Ethylene glycol poisoning

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Caption = Ethylene glycol
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eMedicineSubj = emerg
eMedicineTopic = 177
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Ethylene glycol poisoning is caused by the ingestion of ethylene glycol. Ethylene glycol is most commonly found as the primary ingredient of automobile antifreeze and hydraulic brake fluids.cite journal |author=Hall TL |title=Fomepizole in the treatment of ethylene glycol poisoning |journal=CJEM |volume=4 |issue=3 |pages=199–204 |year=2002 |month=May |pmid=17609006 |doi= |url=http://caep.ca/template.asp?id=970248A8612440CF8E59ABADF87FC391] It is a highly toxic, colorless, odorless, almost nonvolatile liquid with a sweet taste. Following ingestion the symptoms of poisoning follow a three step progression starting with intoxication and vomiting, before causing metabolic acidosis, cardiovascular dysfunction, and finally kidney failure. The major cause of toxicity is not the ethylene glycol itself but the metabolites of ethylene glycol when it is metabolized.

Medical diagnosis of poisoning is most reliably done by measurement of ethylene glycol in the blood. However many hospitals do not have the facilities to perform this test and need to rely on abnormalities in the body’s biochemistry to diagnose poisoning. Treatment consists of initially stabilizing the patient followed by the use of antidotes. The antidotes used are either ethanol or fomepizole. The antidotes work by blocking the enzyme responsible for metabolizing ethylene glycol and therefore halt the progression of poisoning. Hemodialysis is also used to help remove ethylene glycol and its metabolites from the blood. As long as medical treatment is undertaken the prognosis is generally good with most patients making a full recovery. Poisoning is relatively common and due to its taste, children and animals will sometimes consume large quantities of ethylene glycol. Many antifreeze products have denatonium benzoate, a bittering agent, added to try and prevent ingestion.

Toxicity

Once thought innocuous, [cite journal |author= Hanzlik PJ, Seidenfeld MA, Johnson CC |title=General properties, irritant and toxic actions of ethylene glycol |journal=J Pharmacol Exp Ther |volume= 41|issue= |pages= 387-406|year= 1931|month= |pmid=|doi= |url=http://jpet.aspetjournals.org/cgi/reprint/41/4/387] ethylene glycol has been shown to be highly toxic to humans. The toxic dose varies but an estimated oral lethal dose in humans has been reported as approximately 1.4 mL/kg of pure ethylene glycol.cite journal | author = Brent J | title = Current management of ethylene glycol poisoning | journal = Drugs | volume = 61 | issue = 7 | pages = 979–88 | year = 2001 | pmid = 11434452 | doi = 10.2165/00003495-200161070-00006] Although survival with medical treatment has occurred with doses much higher than this, death has occurred with just 30 mL of the concentrate in an adult. [cite journal |author=Eder AF, McGrath CM, Dowdy YG, Tomaszewski JE, Rosenberg FM, Wilson RB, Wolf BA, Shaw LM |title=Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis |journal=Clin. Chem. |volume=44 |issue=1 |pages=168–77 |year=1998 |month=January |pmid=9550575 |doi= |url=http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=9550575] [cite journal |author=Field DL |title=Acute ethylene glycol poisoning |journal=Crit. Care Med. |volume=13 |issue=10 |pages=872–3 |year=1985 |month=October |pmid=4028762 |doi= |url=] [cite journal |author=Amathieu R, Merouani M, Borron SW, Lapostolle F, Smail N, Adnet F |title=Prehospital diagnosis of massive ethylene glycol poisoning and use of an early antidote |journal=Resuscitation |volume=70 |issue=2 |pages=285–6 |year=2006 |month=August |pmid=16808995 |doi=10.1016/j.resuscitation.2005.12.014 |url=] A toxic dose requiring medical treatment is considered more than 0.1 mL/kg of pure substance. Poison control centers often use more than a lick or taste in a child or more than a mouthful in an adult as a dose requiring hospital assessment. Because of its low vapor pressure and as it poorly absorbed through skin, ethylene glycol poisoning is uncommon following inhalational or dermal exposure. [cite journal |author=Driver J, Tardiff RG, Sedik L, Wester RC, Maibach HI |title=In vitro percutaneous absorption of [14C] ethylene glycol |journal=Journal of exposure analysis and environmental epidemiology |volume=3 |issue=3 |pages=277–84 |year=1993 |pmid=8260837 |doi= |url=] [cite journal |author=Hodgman MJ, Wezorek C, Krenzelok E |title=Toxic inhalation of ethylene glycol: a pharmacological improbability |journal=Journal of toxicology. Clinical toxicology |volume=35 |issue=1 |pages=109–11 |year=1997 |pmid=9022663 |doi= |url=]

igns and symptoms

Symptoms of ethylene glycol poisoning usually follow a three-step progression, although poisoned individuals will not always develop each stage.
* Stage 1 (0.5 to 12 hours) consists of neurological and gastrointestinal symptoms; victims may appear to be intoxicated, exhibiting symptoms such as dizziness, incoordination of muscle movements, nystagmus, headaches, slurred speech, and confusion. Irritation to the stomach may cause nausea and vomiting. Over time, the body metabolizes ethylene glycol into other toxins.
* Stage 2 (12 to 36 hours) is a result of accumulation of organic acids formed by the metabolism of ethylene glycol and consists of increased heart rate, high blood pressure, hyperventilation, and metabolic acidosis. Additionally low calcium levels in the blood, overactive muscle reflexes, muscle spasms, QT interval prolongation, and congestive heart failure may occur. If untreated, death most commonly occurs during this period.
* Stage 3 (24 to 72 hours) of ethylene glycol poisoning is the result of kidney injury. Symptoms include acute tubular necrosis, red blood cells in the urine, excess proteins in the urine, lower back pain, decreased production of urine, absent production of urine, elevated blood level of potassium, and kidney failure.cite journal | author=Barceloux DG, Krenzelok EP, Olson K, Watson W. | title=American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee | journal=J Toxicol Clin Toxicol | year=1999 | pages=537–60 | volume=37 | issue=5 | pmid=10497633 | doi=10.1081/CLT-100102445] [cite journal |author=Bobbitt WH, Williams RM, Freed CR |title=Severe ethylene glycol intoxication with multisystem failure |journal=West. J. Med. |volume=144 |issue=2 |pages=225–8 |year=1986 |month=February |pmid=3953092 |pmc=1306577 |doi= |url=] If kidney failure occurs it is typically reversible, although weeks or months of supportive care including hemodialysis may be required before kidney function returns.

Pathophysiology

The toxic mechanism of ethylene glycol poisoning is mainly due to the metabolites of ethylene glycol. Initially it is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then oxidized to glycolic acid. The glycolic acid is metabolized to glyoxylic acid and finally to oxalic acid. Oxalic acid binds with calcium to form calcium oxalate crystals which may deposit and cause damage to many areas of the body including the brain, heart, kidneys, and lungs. The rate-limiting step in this cascade is the conversion of glycolic to glyoxylic acid. [cite journal |author=Gabow PA, Clay K, Sullivan JB, Lepoff R |title=Organic acids in ethylene glycol intoxication |journal=Ann. Intern. Med. |volume=105 |issue=1 |pages=16–20 |year=1986 |month=July |pmid=3717806 |doi= |url=] Accumulation of glycolic acid in the body is mainly responsible for toxicity. [cite journal |author=Clay KL, Murphy RC |title=On the metabolic acidosis of ethylene glycol intoxication |journal=Toxicol. Appl. Pharmacol. |volume=39 |issue=1 |pages=39–49 |year=1977 |month=January |pmid=14421 |doi= |url=]

The three main systems affected by ethylene glycol poisoning are the central nervous system, metabolic processes, and the kidneys. The central nervous system is affected early in the course of poisoning as the result of a direct action of ethylene glycol. Similar to ethanol, it causes intoxication, followed by drowsiness or coma. As time passes, the increase in metabolites causes encephalopathy or cerebral edema. [cite journal |author=Maier W |title=Cerebral computed tomography of ethylene glycol intoxication |journal=Neuroradiology |volume=24 |issue=3 |pages=175–7 |year=1983 |pmid=6828232 |doi= |url=] Seizures may occur due to a direct effect or due to hypocalcemia. The metabolic effects are primarily metabolic acidosis which is caused by accumulated glycolic acid. Additionally, as a side effect of the first two steps of metabolism, an increase in the blood concentration of lactic acid occurs contributing to acidosis. The formation of acid metabolites also causes inhibition of other metabolic pathways, such as oxidative phosphorylation. The renal toxicity of ethylene glycol is caused by direct cytotoxic effects of glycolic acid. In addition, accumulation of calcium oxalate crystals in the kidneys causes kidney damage leading to oliguric or anuric kidney failure.

Diagnosis

As many of the clinical signs and symptoms of ethylene glycol poisoning are nonspecific and occur in many poisonings the diagnosis is often difficult. It is most reliably diagnosed by the measurement of the blood ethylene glycol concentration. Ethylene glycol in biological fluids can be determined easily by gas chromatography. [cite journal |author=Aarstad K, Dale O, Aakervik O, Ovrebø S, Zahlsen K |title=A rapid gas chromatographic method for determination of ethylene glycol in serum and urine |journal=Journal of analytical toxicology |volume=17 |issue=4 |pages=218–21 |year=1993 |pmid=8371550 |doi= |url=] Many hospital laboratories do not have the ability to perform this blood test and in the absence of this test the diagnosis must be made based on the clinical presentation of the patient. In this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap. The patients' serum osmolality is measured by freezing point depression and then compared with the predicted osmolality based on the patients' measured sodium, glucose, blood urea nitrogen, and any ethanol that may have been ingested. The presence of a large osmolal gap supports a diagnosis of ethylene glycol poisoning. However, a normal osmolar gap does not rule out ethylene glycol exposure because of wide individual variability. [cite journal |author=Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR |title=Osmol gaps revisited: normal values and limitations |journal=J. Toxicol. Clin. Toxicol. |volume=31 |issue=1 |pages=81–93 |year=1993 |pmid=8433417 |doi= |url=]

, or renal failure may also produce an elevated osmolal gap leading to a false diagnosis.

Other laboratory abnormalities may suggest poisoning, especially the presence of a metabolic acidosis, particularly if it is characterized by a large anion gap. Large anion gap acidosis is usually present during the initial stage of poisoning. However, acidosis has a large number of differential diagnosis, including poisoning from methanol, salicylates, iron, isoniazid, paracetamol, theophylline, or from conditions such as uremia or diabetic and alcoholic ketoacidosis. The diagnosis of ethylene glycol poisoning should be considered in any patient with a severe acidosis. Urine microscopy can reveal needle or envelope-shaped calcium oxalate crystals in the urine which can suggest poisoning; although these crystals may not be present until the late stages of poisoning. [cite journal |author=Jacobsen D, Akesson I, Shefter E |title=Urinary calcium oxalate monohydrate crystals in ethylene glycol poisoning |journal=Scandinavian journal of clinical and laboratory investigation |volume=42 |issue=3 |pages=231–4 |year=1982 |month=May |pmid=7134806 |doi= |url=] Finally, many commercial radiator antifreeze products have fluorescein added to enable radiator leaks to be detected using a Wood's lamp. Following ingestion of antifreeze products containing ethylene glycol and fluorescein, a Wood's lamp may reveal fluorescence of a patient’s perioral area, clothing, vomitus, or urine which can help to diagnose poisoning. [cite journal |author=Winter ML, Ellis MD, Snodgrass WR |title=Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions |journal=Ann Emerg Med |volume=19 |issue=6 |pages=663–7 |year=1990 |month=June |pmid=2344083 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0196-0644(05)82472-2] [cite journal |author=Wallace KL, Suchard JR, Curry SC, Reagan C |title=Diagnostic use of physicians' detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze |journal=Ann Emerg Med |volume=38 |issue=1 |pages=49–54 |year=2001 |month=July |pmid=11423812 |doi=10.1067/mem.2001.115531 |url=http://linkinghub.elsevier.com/retrieve/pii/S0196-0644(01)53496-4]

Treatment

Initial treatment consists of stabilizing the patient and gastric decontamination. As ethylene glycol is rapidly absorbed, gastric decontamination needs to be performed soon after ingestion to be of benefit. Gastric lavage or nasogastric aspiration of gastric contents are the most common methods employed in ethylene glycol poisoning. Although the usefulness of gastric lavage has been questioned in poisoning situations. [cite journal |author=Vale JA, Kulig K |title=Position paper: gastric lavage |journal=J. Toxicol. Clin. Toxicol. |volume=42 |issue=7 |pages=933–43 |year=2004 |pmid=15641639 |doi=10.1081/CLT-200045006 |url= ] Ipecac-induced vomiting is not recommended. As activated charcoal does not adsorb glycols, it is not indicated [cite journal |author=Fountain JS, Beasley DM |title=Activated charcoal supercedes ipecac as gastric decontaminant |journal=The New Zealand Medical Journal |volume=111 |issue=1076 |pages=402–4 |year=1998 |month=October |pmid=9830429 |doi= |url=] and should only be used in the presence of a toxic dose of a co-ingestant.cite journal |author=Jacobsen D, McMartin KE |title=Antidotes for methanol and ethylene glycol poisoning |journal=J. Toxicol. Clin. Toxicol. |volume=35 |issue=2 |pages=127–43 |year=1997 |pmid=9120880 |doi=10.3109/15563659709001182 |url= ] Patients with significant poisoning often present in a critical condition. In this situation stabilization of the patient including airway management with endotracheal intubation is the most important initial management. Patients presenting with metabolic acidosis or seizures require treatment with sodium bicarbonate and anticonvulsives such as a benzodiazepine respectively. Sodium bicarbonate should be used cautiously as it can worsen hypocalcemia by increasing the plasma protein binding of calcium. If hypocalcemia occurs it can be treated with calcium replacement although calcium supplementation can increase the precipitation of calcium oxalate crystals leading to tissue damage.

Following decontamination and the institution of supportive measures, the next priority is inhibition of further ethylene glycol metabolism using antidotes. The antidotes for ethylene glycol poisoning are ethanol or fomepizole, both ofwhich act by inhibiting the enzyme alcohol dehydrogenase. This antidotal treatment forms the mainstay of management of ethylene glycol poisoning. Pharmaceutical grade ethanol is usually given intravenously as a 5 or 10% solution in 5% dextrose, but it is also sometimes given orally in the form of a strong spirit such as whisky, vodka, or gin. Ethanol acts by competing with ethylene glycol for alcohol dehydrogenase. Alcohol dehydrogenase has about a 100 times greater affinity for ethanol than for ethylene glycol; ethanol therapy saturates the enzyme inhibiting further ethylene glycol metabolism thus limiting the formation of toxic metabolites.

Fomepizole is a potent inhibitor of alcohol dehydrogenase, similar to ethanol it acts to block the formation of the toxic metabolites.cite journal | author = Brent J, McMartin K, Phillips S, Burkhart K, Donovan J, Wells M, Kulig K | title = Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group | journal = N Engl J Med | volume = 340 | issue = 11 | pages = 832–8 | year = 1999 | pmid = 10080845] Fomepizole has been shown to be highly effective as an antidote for ethylene glycol poisoning. It is the only antidote approved by the USA FDA for the treatment of ethylene glycol poisoning. Both antidotes has advantages and disadvantages. Ethanol is readily available in most hospitals, inexpensive, and can be administered orally as well as intravenously. Although its adverse effects include intoxication, hypoglycemia in pediatric patients, and possible hepatotoxicity. Patients receiving ethanol therapy also require frequent blood ethanol level measurements and dosage adjustments to maintain a therapeutic ethanol concentration. Patients therefore must be monitored in an intensive care unit. Alternatively, the adverse side effects of fomepizole are minimal and the approved dosing regimen maintains therapeutic concentrations without the need to monitor serum levels of the drug. The disadvantage of fomepizole is that it is expensive. Costing 1,000 United States dollars per gram; an average course used in an adult poisoning would cost approximately $3,500 to 4,000. [cite journal |author=Shannon M |title=Toxicology reviews: fomepizole--a new antidote |journal=Pediatr Emerg Care |volume=14 |issue=2 |pages=170–2 |year=1998 |month=April |pmid=9583406 |doi= |url=] [cite journal |author=Scalley RD, Ferguson DR, Piccaro JC, Smart ML, Archie TE |title=Treatment of ethylene glycol poisoning |journal=Am Fam Physician |volume=66 |issue=5 |pages=807–12 |year=2002 |month=September |pmid=12322772 |doi= |url=] Despite the cost, fomepizole is gradually replacing ethanol as the antidote of choice in ethylene glycol poisoning.cite journal |author=Borron SW, Mégarbane B, Baud FJ |title=Fomepizole in treatment of uncomplicated ethylene glycol poisoning |journal=Lancet |volume=354 |issue=9181 |pages=831 |year=1999 |month=September |pmid=10485727 |doi=10.1016/S0140-6736(99)80015-4 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(99)80015-4] Adjunct agents including thiamine and pyridoxine are often given based on the fact that they may help prevent the formation of oxalic acid. The use of these agents is based on theoretical observations and there is limited evidence to support their use in treatment; they may be of particular benefit in people who could be deficient in these vitamins such as malnourished or alcoholic patients.

In addition to antidotes, an important treatment for poisoning is the use of hemodialysis. Hemodialysis is used to enhance the removal of unmetabolized ethylene glycol, as well as its metabolites from the body. It has been shown to be highly effective in the removal of ethylene glycol and its metabolites from the blood. [cite journal |author=Gabow PA, Clay K, Sullivan JB, Lepoff R |title=Organic acids in ethylene glycol intoxication |journal=Ann. Intern. Med. |volume=105 |issue=1 |pages=16–20 |year=1986 |month=July |pmid=3717806 |doi= |url=] [cite journal |author=Moreau CL, Kerns W, Tomaszewski CA, McMartin KE, Rose SR, Ford MD, Brent J |title=Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group |journal=J. Toxicol. Clin. Toxicol. |volume=36 |issue=7 |pages=659–66 |year=1998 |pmid=9865233 |doi= |url=] Hemodialysis also has the added benefit of correcting other metabolic derangements or supporting deteriorating kidney function. Hemodialysis is usually indicated in patients with severe metabolic acidosis (blood pH less than 7.3), renal failure, severe electrolyte imbalance, or if the patients condition is deteriorating despite treatment. Often both antidotal treatment and hemodialysis are used together in the treatment of poisoning. Because hemodialysis will also remove the antidotes from the blood, doses of antidotes need to be increased to compensate. If hemodialysis is not available, then peritoneal dialysis also removes ethylene glycol, although less efficently. [cite journal |author=Aakervik O, Svendsen J, Jacobsen D |title= [Severe ethylene glycol poisoning treated wtih fomepizole (4-methylpyrazole)] |language=Norwegian |journal=Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række |volume=122 |issue=25 |pages=2444–6 |year=2002 |month=October |pmid=12448112 |doi= |url=]

Prognosis

Generally if the patient is treated and survives then a full recovery is expected. Patients who present early to medical facilities and have prompt medical treatment typically have a favorable outcome. [cite journal |author=Velez LI, Shepherd G, Lee YC, Keyes DC |title=Ethylene glycol ingestion treated only with fomepizole |journal=J Med Toxicol |volume=3 |issue=3 |pages=125–8 |year=2007 |month=September |pmid=18072148 |doi= |url=http://jmt.pennpress.org/strands/jmt/pdfHandler.pdf?issue=20070303&file=20070303_125_128.pdf] Alternatively, patients presenting late with signs and symptoms of coma, hyperkalemia, seizures, or severe acidosis have a poor prognosis. Patients who develop severe central nervous system manifestations or cerebral infarcts who survive may have long term neurologic dysfunction; in some cases they may recover, although convalescence may be prolonged. [cite journal |author=Jacobsen D, McMartin KE |title=Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment |journal=Medical toxicology |volume=1 |issue=5 |pages=309–34 |year=1986 |pmid=3537623 |doi= |url=] [cite journal |author=Berger JR, Ayyar DR |title=Neurological complications of ethylene glycol intoxication. Report of a case |journal=Arch. Neurol. |volume=38 |issue=11 |pages=724–6 |year=1981 |month=November |pmid=7305705 |doi= |url=] [cite journal |author=Lewis LD, Smith BW, Mamourian AC |title=Delayed sequelae after acute overdoses or poisonings: cranial neuropathy related to ethylene glycol ingestion |journal=Clinical pharmacology and therapeutics |volume=61 |issue=6 |pages=692–9 |year=1997 |month=June |pmid=9209253 |doi=10.1016/S0009-9236(97)90105-3 |url=] [cite journal |author=Spillane L, Roberts JR, Meyer AE |title=Multiple cranial nerve deficits after ethylene glycol poisoning |journal=Annals of emergency medicine |volume=20 |issue=2 |pages=208–10 |year=1991 |month=February |pmid=1996809 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0196-0644(05)81226-0] The most significant long-term complication is related to the kidneys. Cases of permanent kidney damage, often requiring chronic dialysis or kidney transplantation, have been reported after severe poisoning. [cite journal |author=Nizze H, Schwabbauer P, Brachwitz C, Lange H |title= [Fatal chronic oxalosis after sublethal ethylene glycol poisoning] |language=German |journal=Pathologe |volume=18 |issue=4 |pages=328–34 |year=1997 |month=July |pmid=9380607 |doi= |url=http://link.springer.de/link/service/journals/00292/bibs/7018004/70180328.htm]

Epidemiology

Ethylene glycol poisoning is a relatively common occurrence worldwide.cite journal |author=Davis DP, Bramwell KJ, Hamilton RS, Williams SR |title=Ethylene glycol poisoning: case report of a record-high level and a review |journal=J Emerg Med |volume=15 |issue=5 |pages=653–67 |year=1997 |pmid=9348055 |doi=10.1016/S0736-4679(97)00145-5|url=http://linkinghub.elsevier.com/retrieve/pii/S0736467997001455] [cite journal |author=Kotwica M, Czerczak S |title=Acute poisonings registered since 1970: trends and characteristics. Analysis of the files collected in the National Poison Information Centre, Łódź, Poland |journal=Int J Occup Med Environ Health |volume=20 |issue=1 |pages=38–43 |year=2007 |pmid=17509968 |doi=10.2478/v10001-007-0010-8 |url=] [cite journal |author=Krenová M, Pelclová D, Navrátil T, Merta M |title=Experiences of the Czech toxicological information centre with ethylene glycol poisoning |journal=Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub |volume=149 |issue=2 |pages=473–5 |year=2005 |month=December |pmid=16601813 |doi= |url=http://publib.upol.cz/~obd/fulltext/Biomed/2005/2/473.pdf] Human poisoning often occurs in isolated cases, but may also occur in epidemics. [cite journal |author= |title=Ethylene glycol intoxication due to contamination of water systems |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=36 |issue=36 |pages=611–4 |year=1987 |month=September |pmid=3114608 |doi= |url=] [cite journal |author=Leikin JB, Toerne T, Burda A, McAllister K, Erickson T |title=Summertime cluster of intentional ethylene glycol ingestions |journal=JAMA |volume=278 |issue=17 |pages=1406 |year=1997 |month=November |pmid=9355997 |doi= |url=] [cite journal |author=Goldsher M, Better OS |title=Antifreeze poisoning during the October 1973 War in the Middle-East: case reports |journal=Mil Med |volume=144 |issue=5 |pages=314–5 |year=1979 |month=May |pmid=113700 |doi= |url=] Many cases of poisoning are the result of using ethylene glycol as a cheap substitute for alcohol or intentional ingestions in suicide-attempts.cite journal |author=Leth PM, Gregersen M |title=Ethylene glycol poisoning |journal=Forensic Sci. Int. |volume=155 |issue=2-3 |pages=179–84 |year=2005 |month=December |pmid=16226155 |doi=10.1016/j.forsciint.2004.11.012 |url=] Less commonly it has been used as a means of homicide. [cite journal |author=Armstrong EJ, Engelhart DA, Jenkins AJ, Balraj EK |title=Homicidal ethylene glycol intoxication: a report of a case |journal=Am J Forensic Med Pathol |volume=27 |issue=2 |pages=151–5 |year=2006 |month=June |pmid=16738434 |doi=10.1097/01.paf.0000203221.17854.38 |url=] [cite web | last = Munro | first = Ian | title = Death by anti-freeze 'perfect murder' | work = | publisher = The Age | date = October 13, 2007 | url = http://www.theage.com.au/news/world/death-by-antifreeze-perfect-murder/2007/10/12/1191696176894.html | format = | doi = | accessdate = 2008-10-01] Children or animals may be exposed by accidental ingestion; children and animals often consume large amounts due to ethylene glycol having a sweet taste.cite book | editor = Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS | title = Goldfrank’s toxicologic emergencies | year = 2002| pages = 980-90 | publisher = McGraw-Hill | id = ISBN 0-07-136001-8] In the United States there were 5816 cases reported to poison centers in 2002.cite journal |author=Caravati EM, Erdman AR, Christianson G, "et al" |title=Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management |journal=Clin Toxicol (Phila) |volume=43 |issue=5 |pages=327–45 |year=2005 |pmid=16235508 |doi=10.1080/07313820500184971 |url=] Additionally, ethylene glycol was the most common chemical responsible for deaths reported by US poison centers in 2003.cite journal |author=Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, Youniss J, Reid N, Rouse WG, Rembert RS, Borys D |title=2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System |journal=Am J Emerg Med |volume=22 |issue=5 |pages=335–404 |year=2004 |month=September |pmid=15490384 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S073567570400141X |issn=] However, these numbers may underestimate actual numbers because not all cases attributable to ethylene glycol are reported to poison control centers.cite journal |author=LaKind JS, McKenna EA, Hubner RP, Tardiff RG |title=A review of the comparative mammalian toxicity of ethylene glycol and propylene glycol |journal=Crit. Rev. Toxicol. |volume=29 |issue=4 |pages=331–65 |year=1999 |month=July |pmid=10451263 |doi= 10.1080/10408449991349230|url=] Most deaths from ethylene glycol are intentional suicides; deaths in children due to unintentional ingestion are extremely rare.cite journal |author=White NC, Litovitz T, White MK, Watson WA, Benson BE, Horowitz BZ, Marr-Lyon L|title=The impact of bittering agents on suicidal ingestions of antifreeze |journal=Clin Toxicol (Phila) |volume=46 |issue=6 |pages=507–14 |year=2008 |month=July |pmid=18584362 |doi=10.1080/15563650802119700 |url=]

In an effort to prevent poisoning, often a bittering agent called denatonium benzoate, known by the trade name Bitrex, is added to ethylene glycol preparations as an adversant to prevent accidental or intentional ingestion. The bittering agent is thought to stop ingestion as part of the human defense against ingestion of harmful substances is rejection of bitter tasting substances. [cite journal |author=Jackson MH, Payne HA |title=Bittering agents: their potential application in reducing ingestions of engine coolants and windshield wash |journal=Vet Hum Toxicol |volume=37 |issue=4 |pages=323–6 |year=1995 |month=August |pmid=8540219 |doi= |url=] In the United States, 3 states (Oregon, California, New Mexico) have made the addition of bittering agents to antifreeze compulsory. [cite journal |author=Neumann CM, Giffin S, Hall R, Henderson M, Buhler DR |title=Oregon's Toxic Household Products Law |journal=J Public Health Policy |volume=21 |issue=3 |pages=342–59 |year=2000 |pmid=11021047 |doi= |url=] Follow up studies assessing the efficacy of bittering agents in preventing toxicity or death have, however, shown limited benefit of bittering ethylene glycol preparations. [cite journal |author=Mullins ME, Zane Horowitz B |title=Was it necessary to add Bitrex (denatonium benzoate) to automotive products? |journal=Vet Hum Toxicol |volume=46 |issue=3 |pages=150–2 |year=2004 |month=June |pmid=15171494 |doi= |url=]

References

External links

[http://www.emedicine.com/emerg/topic177.htm eMedicine: Ethylene Glycol toxicity]