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. © 2021 MJH Life Sciences™ and DVM 360. Toxicity Summary; Range of Toxicity; Laboratory; Carcinogenicity Evidence; Environment. The impact of bittering agents on pediatric ingestions of antifreeze. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 26. 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 is a type of toxic leukoencephalopathy.  |  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. • Supportive care (correct fluid, acid-base, and electrolyte imbalances). These metabolic intermediates (organic acids) induce severe metabolic acidosis, kidney failure and subsequent death, in exposed animals and humans. -, Jacobsen D, Hewlett TP, Webb R, Brown ST, Ordinario AT, McMartin KE. • 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. Ethanol infusion is the traditional therapy for such overdoses. Unfortunately these products can taste sweet making them appealing to children. 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. Toxic alcohol diagnosis and management: an emergency medicine review. • Dog: 20mg/kg IV initially, followed by 15 mg/kg IV @12 and 24h, and 5mg/kg IV @ 36h. Non-reproductive organ system toxicity (high), Occupational hazards (high), and Contamination concerns (high) fragrance ingredient, humectant, solvent, viscosity decreasing agent, and viscosity controlling. 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. In applications where toxicity is NOT a concern, ethylene glycol is often the heat transfer fluid of choice. 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. • 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. Trends in toxic alcohol exposures in the United States from 2000 to 2013: a focus on the use of antidotes and extracorporeal treatments. In cats, the kidneys become enlarged and painful on palpation. 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. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. HHS In: StatPearls [Internet]. Jun 26, Methanol Toxicity. Glaser DS. Epub 2018 Feb 9. Absorption through the skin from topical products that contain ethylene glycol has caused toxicity in cats. • 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). Reduce Ethylene glycol metabolism – Alcohol dehydrogenase Inhibitor: Although ADH induces diuresis or hyperosmolality at recommended dosage, 4-. The primary treatments are either ethanol or fomepizole and, occasionally, dialysis. Since the metabolites rather than parent compound (ethylene glycol), are the primary toxins, toxicity is best characterized as lethal synthesis. Hodgman M, Marraffa JM, Wojcik S, Grant W. Serum Calcium Concentration in Ethylene Glycol Poisoning. Ethylene glycol exposure can be extremely dangerous, with significant morbidity and mortality if left untreated. After absorption, ethylene glycol is distributed in internal fluids. In: StatPearls [Internet]. Ann Emerg Med 27(3):343-6. 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. drunk: automotive antifreeze, solvent, polish, paints, cosmetics, brake fluid, car wash fluid. "Based on a rather extensive database, it induces skeletal variations and malformations in rats and mice by all routes of exposure." Its concentration in automotive radiator fluid is high (95%), a source to which pets (dogs and cats) have easy access. Ethylene glycol, hazardous substance in the household. Hemodialysis has been attempted, renal transplantation (cats). 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. 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). Ethylene glycol detection in Blood: - test kit: detection limit >50mg/dl. Methylpyrazole (fomepizole, antizol-Vet) is the preferred antidote in both cats and dogs. Propylene Glycol vs Ethylene Glycol Toxicity. Production of toxic metabolites (glycoaldehyde, glycolic acid, glyoxylic acid, oxalic acid, formic acid etc.) 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/. 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. Ethylene glycol (EG) metabolic pathway 2. The systemic toxicity of the ethylene-based glycol ethers is mediated by their metabolism to the corresponding alkoxyacetic acids. Ethylene glycol intoxication: evaluation of kinetics and crystalluria. 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. 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. The term “toxic alcohols” is a collective term that includes methanol, ethylene glycol, and isopropyl alcohol. All rights reserved. Ashurst JV, Nappe TM. 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. NLM Medical education. Ethylene glycol (C2H6O2) is a toxic alcohol that is found in various household and industrial agents. Ethylene glycol toxicity associated with ischemia, perforation, and colonic oxalate crystal deposition. Am J Clin Pathol 1966; 45:46. Ethylene glycol is a colorless, sweet-tasting liquid most commonly found in antifreeze, but … 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. Clin Toxicol (Phila) 2017 Dec;55(10):1072-1252. • 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. 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. 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. Antidotes for poisoning by alcohols that form toxic metabolites. The detailed report by Swor et al. Methyl- and ethyl-substituted ethylene glycol ethers can cause bone marrow depression, testicular atrophy, developmental toxicity, and immunotoxicity in animals. 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