Low inhalation hazard unless heated because of low vapor pressure.
Low acute toxicity. Probable lethal dose to humans is 0.5-5 g/kg. Causes nerve depression, liver and kidney lesions and anuria (urination retardation). Causes irritation to the gastrointestinal tract. Symptoms may include nausea, vomiting and diarrhea.
May be an irritant to skin on prolonged exposure.
May be an irritant to eyes and surrounding tissue.
Liver and kidney lesions and damage.
Aggravation of Pre-existing Conditions:
Persons with pre-existing skin disorders or eye problems or impaired liver or kidney function may be more susceptible to the effects of the substance.
Diethylene glycol is used in the manufacture of unsaturated polyester resins, polyurethanes and plasticizers. DEG is used as a building block in organic synthesis, e.g. of morpholine and 1,4-dioxane. It is a solvent for nitrocellulose, resins, dyes, oils, and other organic compounds. It is a humectant for tobacco, cork, printing ink, and glue. It is also a component in brake fluid, lubricants, wallpaper strippers, artificial fog solutions, and heating/cooking fuel. In personal care products (e.g. skin cream and lotions, deodorants) DEG is often replaced by selected diethylene glycol ethers. A dilute solution of diethylene glycol can also be used as a coolant; however, ethylene glycol is much more commonly used. Most ethylene glycol antifreeze contains a few percent diethylene glycol, present as an inadvertent byproduct of ethylene glycol production.
Despite the discovery of DEG’s toxicity in 1937 and its involvement in mass poisonings around the world, the information available regarding human toxicity is limited. Some authors suggest that minimum toxic dose is estimated at 0.14 mg/kg of body weight and lethal dose between 1 and 1.63 g/kg of body weight, while some suggest that the LD50 in adults is of ~1 mL/kg, and others suggest that this is the LD30. Because of its adverse effects on humans, diethylene glycol is not allowed for use in food and drugs. The U.S. Code of Federal Regulations allows no more than 0.2% of diethylene glycol in polyethylene glycol when the latter is used as a food additive.
Diethylene glycol has moderate acute toxicity in animal experiments. The LD50 for small mammals has been tested at between 2 and 25 g/kg, less toxic than its relative ethylene glycol but still capable of causing toxicity in humans. It appears diethylene glycol is more hazardous to humans than implied by oral toxicity data in laboratory animals.
Although there is limited information about toxicokinetics in humans, observations in mass poisonings and experimental studies suggest the following information:
Absorption and distribution
The principal method of absorption is through oral ingestion. Dermal absorption is very low, unless it is administered on broken or damaged skin. After ingestion, DEG is absorbed through the gastrointestinal tract and distributed by the bloodstream throughout the body, reaching peak blood concentrations occurring within 30 to 120 minutes. Once DEG reaches the liver, it is metabolized by enzymes.
Metabolism and elimination
At first, scientists thought that DEG metabolized into ethylene glycol, which is poisonous due to the metabolic production of glycolic acid, glyoxylic acid, and ultimately oxalic acid. The major cause of ethylene glycol toxicity is the accumulation of glycolic acid in the body, but the accumulation of calcium oxalate crystals in the kidneys can also lead to acute kidney failure. In the case of DEG, observations demonstrated there were no calcium oxalate crystal deposits in the kidneys, implying that ethylene glycol is not on the DEG metabolic pathway. Rat models suggest that DEG is metabolized in the liver by enzyme NAD-dependent alcohol dehydrogenase (ADH) into a hydrogen ion, NADH and 2-hydroxyethoxyacetaldehyde (C4H8O3). Shortly after, 2-hydroxyethoxyacetaldehyde (C4H8O3) is metabolized by the enzyme aldehyde dehydrogenase (ALDH) into the weak acid 2-hydroxyethoxyacetic acid (HEAA) with chemical formula C4H8O4. Later on, HEAA leaves the liver through the bloodstream, being partially filtered in the kidneys for elimination.
Mechanisms of toxicity
Based on available literature, scientists suggest that unmetabolized DEG and HEAA are partially reabsorbed through glomerular filtration. As a consequence, the concentrations of the weak acid HEAA and metabolites may cause renal delay, leading to metabolic acidosis and further liver and kidney damage.
The symptoms of poisoning typically occur in three characteristic intervals:
First phase: Gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea develop. Some patients may develop early neurological symptoms like altered mental status, central nervous system depression, coma and mild hypotension.
Second phase: In 1 – 3 days after ingestion (and dependent on dose ingested), patients develop metabolic acidosis, which causes acute kidney failure, oliguria, increasing serum creatinine concentrations, and later anuria. Other symptoms reported and secondary to acidosis and/or renal failure are: hypertension, tachycardia, cardiac dysrhythmia, pancreatitis, hyperkalemia or mild hyponatremia.
Final phase: At least 5 – 10 days after ingestion, most of the symptoms are related to neurological complications like: progressive lethargy, facial paralysis, dysphonia, dilated and nonreactive pupils, quadriplegia, and coma leading to death.
Although it is not an approved procedure and there are no studies supporting successful removal of DEG, patients are subject to hemodialysis once diagnosis is made. Hemodialysis might be administered alone or with ethanol or fomepizole, which are competitive inhibitors of the enzyme NAD-dependent alcohol dehydrogenase (ADH):
With no medication: the low molecular weight and little or no plasma protein binding suggest that DEG should be removed through this method.
With Fomepizole: an ADH inhibitor with 8,000 times more affinity than ethanol and with minimal adverse effects because of constant serum concentration. However, it is a very expensive medication (approximately $3,000 U.S. dollars per treatment)
With Ethanol: an ADH inhibitor used when fomepizole is not available. A constant high blood concentration of ethanol should be maintained to acceptably saturate the enzyme, which can cause ethanol intoxication. To avoid this adverse effect, frequent serum monitoring and dosage adjustment is necessary.
For late diagnosis where ethanol or fomepizole is ineffective, because DEG has already been metabolized, hemodialysis becomes the only treatment available.
Prognosis depends on prompt diagnosis and treatment due to the high mortality rate that DEG intoxication produces. Patients that survive but who develop renal failure remain dialysis dependent. All patients are likely to suffer significant morbidity.
^ a b c d e f g h i j k l m Schep LJ, Slaughter RJ, Temple WA, Beasley DM (2009). "Diethylene glycol poisoning". Clin Toxicol (Phila) 47 (6): 525–35. doi:10.1080/15563650903086444. PMID 19586352.
^ Siegfried Rebsdat and Dieter Mayer "Ethylene Glycol” in Ullmann’s Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim.doi:10.1002/14356007.a10_101.
^ a b c d e f Marraffa JM, Holland MG, Stork CM, Hoy CD, and Hodgman MJ. (2008). "Dietylene Glycol: Widely Used Solvent Presents Serious Poisoning Potential.". J Emerg Med. 35 (4): 401–406. doi:10.1016/j.jemermed.2007.06.025. PMID 18024066.
^ O’Neil M. The Merck Index. 14th ed. Whitehouse Station, NJ: Merck & Co; 2006.
^ a b c d Kraut JA, Kurtz I. (2008). "Toxic alcohol ingestions: clinical features, diagnosis, and management". Clin J Am Soc Nephrol 3 (1): 208–225. doi:10.2215/CJN.03220807. PMID 18045860.
^ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN: Polyethylene glycol, Code of Federal Regulations, Title 21, Vol.3, Part 172, Sec. 172.820, Revised as of April 1, 2006
^ a b Brent, J. (2001). "Current Management of Ethylene Glycol Poisoning". Drugs 61 (7): 979–88. doi:10.2165/00003495-200161070-00006. ISSN 0012-6667. PMID 11434452.
^ Clay, K. L.; Murphy, R. C. (1977). "On the Metabolic Acidosis of Ethylene Glycol Intoxication". Tox. Appl. Pharm. 39 (1): 39–49. doi:10.1016/0041-008X(77)90175-2. ISSN 0041-008X. PMID 14421.
^Internal Medicine Residency Program of the College of Medicine of Wake Forest University, North Caroline, U.S.A. Retrieved December 8, 2009.