C -Tech Corporation while doing this path breaking research identified 75 products commonly found in homes, which are poisonous to pets, similarly Children especially younger children are also at risk from these substances. Ingestion of these substances can cause death, it is wrong to call such deaths as accidental as these can easily be avoided by addition of very small quantities of Denatonium benzoate.

ETHYLENE GLYCOL POISONING & TOXICITY OF GLYCOLS

Ethylene Glycol is an extremely toxic substance.

Ethylene glycol is a clear, colourless, odourless, viscous liquid with a sweet taste that can produce dramatic toxicity. It is commonly found in homes in products including antifreeze, de-icing products, detergents, paints, and even cosmetics. It is found most commonly in antifreeze, automotive cooling systems, and hydraulic brake fluids. In an industrial setting it is used as a solvent or as the raw material for a variety of processes.

Many cases of ethylene glycol poisoning results from accidental ingestion by children who can take in large amounts since the substance tastes good. Alcoholics may also ingest this substance as an ethanol substitute.

Because it is readily available and relatively inexpensive, it is often used in suicide attempts. Ingestion is the primary route of exposure.

The potential lethal dose is reported to be 100 ml (1.0 to 1.5 ml/kg) in adults.

General Indications of poisoning in animals.

Muscle tremors or seizures, Vomiting and/or diarrhoea, sometimes with blood

Excessive salivation - drooling or foaming

Redness of skin, ears, eyes

Mental depression or excitement (may be easily excitable)

Bleeding (as with rat poison ingestion)

Ulceration or blisters of the mouth or skin

Excessive pawing at the mouth, excessive licking

Swelling (i.e. of a limb or face, commonly seen with insect bites and stings)

Elevated or depressed body temperature (elevations usually due to increased muscle activity - tremors, seizures)

Poisoning occurring following the ingestion of automobile antifreeze which consists almost entirely of Mono Ethylene Glycol (or other sources of ethylene glycol). This poison produces a profound metabolic acidosis (A disturbance of the body acid-base balance in which there is excessive acidity of body fluids or loss of alkali (base). which can damage the kidneys and other organs and cause blindness or death.

Fomepizole is found to be highly effective as an antidote to ethylene glycol poisoning. This new drug for antifreeze poisoning, however, is costly reportedly - $4,000 for one patient. (Ref : Leary WE. Antidote for pretty poison is found, but at big price. New York Times 1999 March 23 : F6 (col. 4).)

Female animals that ate large amounts of ethylene glycol had babies with birth defects, while male animals had reduced sperm counts. However, these effects were seen at very high levels and would not be expected in people exposed to lower levels at hazardous waste sites.

Ethylene glycol affects the body's chemistry by increasing the amount of acid, resulting in metabolic problems. Similar to ethylene glycol, propylene glycol increases the amount of acid in the body. However, larger amounts of propylene glycol are needed to cause this effect. Since both chemicals break down very quickly in the body, they are very difficult to detect, even though symptoms may be present. Another consideration is that all antifreezes pick up heavy metal contamination during service. When contaminated (particularly with lead) any used antifreeze can be considered hazardous. Because of metal contamination many people feel that the toxicity of used antifreeze is the same regardless of glycol. The acute toxicity of PG, especially in humans, is substantially lower than that of EG. Propylene glycol, like alcohol, is not toxic at low levels. However at higher levels it too is toxic.

Pharmacology: Ethylene glycol is rapidly absorbed once it is ingested and is then widely distributed into body tissues. Peak blood levels are generally seen in 1-4 hours. Exposure to the skin and lungs may cause irritation but does not cause the systemic toxicity in the way that methanol does. Lethal quantities in adults are considered to be 100 ml, but in children much less may cause serious cardiac, renal, and CNS toxicity.

Ethylene glycol itself is relatively non toxic. After absorption the unchanged compound undergoes glomerular filtration and passive reabsorption. It is then broken down into metabolites that are highly toxic and cause the associated findings of ethylene glycol toxicity. Ethylene glycol is converted to glycoaldehyde by alcohol dehydrogenase. This is the rate limiting step of a reaction in the liver that continues to breakdown the glycoaldehyde into glycolate, glyoxylate, and oxylate (see below).

Ethylene Glycol-------- Alcohol Dehydrogenase------Glycoaldehyde --------- Glycolic Acid ----------- Glyoxylic acid ------------- Oxalate

These metabolites inhibit oxidative phosphorylation, sulfhydrl-containing enzymes, and protein synthesis. Glycolic acid is the major cause of the metabolic acidosis that is seen in ethylene glycol toxicity, although glyoxylic acid also may contribute. Toxicity from ethylene glycol is produced from the above metabolites and the fact that they cause a severe acidosis, as well as from the fact that oxalate precipitates with calcium to produce widespread tissue injury in the kidney, brain, liver, blood vessels, and pericardium. Hypocalcemia may also result.

Clinical Presentation: The clinical presentation of ethylene glycol toxicity is generally divided into three fairly well defined phases.

Phase I (CNS depression phase): The first phase occurs within 30 minutes to 12 hours. At this phase, the patient may appear intoxicated with nausea, vomiting, ataxia, absent reflexes, nystagmus, and myoclonic jerks but has no smell of alcohol. Coma and seizures (focal or generalized) may occur or there may be tetany if hypocalcemia is present. CNS depression may be from the ethylene glycol itself or from the metabolites. Abdominal pain, myalgias, and hematemesis may be present. Dilated pupils with loss of the light reflexes, papilledema, and blurred optic discs have been reported with ethylene glycol intoxication, but are much more common in methanol poisoning.

Phase II (Cardiopulmonary toxicity phase): This phase usually begins at 12-72 hours after ingestion. At this point mild hypertension, tachycardia, and tachypnea may be seen. If toxicity is severe this may progress to congestive heart failure, pulmonary edema, and pneumonitis. This phase is thought to be the result of calcium oxylate crystals within the vascular tree, lung parenchyma, and the myocardium.

Phase III (Renal Toxicity Phase): This phase occurs 24-72 hours after ingestion and consists of flank and abdominal pain with evidence of acute tubular necrosis that is manifest as oliguric renal failure.

While some patients may clearly manifest these classic phases of poisoning many people will not have such clear progression. Some patients will develop mild hypothermia with bradycardia and hypertension. Coma with cerebral edema, renal failure, and pancytopenia has also been described. In cases of ethylene glycol from child abuse the presenting signs were unexplained recurrent metabolic acidosis with severe vomiting. This diagnosis should be considered in children with a metabolic acidosis.

Diagnosis: Making the diagnosis of ethylene glycol poisoning rests on clinical suspicion and the finding of an elevated anion gap metabolic acidosis with an elevated osmolol gap. As has already been discussed, many substances may elevate either the anion or osmolol gaps, but only ethylene glycol, methanol, alcoholic ketoacidosis, and DKA elevate both. The metabolic acidosis seen with ethylene glycol is from the toxic metabolites while the osmolol gap is from the ethylene glycol itself. Thus, as the ethylene glycol is metabolized the osmolol gap may decrease but the anion gap will increase due to the increasing accumulation of glycolic acid. As was seen in methanol poisoning, if the patient has ingested ethanol along with the ethylene glycol there may be a delay in the formation of the toxic metabolites which may result in an elevated osmolol gap but no anion gap.

In addition to the lab findings mentioned there are urinary findings that may aid in the diagnosis. Crystalluria in the form of birefringet octahedral, envelope-shaped calcium oxalate dihydrate, or needle shaped calcium oxalate monohydrate crystals are highly suggestive of the diagnosis. Additional findings include renal epithelial cells, proteinuria, and microscopic hematuria. The absence of crystals does not rule out the diagnosis of ethylene glycol poisoning. In addition to the search for urinary crystal, examination of the urine under a Wood's lamp may reveal fluorescence since most ethylene glycol containing antifreeze products have fluorescein as an additive.

Ethylene glycol levels can be requested and may confirm the diagnosis. Other lab tests for the metabolic products of ethylene glycol are available, but may take considerable time to come back.

Treatment: As with all patients the initial concern is the maintenance of the ABC's. As with methanol the absorption of ethylene glycol is rapid and unless lavage can be performed within the first hour it is not useful. Charcoal is probably not useful unless there is a suspicion of co-ingestion.

As was seen with methanol intoxication there are three major considerations in treatment:

(1) prevent the formation of toxic metabolites

(2) removal of the toxin

(3) treatment of the severe metabolic acidosis.

** Ethanol has been recognized as an antidote for ethylene glycol poisoning since the 1960's. Alcohol dehydrogenase has a much greater affinity for ethanol than for ethylene glycol and the presence of ethanol inhibits the production of the toxic metabolites of ethylene glycol. The desired ethanol level is greater than 100 mg/dl, and this level can be achieved by using the formula on table 2 above. The level of ethanol should be checked frequently to be sure it is adequate. Hypoglycemia may occur, particularly in children, and should be followed. Indications for ethanol therapy include a history of ethylene glycol ingestion when a blood level cannot be easily obtained, elevated anion gap metabolic acidosis, symptoms in a patient suspected of ingesting ethylene glycol, and ethylene glycol blood level greater than 20 mg/dl.

** Dialysis is the definitive treatment for ethylene glycol intoxication. Hemodialysis can remove ethylene glycol, as well as the toxic metabolites of ethylene glycol. Indications for dialysis include severe metabolic acidosis, renal dysfunction, or ethylene glycol levels above 25-50 mg/dl. Ethanol therapy should be continued during dialysis and the amount of ethanol used must be increased. Dialysis is continued until the ethylene glycol level decreases below 10 mg/dl

** Metabolic acidosis in which the pH has gone below 7.2 should be treated with sodium bicarbonate. This decreases some of the systemic complications but must be closely followed to insure electrolyte abnormalities do not occur.

In addition to the above treatment it is important to provide adequate fluids to maintain adequate urine output. Once the patient has been well hydrated lasix may be used to help maintain the urine output. It is also important to monitor calcium and magnesium (particularly in chronic alcoholics) levels as they may become critically low in ethylene glycol intoxication. Magnesium is a necessary co-factor for the conversion of glyoxylic acid to non-toxic metabolites. If the magnesium levels are not low there is no need to give additional magnesium. Other co-factors that should be given in cases of ethylene glycol poisoning include pyridoxine and thiamine. Pyridoxine is a co-factor that is needed toconvert glyoxylate to non-toxic glycine. This is usually given as 100 mg (or 1 mg/kg) daily until the metabolic acidosis has resolved. Thiamine appears to help stimulate the conversion of glyoxylate to non-toxic byproducts. This is given as 100 mg IV doses daily until the metabolic acidosis has resolved.

Pediatric considerations: The treatment is essentially the same in pediatric ethylene glycol intoxications as it is in adults. Recall that children have increased risk of CNS depression, hypoglycemia, and hypothermia when they are treated with ethanol than do adults.

POISONING IN ANIMALS

Cats and dogs are attracted to the sweet smell and taste of antifreeze, and will often sample some if left out in a container or spilled on the garage floor. Acute cases (within 12 hours of ingestion) often present as if the animal was intoxicated with alcohol: stumbling, vomiting and depression are common signs. The kidneys are most severely affected, and even if the animal seems to improve initially with treatment, they may succumb shortly after to kidney failure. The kidneys shut down, and the animal is unable to produce urine. This type of kidney failure usually happens 12-24 hours after ingestion in cats, and 36-72 hours post ingestion in dogs. Success of treatment is dependent upon quick treatment.