Because hemodialysis will also remove the antidotes from the blood, doses of antidotes need to be increased to compensate.  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. The course of ethylene glycol toxicity is classically divided into three broad overlapping categories of adverse health effects. J  When broken down by the body it results in glycolic acid and oxalic acid which cause most of the toxicity. et al.  Small amounts of ethylene glycol may be contained in holiday ornaments such as snow globes. Brown In the original method proposed by Catachem (Bridgeport, CT), the difference between the absorbance readings at 2 time points was used to determine the ethylene glycol concentration. Jacobsen Because ethanol has a much higher affinity for alcohol dehydrogenase, about a 100-times greater affinity, it successfully blocks the breakdown of ethylene glycol into glycolaldehyde, which prevents the further degradation. A toxic dose requiring medical treatment varies but is considered more than 0.1 mL per kg body weight (mL/kg) of pure substance. Alternatively, the adverse side effects of fomepizole are minimal[clarification needed] and the approved dosing regimen maintains therapeutic concentrations without the need to monitor blood concentrations of the drug.  In the EU classification of dangerous substances it is 'harmful' (Xn) while more toxic substances are classified as 'toxic' (T) or 'very toxic' (T+). , The most significant source of ethylene glycol is from aircraft de-icing and anti-icing operations, where it is released onto land and eventually to waterways near airports experiencing cold winter climates.  Another study found the toxicity to aquatic and other organisms was relatively low, but the oxygen-depletion effect of biodegradation was more serious (p. The person' serum osmolality is measured by freezing point depression and then compared with the predicted osmolality based on the person's measured sodium, glucose, blood urea nitrogen, and any ethanol that may have been ingested. Juenke Online Course: Ethylene Glycol and Propylene Glycol Toxicity; Emergency Response Card: Information for First Responders Agent-specific identification, medical symptoms, prevention & personal protective equipment, fire fighting, sampling & analytical methods, decontamination, spillage disposal, packaging & labeling information. , Following decontamination and the institution of supportive measures, the next priority is inhibition of further ethylene glycol metabolism using antidotes.  Field studies in the vicinity of an airport have reported toxic signs consistent with ethylene glycol poisoning, fish kills, and reduced biodiversity, although those effects could not definitively be ascribed to ethylene glycol (p. Testing for glycolic acid remains a clear advantage of GC, which can readily assay ethylene glycol and its toxic metabolite. As the metabolism of ethylene glycol progresses there will be less ethylene glycol and this will decrease the blood ethylene glycol concentration and the osmolal gap making this test less useful. FREE real person client care by email or phone Mon to Thu 9:00 AM – 4 PM ( MST) and Fridays 9:00 AM to 3:00 PM MST Wiley FH, Hueper WC, von Oettingen WF.The toxicity and potential dangers of ethylene glycol.J 3. Ethylene glycol poisoning is poisoning caused by drinking ethylene glycol. A relevant clue to isopropanol ingestion is positivity for acetone in the urine or blood without attendant hyperglycemia. Costing US$1,000 per gram, an average course used in an adult poisoning would cost approximately $3,500 to $4,000. It has been shown to be highly effective in the removal of ethylene glycol and its metabolites from the blood. et al. The diagnosis of ethylene glycol poisoning should be considered in any people with a severe acidosis.  People presenting with metabolic acidosis or seizures require treatment with sodium bicarbonate and anticonvulsives such as a benzodiazepine respectively. TP Storing antifreeze in clearly marked original sealed containers, in areas that are inaccessible to pets. White Most clinical laboratories are equipped to accurately quantitate ethanol levels, mainly by an enzymatic assay on an automated chemistry analyzer platform. If the lighted gunpowder sparked or Incoordination, excessive urination, excessive thirst, vomiting, and lethargy are amongst the first signs to appear.  Accumulation of glycolic acid in the body is mainly responsible for toxicity.  Further, "Anaerobic biodegradation may also release relatively toxic byproducts such as acetaldehyde, ethanol, acetate, and methane (p. The disadvantage of fomepizole is that it is expensive. , Ethylene glycol is a colorless, odorless, sweet liquid, commonly found in antifreeze. This damage can be identified in a serum biochemistry profile by increases in the metabolites creatinine and BUN (blood urea nitrogen) that are normally removed from the blood by the kidneys. Ethylene glycol is a colorless, odorless, sweet-tasting liquid commonly found in antifreeze, as well as in industrial agents.  Human poisoning often occurs in isolated cases, but may also occur in epidemics. Thus, for methanol and isopropanol, gas chromatography (GC) is the confirmatory assay.  The metabolic effects occur 12 to 36 hours post ingestion, causing primarily metabolic acidosis which is due mainly to accumulated glycolic acid. Its adverse effects include intoxication, hypoglycemia in children, and possible liver toxicity.  People with significant poisoning often present in a critical condition. 12). Ethylene glycol in biological fluids can be determined by gas chromatography. JM 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. Urinary crystals result from. Ethylene glycol also forms acidic chemicals in the body, which can change the body's acid/base balance and affect your nervous system, lungs, and heart,” a … I-3).  The most significant effect is accumulation of calcium oxalate crystals in the kidneys which causes kidney damage leading to oliguric or anuric acute kidney failure. This page was last edited on 26 December 2020, at 15:11. A 100 proof spirit contains 50% ethanol. When A Dog’s Sweet Tooth And Cars Collide.  In Australia there were 17 cases reported to the Victorian poison center and 30 cases reported to the New South Wales poison center in 2007. W Oxalate is a minor metabolite of ethylene glycol and crystals are commonly seen in urine.  Despite the cost, fomepizole is gradually replacing ethanol as the antidote of choice in ethylene glycol poisoning.  A report in 2000 stated that ethylene glycol was becoming less popular for aircraft deicing in the U.S., due to its reporting requirements and adverse environmental impacts (p. 213), and noted a shift to the use of propylene glycol (p. Addressing the Challenges of Eosinophilia and Mastocytosis: Reactive Eosinophil Proliferations in Tissue and the Lymphocytic Variant of Hypereosinophilic Syndrome: Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of.  Intubation and respiratory support may be required in severely intoxicated people; people with hypotension require treatment with intravenous fluids and possibly vasopressors. , Ethylene glycol poisoning is a relatively common occurrence worldwide.  Finally, many commercial radiator antifreeze products have fluorescein added to enable radiator leaks to be detected using a Wood's lamp. Simply add your sample to the fill line, break the three ampules in order and wait 30 seconds for color to form.  In the United States there were 5816 cases reported to poison centers in 2002. Antifreeze's main component is usually ethylene glycol, and this can be detected in the blood. [unreliable source?]. . However, these instruments and the needed expertise are not readily available in most clinical laboratories. The modified assay, in addition to being precise (intra-assay coefficient of variation, <3.0%; interassay coefficient of variation, <8.0% ) and linear (up to 300 mg/dL), was also able to eliminate false-positives from a variety of interfering substances, including combinations of ethylene glycol, glycerol, propylene glycol, 2,3-butanediol, formic acid, n-propanol, isopropanol, acetone, methanol, ethanol, glycolic acid, polyethylene glycol, oxalic acid, glyoxal solution, glyoxylic acid, 1,2-butanediol, 1,4-butanediol, 1,3-propanediol, 1-butanol, 1,3-butanediol, DOT 3 brake fluid, and 1-octanol. Ishwarlal Jialal, MD, PhD, FRCPath, DABCC, Sridevi Devaraj, PhD, DABCC, Laboratory Diagnosis of Ethylene Glycol Poisoning: The Cup Is Half Full?, American Journal of Clinical Pathology, Volume 136, Issue 2, August 2011, Pages 165–166, https://doi.org/10.1309/AJCPTZO0HRPKVPWM. Signs of ethylene glycol poisoning depend upon the time after ingestion. 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. Oxalate binds calcium, leading to calcium oxalate crystals, which are deposited in many tissues but are most readily detected in the urine. Martens  Treatment consists of stabilizing the person, followed by the use of an antidote. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only.  Children or animals may be exposed by accidental ingestion; children and animals often consume large amounts due to ethylene glycol having a sweet taste. 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. J.J. Mackenzie, "Prevent Antifreeze Poisoning", in Laurie Halse Anderson, elevated blood concentration of potassium, EU classification of dangerous substances, "College of Veterinary Medicine: Pet Health Topics: Antifreeze Poisoning", "Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data", "Antifreeze Poisoning in Dogs & Cats (Ethylene Glycol Poisoning)", "Severe ethylene glycol intoxication with multisystem failure", "Government of Canada: Environment Canada: Ethylene Glycol (Final Content)", "Cerebral computed tomography of ethylene glycol intoxication", "Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis", "Fomepizole in the treatment of ethylene glycol poisoning", "Oklahoma Veterinary Medical Association: ASPCA answers questions about antifreeze poisoning", "Ethylene glycol ingestion treated only with fomepizole", "[Fatal chronic oxalosis after sublethal ethylene glycol poisoning]", "Experiences of the Czech toxicological information centre with ethylene glycol poisoning", "Ethylene glycol toxicosis in a free-ranging raccoon (Procyon lotor) from Prince Edward Island", "The Merck Veterinary Manual: Overview of Ethylene Glycol Toxicity", "General properties, irritant and toxic actions of ethylene glycol", "Concise International Chemical Assessment Document 22: Ethylene Glycol: Environmental Aspects", "Preliminary Data Summary: Airport Deicing Operations (Revised)", "Glycol Mitigation Strategies: The Canadian Approach". C Urinary Crystals. Klein-Schwartz Grauer et al. et al. McMillin 2. Large anion gap acidosis is usually present during the initial stage of poisoning. The most definitive and direct method to detect ethylene glycol poisoning is gas chromatography-mass spectrometry, or GC-MS.  It is only used in the presence of a toxic dose of another poison or drug. However, you'd have to think of antifreeze poisoning in the first place to think to do the test. The glycolic acid is then metabolized to glyoxylic acid and finally to oxalic acid. Antifreeze Poisoning (Ethylene Glycol Poisoning) Drugs Scan (Comprehensive Drugs Scan ) Cyanide Poisoning Detection; We are ready to serve you NOW!  Detailed mitigation plans include storage and handling issues (p. 27), spill response procedures, and measures taken to reduce volumes of fluid (p. Ethanol acts by competing with ethylene glycol for alcohol dehydrogenase, the first enzyme in the degradation pathway. Standefer , Ethylene glycol involved in aircraft de-icing and anti-icing operations is released onto land and eventually to waterways. If a dark blue color forms in the pouch there is ethylene glycol present in the sample. Urine Fluorescence Using a Wood's Lamp to Detect the Antifreeze Additive Sodium Fluorescein: A Qualitative Adjunctive Test in Suspected Ethylene Glycol Ingestions.  Numerous cases of poisoning have been reported since then, and it has been shown to be toxic to humans. Without oxalic acid formation, the nephrotoxic effects can be avoided, but the ethylene glycol is still present in the body. Hewlett  Some people put antifreeze into their cabin's toilet to prevent it from freezing during the winter, resulting in toxicities when animals drink from the toilet.  Fomepizole has been shown to be highly effective as an antidote for ethylene glycol poisoning.  The rate-limiting step in this cascade is the conversion of glycolic to glyoxylic acid. , Other laboratory abnormalities may suggest poisoning, especially the presence of a metabolic acidosis, particularly if it is characterized by a large anion gap. Ethylene glycol is poisonous. The Catachem assay is based on a bacterial enzyme, glycerol dehydrogenase.5–7 This enzyme oxidizes ethylene glycol in the presence of NAD (nicotinamide adenine dinucleotide), generating NADH (the reduced form of NAD), resulting in an increase in absorbance at 340 nm, which is detected spectrophotometrically by automated chemistry analyzers.  People receiving ethanol therapy also require frequent blood ethanol concentration measurements and dosage adjustments to maintain a therapeutic ethanol concentration.  The toxic mechanism of ethylene glycol poisoning is mainly due to the metabolites of ethylene glycol. That is roughly 16 mL of 50% ethylene glycol for an 80 kg adult and 4 mL for a 20 kg child. This depression appears similar to ethanol intoxication, but without the characteristic odor of alcohol. Dogs like sweet things. 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.  Hemodialysis also has the added benefit of correcting other metabolic derangements or supporting deteriorating kidney function. JM  A report prepared for the World Health Organization in 2000 stated that laboratory tests exposing aquatic organisms to stream water receiving runoff from airports have shown toxic effects and death (p. The gap is caused by the presence of osmotically active particles (eg, ethylene glycol) in the serum that are not factored into the above equation. N The ethylene glycol in antifreeze affects the central nervous system first. Stage 3 (24 to 72 hours) kidney failure is the result of ethylene glycol poisoning. The preferred assays are summarized in Table 1. ", In Canada, Environment Canada reports that "in recent years, management practices at Canada’s major airports have improved with the installation of new ethylene glycol application and mitigation facilities or improvements to existing ones. Ethylene glycol is a type of alcohol found in automotive and household products. Juenke et al. The assay needs to be embraced by laboratorians to confirm its validity in identifying this serious form of intoxication, which constituted 2% of poisonings reported in the United States in 1999.9. Initially it is metabolized by alcohol dehydrogenase to glycolaldehyde, which is then oxidized to glycolic acid by aldehyde dehydrogenase. for a 20 kg child. , The orally lethal dose in humans has been reported as approximately 1.4 mL/kg of pure ethylene glycol. The advantage of this automated assay over the GC method is a substantial decrease in labor costs and a significant reduction in turnaround times by approximately 10 hours. In addition to an increase in the osmolal gap and anion gap acidosis, ethylene glycol ingestion can result in a positive urine analysis for the presence of calcium oxalate crystals (monohydrate and dihydrate) because it is converted to oxalate, which can chelate calcium and result in hypocalcemia. Blackwell  Ethylene glycol is not well absorbed through skin meaning poisoning following dermal exposure is also uncommon. While there are differences between methanol and ethylene glycol poisoning, there is substantial overlap, and both the similarities and differences are described below. Libeer  The preferred antidote is fomepizole with ethanol used if this is not available.  However, these numbers may underestimate actual numbers because not all cases attributable to ethylene glycol are reported to poison control centers. et al. Devleeschouwer In addition, methanol, ethanol, and ethylene glycol also result in an increase in metabolic acidosis with an increased anion gap, separating them from isopropanol. Differential Diagnosis of Alcohol Poisoning. L , Signs of ethylene glycol poisoning depend upon the time after ingestion. The presence of a large osmolal gap supports a diagnosis of ethylene glycol poisoning. Litovitz , The increased osmolal gap is caused by the ethylene glycol itself. The goal of pharmacotherapy is to prevent the formation of these metabolites. LA The presence of calcium oxalate or hippurate crystals in the urine, together with an elevated anion gap or osmolal gap, strongly suggests ethylene glycol poisoning (Albertson 1999). The major toxic alcohols that pose a risk to human health and for which measurement of levels is requested from the clinical laboratory include ethanol, ethylene glycol, isopropanol, and methanol. In this situation stabilization of the person including airway management with intubation should be performed in preference to gastrointestinal decontamination.  Hemodialysis may also be used in those where there is organ damage or a high degree of acidosis. , The kidney toxicity of ethylene glycol occurs 24 to 72 hours post ingestion and is caused by a direct cytotoxic effect of glycolic acid. , Ethylene glycol has been shown to be toxic to humans and is also toxic to domestic pets such as cats and dogs. GA However, these instruments and the needed expertise are not readily available in most clinical laboratories. McKay  People who present early to medical facilities and have prompt medical treatment typically will have a favorable outcome.  The most significant long-term complication is related to the kidneys. Hardy The toxicity of ethylene glycol comes from its metabolism to glycolic acid and oxalic acid. AH Also, assays for glycolic acid need to be more readily available because levels correlate with symptomatology and mortality.  Many cases of poisoning are the result of using ethylene glycol as a cheap substitute for alcohol or intentional ingestions in suicide attempts. Ethylene glycol itself is not toxic, but it is metabolized in the animal's body to several extremely toxic chemicals that are responsible for its potentially lethal effects. PI  In this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap. For ethylene glycol, the preferred method is GC–flame ionization detection (FID). For full access to this pdf, sign in to an existing account, or purchase an annual subscription. , In the U.S., airports are required to obtain stormwater discharge permits and ensure that wastes from deicing operations are properly collected and treated. When using antifreeze products containing ethylene glycol, recommended safety measures include: The most important initial treatment for ethylene glycol poisoning is stabilizing the person. Although survival with medical treatment has occurred with doses much higher than this, death has occurred with 30 mL of the concentrate in an adult.  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 presentation of the person. As ethylene glycol is rapidly absorbed, gastric decontamination is unlikely to be of benefit unless it is performed within 60 minutes of ingestion.  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 those who are malnourished or alcoholic. Ethanol Therapy for Ethylene Glycol and Methanol Toxicity Did you know? For ethylene glycol, the preferred method is GC–flame ionization detection (FID).  Other sources of ethylene glycol include windshield deicing agents, brake fluid, motor oil, developing solutions for hobby photographers, wood stains, solvents, and paints.  The process of biodegrading of glycols also increases the risk to organisms, as oxygen levels become depleted in surface waters (p.  In 2006, approximately 1540 kilotonnes of ethylene glycol were manufactured in Canada by three companies in Alberta, with most of the production destined for export. They have taste buds that detect sugars just like we do. As the ethylene glycol is metabolized, animals often appear to recover from the direct effects of the poisoning only to rapidly deteriorate as glycolic acid concentration builds. They both have a high boiling point, low vapour pressure, excellent heat transfer abilities and the ability to depress the freezing point of water, but ethylene glycol is a slightly more effective freezing point depressant.  Considering factors such as the "seasonal nature of releases, ambient temperatures, metabolic rates and duration of exposure", Environment Canada stated in 2014 that "it is proposed that ethylene glycol is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity".  Antifreeze products sometimes have a substance to make it bitter added to discourage drinking by children and other animals but this has not been found to be effective. TL Calcium oxalate crystalluria may be observed as early as 3 and 6 hr after ingestion in cats and dogs, respectively. Furthermore, there seemed to be no interference with glycerol under the defined assay conditions. Thus, while the tests provide valuable clues to clinicians for differential diagnosis, measurement of the relevant alcohol is the most definite test to rule in or exclude a certain alcohol poisoning or ingestion. Testing for antifreeze (ethylene glycol) in water is quick and easy. J Tm'cd clin Tm-cot 1995;33:553. The advent of this modified enzymatic assay goes a long way in enhancing the role of the laboratory in the management of the life-threatening condition, ethylene glycol poisoning. This testing method is very accurate, but not always available in the middle of the night.  Long term outcomes may include kidney failure and brain damage. MA Ethylene glycol poisoning usually occurs due to ingestion, and its toxicity is mediated by its metabolites, glycolic acid, and oxalate.  Airports that discharge the collected aircraft deicing fluid directly to waters of the U.S. must also meet numeric discharge requirements for chemical oxygen demand. , Ethylene glycol has a low vapor pressure; it does not evaporate readily at normal temperatures and therefore high concentrations in air or intoxication are unlikely to occur following inhalational exposures. Future studies will need to confirm the performance and usefulness of this automated testing in other clinical laboratories. R  These studies did not focus on poisoning of domestic pets or livestock, for example, or inadvertent exposure to bittered antifreeze among a large population (of non-preschool age children).  Alternatively, people presenting late with signs and symptoms of coma, hyperkalemia, seizures, or severe acidosis have a poor prognosis.  Diagnosis may be confirmed by measuring ethylene glycol levels in the blood; however, many hospitals do not have the ability to perform this test. Eosinophilia/Hypereosinophilia in the Setting of Reactive and Idiopathic Causes, Well-Defined Myeloid or Lymphoid Leukemias, or Germline Disorders: About American Journal of Clinical Pathology, About the American Society for Clinical Pathology, Receive exclusive offers and updates from Oxford Academic, Copyright © 2020 American Society for Clinical Pathology. FK 13). The detection of glycolic acid is only of use in the setting of a delayed presentation where the entire parent ethylene glycol has been metabolized. The U.S. Environmental Protection Agency generally puts substances which are lethal at more than 30 g to adults in Toxicity Class III.  An outbreak of deaths in 1937 due to a medication mixed in a similar compound, diethylene glycol, resulted in the Food, Drug, and Cosmetic Act of 1938 in the United States, which mandated evidence of safety before new medications could be sold. https://en.wikipedia.org/w/index.php?title=Ethylene_glycol_poisoning&oldid=996426608, Toxic effects of substances chiefly nonmedicinal as to source, CS1 maint: DOI inactive as of December 2020, Articles with dead external links from September 2017, Articles with permanently dead external links, Short description is different from Wikidata, Articles with unsourced statements from July 2019, Articles lacking reliable references from October 2012, Wikipedia articles needing clarification from March 2012, Wikipedia medicine articles ready to translate, Creative Commons Attribution-ShareAlike License, Stage 1 (30 minutes to 12 hours) consists of. , In addition to antidotes, an important treatment for poisoning is the use of hemodialysis.  The treatment is generally the same, although vodka or rectified spirits may be substituted for pharmaceutical grade ethanol in IV injections.  That is approximately 224 mL (7.6 oz.)  Once kidney failure develops, the prognosis is poor. 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. This unit of measurement was derived by the British Navy when it was suspected that the rum ration was being diluted. Hemodialysis is used to enhance the removal of unmetabolized ethylene glycol, as well as its metabolites from the body. Thus, for methanol and isopropanol, gas chromatography (GC) is the confirmatory assay. We are aware of only 4 hospital laboratories in California that can perform this test on a \"stat\" basis. Letter to the Editor 111 REFERENCES 1. Drowsiness or coma ] early symptoms include intoxication, but the ethylene present! 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