Diethylene glycol (DEG) is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
with the formula (HOCH
2CH
2)
2O. It is a colorless, practically
odor
An odor (American English) or odour (Commonwealth English; see spelling differences) is caused by one or more volatilized chemical compounds that are generally found in low concentrations that humans and animals can perceive via their sense ...
less, and
hygroscopic
Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance ...
liquid with a sweetish taste. It is a four
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes ...
dimer of
ethylene glycol
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
. It is
miscible in
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as ...
,
alcohol,
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again b ...
,
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscible wi ...
, and
ethylene glycol
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
.
DEG is a widely used solvent.
[Siegfried Rebsdat and Dieter Mayer "Ethylene Glycol" in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim..] It can be a
contaminant in consumer
products; this has resulted in numerous epidemics of poisoning since the early 20th century.
Preparation
DEG is produced by the partial
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
of
ethylene oxide
Ethylene oxide is an organic compound with the formula . It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly sw ...
. Depending on the conditions, varying amounts of DEG and related glycols are produced. The resulting product is two ethylene glycol molecules joined by an ether bond.
"Diethylene glycol is derived as a co-product with
ethylene glycol
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
(MEG) and
triethylene glycol. The industry generally operates to maximize MEG production. Ethylene glycol is by far the largest volume of the glycol products in a variety of applications. Availability of DEG will depend on demand for derivatives of the primary product, ethylene glycol, rather than on DEG market requirements."
Structure of DEG and related polyols
Diethylene glycol is one of several glycols derived from ethylene oxide. Glycols related to and coproduced with diethylene glycol and have the formula HOCH
2CH
2(OCH
2CH
2)
''n''OH are:
*''n'' = 0
ethylene glycol
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
("antifreeze"); monoethylene glycol MEG
*''n'' = 1 DEG
*''n'' = 2
triethylene glycol, TEG, or triglycol
*''n'' = 3 tetraethylene glycol
*''n'' = 4 pentaethylene glycol
*''n'' > 4
polyethylene glycol
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...
These compounds are all
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
, more so than most
diol
A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified.
The most common industrial diol is ...
s, by virtue of the
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again b ...
functionality.
Uses
Diethylene glycol is used in the manufacture of saturated and unsaturated
polyester resins Polyester resins are synthetic resins formed by the reaction of dibasic acid, dibasic organic acids and polyhydric alcohols. Maleic anhydride is a commonly used raw material with diacid functionality in Unsaturated bond, unsaturated polyester resins ...
,
polyurethanes, and
plasticizers
A plasticizer ( UK: plasticiser) is a substance that is added to a material to make it softer and more flexible, to increase its plasticity, to decrease its viscosity, and/or to decrease friction during its handling in manufacture.
Plasticiz ...
.
DEG is used as a building block in
organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
, e.g. of
morpholine and
1,4-dioxane
1,4-Dioxane () is a heterocyclic organic compound, classified as an ether. It is a colorless liquid with a faint sweet odor similar to that of diethyl ether. The compound is often called simply dioxane because the other dioxane isomers ( 1,2 ...
. It is a
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
for
nitrocellulose
Nitrocellulose (also known as cellulose nitrate, flash paper, flash cotton, guncotton, pyroxylin and flash string, depending on form) is a highly flammable compound formed by nitrating cellulose through exposure to a mixture of nitric acid and ...
,
resins
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on nat ...
,
dyes,
oils
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturat ...
, and other
organic compounds
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
. It is a
humectant
A humectant is a hygroscopic (water-absorbing) substance used to keep things moist. They are used in many products, including food, cosmetics, medicines and pesticides. When used as a food additive, a humectant has the effect of keeping moisture ...
for
tobacco
Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ch ...
,
cork, printing
ink, and
glue
Adhesive, also known as glue, cement, mucilage, or paste, is any non-metallic substance applied to one or both surfaces of two separate items that binds them together and resists their separation.
The use of adhesives offers certain advant ...
. It is also a component in
brake fluid,
lubricants
A lubricant (sometimes shortened to lube) is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, t ...
, wallpaper strippers,
artificial fog Theatrical smoke and fog, also known as special effect smoke, fog or haze, is a category of atmospheric effects used in the entertainment industry. The use of fogs can be found throughout motion picture and television productions, live theatre, conc ...
and haze 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
cryoprotectant; however,
ethylene glycol
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
is much more commonly used. Most ethylene glycol
antifreeze
An antifreeze is an additive which lowers the freezing point of a water-based liquid. An antifreeze mixture is used to achieve freezing-point depression for cold environments. Common antifreezes also increase the boiling point of the liquid, al ...
contains a few percent diethylene glycol, present as a byproduct of ethylene glycol production.
Toxicology
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 the minimum toxic dose is estimated at 0.14 mg/kg of body weight and the lethal dose is between 1.0 and 1.63 g/kg of body weight,
while some suggest the
LD50 in adults is of ~1 mL/kg,
and others suggest this is the
LD30.
Because of its adverse effects on humans, diethylene glycol is not allowed for use in food and drugs (in many countries). The U.S. Code of Federal Regulations allows no more than 0.2% of diethylene glycol in
polyethylene glycol
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...
when the latter is used as a food additive. The
Government of Australia does not allow DEG as a food additive due to its toxicity; it is only allowed at less than 0.25% w/w of DEG as an impurity of polyethylene glycol (PEG) even in toothpaste.
Diethylene glycol has "moderate to low"
acute toxicity
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...
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
Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an od ...
, but still capable of causing toxicity in humans (in high concentration only). It appears diethylene glycol may be more hazardous to humans than implied by oral toxicity data in laboratory animals.
Toxicokinetics
Although there is limited information about
toxicokinetics in humans, observations in mass
poisoning
A poison can be any substance that is harmful to the body. It can be swallowed, inhaled, injected or absorbed through the skin. Poisoning is the harmful effect that occurs when too much of that substance has been taken. Poisoning is not to ...
s and experimental studies suggest the following information:
Absorption and distribution
The principal method of absorption is through oral
ingestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms ingest ...
. 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 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
Oxalic acid is an organic acid with the systematic name ethanedioic acid and formula . It is the simplest dicarboxylic acid. It is a white crystalline solid that forms a colorless solution in water. Its name comes from the fact that early inve ...
.
The major cause of ethylene glycol toxicity is the accumulation of glycolic acid in the body, but the accumulation of
calcium oxalate
Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydrate ...
crystal
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macr ...
s in the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
s can also lead to
acute kidney failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
.
In the case of DEG, observations demonstrated there were no calcium oxalate crystal deposits in the kidneys, implying ethylene glycol is not on the DEG metabolic pathway. Rat models suggest DEG is metabolized in the liver by
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
NAD-dependent alcohol dehydrogenase (ADH) into a
hydrogen ion
A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particl ...
, NADH and 2-hydroxyethoxyacetaldehyde (C
4H
8O
3). Shortly after, 2-hydroxyethoxyacetaldehyde (C
4H
8O
3) is metabolized by the enzyme aldehyde dehydrogenase (ALDH) into the
weak acid 2-hydroxyethoxyacetic acid (HEAA) with chemical formula C
4H
8O
4. Later on, HEAA leaves the liver through the bloodstream, being partially filtered in the kidneys for elimination.
Mechanisms
Based on available literature, scientists suggest 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
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidne ...
and further liver and kidney damage.
Signs and symptoms
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
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
.
*Second phase: In one to three days after ingestion (and dependent on dose ingested), patients develop
metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidne ...
, which causes
acute kidney failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
,
oliguria, increasing
serum
Serum may refer to:
*Serum (blood), plasma from which the clotting proteins have been removed
**Antiserum, blood serum with specific antibodies for passive immunity
* Serous fluid, any clear bodily fluid
* Truth serum, a drug that is likely to mak ...
creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an import ...
concentrations, and later
anuria. Other symptoms reported and secondary to acidosis and/or
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
failure are:
hypertension,
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
,
cardiac dysrhythmia,
pancreatitis
Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...
,
hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occa ...
or mild
hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...
.
*Final phase: At least five to 10 days after ingestion, most of the symptoms are related to neurological complications, such as: progressive
lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwor ...
, facial
paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 5 ...
,
dysphonia, dilated and nonreactive pupils,
quadriplegia, and
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
leading to death.
Treatment
Fomepizole or
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...
should be quickly administered to prevent diethylene glycol being metabolized to the compound or compounds that cause the real damage.
[
* Fomepizole: an alcohol dehydrogenase (ADH) inhibitor with 8,000 times more affinity than ethanol. This treatment has minimal adverse effects because of constant serum concentration.] However, it is a very expensive medication (approximately $3,000 U.S. per treatment).
*Ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...
: ethanol is a competitive ADH substrate. A constant blood concentration of 1 to 1.5 g/L (corresponding to 0.5 to 0.75 mg/L in the breath) should be maintained to acceptably saturate the enzyme. An initial dose of 0.6 to 0.7 g ethanol per kilogram body weight should be given (ca 0.8 mL/kg or 0.013 fl.oz./lb). This will cause ethanol intoxication
Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main ps ...
. To avoid adverse effects, frequent serum monitoring and dosage adjustments should be done.
For late diagnosis where ethanol or fomepizole is ineffective, because DEG has already been metabolized, hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
becomes the only treatment available. Hemodialysis may either be administered alone or in combination with ethanol or fomepizole.
Prognosis
The prognosis
Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
depends on prompt diagnosis and treatment due to the high mortality rate DEG intoxication produces. Patients who survive but develop kidney failure remain dialysis-dependent. All patients are likely to suffer significant morbidity.
Epidemiology
The physical properties of diethylene glycol make it an excellent counterfeit for pharmaceutical-grade glycerine (also called glycerol) or propylene glycol
Propylene glycol ( IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH.
Containing two alcohol groups, it is classed as a diol. It ...
, and has caused many deaths in different countries. Incidents include its use in China as a component of cheap toothpaste, and by winemakers in Europe as an adulterant to create a "sweet" wine.
1937 – The Massengill incident (United States)
In 1937, S. E. Massengill Co. (a Tennessee drug company), manufactured sulfanilamide dissolved with diethylene glycol, to create a liquid alternative of this drug. The company tested the new product, Elixir sulfanilamide, for viscosity, appearance and fragrance. At the time, the food and drug laws did not require toxicological analysis before releasing for sale. When 105 people died in 15 states during the months of September and October, the trail led back to the elixir, and the toxic potential of this chemical was revealed. This episode was the impetus for the Federal Food, Drug, and Cosmetic Act of 1938. This law, though extensively amended in subsequent years, remains the central foundation of FDA regulatory authority to the present day.
1969 – South Africa
In Cape Town, South Africa, seven children developed vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...
, and dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mi ...
, and died of kidney failure after administration of over-the-counter sedatives. Soon, patients started to present anuria, acidic breathing, hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an ab ...
, and unresponsiveness. Patients were treated with fluid hydration and correction of acidosis, but some were not able to survive. Postmortem examination revealed damage in the kidneys and liver, and laboratory testing found DEG instead of propylene glycol in the sedatives.
1985 – Spain
Patients being treated for burns developed sudden anuric kidney failure. Further investigation revealed all patients were treated with topical silver sulfadiazine ointment that contained 7 g/kg of DEG. This event caused the death of five patients.
1985 – Wine scandal (Austria)
During the month of July 1985, Austrian wines were found to contain up to 1,000 parts per million of DEG, giving them a desirable sweetness. Austrian wine was banned in many countries and the U.S. Bureau of Alcohol, Tobacco and Firearms
The Bureau of Alcohol, Tobacco, Firearms and Explosives (BATFE), commonly referred to as the ATF, is a domestic law enforcement agency within the United States Department of Justice. Its responsibilities include the investigation and prevent ...
started to test all imported wine.
In November, ''The New York Times
''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...
'' published a wine recall that the Federal Government released after the Bureau of Alcohol, Tobacco and Firearms
The Bureau of Alcohol, Tobacco, Firearms and Explosives (BATFE), commonly referred to as the ATF, is a domestic law enforcement agency within the United States Department of Justice. Its responsibilities include the investigation and preven ...
tested 1,000 bottles. 45 Austrian, 5 German and 12 Italian wines tested positive for DEG. Some wines contained less than 10 parts per million of DEG, a small amount that could not be detected by laboratory analysis in Europe. This triggered the installation of more sensitive laboratory equipment in Banafi laboratories, Italy, and stronger alcohol regulations in Austria.
After recalling millions of wine bottles, the Austrian Government experienced difficulty in finding a way to destroy the product. During September 1986, the Ministry of Public Works started testing a mixture of wine with salt to melt hazardous ice during winter. The primary results revealed that the mixture was more effective than using salt alone. The next year, an Austrian electric power plant (Österreichische Draukraftwerke) in Carinthia announced that technicians developed a way to produce energy through burning 30 million liters of contaminated wine.
1986 – India
At a hospital in Bombay
Mumbai (, ; also known as Bombay — the official name until 1995) is the capital city of the Indian state of Maharashtra and the '' de facto'' financial centre of India. According to the United Nations, as of 2018, Mumbai is the sec ...
, India
India, officially the Republic of India ( Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the ...
, patients were admitted to be treated for diverse health problems. Doctors prescribed glycerine for its osmotic diuretic effect, but patients started to develop kidney failure. Fourteen patients received hemodialysis, but the treatment failed. The episode resulted in the deaths of 21 patients and the discovery of glycerin contaminated with 18.5% v/v of DEG.
1990 – Nigeria
During the summer months, 47 children were admitted to the Jos University teaching hospital, Nigeria
Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf of G ...
, with anuria, fever and vomiting. The children later developed kidney failure and died. All the children had received acetaminophen syrup to treat upper respiratory infections related with malaria. Once physicians identified a suspect paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferi ...
syrup, samples were shipped to the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) in the U.S., which identified DEG. It was assumed that DEG was used as a substitute of propylene glycol, and this incident encouraged the Nigerian government to develop pharmaceutical quality control guidelines.
1990–1992 – Bangladesh
In Bangladesh
Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world, with a population exceeding 165 million pe ...
between 1990 and 1992, 339 children developed kidney failure, and most of them died, after being given paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferi ...
(acetaminophen) syrup contaminated with diethylene glycol. The outbreak forced the government to ban the sale of paracetamol elixirs in December 1992, causing a decline of 53% in the admission of patients with kidney failure and an 84% decline in admissions by unexplained kidney failure.
1992 – Argentina
A propolis
Propolis or bee glue is a resinous mixture that honey bees produce by mixing saliva and beeswax with exudate gathered from tree buds, sap flows, or other botanical sources. It is used as a sealant for unwanted open spaces in the beehive. P ...
syrup manufactured by Huilen Laboratories in Buenos Aires
Buenos Aires ( or ; ), officially the Autonomous City of Buenos Aires ( es, link=no, Ciudad Autónoma de Buenos Aires), is the Capital city, capital and primate city of Argentina. The city is located on the western shore of the Río de la Plata ...
, Argentina
Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, t ...
, contained between 24 and 66.5% DEG, and caused the death of 29 people.
1995–1996 – Haiti
In the poorest country in the Western Hemisphere, disease outbreaks are not recognized unless widespread or unusual. Between November 1995 and June 1996, almost 109 children admitted to the University Hospital in Port-au-Prince
Port-au-Prince ( , ; ht, Pòtoprens ) is the capital and most populous city of Haiti. The city's population was estimated at 987,311 in 2015 with the metropolitan area estimated at a population of 2,618,894. The metropolitan area is defin ...
, Haiti
Haiti (; ht, Ayiti ; French: ), officially the Republic of Haiti (); ) and formerly known as Hayti, is a country located on the island of Hispaniola in the Greater Antilles archipelago of the Caribbean Sea, east of Cuba and Jamaica, and ...
, presented with acute kidney failure. By June 1996, with no idea what was causing the epidemic, the Pan American Health Organization (PAHO) Haiti representative contacted the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO, the parent agency of PAHO), and WHO requested that the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
investigate.[ ][ ][ ]
Lead CDC investigator Dr. Katherine O'Brien
Katherine "Kate" L. O'Brien (born 1963) is a Canadian American pediatric infectious disease physician, epidemiologist, and vaccinologist who specializes in the areas of pneumococcal epidemiology, pneumococcal vaccine trials and impact studies, a ...
conducted a case-control investigation, looking for potential clues to the epidemic. The study revealed a strong association between ingestion of two locally produced acetaminophen liquid products (Afebril and Valodon) and illness. Laboratory testing at CDC of samples taken from parents revealed significant contamination with DEG. The factory of the medication manufacturer, Pharval, was subsequently investigated by Dr. Joel Selanikio (also of CDC, and an Epidemic Intelligence Service classmate of Katherine O'Brien). Testing of medication samples taken from the factory samples by both CDC and by an independent commercial lab located in Miami, revealed contamination by DEG of 16.4% and higher. With the available technology of the era, the CDC determined the glycerin used in the syrup preparation was contaminated with approximately 24% DEG. As a result of the case-control findings, and subsequent investigation at the factory, public warnings were issued by the Ministry of Health and bottles of the two medications were taken from pharmacy shelves and destroyed. These measures quickly ended the advance of the epidemic.
Only 88 children deaths were recalled by doctors or had medical records. Nearly half of the victims were under the age of two.
Ending June 1996, the FDA had discovered counterfeit glycerin traced back to Chemical Trading and Consulting (a German broker), which bought 72 barrels of the syrup from Vos B.V., a Dutch company. Vos records revealed the syrup had been bought from Sinochem International Chemicals Company through a German trader, Metall-Chemie. In July 1996, the American Embassy in China contacted Sinochem and requested a list of Chinese glycerin makers, but the company refused to reveal the names. It was not until September 1996 that Sinochem provided a name of the manufacturer of the tainted syrup. They identified Tianhong Fine Chemicals Factory as the manufacturer. While the FDA tried to find out Tianhong's address, Chinese officials were reluctant to become involved. One year and a half after the FDA began to trace the poisonous shipments, an inspector, Ted Sze, finally visited the Tianhong Fine Chemicals Factory in Dalian, northeastern China. Once he was inside, there was nothing to do: the plant had already been shut down. The Dutch authorities assessed a $250,000 fine against Vos B.V., for not alerting anyone when they tested the syrup and found impurities.
2006 – China
Wang Guiping discovered how easy it was to enter China's pharmaceutical supply business and earn extra money. Records also revealed that to fool buyers, Wang falsified his license and laboratory analysis reports.
Wang declared that after making the first order of counterfeit syrup, he swallowed some of it. Once verifying that he was fine, he shipped it to Qiquihar No. 2 Pharmaceutical in 2005. Some time later, Wang found a reference to diethylene glycol in a chemical book. After manufacturing a second batch of syrup containing diethylene glycol for Qiquhar Pharmaceutical, no taste-test was performed. The counterfeit syrup ended in ampules of Amillarisin A, a medication for gall bladder problems; special pediatric enema
An enema, also known as a clyster, is an injection of fluid into the lower bowel by way of the rectum.Cullingworth, ''A Manual of Nursing, Medical and Surgical'':155 The word enema can also refer to the liquid injected, as well as to a devic ...
fluid; blood vessel disease injections; intravenous pain reliever; and an arthritis
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...
medication.
In April 2006, the Guangdong Province Hospital of Guangzhou began administering Amillarisin A to their patients. Soon thereafter, patients died after receiving the medication. Mr. Wang was caught and Qiquihar was shut down by the authorities. Besides Wang, five employees of Qiquihar were prosecuted.
2006 – Panama
Ending September 2006, the Arnulfo Arias Madrid Hospital at Panama City was getting full with patients with contradictory symptoms. The symptoms seemed to match with Guillain–Barré syndrome, but these patients were also losing their ability to urinate, a symptom not related to Guillain–Barré. The death rate of this mysterious illness was nearly 50%, when hospital management decided to isolate all the patients with the illness in a large room and doctors could compare notes and theories. Soon, patients from other parts of the country started to arrive at hospitals. Doctors had no idea what was happening: the mysterious illness was attacking elderly citizens with hypertension and diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
history. About half were receiving Lisinopril (a blood pressure medicine), and many did not remember clearly if they had been taking other drugs. Suspecting something wrong with Lisinopril, the medicine was removed from the pharmacies while the U.S. Food and Drug Administration conducted lab analyses, revealing the blood pressure drug was safe; CDC epidemiologists were then invited to participate.
When a patient admitted for a heart attack developed the mysterious illness at the hospital, Dr. Nestor Sosa, an infectious disease specialist, analyzed the medical record. Because patients treated with Lisinopril developed a cough (a common side effect of ACE inhibitors), they were prescribed an expectorant. Immediately, biological samples and the syrup were sent by jet to CDC for analysis. When urine analyses for a series of metals, pesticides or their metabolites resulted negative, CDC scientists recalled the Nigeria and Haiti incidents. The CDC employed modern laboratory equipment to analyze the samples and confirm the results: the samples contained approximately 8% v/v DEG. Later, raw glycerin was analyzed and results revealed 22.2% v/v DEG.
The Panamanian Government made a nationwide campaign, collecting around 6,000 bottles of cough syrup and three other products with the tainted glycerin manufactured by Social Security Laboratories. The 46 barrels of syrup were bought by Social Security Laboratories through a Panamanian middleman, Grupo Comercial Medicom, who bought the product from Rasfer Internacional, a Spanish company. In fact, Rasfer received the product from CNSC Fortune Way, which in turn bought it from the Taixing Glycerine Factory. At the request of the United States, the State Food and Drug Administration of China investigated Taixing Glycerine Factory and CNSC Fortune Way, but the agency concluded it is not under their jurisdiction because the factory is not certified to make medicine.
Taixing sold the syrup as “TD glycerin”, wording that neither Chinese inspectors nor Spanish medical authorities comprehended. Unfortunately, Taixing used “TD” for the Chinese word , meaning “substitute”. A New York Times reporter tried to obtain a comment from CNSC Fortune Way at the CPHI Worldwide (the world's largest annual pharmaceutical convention) held in Milan, Italy, during 2007, but their representatives refused to comment.
In August 2009, the Supreme Court decided to send the diethylene glycol file to the Public Ministry for an extension. The following month, the Toxicology Department of the Institute of Legal Medicine and Forensic Science published a list of 1,155 names whose medicine bottles tested positive for DEG. Only approximately 3,000 bottles had been analyzed from the total 6,000 bottles collected. The fiscal attorney urged affected citizens to approach the Public Ministry to update the official legal file and for further medical analysis. Two months later, findings revealed that 145 were proven to die by DEG intoxication, but the DA still has to investigate 953 lawsuits.
The New York Times
''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...
reported that Taixing was closed by the Chinese government and CNSC Fortune Way, which is also owned by the Chinese government, was never sanctioned. In Spain, Rasfer International declared bankruptcy after the lawyer of Medicom filed a lawsuit of $400 million in July 2008. Spanish authorities are prosecuting Asunción Criado, general manager of Rasfer Internacional, S.A., and await Panamanian citizens, René Luciani (former Social Security Director) and Jéssica Rodríguez (former Purchase National Director) for their hearings. Meanwhile, in Panama, De la Cruz, legal representative of Medicom, remains in jail pending a trial. Seventeen other persons have also been charged related to this incident. Panama awaits the extradition of Criado for her hearing.
Panama's case made CDC set standardized methodology for DEG identification, hoping to have more timely response in future events. The agency also identified urinary DEG as a biomarker for DEG exposures. The United States Food and Drug Administration also issued an Industry Guidance Document “intended to alert pharmaceutical manufacturers, pharmacy compounders, repackers, and suppliers to the potential public health hazard of glycerin contaminated with diethylene glycol (DEG)” and recommended appropriate testing procedures for the use of glycerin.
During June 2011, the number of confirmed deaths according to the official list rose to 219 victims
2007 – Worldwide toothpaste incident
In May 2007, a Panamanian named Eduardo Arias
Eduardo Arias (1956 – 1 August 2020) was a Panamanian Guna people, Guna, whose discovery of contaminated toothpaste saved lives by alerting the public to potentially poisonous products purchased from the People's Republic of China (PRC).
Early ...
discovered a 59-cent toothpaste that was labeled containing DEG. Panamanian officials traced the toothpaste to a local company in the Colón Free Trade Zone. In fact, the company bought the product in China and had already re-exported toothpaste to Costa Rica, Dominican Republic and Haiti, making Panama kick off a local warning. For the end of the month, the Chinese government committed to investigate the “supposedly” tainted toothpaste that had been recalled in Panama and Dominican Republic, but stated that, as per an essay written in 2000, a toothpaste containing 15.6% was not dangerous.
On June 1, 2007, the FDA warned consumers to avoid toothpaste from China, although there was no information if these toothpastes had already entered the US, and started testing any imported Chinese toothpaste. Days later, Colgate-Palmolive found counterfeit toothpaste with its name, which was contaminated with DEG and found at dollar-type discount stores in New York, New Jersey, Pennsylvania and Maryland. The toothpaste was labeled as “Manufactured in South Africa” and contained misspellings like "isclinically", "SOUTH AFRICA" and "South African Dental Assoxiation". Although there were no reports of anyone harmed, several people in the eastern US reported experiencing headaches and pain after using the product. It was later discovered that a great number of tubes with poison ended up in hospitals for the mentally ill, prisons, juvenile detention centers, other hospitals and many other state institutions.
In July 2007, health authorities in the UK detected a counterfeit Sensodyne toothpaste on sale at a car boot sale in Derbyshire. Soon, other countries also recalling Chinese-made toothpaste were Belize, Canada, Mozambique, Saudi Arabia, New Zealand, Spain, Italy, Japan, and Ireland, plus an Indianapolis, Indiana US hotel-supplier that distributed Chinese toothpaste in Barbados, Belgium, Bermuda, Britain, Canada, Dominican Republic, France, Germany, Ireland, Italy, Mexico, Spain, Switzerland, Turks and Caicos, the United Arab Emirates and United States. What began as a local alert revealed a global problem in more than 30 countries and involving more than thirty brands. The world outcry made Chinese officials ban the practice of using diethylene glycol in toothpaste.
2008 – Nigeria
Ending November 2008, infants started to die after developing unexplained fevers and vomiting. Investigations revealed that all had taken a medicine called “My Pikin Baby”, a teething mixture tainted with diethylene glycol. The poison had caused the death of at least 84 Nigerian children between ages of two months and seven years.
The Nigerian government traced the diethylene glycol to an unlicensed chemical dealer in Lagos, who sold it to a local pharmaceutical manufacturer. Barewa Pharmaceuticals was shut down and the product was pulled off the shelves. They also arrested 12 people in connection with the incident. This being the second incident involving counterfeit glycerine, it prompted the Nigerian National Agency for Food And Drug Administration and Control (NAFDAC) to adopt zero tolerance for counterfeits.
2019/2020 - Brazil
In December 2019, some people in the city of Belo Horizonte, initially all from the same neighbourhood, started having symptoms such as nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues.
Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...
, acute kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, facial nerve paralysis
Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial ...
, blurred vision
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressu ...
, temporary blindness and sensory changes. On 9 January 2020, a police report indicated quantities of diethylene glycol in one brand of beer
Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from cer ...
from the small upscale brewery Backer that could have poisoned 18 people in Belo Horizonte and other cities in Minas Gerais
Minas Gerais () is a state in Southeastern Brazil. It ranks as the second most populous, the third by gross domestic product (GDP), and the fourth largest by area in the country. The state's capital and largest city, Belo Horizonte (literall ...
state
State may refer to:
Arts, entertainment, and media Literature
* ''State Magazine'', a monthly magazine published by the U.S. Department of State
* ''The State'' (newspaper), a daily newspaper in Columbia, South Carolina, United States
* '' Our ...
. On 17 January, the police confirmed the fourth death from symptoms matching DEG poisoning, and DEG contamination had been found in eight brands of beer from the same brewery. On 9 June, the police indicted 11 people, including brewery owners and employees, for manslaughter, unintentional bodily harm and food contamination. On 18 July, the 10th victim died in a Belo Horizonte hospital, a 65-year-old man who had been hospitalized since December 2019 due to the poisoning. The investigation revealed that DEG had been used as a coolant for the brewery equipment, in what should have been a closed circuit, but an undetected leak in the system contaminated some batches of beer.
2020 - India
In the first week of 2020, around 17 children from Ramnagar Ramnagar may refer to the following places:
Bangladesh
* Ramnagar, Bangladesh, a village in Chittagong Division
* Ramnagar Union, Jessore Sadar
India Jammu and Kashmir
* Ramnagar, Udhampur, a town in Jammu and Kashmir
** Ramnagar Fort Udha ...
, in the union territory of Jammu and Kashmir Jammu and Kashmir may refer to:
* Kashmir, the northernmost geographical region of the Indian subcontinent
* Jammu and Kashmir (union territory), a region administered by India as a union territory
* Jammu and Kashmir (state), a region administered ...
, were hospitalised, more than half of whom died of kidney failure. The regional drug controller authorities after investigation found out that a faulty batch of the Coldbest PC cough syrup contained 34.97% of diethylene glycol, which resulted in poisoning and subsequent renal failures. The product was recalled and after an investigation, the Drug Controller General of India, VG Somani, said at India Pharma 2020, that the GMP was not followed, and negligence was found during the production process itself. The Himachal Pradesh
Himachal Pradesh (; ; "Snow-laden Mountain Province") is a state in the northern part of India. Situated in the Western Himalayas, it is one of the thirteen mountain states and is characterized by an extreme landscape featuring several peak ...
government is filing a criminal case against the company and its executives.
2022 - India/Gambia/Indonesia
The WHO issued a medical product alert for four “contaminated” Indian pediatric medicines, manufactured by a firm in Haryana’s Sonepat, saying these drugs identified in Gambia had been potentially linked with acute kidney injuries and 70 deaths among children in the west African country. The cough and cold syrups produced by Maiden Pharmaceuticals Limited, Sonepat in India.
WHO said laboratory analysis of samples of each of the four products confirmed that they contain unacceptable amounts of diethylene glycol and ethylene glycol as contaminants.
Subsequently, on 21 October 2022, 99 children were reported dead in Indonesia after ingesting the cough syrups. As a result authorities in Indonesia banned all syrup medicines. However, they advised that the syrups suspected of causing the deaths in Gambia, were not sold locally in Indonesia.
See also
*Counterfeit medications
A counterfeit medication or a counterfeit drug is a medication or pharmaceutical item which is produced and sold with the intent to deceptively represent its origin, authenticity, or effectiveness. A counterfeit drug may contain inappropriate qu ...
*Ethylene
Ethylene ( IUPAC name: ethene) is a hydrocarbon which has the formula or . It is a colourless, flammable gas with a faint "sweet and musky" odour when pure. It is the simplest alkene (a hydrocarbon with carbon-carbon double bonds).
Ethylene ...
* Ethylene glycol poisoning
*Polyethylene glycol
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...
References
;Sources
*''Merck Index'', 12th Edition, 3168.
External links
The Elixir Sulfanilamide Disaster
{{Authority control
Alcohol solvents
Diols
Adulteration
Mass poisoning
Nephrotoxins
Glycol ethers