ETHYLENE GLYCOL
General Information
| Mainterm | ETHYLENE GLYCOL |
| CAS Reg.No.(or other ID) | 107-21-1 |
| Regnum |
175.105 175.300 175.320 176.180 175.390 177.1500 177.1630 176.210 176.300 177.1390 177.2420 177.1680 177.1315 172.820 177.1637 177.1320 178.1345 |
From www.fda.gov
Toxicity Profile
| Route of Exposure | Oral ; dermal |
|---|---|
| Mechanism of Toxicity | Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids. Ethylene glycol produces central nervous system depression. The glycol probably causes the initial CNS depression; oxalate and the other intermediates seem to be responsible for nephrotoxicity. Glycoaldehyde and glyoxylate may be the principal metabolites responsible for EG nephrotoxicity and do so by causing ATP depletion and phospholipid and enzyme destruction. Glycine and acidosis, by-products of EG metabolism, can attenuate glyoxylate-mediated injury. This suggests that naturally occurring but incomplete protective pathways may be operative during the evolution of EG cytotoxicity. |
| Metabolism | The main steps in degradation of ethylene glycol are as follows: ethylene glycol--> glycoaldehyde--> glycolic and glyoxylic acid. Glyoxylic acid is then metabolized into a number of chemicals that have been identified in expired air, urine, or blood. The metabolism of ethylene glycol to glycoaldehyde is mediated by alcohol dehydrogenase. Glycoaldehyde is metabolized to glycolic acid by aldehyde oxidase or to a lesser extent to glyoxal. Glyoxal is changed both to glycolic acid in the presence of lactic dehydrogenase, aldehyde oxidase, or possibly both enzymes, and to glyoxylic acid via some oxidative mechanism. The main path of the degradation of glycolic acid is to glyoxylic acid. This reaction is mediated by lactic dehydrogenase or glycolic acid oxidase. Once glyoxylic acid is formed, it is apparently degraded very rapidly to a variety of products, a few of which have been observed. Its breakdown to 2-hydroxy-3-oxoadipate it is thought, is mediated by thiamine pyrophosphate in the presence of magnesium ions. The formation of glycine involves pyridoxal phosphate and glyoxylate transaminase, whereas the formation of carbon dioxide and water via formic acid apparently involves coenzyme A (CoA) and flavin mononucleotides. Oxalic acid formation from glyoxylic acid, has been considered to be the results from the action of lactic dehydrogenase or glycolic acid oxidase. |
| Toxicity Values | LD50: 4700 mg/kg (Oral, Rat) LD50: 5010 mg/kg (Intraperitoneal, Rat) LD50: 3260 mg/kg (Intravenous, Rat) LD50: 2800 mg/kg (Subcutaneous, Rat) LD50: 9530 mg/kg (Dermal, Rabbit) |
| Lethal Dose | |
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
| Minimum Risk Level | Acute Inhalation: 2 mg/m3 Acute Oral: 0.8 mg/kg/day |
| Health Effects | Health effects of ethylene glycol poisoning include tachycardia, hypertension, hyperventilation, and metabolic acidosis. Stage 3 of ethylene glycol poisoning is the result of kidney injury, leading to acute kidney failure. Oxalic acid reacts with calcium and forms calcium oxalate crystals in the kidney (L1023). |
| Treatment | Initial treatment consists of stabilizing the patient and gastric decontamination. Gastric lavage or nasogastric aspiration of gastric contents are the most common methods employed in ethylene glycol poisoning. Ipecac-induced vomiting or activated charcoal. The antidotes for ethylene glycol poisoning are ethanol or fomepizole; antidotal treatment forms the mainstay of management following ingestion. Ethanol (usually given IV as a 5 or 10% solution in 5% dextrose and water, but also sometimes given in the form of a strong spirit such as whisky, vodka or gin) acts by competing with ethylene glycol for the enzyme alcohol dehydrogenase thus limiting the formation of toxic metabolites. Fomepizole acts by inhibiting alcohol dehydrogenase, thus blocking the formation of the toxic metabolites. |
| Reference |
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From T3DB