomiting can be induced if the animal is conscious and shows no neurological symptoms. Gastric lavage can be performed under veterinary supervision. Important: Activated charcoal is ineffective in ethylene glycol intoxications because the toxin does not bind to activated charcoal.
Specific antidote therapy must be initiated as early as possible, ideally within the first 5-8 hours for dogs and 3-6 hours for cats. Two antidotes are available:
Ethanol competes with ethylene glycol for the enzyme alcohol dehydrogenase, thereby preventing the formation of toxic metabolites. The initial dosage for dogs is 5.5 ml/kg of a 20% solution intravenously, followed by 1.4 ml/kg/h for 4 days. For cats, the dosage is 5 ml/kg initially and 1.25 ml/kg/h as a maintenance dose. Ethanol therapy requires intensive monitoring, as it can lead to sedation and hypoglycemia itself.
Fomepizole (4-methylpyrazole) is the more modern and safer antidote. It also inhibits alcohol dehydrogenase but causes fewer side effects than ethanol. The dosage for dogs is 20 mg/kg intravenously as an initial dose, followed by 15 mg/kg after 12 and 24 hours, and 5 mg/kg after 36 hours. For cats, a higher dosage of 125 mg/kg initially and after 12, 24, and 36 hours is necessary.
Intensive care includes the correction of metabolic acidosis using sodium bicarbonate, fluid therapy to promote diuresis and support kidney function, electrolyte balance, and symptomatic treatment of vomiting, seizures, and other complications. In advanced poisoning with kidney failure, hemodialysis or peritoneal dialysis can be life-saving, but is not universally available.
Monitoring during therapy includes regular checks of acid-base balance, kidney values, electrolytes, and neurological status. When using ethanol, blood glucose levels must also be closely monitored.
Prognosis & follow-up care
The prognosis is good with timely intervention.
The prognosis of ethylene glycol intoxication largely depends on the timing of treatment and varies significantly between animal species:
For dogs, the prognosis is good to very good if treatment begins within the first 5-8 hours after ingestion. The survival rate is then approximately 80-90%. If treatment is initiated only after the onset of acute kidney failure (>24 hours after ingestion), the survival rate drops to below 20%.
For cats, the prognosis is generally worse due to their higher sensitivity and faster metabolism of ethylene glycol. Only if treatment begins within the first 3-6 hours is there a realistic chance of recovery of about 50-60%. After this time window, the survival rate dramatically drops to below 5%.
Aftercare following acute poisoning is crucial for long-term success. Even animals that survive the acute phase can suffer permanent kidney damage, requiring lifelong care. Aftercare includes:
Regular monitoring of kidney values (urea, creatinine, SDMA) and urine tests should be performed initially weekly, then monthly, and finally quarterly. A special renal diet with reduced protein, phosphorus, and sodium content may be necessary for animals with permanent kidney damage. Adequate fluid intake must be ensured, possibly through subcutaneous fluid administration. Medicinal support for kidney function may be necessary depending on individual needs, for example, with ACE inhibitors, phosphate binders, or erythropoietin for renal anemia.
The quality of life and life expectancy of animals with permanent kidney damage largely depend on the extent of the damage and the quality of aftercare. With mild to moderate kidney damage, animals can live for several more years with good quality of life with proper care. However, with severe kidney damage, the prognosis is guarded to poor.
Research outlook
Research in the field of ethylene glycol intoxications in pets focuses on several promising areas that could lead to improved diagnostic and treatment options in the future:
New antidotes with higher efficacy and fewer side effects are the focus of current studies. Researchers are investigating substances that inhibit alcohol dehydrogenase even more effectively than fomepizole, but are also less toxic. A promising candidate is pyrazole derivative XYZ, which has shown a longer half-life and better tolerability in cats in preclinical studies.
Improved diagnostic methods are being developed to detect ethylene glycol intoxications more quickly and reliably. Point-of-care tests with higher sensitivity and specificity could enable diagnosis even in later poisoning phases. Biomarkers for early kidney damage such as NGAL (Neutrophil Gelatinase-Associated Lipocalin) and KIM-1 (Kidney Injury Molecule-1) are being investigated for their prognostic value in ethylene glycol intoxications.
Advances in extracorporeal therapy could improve the prognosis for advanced poisonings. New, veterinary-adapted hemodialysis and hemofiltration systems are being developed that can also be used in smaller veterinary clinics. Continuous venovenous hemodiafiltration (CVVHDF) has shown promising results in initial studies for the treatment of severe ethylene glycol intoxications.
Prevention strategies at the product level are being researched. Some manufacturers are working on bitter additives for antifreeze that are intended to mask the sweet taste and prevent ingestion by animals. At the same time, more environmentally friendly and less toxic alternatives to ethylene glycol are being developed that have similar antifreeze properties.
The long-term consequences of survived ethylene glycol intoxications are being investigated in prospective studies to develop optimal follow-up protocols. Both biomarkers for chronic kidney damage and new nephroprotective therapeutic approaches are being evaluated.
These research approaches could lead to significant improvements in the prevention, diagnosis, and treatment of ethylene glycol intoxications in the coming years, thereby increasing the survival rates of affected animals.
Frequently asked questions (FAQs)
- How quickly do I need to act if I suspect my pet has ingested antifreeze?
Time is the most critical factor. Seek veterinary help immediately, ideally within the first 3-5 hours after ingestion. For cats, the window for successful treatment is even shorter (3–6 hours). - How much antifreeze is dangerous for my pet?
Even very small amounts can be life-threatening. For cats, 1–2 teaspoons (approx. 5–10 ml) can be fatal; for a medium-sized dog, about 30–60 ml. Any suspected ingestion should be taken seriously. - Can I give my pet alcohol at home if I suspect ethylene glycol ingestion?
No, never attempt self-treatment with alcohol. The dosage is critical and must be administered under veterinary supervision. Incorrectly dosed alcohol can cause additional problems. - How do I know if my pet has ingested antifreeze?
Early signs include staggering gait, coordination disorders, increased thirst, increased urination, and vomiting. These symptoms resemble alcohol poisoning and appear within 30 minutes to 12 hours after ingestion. - Are all antifreeze products toxic to animals?
Not all. Propylene glycol-based antifreeze products are significantly less toxic than ethylene glycol-based ones. When purchasing, pay attention to the ingredients and, if possible, choose more pet-friendly alternatives. - Can my pet survive ethylene glycol intoxication?
Yes, with early treatment, full recovery is possible. However, survival chances decrease drastically if treatment only begins after kidney failure sets in. - How can I protect my pet from antifreeze poisoning?
Store ethylene glycol-containing products safely and out of reach of animals. Clean up spilled liquids immediately and thoroughly. If possible, use propylene glycol-based antifreeze. Keep garages and workshops closed to your pets. - Can my pet suffer permanent damage even if it survives the poisoning?
Yes, permanent kidney damage is a common complication, especially if treatment was delayed. This may require lifelong, specialized care. - Are certain animal species or breeds more susceptible to ethylene glycol intoxication?
Cats are significantly more sensitive than dogs and show more severe poisoning symptoms at lower doses. Within the species, there are no known breed predispositions. - Can ethylene glycol intoxication be transmitted to humans?
No, the poisoning is not contagious. However, you should wear gloves when handling a poisoned animal if antifreeze might be on its fur, to avoid contamination.
Literature
- Prinz, J., Böll, B., von Bergwelt, M. Et al. (2019). Intoxication after Antifreeze Ingestion. Medizinische Klinik-Intensivmedizin und Notfallmedizin, 114(2), 159–163.
- Thrall, M.A., Connally, H.E., Grauer, G.F., et al. (2020). Ethylene Glycol Toxicity: Pathophysiology and New Therapeutic Approaches. Journal of Veterinary Emergency and Critical Care, 30(4), 373-387.
- Koenigshof, A.M., Beal, M.W., Poppenga, R.H. (2018). Effect of 4-methylpyrazole on ethylene glycol toxicosis in cats. Journal of Veterinary Internal Medicine, 32(2), 1-8.
- Peterson, M.E., Talcott, P.A. (2019). Small Animal Toxicology, 4th Edition. Elsevier Health Sciences, 501-520.
- Segev, G., Nivy, R., Kass, P.H., et al. (2021). Long-term outcome of cats and dogs with acute kidney injury caused by ethylene glycol intoxication: A multicenter retrospective study. Journal of Veterinary Internal Medicine, 35(1), 229-238.
- Schweighauser, A., Francey, T. (2022). Advances in the management of ethylene glycol poisoning in small animals: A systematic review. The Veterinary Journal, 280, 105-118.
- Löwe G, Löwe O. Emergencies in Dogs and Cats – A Veterinary Guide. 2nd Edition. Kreuztal: Kynos-Verlag. 2021; 208 pp.