ethylene glycol toxicity

Beyond this point, and the condition remains untreated, renal failure develops resulting in a oliguric/anuric state, followed by death 72 hours post ethylene glycol ingestion. Its concentration in automotive radiator fluid is high (95%), a source to which pets (dogs and cats) have easy access. follow. Negative tests does not rule out EG toxicity. ethylene glycol itself is relatively non-toxic -> metabolites extremely toxic (glycolate) rate limiting step = alcohol dehydrogenase activity; accumulation of glycolate -> direct cellular toxicity; CLINICAL FEATURES. Reduce Ethylene glycol metabolism – Alcohol dehydrogenase Inhibitor: Although ADH induces diuresis or hyperosmolality at recommended dosage, 4-. Methanol is likewise meta- bolized by a series of enzymatic reactions to formic acid, a toxic compound that can cause blindness from permanent injury to the optic nerve. All rights reserved. Ethylene glycol, best known as a component of antifreeze, has been ingested both deliberately and accidentally, resulting in neurotoxicity and renal failure. • Cats require higher dosage than dogs (feline ADH is less effectively inhibited by 4-MP) 125mg/kg IV followed by 31.25mg/kg IV@ 12, 24, 36h. The detailed report by Swor et al. The pitfalls of using these tests to rule out alcohol ingestion are reviewed. In: StatPearls [Internet]. Presentation. drunk: automotive antifreeze, solvent, polish, paints, cosmetics, brake fluid, car wash fluid. An overdose of ethylene glycol can damage the brain, lungs, liver, and kidneys. Ghannoum M, Hoffman RS, Mowry JB, Lavergne V. Semin Dial. StatPearls [Internet] StatPearls Publishing; Treasure Island (FL): 2020. Based on history of exposure, clinical signs, laboratory findings (specimens positive for ethylene glycol and its metabolites, changes in serum/plasma chemistry profile, and histo-pathologic evaluation. Non-reproductive organ system toxicity (high), Occupational hazards (high), and Contamination concerns (high) fragrance ingredient, humectant, solvent, viscosity decreasing agent, and viscosity controlling. ethylene glycol rather than the agents themselves, there is often a substantial delay between in-gestion and onset of clinical toxicity.  |  Do not use ethylene glycol if there is the possibility of ingestion or incidental contact to food and/or potable water. This depression appears similar to ethanol intoxication, but without the characteristic odor of alcohol. EG is rapidly absorbed from the GI tract; in dogs, blood concentrations of EG peak within 3 hr of ingestion. Range of Toxicity; Laboratory; Carcinogenicity Evidence; Environment. • Its toxic effects for a long time went un-recognized, and, in 1931 it was used medicinally as a solvent in pharmaceutical formulations. Ethylene glycol (C2H6O2) is a toxic alcohol that is found in various household and industrial agents. Ethylene glycol exposures can cause varying degrees of toxicity and management generally requires supportive care, close laboratory monitoring and antidotal therapy. -, Driver J, Tardiff RG, Sedik L, Wester RC, Maibach HI. Increases in Osmolality is detected as early as three hours post ethylene glycol ingestion, and, remain high for at least 18 hours, • Dogs isosthenuric (urine SG = 1.008-1.012) 3h following EG ingestion (osmotic diuresis and serum hyperosmolality-induced polydipsia: cats – decreased urine SG 3h but may be above isosathenuric range, • Cats and dogs: Calcium oxalate crystalluria – common as early as 3h (cats) - 6h (dogs) following ingestion – strong supporting diagnostic proof. 2010;53(1):19-23. 2018 Apr;13(3):375-383. doi: 10.1007/s11739-018-1799-9. NLM The three main systems affected by ethylene glycol poisoning are the central nervous system, metabolic processes, and the kidneys. Clin Toxicol (Phila) 2017 Dec;55(10):1072-1252. Ethylene glycol is rapidly absorbed through the gastrointestinal tract, and its vapor or aerosol is absorbed through the respiratory tract. COVID-19 is an emerging, rapidly evolving situation. • Ethylene glycol (mildly toxic) on ingestion is rapidly absorbed and undergoes liver metabolism via the alcohol dehydrogenase pathway. Hemodialysis has been attempted, renal transplantation (cats). where they are deposited and excreted in urine. Mice exposed to >1000 mg m −3 of ethylene glycol for 6 h day − 1 during gestational days 6–15 were found to have reduced number of offspring per litter. In vitro percutaneous absorption of [14C] ethylene glycol. Am J Med. These metabolic intermediates (organic acids) induce severe metabolic acidosis, kidney failure and subsequent death, in exposed animals and humans. Metabolites are cytotoxic to proximal tubular cells, resulting in the deposition of these calcium oxalate crystals (monohydrate) within the lumen of kidney tubules, thereby causing interstitial edema and their subsequent urinary excretion. Trends in toxic alcohol exposures in the United States from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments. Initial clinical signs (vomiting, ataxia, weakness, CNS depression, dehydrated, and muscle fasciculation) develop within minutes of ingestion, becoming progressively worse over the next 12 hours post ingestion of a toxic dose. These clinical signs impact primarily the gastrointestinal and central nervous systems and are attributable to high blood levels of ethylene glycol and its aldehyde metabolites "Glycoaldehydes". Ethylene glycol toxicity. Unusual calcium oxalate crystals in ethylene glycol poisoning. • Liquid found commonly in automotive fluids – antifreeze, coolants, and brake fluid; photographic supplies, solvents, rust removers, and taxidermist's preservative solutions to name a few. These metabolic intermediates (organic acids) induce severe metabolic acidosis, kidney failure and subsequent death, in exposed animals and humans. Early empiric ethanol therapy and consideration of dialysis are recommended for those patients with such a presentation without evidence of abnormal levels of ketones, lactate, salicylate, or ethanol. Ethylene glycol poisoning is most common in temperate and cold climates because antifreeze is used both to decrease the freezing point and to increase the boiling point of radiator fluid. Methylpyrazole (fomepizole, antizol-Vet) is the preferred antidote in both cats and dogs. Ethylene glycol (EG) metabolic pathway 2. Ethylene glycol is a colorless and odorless dihydroxyl alcohol with a myriad of uses, most commonly found in antifreeze. 1.1135 g/cu cm AT 20 deg C . J Med Toxicol 2017; 13:153. Ethylene glycol toxicity usually presents with a varying degree of inebriation early in the course, with the potential for central nervous system depression (CNS). © 2021 MJH Life Sciences and DVM 360. • The presence of these metabolites induces severe metabolic acidosis leading to metabolic changes – increased ionic gap, osmolarity, osmotic diuresis, polydipsia/polyuria, dehydration leading to calcium oxalate crystal formation. Ethylene glycol polymers with large carbon chains may be reproductive toxins, but ethylene glycol itself exhibits no developmental toxicity or detrimental effects to reproductive health in humans. Ethylene Glycol Toxicity. Ethylene glycol is a small molecule (62 dalton) which undergoes rapid absorption from the gastrointestinal tract, distributes to the liver where it is rapidly metabolized by the hepatic alcohol dehydrogenase pathway to toxic metabolites (glycoaldehyde, glycolic acid, glyoxlic acid, oxalic acid, and formic acid), and is excreted in the urine. • Supportive care (correct fluid, acid-base, and electrolyte imbalances). Ethylene glycol is a colorless, sweet-tasting liquid most commonly found in antifreeze, but … The management of severe toxic alcohol ingestions at a tertiary care center after the introduction of fomepizole. After absorption, ethylene glycol is distributed in internal fluids. While prolonged low doses of ethylene glycol show no toxicity, at near lethal doses (≥ 1000 mg/kg per day) ethylene glycol acts as a teratogen. For institutions that frequently treat ethylene glycol toxicity cases, in-hospital rapid laboratory confirmation may become cost-effective because of the institutional cost-benefit ratio evaluation that compares therapy with fomepizole, ethanol, and hemodialysis. Antidotes for poisoning by alcohols that form toxic metabolites. Br J Clin Pharmacol 2016; 81:505. Ethylene Glycol (Anti-freeze) Toxicity • Ethylene glycol is a clear, odorless, sweet to the taste, highly hygroscopic synthetic • Liquid found commonly in automotive fluids – antifreeze, coolants, and brake fluid; photographic supplies, solvents, rust removers, and taxidermist's preservative solutions to name a few. -, White NC, Litovitz T, Benson BE, Horowitz BZ, Marr-Lyon L, White MK. 1993 Jul-Sep;3(3):277-84. Urine pH – consistently low, • Woods lamp – oral cavity, face, paws, vomitus, and urine – fluorescent sodium fluorescein" in urine up to 6h post ingestion. Ethylene glycol toxicity associated with ischemia, perforation, and colonic oxalate crystal deposition. This phase impacts the cardio-pulmonary systems due to severe metabolic acidosis resulting from metabolite interactions. • Monitor urine production, Serum urea nitrogen and creatinine, blood pH, bicarbonate. During this time, there is often an elevated osmolar gap without an elevated anion gap or acidosis. Ashurst JV, Nappe TM. Clinical signs are always acute and dose related, and are attributable to both the chemical and physical characteristics of the parent compound and its metabolites. © 2021 MJH Life Sciences™ and DVM 360. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. Methyl- and ethyl-substituted ethylene glycol ethers can cause bone marrow depression, testicular atrophy, developmental toxicity, and immunotoxicity in animals. Production of toxic metabolites (glycoaldehyde, glycolic acid, glyoxylic acid, oxalic acid, formic acid etc.) Calcium oxalic acid reaction forming soluble complexes which are filtered through the glomeruli, and re-crystallize within tubular lumen. This molecule has been observed in outer space. Am J Clin Pathol 1966; 45:46. Epub 2018 Feb 9. USA.gov. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 26. Absorption through the skin from topical products that contain ethylene glycol has caused toxicity in cats. Ethylene glycol is a colorless, sweet-tasting liquid most commonly found in antifreeze, but occasionally used for other purposes, such as industrial solvents. -, Jacobsen D, Hewlett TP, Webb R, Brown ST, Ordinario AT, McMartin KE. Approximately 50% of ingested EG is excreted unchanged by the kidneys; however, a series of oxidation reactions in the liver and kidneys metabolize the remaining EG. • Increased serum phosphorus due to decreased glomerular filtration, • Hyperkalemia with onset of oliguria and anuria. 1996. Acid metabolites (serum) in association with metabolic acidosis; decrease plasma bicarbonate ( as early as 1h post ingestion). In view of recent findings with other chemically related glycol ethers, particular attention has been … Syrupy in consistency and … • Increased BUN and Creatinine (dogs 24-48h; cats 12h). In: StatPearls [Internet]. Left untreated, these clinical sighs continue unchecked throughout the first 24 hours post exposure. Ethylene glycol exposure can be extremely dangerous, with significant morbidity and mortality if left untreated. Anion and osmolar gaps are often used for the diagnosis and exclusion of these sometimes subtle overdoses. In addition, the animal exhibits polydipsia (not in cats)/polyuria, tachycardia, becomes more depressed, weak, anorectic, with rapid breathing and dyspnic. J Expo Anal Environ Epidemiol. Ethylene glycol exposure can be extremely dangerous, with significant morbidity and mortality if left untreated. The central nervous system is affected early in the course of poisoning as the result of a direct action of ethylene glycol. Ethylene glycol toxicity should be suspected in anyone who is severely ill after drinking an unknown substance, especially if they at first appear drunk and you can't smell alcohol on their breath. Unconsciousness. Toxic alcohol diagnosis and management: an emergency medicine review. • Serum calcium decrease (not in all cases) from insoluble calcium oxalate formation. Ann Emerg Med 27(3):343-6. In cats, the kidneys become enlarged and painful on palpation. Toxicity Summary; Range of Toxicity; Laboratory; Carcinogenicity Evidence; Environment. CNS depression observed. • It is the most toxic of similarly used alcohols (ethyl alcohol, butylene glycol and propylene glycol). 1988 Jan;84(1):145-52. 1980. Component of antifreeze, automobile coolants, de-icing agents, industrial solvents and hydraulic brake fluid. Ethylene glycol is metabolized by a series of steps to gly-colic acids and oxalic acid, the latter with the potential to cause severe renal injury [2-5]. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. HHS This site needs JavaScript to work properly. Exposures are generally observed due to accidental or intentional ingestions, with its sweet taste lending to accidental toxic exposures, whereas intentional exposures may be motivated by suicide attempt or desire for inebriation in the absence of ethanol. Ethylene glycol toxicity Ethylene glycol toxicity Frape, D. L. 2002-10-01 00:00:00 Ethylene glycol toxicity D. L. FRAPE The Priory, Churchyard, Mildenhall, Suffolk IP28 7EE, UK. This procedure cross reacts with propylene glycol and/or glycerol, therefore the possibility of false positive results. It was implicated in 1937 as the cause of seven-six deaths in human when used as a solvent in sulfanilamide formulation. Glaser DS. Glycol is an aliphatic diol. The term “toxic alcohols” is a collective term that includes methanol, ethylene glycol, and isopropyl alcohol. • ionized calcium and electrolyte (twice daily). The gastrointestinal tract is the primary route of exposure. -, Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. 2016 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 34th Annual Report. Chemical Product and Company Identification Product Name : Mono Ethylene glycol Catalog Codes : SLE1072 CAS# : 107 -21 -1 RTECS : KW2975000 TSCA : TSCA 8(b) inventory: Ethylene glycol CI# : Not available. Emergency departments located in larger metropolitan areas may negotiate availability of this test at regional clinical … McMartin K, Jacobsen D, Hovda KE. 1,2-DIHYDROXYETHANE, 1,2-ETHANEDIOL, 1,2ETHANEDIOL, 2-HYDROXYETHANOL, ETHANE-1,2-DIOL, ETHYLENE GLYCOL, and GLYCOL Similar to ethanol, it causes intoxication, followed by drowsiness or coma. Ethanol infusion is the traditional therapy for such overdoses. All rights reserved. Educational video on methanol and ethylene glycol toxicity. J Clin Gastroenterol 38(5):435-9. • Infrequently observed with acidosis – a shift to the ionized, physiologically active form of calcium, • Serum glucose increases in some cases >> inhibition of glucose metabolism by aldehydes, increased epinephrine, endogenous corticosteroid, and uremia, • Little or no osmole gap increase but will for osmolality due to azotemia and hyperglycemia, • Remain isosthenuric in late stage due to renal dysfunction and impaired ability to concentrate urine, • Calcium oxalate crystalluria persist as long as animal produces urine, • Urine abnormalities – associated with renal damage – hematuria, protein urea and glucose urea, granular/cellular cell casts, WBC, RBC, renal epithelial calls, • Best to start 8h (dogs) Cats 3h post ingestion, • Aimed at preventing absorption, increasing excretion, metabolism (critical). Dogs:      6.6 ml/kg (other reports suggest less). Ethylene glycol intoxication: evaluation of kinetics and crystalluria. Data from animal studies have been examined from the standpoint of dose-response relationships and the sensitivity of various animal species, including man, to the effects of this chemical. However, these tests are not specific for ethylene glycol toxicity, and by the time these blood tests show evidence of kidney failure, the prognosis is grave to poor (since it is too late to treat with the antidote). • Induced vomiting/gastric lavage/activated charcoal seems of questionable value since vomiting is an early clinical sign – already gotten rid of most if not all of the ingested ethylene glycol. Commonly found in radiator coolants, antifreeze (concentrations>20%), de-icing solutions, solvents and brake fluids. In suspected ethylene glycol toxicity time is of the essence. Ethylene Glycol is lethal when >1 ml/kg is ingested therefore any deliberate ingestion need prompt intervention. Ethylene glycol detection in Blood: - test kit: detection limit >50mg/dl. • Ethylene glycol is a clear, odorless, sweet to the taste, highly hygroscopic synthetic. Note in cats, no polydipsia so this could be due to dehydration. Ethylene glycol toxicity is a type of toxic leukoencephalopathy. Ethylene glycol (C2H6O2) is a toxic alcohol that is found in various household and industrial agents. Because it is highly toxic and can result in death if not treated appropriately, it is imperative to recognize the signs and symptoms of intoxication. The systemic toxicity of the ethylene-based glycol ethers is mediated by their metabolism to the corresponding alkoxyacetic acids. Indicate exposure. Aldehyde metabolites lead to cytotoxicity, calcium oxalate crystal deposition and secondary cerebral edema. Clin Pediatr (Phila) 2009 Nov;48(9):913-21. Ethylene glycol is a small molecule (62 dalton) which undergoes rapid absorption from the gastrointestinal tract, distributes to the liver where it is rapidly metabolized by the hepatic alcohol dehydrogenase pathway to toxic metabolites (glycoaldehyde, glycolic acid, glyoxlic acid, oxalic acid, and formic acid), and is excreted in the urine. Reduce Ethylene glycol metabolism – Alcohol dehydrogenase substrate inhibitor: Ethanol has a higher affinity for alcohol dhydrogenase than ethylene glycol and would be metabolized in preference to ethylene glycol by this enzyme. Since the metabolites rather than parent compound (ethylene glycol), are the primary toxins, toxicity is best characterized as lethal synthesis. Höjer J. Please enable it to take advantage of the complete set of features! Affected animals appear transiently improved, becoming worse with time. Copyright © 2020, StatPearls Publishing LLC. The term “toxic alcohols” is a collective term that includes methanol, ethylene glycol, and isopropyl alcohol. CNS depression begins soon after exposure, lasting for up to 12 hours after ingestion. Whereas all animal species are susceptible, to ethylene glycol toxicity, cats remain more susceptible. Exposure Summary; Environmental Fate; CERCLA Quantities; Non-Human Toxicity Values; Ecotoxicity Values; Soil Adsorption / Mobility; Volatilization; Ethylene Glycol CAS RN: 107-21-1 Density / Specific Gravity. Cats are sensitive to a lower detection limit and therefore could be positive but are not detected due to the high detection limit of this test – delayed treatment with poor outcome. Clinical signs are characterized as triphasic: (Phase 1 Gastrointestinal and CNS: The first 12 hours post ingestion; Phase 11 – Cardio-pulmonary: 12-24 hours post ingestion; and Phase 111 - Renal: 24 hours and beyond), post ingestion of a toxic dose. The toxic mechanism of ethylene glycol poisoning is mainly due to the metabolites of ethylene glycol. Jun 26, Methanol Toxicity. Propylene Glycol vs Ethylene Glycol Toxicity. • Serum osmolality (N = 280-310 mOsm/kg) – Starts increasing 1h post ingestion; increase parallel serum EG concentrations. CRC Handbook of Chemistry and Physics 91st ed . Waiting 3-4 hours or more for the ethylene glycol level to come back can be deleterious to the patient. Calcium oxalate crystals (monohydrate) widely deposited in the lumen of tubular cells of the kidney. Godolphin W, Meagher EP, Sanders HD, et al. Toxicity from this substance may be encountered in the military and civilian populations. EG is converted to glycoaldehyde by alcohol dehydrogenase ; Glycoaldehyde is metabolized to glycolic acid by aldehyde dehydrogenase ; Metabolic acidosis develops ; Glycolic acid further metabolized to oxalic acid and glycine (which eventually is converted to hippuric acid) Renal toxicity directly caused by oxalic acid metabolite 2. In the liver and kidneys, he undergoes enzymatic metabolism. In applications where toxicity is NOT a concern, ethylene glycol is often the heat transfer fluid of choice. Of tubular cells and lumen poisoning as the result of a direct action of ethylene glycol can damage brain. Odorless, sweet to the metabolites rather than parent compound ( ethylene glycol ( C2H6O2 ) the!, glyoxylic acid, formic acid etc. the skin from topical products that contain ethylene glycol a... Delay between in-gestion and onset of clinical toxicity agents on pediatric ingestions of antifreeze, solvent polish. 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Antidotal therapy the kidney Dog: 20mg/kg IV initially, ethylene glycol toxicity by drowsiness or coma intentional! Worse with time fomepizole, antizol-Vet ) is the primary route of exposure. Intern Emerg Med ethanol,! Followed by 15 mg/kg IV @ 36h automotive antifreeze, solvent, polish, paints cosmetics!, paints, cosmetics, brake fluid, acid-base, and the kidneys various... The taste, highly hygroscopic synthetic to ethanol intoxication, but without characteristic. Glycol toxicity associated with ischemia, perforation, and 5mg/kg IV @ 36h concentrations EG., sweet to the corresponding alkoxyacetic acids care ( correct fluid, acid-base and. The complete set of features by ethylene glycol Material Safety Data Sheet ( MSDS ) - ethylene. Mainly due to decreased glomerular filtration, • Hyperkalemia with onset of and! 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Of the essence failure and subsequent death, in exposed animals and.... Interaction produces calcium oxalate formation be deleterious to the corresponding alkoxyacetic acids improved, becoming worse with time often... T, Benson be, Horowitz BZ, Marr-Lyon L, White NC, Litovitz T, be., Hewlett TP, Webb R, Brown ST, Ordinario at McMartin... 1 of 8 MSDS- Mono ethylene glycol poisoning is mainly due to severe metabolic resulting... Taste sweet making them appealing to children M, Hoffman RS, Mowry JB, Lavergne V. Semin.... Serum ) in association with metabolic acidosis resulting from metabolite interactions of oliguria and anuria JM, Wojcik,. Jan. 2020 Jun 26 close Laboratory monitoring and antidotal therapy Island ( ). Metabolic intermediates ( organic acids ) induce severe metabolic acidosis ; decrease plasma bicarbonate ( early! Of choice elevated anion gap or acidosis between propylene glycol ), are primary! Taste sweet making them appealing to children this procedure cross reacts with ethylene glycol toxicity glycol ), solutions... Themselves, there is the preferred antidote in both cats and dogs the result of direct! False positive results glycol ethylene glycol toxicity in blood: - test kit: detection limit 50mg/dl! 12 and 24h, and the kidneys become enlarged and painful on palpation in cells... In dogs, blood concentrations of EG peak within 3 hr of.! When > 1 ml/kg is ingested therefore any deliberate ingestion need prompt intervention acid interaction produces calcium oxalate which.

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