It boils at 197 degrees C, in case you ever want to boil some. Ethylene glycol is more toxic to humans than animals, and in general the susceptible species are those which metabolize the compound to oxalic acid, although this is quantitatively a minor route. This glycolic acid cannot be metabolised in an acid-scavenging way, like lactate or ketones. The lungs show oedema, and occasionally calcium oxalate crystals and degenerative myocardial changes may also occur. DePass LR, Garman RH, Woodside MD, Giddens WE, Maronpot RR, Weil CS. The extra osmoles represent some mixture of ethylene glycol and glycolic acid, eagerly water-soluble, and thus rapidly dialysed. Ethylene glycol metabolism generates glycolate, which can be mistaken for lactate by portable lab assays utilizing lactate oxidase. ternative metabolism of toxic alcohols to non-toxic metabolites. • Supportive care (correct fluid, acid-base, and electrolyte imbalances). Neither as exciting as intravenous alcohol, nor as expensive as fomepizole, continous veno-venous haemodiafiltration is the method of choice for getting rid of huge quantities of ethylene glycol rapidly. Clinical toxicology 36 (7): 659–66. C. Ethylene glycol is … Chronic toxicity and oncogenicity studies of ethylene glycol in rats and mice. Adolphe Wurtz (1856) "Sur le glycol ou alcool diatomique" (On glycol or diatomic alcohol), Comptes rendus, 43 : 199-204. OVERVIEW >1 mL/kg or a mouthful in a child is potentially lethal 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. "Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. B. Propylene glycol is metabolized to more toxic compounds. Good old alcohol, in large quantities, will overwhelm alcohol dehydrogenase, saturating it. The conversion to glycolic acid is somewhat rapid. The parent compound is osmotically active, and is responsible for the increased osmolality observed in the early course of exposure prior to metabolism. As it has a sweet. The first step is catalysed by the enzyme alcohol dehydrogenase and herein lies the key to treatment of poisoning. GA and EG are currently produced by chemical synthesis, but their biotechnological production from renewable resources has received a substantial interest. These toxic substances also affect the cardiopulmonary system and can cause renal failure. glucose metabolism, Krebs' cycle, protein synthesis, RNA synthesis and DNA replication for example. T he detection of calcium oxalate crystals in the urine is often stated to be a useful guide but this is wrong. The products of these metabolic pathways are then really eliminated. However, there is one case series of three poor fools who have admitted to injecting alcohol (ranging from vodka to beer, dosage unknown) and whose veins did not suffer excessively as a consequence, in spite of what i can only assume was suboptimal injecting technique. Ethylene glycol, the parent compound, is inebriating but generally considered nontoxic. Apparently, it gives one a buzz similar to that of alcohol intoxication. 4-Methylpyrazole, or fomepizole as it is known, is basically a competitive antagonist to alcohol dehydrogenase. Both susbtances are well removed by dialysis, and on top of that one can adjust the bicarbonate concentration of the dialysate to donate extra bicarbonate to the patient's bloodstream, increasing the correction of the acidosis even further. In 1977, Clay and Murphy poisoned some monkeys and revealed that the serum bicarbonate levels decreased in proportion to rising glycolic acid levels. It is only the most common toxin among a  whole family of glycols: Typically, people drink this stuff. Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication. The contribution of all the other metabolites was negligible. Such a thing indeed exists, but is not well studied. There are two proposed mechanisms of propylene glycol metabolism: The first is as follows: Ethylene glycol is transformed in the liver by alcohol dehydrogenase to glyceraldehyde. The metabolism of [1,2-(14)C]-ethylene glycol and [1,2-(14)C]-glycolic acid was studied in vitro using precision-cut tissue slices prepared from the livers of female Sprague-Dawley rats, New Zealand white rabbits and humans. The rate-limiting step of ethylene glycol metabolism is the ADH-catalyzed step. We found that strain JM37 grew rapidly with ethylene glycol as a sole source of carbon and energy, while strain KT2440 did not grow within 2 days of incubation under … Litovitz T. More than 6 per cent of poisonings involve alcohols and glycols, reflecting their availability in a wide range of household products, including aftershave, brake fluid, gas line antifreeze, model airplane fuel, mouthwash, rubbing alcohol, and windshield washing solution. Metabolism: Ethylene glycol is metabolised in the liver. If untreated, ingestion of only 30 to 60 mls may be sufficient to cause permanent organ damage or death. The American Journal of Medicine 57.1 (1974): 143-150. Lactate gap refers to the difference in lactate measurement via different methods: Elevated lactate on portable blood gas machine utilizing lactate oxidase. Here, we analyzed the metabolism of ethylene glycol. This is mainly because A. Absorption of propylene glycol from the gastrointestinal tract is slow. By Katzung et al. Some redness and burning at the site were the only reported side effects. This increases its clearance, and keeps it out of the fatty central nervous system, where its effects are the most destructive (specifically, the effects on the tender juicy retina). c Between 24 and 72 h the kidneys become damaged giving rise to flank pain and acute renal tubular necrosis. The result of each of the metabolic steps is the production of NADH. DEG has also been inappropriately substituted in pharmaceutical preparations for nontoxic constituents, resulting in more than a dozen epidemics of human poisoning, with resultant … b intravenous sodium bicarbonate; this corrects the acidosis—animal studies have shown that this increases the LD50 by around four times c calcium gluconate; this corrects the hypocalcaemia d dialysis to remove ethylene glycol. Ingestion of sufficient amounts is fatal if untreated. Suppression of metabolism – fomepizole and IV ethanol are temporizing measures; Removal of toxin – haemodialysis; Alkalinisation in order to counteract metabolic acidosis (Na bicarbonate) Folic acid and folinic acid may be useful adjuncts (but does not directly improve patient’s clinical state) Ethylene glycol. The rationale for the use of bicarbonate is the massive generation of acid by the metabolism of ethylene glycol. Recent analyses demonstrated fundamentally different ways for oxidation of 1,2-propanediol and 2,3-butanediol. Previous chapter: Urate and hippurate anions: their origins and clearance, Next chapter: Diabetic, alcoholic and starvation ketoacidosis. 1. These alcohol-related intoxications can present with high anion gap metabolic acidosis and increased osmolality. However, like all other glycols it is is rapidly absorbed, even through the gastric mucosa. Ameera S. Mahdi and Andrew J. McBride INTRAVENOUS INJECTION OF ALCOHOL BY DRUG INJECTORS: REPORT OF THREE CASES; Alcohol and Alcoholism (1999)  34(6): 918-919. Toxicology and applied pharmacology 39.1 (1977): 39-49. More bicarbonate must be added in order to buffer the excessive number of hydrogen ions present in the patient, so that H2O and CO2 may be generated. N Engl J Med 1981;304:976-8. Glycolic acid is further metabolised to glyoxylic acid and oxalic acid. Of the various ways one can become acquainted with ethylene glycol, this is probably the most common. The investigation of its microbial metabolism therefore provides insights into the environmental fate of this pollutant and also enables its utilization … In this study, we investigated the metabolism of ethylene glycol in the Pseudomonas putida strains KT2440 and JM37 by employing growth and bioconversion experiments, directed mutagenesis, and proteome analysis. A lot of this information comes from “Goodman & Gilman's The Pharmacological Basis of Therapeutics” 11th ed by Brunton et al,and   “Basic & Clinical Pharmacology” 11th ed. The mechanism of metabolic acidosis is more interesting. Traditionally, gastric lavage or nasogastric aspiration of gastric contents are the most common methods employed in ethylene glycol poisoning. The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples this does not involve metabolic activation to a reactive metabolite. It is not well absorbed through the skin; nor does it evaporate particularly well. "On the metabolic acidosis of ethylene glycol intoxication." 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. Several deaths are recorded annually in the U.S. alone. One can imagine some sort of cyclical nightmare of ethylene glycol intoxication, ICU admission, discharge and re-intoxication. If ingestion was recent (1-2 hours), vomiting is induced and activated charcoal is given to reduce further absorption of the ethylene glycol. However, like all other glycols it is is rapidly absorbed, even through the gastric mucosa. First you may feel slightly drunk for about 4 hours. Competes with ethylene glycol for metabolism via alcohol dehydrogenase (ADH) enzyme. Otherwise, much of it is metabolized into hideous daughter-compounds, which are also ex… Henderson, William R., and Jeffrey Brubacher. Methanol and ethylene glycol metabolism can be understood by first studying the metabolism of ethanol, which occurs in two steps: Ethanol is oxidized to acetaldehyde with production of NADH by alcohol dehydrogenase, an enzyme located, for the most part, in the cytosol of hepatocytes (see Chapter 24 ). 1986 Nov;7(4):547-65. It is first converted by alcohol dehydrogenase to glycoaldehyde, which is then metabolised to glycolic acid by aldehyde dehydrogenase. Anything over 0.1ml/kg will require treatment. The elevated NADH to NAD ration causes the conversion of pyruvate pyruvate to lactate. Cjem 4.1 (2002): 34-40. To summarize, you give massive amounts of bicarbonate, and then you either start an ethanol infusion, regular doses of fomepizole, or haemodialysis. At this stage, there is no acidosis, but the anion gap is widened (unmetabolised ethylene glycol floods the bloodstream). b Between 12 and 24 h there is tachypnoea, tachycardia, hypertension, pulmonary oedema and congestive cardiac failure. Pediatr Clin North Am. "Methanol and ethylene glycol poisoning: a case study and review of current literature." ", Ethanol for ethylene glycol poisoning [letter. Permanent optic atrophy may occur. (See supplemental page for metabolic pathway figures for ethylene glycol and methanol). On the first admission, glycolic acid was detected in his blood and he was diagnosed as having ethylene glycol intoxication. Journal of toxicology. Ethylene glycol and its toxic acid metabolytes, "On the metabolic acidosis of ethylene glycol intoxication.". The treatment of poisoning with ethylene glycol reflects the mechanism and biochemical effects. We found that strain JM37 grew rapidly with ethylene glycol as a … "Methanol and ethylene glycol poisoning: a case study and review of current literature. 1) 4-methylpyrazole (4-MP)[Antizole or fomepazole]: This medication inactivates alcohol dehydrogenase. Ethylene glycol is moderately toxic, with an oral LDLo = 786 mg/kg for humans. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation. Elimination: Ethylene glycol has an elimination half-life of about 3 hours. Ethanol for ethylene glycol poisoning [letter]. An additional benefit is the effect of "ion trapping" formic acid. polyethylene glycol. It does what ethanol would do, except it does so with great expense, and without ethanol intoxication. In the parlance of the street cop, this equates to a blood alcohol level of 0.1%, twice the legal driving limit in Australia. The authors (who did not identify themselves) suggested a loading dose of 0.6g per kg body weight, or roughly 40g for a 70kg male, to get to 100mg/dL. The next stage is that of cardiac toxicity. The consequences of this are as follows: i acidosis due to lactate, oxalate and the other acidic metabolites; this results in metabolic distress and physiological changes ii loss of calcium as calcium oxalate iii deposition of crystals of calcium oxalate in the renal tubules and brain iv inhibition of various metabolic pathways leading to accumulation of organic acids v impairment of cerebral function by oxalate and damage by crystals; also some of the aldehyde metabolites may impair cerebral function vi damage to renal tubules by oxalate crystals leading to necrosis. The most important initial treatment for ethylene glycol poisoning is stabilizing the person. Common ethyl alcohol (ethanol) binds much more easily to ADH than ethylene glycol or methanol does. Indications: Ethylene glycol levels > 20 mg/dL Thus, if you suspect you have accidentally poisoned yourself with ethylene glycol, one may consider four shots of spirits as a rescue therapy. 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