Diethylene glycol: Difference between revisions

{{Short description|Chemical compound}}

|Watchedfields = changed

|verifiedrevid = 451167856

|ImageFile = Diethylene glycol structure.svg

|ImageSize = 230

|ImageAlt = Skeletal formula of diethylene glycol

|ImageFile1 = Diethylene glycol 3D ball.png

|ImageSize1 = 230

|ImageAlt1 = Ball-and-stick model of the diethylene glycol molecule

|IUPACName = 2,2′-Oxydiethanol<ref>{{cite web | url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=46807 | title=Diethylene glycol (CHEBI:46807) }}</ref>

|OtherNames = 2,2′-Oxybis(ethan-1-ol)<br />2-(2-Hydroxyethoxy)ethan-1-ol<br />Diethylene glycol<br />Ethylene diglycol<br />Diglycol<br />2,2′-Oxybisethanol<br />2,2′-Oxydiethanol<br />3-Oxa-1,5-pentanediol<br />Dihydroxy diethyl ether<br />Digenos<br />Digol

|Section1={{Chembox Identifiers

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 13835180

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = 61BR964293

|KEGG_Ref = {{keggcite|correct|kegg}}

|KEGG = C14689

|InChI = 1/C4H10O3/c5-1-3-7-4-2-6/h5-6H,1-4H2

|InChIKey = MTHSVFCYNBDYFN-UHFFFAOYAK

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C4H10O3/c5-1-3-7-4-2-6/h5-6H,1-4H2

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = MTHSVFCYNBDYFN-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 111-46-6

|PubChem = 8117

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 46807

|SMILES = OCCOCCO

}}

|Section2={{Chembox Properties

|Formula = C₄H₁₀O₃

|MolarMass = 106.12 g/mol

|Appearance = Colorless liquid

|Density = 1.118 g/mL

|MeltingPtC = −10.45

|BoilingPtC = 244 to 245

|Solubility = miscible

}}

|Section3={{Chembox Hazards

|MainHazards = Flammable, mildly toxic

|GHSPictograms = {{GHS02}}{{GHS06}}{{GHS07}}

|NFPA-H = 2

|NFPA-F = 1

|NFPA-R = 0

|FlashPt = Combustible

|LD50 = 2 — 25 g/kg (orally, rats)<ref>DEG: LD50 for rats</ref>

}}

|Section8={{Chembox Related

|OtherFunction = [[ethylene glycol]], [[triethylene glycol]]

|OtherFunction_label = [[diol]]s

'''Diethylene glycol''' ('''DEG''') is an [[organic compound]] with the formula (HOCH₂CH₂)₂O. It is a colorless, practically [[odor]]less, and [[hygroscopic]] liquid with a sweetish taste. It is a four [[carbon]] [[Dimer (chemistry)|dimer]] of [[ethylene glycol]]. It is [[miscible]] in [[water]], [[ethanol|alcohol]], [[diethyl ether|ether]], [[acetone]], and ethylene glycol.<ref name="Schep" /> DEG is a widely used solvent.<ref name=Ullmanns>Siegfried Rebsdat and Dieter Mayer "Ethylene Glycol" in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim.{{doi|10.1002/14356007.a10_101}}</ref> It can be a normal ingredient in various consumer [[product (business)|products]], and it can be a [[contaminant]]. DEG has also been misused to sweeten wine and beer, and to viscosify oral and topical pharmaceutical products. Its use has resulted in many epidemics of poisoning since the early 20th century.<ref name="Schep" />

== Preparation ==

DEG is produced by the partial [[hydrolysis]] of [[ethylene oxide]]. 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.<ref name="Marraffa">{{cite journal |vauthors=Marraffa JM, Holland MG, Stork CM, Hoy CD, Hodgman MJ |title=Dietylene Glycol: Widely Used Solvent Presents Serious Poisoning Potential |journal=J Emerg Med |volume=35 |issue=4 |pages=401–406 |year=2008 |pmid=18024066 |doi=10.1016/j.jemermed.2007.06.025 }}</ref>

"Diethylene glycol is derived as a co-product with [[ethylene glycol]] (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."<ref name = availability>{{Cite web | url=http://www.chemicalland21.com/petrochemical/DEG.htm | title=Diethylene Glycol (DEG)}}</ref>

== Structure of DEG and related polyols ==

Diethylene glycol is one of several glycols derived from ethylene oxide. Glycols related to and co-produced with diethylene glycol and having the formula HOCH₂CH₂(OCH₂CH₂)_''n''OH are:

These compounds are all [[hydrophilic]], more so than most [[diol]]s, by virtue of the [[diethyl ether|ether]] functionality.

== Uses ==

Diethylene glycol is used in the manufacture of saturated and unsaturated [[polyester resins]], [[polyurethanes]], and [[plasticizers]].<ref name="availability" /> DEG is used as a building block in [[organic synthesis]] of, for example, [[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 material|cork]], printing [[ink]], and [[glue]].<ref>O'Neil M. The Merck Index. 14th ed. Whitehouse Station, NJ: Merck & Co; 2006.</ref> It is also a component of [[brake fluid]], [[lubricants]], wallpaper strippers, [[artificial fog]] and haze solutions, and heating/cooking fuel.<ref name="Schep" /> In personal care products (e.g. skin cream and lotions and deodorants), DEG is often replaced by selected [[Glycol ethers|diethylene glycol ethers]]. A dilute solution of diethylene glycol can also be used as a [[cryoprotectant]]; however, [[ethylene glycol]] is much more commonly used. Most types of ethylene glycol [[antifreeze]] contain a few percent of diethylene glycol, present as a by-product of ethylene glycol production.

== Toxicology ==

Despite the [[Elixir sulfanilamide|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 the minimum toxic dose is 0.14 mg/kg body weight and the lethal dose between 1.0 and 1.63 g/kg.<ref name="Kraut">{{cite journal |vauthors=Kraut JA, Kurtz I |title=Toxic alcohol ingestions: clinical features, diagnosis, and management|journal=Clin J Am Soc Nephrol |volume=3 |issue=1 |pages=208–225 |year=2008 |pmid=18045860 |doi=10.2215/CJN.03220807 |doi-access=free }}</ref> Some suggest that the [[median lethal dose|LD₅₀]] in adults is about 1 mL/kg,<ref name="Schep" /> while others suggest that that is the [[lethal dose|LD]]₃₀.<ref name="Marraffa" /> Because of its adverse effects in humans, diethylene glycol is not allowed to be used in foods and drugs<ref>DEG: application restrictions</ref> (in many countries). 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.<ref>[http://frwebgate5.access.gpo.gov/cgi-bin/waisgate.cgi?WAISdocID=98477222302+20+0+0&WAISaction=retrieve ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN: Polyethylene glycol]{{Dead link|date=July 2019 |bot=InternetArchiveBot |fix-attempted=yes }}, Code of Federal Regulations, Title 21, Vol.3, Part 172, Sec. 172.820, Revised as of April 1, 2006</ref> The [[Government of Australia]] does not allow DEG as a food additive, because of its toxicity; it is only allowed at less than 0.25% w/w of DEG as an impurity in polyethylene glycol (PEG),<ref>[http://www.nicnas.gov.au/Publications/CAR/Other/DEG_Hazard_Assessment_Report_PDF.pdf Existing Chemical Hazard Assessment Report] {{Webarchive|url=https://web.archive.org/web/20100120041540/http://www.nicnas.gov.au/Publications/CAR/Other/DEG_Hazard_Assessment_Report_PDF.pdf |date=2010-01-20 }}, June 2009</ref> even in toothpaste.<ref name=tcmt>{{cite web|publisher=[[Australian Competition & Consumer Commission]]|title=Toothpaste containing more than 0.25 per cent by weight of diethylene glycol (DEG)|url=http://www.accc.gov.au/content/index.phtml/itemId/794351|access-date=1 December 2009|url-status=dead|archive-url=https://web.archive.org/web/20090621173806/http://www.accc.gov.au/content/index.phtml/itemId/794351|archive-date = 21 June 2009}}</ref>

Diethylene glycol has "moderate to low" [[acute toxicity]]<ref>Diethylene glycol toxicity</ref> in animal experiments. The [[median lethal dose|LD₅₀]] for small mammals is between 2 and 25 g/kg, less toxic than its relative [[ethylene glycol]] but still capable of causing toxicity in humans (in high concentrations only).<ref>Diethylene glycol: Human toxicity data</ref> It appears that diethylene glycol may be more hazardous to humans<ref>DEG: why it more hazardous to humans, than animals?</ref> than implied by oral toxicity data in laboratory animals.<ref name="Schep">{{cite journal |vauthors=Schep LJ, Slaughter RJ, Temple WA, Beasley DM |title=Diethylene glycol poisoning |journal=Clin Toxicol |volume=47 |issue=6 |pages=525–35 |year=2009 |pmid=19586352 |doi=10.1080/15563650903086444 |s2cid=22023562 }}</ref>

=== Toxicokinetics ===

Although there is limited information about [[toxicokinetics]] in humans, observations in mass [[poisoning]]s 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 via the gastrointestinal tract and distributed by the bloodstream throughout the body, reaching peak blood concentrations within 30 to 120 minutes. In the liver DEG is metabolized by enzymes.<ref name="Schep" /><ref name="Kraut" />

==== Metabolism and elimination ====

At first, scientists thought that DEG was converted in the liver to ethylene glycol, which is [[Ethylene glycol poisoning|poisonous]] because of the metabolic production of [[glycolic acid]], [[glyoxylic acid]], and ultimately [[oxalic acid]].<ref name="Brent">{{cite journal | author = Brent, J. | title = Current Management of Ethylene Glycol Poisoning | journal = [[Drugs (journal)|Drugs]] | volume = 61 | issue = 7 | pages = 979–88 | year = 2001 | pmid = 11434452 | doi = 10.2165/00003495-200161070-00006 | s2cid = 22954381 | issn = 0012-6667}}</ref> The major cause of ethylene glycol toxicity is the accumulation of glycolic acid in the body,<ref>{{cite journal |author1=Clay, K. L. |author2=Murphy, R. C. |title=On the Metabolic Acidosis of Ethylene Glycol Intoxication |journal=[[Toxicology and Applied Pharmacology|Toxicol. Appl. Pharmacol.]] |volume=39 |issue=1 |pages=39–49 |year=1977 |pmid=14421 |doi= 10.1016/0041-008X(77)90175-2|issn=0041-008X}}</ref> but accumulation of [[calcium oxalate]] [[crystal]]s in the [[kidney]]s can also lead to [[acute kidney failure]].<ref name="Brent" /> In the case of DEG, calcium oxalate crystal are not deposited 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]] [[Nicotinamide adenine dinucleotide|NAD]]-dependent alcohol dehydrogenase (ADH) to a [[hydrogen ion]], NADH, and 2-hydroxyethoxyacetaldehyde (C₄H₈O₃). Shortly after that, 2-hydroxyethoxyacetaldehyde (C₄H₈O₃) is metabolized by the enzyme aldehyde dehydrogenase (ALDH) to the [[weak acid]] 2-hydroxyethoxyacetic acid (HEAA), chemical formula C₄H₈O₄. Later, HEAA leaves the liver through the bloodstream, being partially filtered in the kidneys for elimination.<ref name="Schep" /><ref name="Kraut" />

=== Mechanisms ===

Based on available literature, scientists suggest that unmetabolized DEG and HEAA are partially reabsorbed through [[glomerular filtration]]. As a consequence, the weak acid HEAA and its metabolites may cause renal delay, leading to [[metabolic acidosis]] and further liver and kidney damage.<ref name="Schep" /><ref name="Kraut" />

=== Signs and symptoms ===

The symptoms of poisoning typically occur in three characteristic intervals:<ref name="Schep" />

*'''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, and coma, as well as mild [[hypotension]].

*'''Second phase:''' In one to three days after ingestion (and depending on the dose ingested), patients develop a [[metabolic acidosis]], which causes [[acute kidney failure]], [[oliguria]], increasing [[blood serum|serum]] [[creatinine]] concentrations, and later [[anuria]]. Other symptoms reported and secondary to acidosis and/or [[kidney]] failure are: [[hypertension]], [[tachycardia]] and other [[cardiac dysrhythmia|cardiac dysrhythmias]], [[pancreatitis]], and [[hyperkalemia]] or mild [[hyponatremia]].

*'''Final phase:''' At least five to ten days after ingestion, most of the symptoms are related to neurological complications, such as: progressive [[lethargy]], facial [[paralysis]], [[dysphonia]], dilated and nonreactive pupils, [[quadriplegia]], and [[coma]], leading to death.

=== Treatment ===

[[Fomepizole]] or [[ethanol]] should be quickly administered to prevent diethylene glycol being metabolized to the compound or compounds that cause renal damage.<ref name=Schep/>

*'''[[Fomepizole]]:''' an [[alcohol dehydrogenase]] (ADH) inhibitor with 8000 times more affinity than ethanol. This treatment has minimal adverse effects.<ref name="Marraffa" /> However, it is very expensive (about $3000 U.S. per treatment).<ref>[http://intmedweb.wfubmc.edu/blurbs/overdoses/methanol.html Internal Medicine Residency Program of the College of Medicine of Wake Forest University, North Caroline, U.S.A.] {{Webarchive|url=https://web.archive.org/web/20100719055007/http://intmedweb.wfubmc.edu/blurbs/overdoses/methanol.html |date=2010-07-19 }} Retrieved December 8, 2009.</ref>

*'''[[Ethanol]]:''' 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 (about 0.8 mL/kg or 0.013 [[fluid ounce|fl.oz]]/lb). This will cause [[ethanol intoxication]]. To avoid adverse effects, frequent serum monitoring and dosage adjustments should be done.<ref name="Schep" />

For late diagnosis, when ethanol or [[fomepizole]] is ineffective, because DEG has already been metabolized, [[hemodialysis]] becomes the only treatment available.<ref name="Marraffa" /> Hemodialysis may be administered either alone or in combination with ethanol or fomepizole.

=== Prognosis ===

The [[prognosis]] depends on prompt diagnosis and treatment, owing to the high mortality from DEG intoxication. Patients who survive but develop kidney failure remain dialysis-dependent. All patients are likely to suffer significant morbidity.<ref name="Marraffa" />

== Epidemiology ==

The physical properties of diethylene glycol make it an excellent counterfeit for pharmaceutical-grade [[glycerine]] (also called glycerol) or [[propylene glycol]], 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.<ref>{{cite journal |vauthors=van der Linden-Cremers PM, Sangster B |title=Medical sequelae of the contamination of wine with diethylene glycol|language=nl |journal=Ned Tijdschr Geneeskd |volume=129|issue=39 |pages=1890–1 |year=1985 |pmid=4069248}}</ref><ref>[http://archive.gulfnews.com/nation/Health/10129845.html Authorities warn against using some toothpastes] {{Webarchive|url=https://web.archive.org/web/20070626055957/http://archive.gulfnews.com/nation/Health/10129845.html |date=2007-06-26 }}, GulfNews, Published 04/06/2007</ref>

=== 1937 – The Massengill incident (United States) ===

{{Main|Elixir sulfanilamide}}

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.<ref>Ballentine, C. [https://www.fda.gov/downloads/AboutFDA/WhatWeDo/History/Origin/ucm125604.doc Taste of Raspberries, Taste of Death – The 1937 Elixir Sulfanilamide Incident]. FDA Consumer Magazine, June 1981.</ref><ref>{{cite news|title=Medicine: Post-Mortem |url=http://www.time.com/time/magazine/article/0,9171,758704,00.html |archive-url=https://web.archive.org/web/20090403071709/http://www.time.com/time/magazine/article/0,9171,758704,00.html |url-status=dead |archive-date=April 3, 2009 |work=[[Time magazine]] |date=December 20, 1937 |access-date=2009-07-19}}</ref><ref>{{cite news |title=Wallace Reveals How Federal Agents Traced Elixir to Halt Fatalities |url=https://www.nytimes.com/1937/11/26/archives/death-drug-hunt-covered-15-states-wallace-reveals-how-federal.html |work=[[The New York Times]] |date=November 26, 1937 |access-date=2009-07-20}}</ref> This episode was the impetus for the [[Federal Food, Drug, and Cosmetic Act]] of 1938.<ref name="Wax">{{cite journal|author =Wax P.M.|title = Elixirs, diluents, and the passage of the 1938 Federal Food, Drug and Cosmetic Act|journal = Ann Intern Med|volume = 122|issue = 6|pages = 456–61|year = 1995|pmid=7856995|doi=10.7326/0003-4819-122-6-199503150-00009|s2cid = 32387092}}</ref> This law, though extensively amended in subsequent years, remains the central foundation of FDA regulatory authority to the present day.<ref>[https://www.fda.gov/AboutFDA/WhatWeDo/History/Origin/ucm054819.htm The History of FDA] at FDA.gov</ref>

=== 1969 – South Africa ===

In [[Cape Town, South Africa]], seven children developed [[vomiting]], [[diarrhea]], and [[dehydration]], and died of kidney failure after administration of over-the-counter sedatives. Soon, patients started to present [[anuria]], acidic breathing, [[hepatomegaly]], 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.<ref name="Schep" /><ref name="Wax" />

=== 1985 – Spain ===

Patients being treated for burns developed sudden anuric kidney failure. Further investigation revealed all patients were treated with topical [[silver sulfadiazine]] [[Topical medication|ointment]] that contained 7&nbsp;g/kg of DEG. This event caused the death of five patients.<ref name="Marraffa" /><ref name="Schier">{{cite journal|vauthors=Schier JG, Rubin CS, Miller D, Barr D, McGeehin MA |title = Medication-associated diethylene glycol mass poisoning: A review and discussion on the origin of contamination|journal = J Public Health Policy|volume = 30|issue = 2|pages = 127–143|year = 2009|pmid = 19597445|doi =10.1057/jphp.2009.2|s2cid = 7016437|url = https://zenodo.org/record/1236014}}</ref><ref>{{cite journal |vauthors=Cantarell MC, Fort J, Camps J, Sans M, Piera L |title=Acute intoxication due to topical application of diethylene glycol |journal=Ann Intern Med|volume= 106|issue=3|pages=478–9|date=Mar 1987 |pmid=3813252 |doi=10.7326/0003-4819-106-3-478_2}}</ref>

=== 1985 – Wine scandal (Austria) ===

{{Main|1985 diethylene glycol wine scandal}}

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 [[Bureau of Alcohol, Tobacco, Firearms and Explosives|U.S. Bureau of Alcohol, Tobacco and Firearms]] started to test all imported wine.

In November, ''[[The New York Times]]'' published a wine recall that the Federal Government released after the Bureau of Alcohol, Tobacco and Firearms 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.<ref>Molotsky, I. [https://www.nytimes.com/1985/11/01/us/popular-wines-found-to-hold-toxic-chemical.html "Popular Wines found to hold toxic chemical."] The New York Times. November 1, 1985. Retrieved December 8, 2009.</ref><ref>Tagliabue, J. [https://www.nytimes.com/1985/08/02/world/scandal-over-poisoned-wine-embitters-village-in-austria.html "Scandal over poisoned wine embitters village in Austria."] The New York Times. August 2, 1985. Retrieved December 8, 2009.</ref><ref>[http://www.ttb.gov/industry_circulars/archives/1986/86-13.html Bureau of Alcohol, Tobacco, and Firearms. Industry Circular No. 86-13.] {{Webarchive|url=https://web.archive.org/web/20090814095121/http://ttb.gov/industry_circulars/archives/1986/86-13.html |date=2009-08-14 }} October 6, 1986. Retrieved December 8, 2009.</ref>

After recalling millions of wine bottles, the [[Government of Austria|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 [[Snow removal|melt hazardous ice]] during winter. The primary results revealed that the mixture was more effective than using salt alone.<ref>[https://news.google.com/newspapers?id=le8VAAAAIBAJ&sjid=HxQEAAAAIBAJ&pg=4847,2789108&dq=austria+diethylene+glycol+wine&hl=en "Tainted wine clear roads."] Wilmington Morning Star. December 22, 1986. Retrieved December 9, 2009.</ref> 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.<ref>[https://archive.today/20121203014608/http://pqasb.pqarchiver.com/thestar/access/472561821.html?dids=472561821:472561821&FMT=ABS&FMTS=ABS:FT&type=current&date=Feb+27,+1987&author=Reuter&pub=Toronto+Star&desc=Austrian+power+plant+to+burn+'bad'+wine&pqatl=google Reuter. "Austrian power plant to burn 'bad' wine."] February 27, 1987. Retrieved December 9, 2009</ref>

=== 1986 – India ===

At a hospital in [[Bombay]], India, 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.<ref name="Schep" /><ref name="Wax" /><ref>{{cite journal |author= Pandya SK|title=Letter from Bombay. An unmitigated tragedy |journal=BMJ|volume= 297|issue=6641|pages=117–9|year=1988|pmid=3408933 |doi= 10.1136/bmj.297.6641.117 |pmc= 1833772}}</ref>

=== 1990 – Nigeria ===

During the summer months, 47 children were admitted to the [[Jos University Teaching Hospital|Jos University teaching hospital]], [[Nigeria]], with [[anuria]], fever and vomiting. The children later developed kidney failure and died. All the children had received [[paracetamol]] (acetaminophen) syrup to treat upper respiratory infections related with malaria. Once physicians identified a suspect paracetamol syrup, samples were shipped to the [[Centers for Disease Control and Prevention]] (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.<ref name="Schep" /><ref name="Wax" /><ref name=1998-JAMA-DEG /><ref>{{cite journal |vauthors=Okuonghae HO, Ighogboja IS, Lawson JO, Nwana EJ |title=Diethylene glycol poisoning in Nigerian children |journal=Ann Trop Paediatr|volume= 12|issue=3|pages=235–8|year=1992|pmid=1280035|doi=10.1080/02724936.1992.11747577 }}</ref>

=== 1990–1992 – Bangladesh ===

In [[Bangladesh]] between 1990 and 1992, 339 children developed kidney failure, and most of them died, after being given [[paracetamol]] (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.<ref name="Hanif">{{cite journal|vauthors=Hanif M, Mobarak MR, Ronan A, Rahman D, ((Donovan JJ Jr)), Bennish ML |title = Fatal renal failure caused by diethylene glycol in paracetamol elixir: the Bangladesh epidemic|journal = BMJ|volume = 311|issue = 6997|pages = 88–91|year = 1995|pmid = 7613408|pmc =2550149|doi=10.1136/bmj.311.6997.88}}</ref>

=== 1992 – Argentina ===

A [[propolis]] syrup manufactured by Huilen Laboratories in [[Buenos Aires]], [[Argentina]], contained between 24 and 66.5% DEG, and caused the death of 29 people.<ref>{{cite journal |vauthors=Ferrari LA, Giannuzzi L |title=Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol |journal=Forensic Sci Int |volume= 153|issue=1|pages=49–51|year=2005|pmid=15979833 |doi= 10.1016/j.forsciint.2005.04.038}}</ref><ref>{{cite journal |vauthors=Schep LJ, Slaughter RJ |title=Comments on diethylene glycol concentrations |journal=Forensic Sci Int |volume= 155|issue=2–3|pages=233|year=2005|pmid=16171962 |doi= 10.1016/j.forsciint.2005.08.001}}</ref><ref>[http://nl.newsbank.com/nl-search/we/Archives?p_product=AK&s_site=ohio&p_multi=AK&p_theme=realcities&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=0EB62E565363C36E&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePM "Toll reaches 20 in tonic poisoning."] Akron Beacon Journal (OH). August 22, 1992. Retrieved December 8, 2009.</ref>

=== 1995–1996 – Haiti ===

[[File:Haiti medications contaminated with DEG.png|thumbnail|right|Medications contaminated with DEG]]

[[File:Haiti 1995-96 DEG epidemic epi curve slide.png|thumbnail|left|Haiti 1996 DEG epidemic curve]]

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]], Haiti, presented with acute kidney failure.<ref name=2010-InsideTheOutbreaks-Haiti>{{cite book|last1=Pendergrast|first1=Mark|title=Inside the Outbreaks: The Elite Medical Detectives of the Epidemic Intelligence Service|date=2010|publisher=Mariner Books/Houghton Mifflin Harcourt|location=Boston|isbn=978-0-547-48723-6|pages=300–301|chapter=Rough Sledding: Death in Haiti|oclc=988018975}}</ref> By June 1996, with no idea what was causing the epidemic, the [[Pan American Health Organization]] (PAHO) Haiti representative contacted the [[World Health Organization]] (WHO, the parent agency of PAHO), and WHO requested that the [[Centers for Disease Control and Prevention]] investigate.<ref name=1996-MMWR-DEG>{{cite journal|last1=Centers for Disease Control and Prevention (CDC)|title=Fatalities associated with ingestion of diethylene glycol-contaminated glycerin used to manufacture acetaminophen syrup--Haiti, November 1995-June 1996.|journal=MMWR. Morbidity and Mortality Weekly Report|date=2 August 1996|volume=45|issue=30|pages=649–50|pmid=8769471}} {{Wikidata+icon|Q45266085|y}}</ref><ref name=1998-JAMA-DEG>{{cite journal|last1=O'Brien|first1=KL|last2=Selanikio|first2=JD|last3=Hecdivert|first3=C|last4=Placide|first4=MF|last5=Louis|first5=M|last6=Barr|first6=DB|last7=Barr|first7=JR|last8=Hospedales|first8=CJ|last9=Lewis|first9=MJ|last10=Schwartz|first10=B|last11=Philen|first11=RM|last12=St Victor|first12=S|last13=Espindola|first13=J|last14=Needham|first14=LL|last15=Denerville|first15=K|title=Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. Acute Renal Failure Investigation Team.|journal=JAMA|date=15 April 1998|volume=279|issue=15|pages=1175–80|doi=10.1001/JAMA.279.15.1175|pmid=9555756|url=https://jamanetwork.com/journals/jama/fullarticle/187441|doi-access=free}} {{Wikidata+icon|Q34465188|y}}</ref><ref name=2007-JAT-DEG>{{cite journal|last1=Barr|first1=Dana B.|last2=Barr|first2=John R.|last3=Weerasekera|first3=Gayanga|last4=Wamsley|first4=Jacob|last5=Kalb|first5=Suzanne R.|last6=Sjödin|first6=Andreas|last7=Schier|first7=Joshua G.|last8=Rentz|first8=E. Danielle|last9=Lewis|first9=Lauren|last10=Rubin|first10=Carol|last11=Needham|first11=Larry L.|last12=Jones|first12=Robert L.|last13=Sampson|first13=Eric J.|title=Identification and Quantification of Diethylene Glycol in Pharmaceuticals Implicated in Poisoning Epidemics: An Historical Laboratory Perspective|journal=Journal of Analytical Toxicology|date=July 2007|volume=31|issue=6|pages=295–303|doi=10.1093/JAT/31.6.295|pmid=17725874|url=https://academic.oup.com/jat/article/31/6/295/682770|doi-access=free}} {{Wikidata+icon|Q34668013|y}}</ref>

Lead CDC investigator Dr. [[Katherine O'Brien]] 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.<ref name=2007-JAT-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.<ref name=2007-NYTimes-DEG>{{cite news|last1=Bogdanich|first1=Walt|title=F.D.A. Tracked Poisoned Drugs, but Trail Went Cold in China|url=https://www.nytimes.com/2007/06/17/health/17poison.html|work=The New York Times|date=17 June 2007}}</ref>

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 [[Netherlands|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.<ref name=2007-NYTimes-DEG />

=== 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 Qiqihar 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 Qiqihar Pharmaceutical, no taste-test was performed. The counterfeit syrup ended in ampules of Amillarisin A, a medication for [[gall bladder]] problems; special pediatric [[enema]] fluid; blood vessel disease injections; intravenous pain reliever; and an [[arthritis]] 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. Wang was caught and Qiqihar No. 2 Pharmaceutical was shut down by the authorities. Besides Wang, five employees of Qiquihar were prosecuted.<ref name="Bogdanich2">{{cite news|author1=Bogdanich, W |author2=Hooker, J.|title=From China to Panama, a trail of Poisoned Medicine.|newspaper=The New York Times|date=June 2007|url=https://www.nytimes.com/2007/05/06/world/americas/06poison.html?pagewanted=print}}</ref>

=== 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]] 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<ref name=Bogdanich2 /> while the U.S. Food and Drug Administration conducted lab analyses, revealing the blood pressure drug was safe; [[Centers for Disease Control and Prevention|CDC]] epidemiologists were then invited to participate.<ref name=1998-JAMA-DEG />

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 [[Cough medicine#Expectorants|expectorant]].<ref name=Bogdanich2 /> 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.<ref name=1998-JAMA-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.<ref name=Otero>{{cite news |author=Otero, J. |title=Aumentan Envenenados con Dietilene Glycol |date=Sep 2009 |url=http://mensual.prensa.com/mensual/contenido/2009/09/18/hoy/panorama/1927591.asp |access-date=2009-12-11 |archive-date=2009-11-26 |archive-url=https://web.archive.org/web/20091126072656/http://mensual.prensa.com/mensual/contenido/2009/09/18/hoy/panorama/1927591.asp |url-status=dead }}</ref> 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 [[National Medical Products Administration|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.<ref name=Bogdanich2 /><ref>{{cite journal |author= Rentz ED, Lewis L, Mujica OJ, Barr DB, Schier JG, Weerasekera G, Kuklenyik P, McGeehin M, Osterloh J, Wamsley J, Lum W, Alleyne C, Sosa N, Motta J, Rubin C. |title=Outbreak of acute renal failure in Panama in 2006: a case-control study |journal=Bull World Health Organ |volume= 86|issue=10|pages=749–56|year=2008|pmid=18949211 |doi= 10.2471/BLT.07.049965|url=http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862008001000010&lng=en&nrm=iso&tlng=en |last12= Alleyne |first12= C |last13= Sosa |first13= N |last14= Motta |first14= J |last15= Rubin |first15= C |format= Free full text |pmc= 2649516}}</ref>

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 {{Transliteration|zh|tidai}}, meaning "substitute".<ref name=Bogdanich2 /> 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.<ref name="Harris">{{Cite news |date=2007-10-31 |title=Video: China's Unwatched Drug Makers |language=en-US |work=The New York Times |url=https://www.nytimes.com/video/world/1194817122573/china-s-unwatched-drug-makers.html |access-date=2022-06-30 |issn=0362-4331}}</ref>

In August 2009, the Supreme Court decided to send the diethylene glycol file to the Public Ministry for an extension.<ref name=Otero2>{{cite news |author=Otero, J. |title=Caso dietilene glycol puede viciarse: Troitiño |date=Aug 2009 |url=http://mensual.prensa.com/mensual/contenido/2009/08/25/hoy/panorama/1900108.asp |access-date=2009-12-11 |archive-date=2009-08-30 |archive-url=https://web.archive.org/web/20090830092916/http://mensual.prensa.com/mensual/contenido/2009/08/25/hoy/panorama/1900108.asp |url-status=dead }}</ref> 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.<ref name=Otero /> Two months later, findings revealed that 145 were proven to die by DEG intoxication, but the DA still has to investigate 953 lawsuits.<ref name=Otero3>{{cite news |author=Otero, J. |title=24 Niños afectados por utilización de tóxico |date=November 2009 |url=http://mensual.prensa.com/mensual/contenido/2009/11/04/hoy/panorama/1983284.asp |access-date=2009-12-11 |archive-date=2010-01-09 |archive-url=https://web.archive.org/web/20100109180848/http://mensual.prensa.com/mensual/contenido/2009/11/04/hoy/panorama/1983284.asp |url-status=dead }}</ref>

[[New York Times|''The New York Times'']] reported that Taixing was closed by the Chinese government and CNSC Fortune Way, which is also owned by the Chinese government, was never sanctioned.<ref name=Harris /> In Spain, Rasfer International declared bankruptcy after the lawyer of Medicom filed a lawsuit of $400 million in July 2008.<ref name=Perez>{{cite news|author=Perez, R. |title=Rasfer Internacional se declara en bancarrota. |date=July 2008 |url=http://mensual.prensa.com/mensual/contenido/2008/07/12/hoy/panorama/1439083.html |url-status=dead |archive-url=https://web.archive.org/web/20110928152844/http://mensual.prensa.com/mensual/contenido/2008/07/12/hoy/panorama/1439083.html |archive-date=2011-09-28 }}</ref> 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.<ref name=Irujo>{{cite news|author= Irujo, J. |title=Panamá bloquea el proceso español por el caso del jarabe asesino |date=Jul 2009 |url=http://www.elpais.com/articulo/sociedad/Panama/bloquea/proceso/espanol/caso/jarabe/asesino/elpepisoc/20090731elpepisoc_9/Tes?print=1 }}</ref>

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.<ref name=1998-JAMA-DEG /> 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.<ref>{{Cite web|url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-glycerin-diethylene-glycol|title=Testing of Glycerin for Diethylene Glycol|date=May 5, 2020|website=U.S. Food and Drug Administration}}</ref>

During June 2011, the number of confirmed deaths according to the official list rose to 219 victims.<ref>{{Cite web | url=http://mensual.prensa.com/mensual/contenido/2011/06/28/hoy/panorama/2646054.asp | title=Son 219 muertos por jarabe | access-date=2011-06-28 | archive-date=2011-07-03 | archive-url=https://web.archive.org/web/20110703235957/http://mensual.prensa.com/mensual/contenido/2011/06/28/hoy/panorama/2646054.asp | url-status=dead }}</ref>

=== 2007 – Worldwide toothpaste incident ===

In May 2007, a Panamanian named [[Eduardo Arias]] 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.<ref>Bogdanich, W.; McLean, R. "Poisoned Toothpaste in Panama Is Believed to Be From China", ''The New York Times'', May 19, 2007.</ref><ref>{{cite web|title =China investigating toothpaste containing potentially deadly chemical|publisher = International Herald Tribune|date = 2007-05-22|url =http://www.iht.com/articles/ap/2007/05/22/asia/AS-GEN-China-Tainted-Toothpaste.php|access-date = 2007-05-22}}</ref><ref>{{cite news|title=U.S. checking all toothpaste imports from China |publisher=CNN |date=2007-05-23 |url=http://www.cnn.com/2007/HEALTH/05/23/china.toothpaste.reut/index.html |access-date=2007-05-23 |archive-url=https://web.archive.org/web/20070526145153/http://www.cnn.com/2007/HEALTH/05/23/china.toothpaste.reut/index.html |archive-date=2007-05-26 |url-status=dead}}</ref> For the end of the month, the [[Government of China|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.<ref name=China>{{cite web|author1=Xiaomin, X |author2=Hongyi, W.|title =Gov't probes 'tainted toothpaste' case|publisher = China Daily|date = 2007-05-24|url =http://www.chinadaily.com.cn/china/2007-05/24/content_879179.htm|access-date = 2009-12-10}}</ref>

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.<ref>Bogdanich, W. "Toxic Toothpaste Made in China Is Found in U.S. ", ''The New York Times'', June 2, 2007.</ref><ref>U.S. Food and Drug Administration Press Release. "FDA Advises Consumers to Avoid Toothpaste From China Containing Harmful Chemical. FDA Detains One Contaminated Shipment, Issues Import Alert", June 1, 2007.</ref> Days later, [[Colgate-Palmolive]] found counterfeit toothpaste with its name, which was contaminated with DEG and found at [[Variety store|dollar-type]] [[Discount store|discount stores]] in [[New York (state)|New York]], [[New Jersey]], [[Pennsylvania]] and [[Maryland]]. The toothpaste was labeled as "Manufactured in South Africa" and contained [[misspellings]] like "isclinically", "SOUTH AFRLCA" and "South African Dental Assoxiation".<ref>Colgate Palmolive Company Press Release. [http://investor.colgate.com/ReleaseDetail.cfm?Archive=&ReleaseDate={ts%20%272007-06-14%2000:00:00%27}&ReleaseID=249085&ReleaseType=Company&header= "Counterfeit Colgate Toothpaste Found"] {{Webarchive|url=https://web.archive.org/web/20090328191943/http://investor.colgate.com/ReleaseDetail.cfm?ReleaseID=249085&ReleaseType=Company&ReleaseDate=%7Bts%20%272007-06-14%2000:00:00%27%7D&header=&Archive= |date=2009-03-28 }}, June 14, 2007.</ref><ref>U.S. Food and Drug Administration Press Release. "Counterfeit Colgate Toothpaste Found", June 14, 2007.</ref> Although there were no reports of anyone harmed, several people in the eastern US reported experiencing headaches and pain after using the product.<ref>{{Cite web |url=http://abclocal.go.com/wabc/story?section=alerts_recalls&id=5399483 |title=7online.com: Toothpaste recall expands 6/18/07 |access-date=2007-06-21 |archive-url=https://web.archive.org/web/20070706085804/http://abclocal.go.com/wabc/story?section=alerts_recalls&id=5399483 |archive-date=2007-07-06 |url-status=dead }}</ref> It was later discovered that a great number of tubes with poison ended up in [[Psychiatric hospital|hospitals for the mentally ill]], [[Prison|prisons]], [[Youth detention center|juvenile detention centers]], other hospitals and many other state institutions.<ref>Bogdanich, W. "Wider Sale Is Seen for Toothpaste Tainted in China ", ''The New York Times'', June 28, 2007.</ref>

In July 2007, health authorities in the UK detected a [[counterfeit]] [[Sensodyne]] toothpaste on sale at a [[car boot sale]] in [[Derbyshire]].<ref>{{cite news| url=http://news.bbc.co.uk/1/hi/england/derbyshire/6896182.stm|work=BBC News|title=Toxin found in fake UK toothpaste|date=July 12, 2007|access-date=May 1, 2010}}</ref> 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]], [[United Kingdom|Britain]], [[Canada]], Dominican Republic, [[France]], [[Germany]], [[Ireland]], Italy, [[Mexico]], Spain, [[Switzerland]], [[Turks and Caicos Islands|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.<ref>[https://www.nytimes.com/imagepages/2007/09/30/world/20071001_PANAMA_GRAPHIC.html "Tainted toothpaste across the world"], ''The New York Times'', September 30, 2007.</ref> The world outcry made Chinese officials ban the practice of using diethylene glycol in toothpaste.<ref>Bogdanich, W. [https://www.nytimes.com/2007/10/01/world/americas/01panama.html "The Everyman Who Exposed Tainted Toothpaste"], ''The New York Times'', October 1, 2007.</ref>

=== 2008 – Nigeria ===

Ending November 2008, infants started to die after developing unexplained fevers and vomiting. Investigations revealed that all had taken the medicine 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.<ref>{{Cite web|url=https://www.reuters.com/article/us-nigeria-drugs/nigeria-child-deaths-from-tainted-syrup-rise-to-84-idUSTRE5154CN20090206|title= Nigeria child deaths from tainted teething mixture rise to 84 |work =Reuters|date = 6 February 2009}}</ref><ref>{{Cite news|url=https://www.nytimes.com/2009/02/07/world/africa/07nigeria.html|title=84 Children Are Killed by Medicine in Nigeria|first=Lydia|last=Polgreen|newspaper=The New York Times|date=February 7, 2009}}</ref>

The [[Federal government of Nigeria|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|National Agency for Food And Drug Administration and Control]] (NAFDAC) to adopt zero tolerance for counterfeits.<ref>{{cite news| url=https://www.nytimes.com/2009/02/12/world/africa/12briefs-12HELDOVERTA_BRF.html?ref=africa|work=The New York Times|title=Nigeria: 12 Held Over Tainted Syrup|date=February 12, 2009|access-date=May 1, 2010}}</ref><ref>{{cite news| url=https://www.nytimes.com/2009/02/07/world/africa/07nigeria.html|work=The New York Times|title=84 Children Are Killed by Medicine in Nigeria|first=Lydia|last=Polgreen|date=February 7, 2009|access-date=May 1, 2010}}</ref><ref>{{cite web |url = http://www.nafdac.gov.ng/index.php?option=com_content&view=article&id=72:nafdac-negotiates-state-of-the-art-anti-counterfeiting-equipment&catid=51:press-statements&Itemid=113 |website = www.nafdac.gov.ng |title = NAFDAC Negotiates State of the art Anti Counterfeiting Equipment |date = 26 August 2009 |archiveurl = https://web.archive.org/web/20110724143216/http://www.nafdac.gov.ng/index.php?option=com_content&view=article&id=72:nafdac-negotiates-state-of-the-art-anti-counterfeiting-equipment&catid=51:press-statements&Itemid=113 |archivedate = 24 July 2011 |access-date = 11 December 2009 |url-status = live }}</ref>

=== 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]], [[vomiting]], [[abdominal pain]], acute [[kidney failure]], [[facial nerve paralysis]], [[blurred vision]], [[Amaurosis|temporary blindness]] and sensory changes.<ref name=":0" /> On 9 January 2020, a police report indicated quantities of diethylene glycol in one brand of [[beer]] from the small upscale brewery Backer that could have poisoned 18 people in Belo Horizonte and other cities in [[Minas Gerais]] [[States of Brazil|state]].<ref name=":0">{{cite news|last1=Cohen|first1=Benny|last2=Ronan|first2=Gabriel|date=January 9, 2020|title=Laudo da Polícia Civil aponta que cerveja adulterada causou doença misteriosa em BH|language=pt|trans-title=Civilian Police report indicates that adulterated beer caused mysterious disease in Belo Horizonte|work=Estado de Minas|location=Belo Horizonte|url=https://www.em.com.br/app/noticia/gerais/2020/01/09/interna_gerais,1113349/laudo-aponta-que-cerveja-adulterada-causou-doenca-misteriosa-em-bh.shtml|access-date=20 July 2020}}</ref> 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.<ref>{{cite news|last1=Borges|first=Stella|date=16 January 2020|title=Polícia confirma 3ª morte por síndrome nefroneural|language=pt|trans-title=Police confirm 3rd death from nephroneural syndrome|work=UOL|location=São Paulo|url=https://noticias.uol.com.br/cotidiano/ultimas-noticias/2020/01/16/policia-confirma-3-morte-por-sindrome-nefroneural.htm|access-date=20 July 2020}}</ref><ref>{{cite news|date=17 January 2020|title=Ministério da Agricultura identifica contaminação em oito rótulos de cervejas da Backer|language=pt|trans-title=Ministry of Agriculture identifies contamination in eight brands of Backer beer|work=G1 Minas|publisher=G1|location=Belo Horizonte|url=https://g1.globo.com/mg/minas-gerais/noticia/2020/01/16/ministerio-da-agricultura-identifica-contaminacao-em-oito-rotulos-de-cervejas-da-backer.ghtml|access-date=20 July 2020}}</ref> On 9 June, the police indicted 11 people, including brewery owners and employees, for manslaughter, unintentional bodily harm and food contamination.<ref name=":1">{{Cite news|last=Augusto|first=Leonardo|date=18 July 2020|title=Morre 10ª vítima por intoxicação de cerveja da Backer|language=pt|trans-title=Tenth victim of Backer beer poisoning dies|work=Terra|url=https://www.terra.com.br/noticias/brasil/cidades/morre-10-vitima-por-intoxicacao-de-cerveja-da-backer,6c3decf5806ccb7e67ce1df56d60ddb026astji0.html|access-date=20 July 2020|ref=terra-backer}}</ref> 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.<ref name=":1" /> 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.<ref name=":1" />

=== 2020 – India ===

In the first week of 2020, around 17 children from [[Ramnagar, Udhampur|Ramnagar]], in the [[union territory]] of [[Jammu and Kashmir (union territory)|Jammu and Kashmir]], 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]] government is filing a criminal case against the company and its executives.<ref>{{cite news|title=Behind killer cough syrup Coldbest: Glaring gaps in regulation and its manufacture |url=https://indianexpress.com/article/india/behind-killer-cough-syrup-glaring-gaps-in-regulation-and-its-manufacture-6310065/|access-date=12 March 2020|publisher=Indian Express|date=March 12, 2020 |language=en}}</ref><ref>{{cite news|title=J&K children deaths: Kids consumed cough syrup with poisonous chemical, probe reveals |url=https://www.moneycontrol.com/news/trends/health-trends/jk-children-deaths-kids-consumed-cough-syrup-with-poisonous-chemical-probe-reveals-5025511.html|access-date=12 March 2020|publisher=Moneycontrol|date=March 12, 2020 |language=en}}</ref>

=== 2022 – India/Gambia/Indonesia/Uzbekistan ===

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 [[The Gambia|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, [[Sonipat|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.<ref>{{cite news|title=Contaminated Indian medicines linked to deaths of 66 children in Gambia: WHO |url=https://www.tribuneindia.com/news/world/cough-syrups-by-indias-maiden-pharma-potentially-tied-to-deaths-in-gambia-who-438458|publisher=Tribune India|date=October 5, 2022 |language=en}}</ref><ref>{{cite news|title=Gambia says child deaths linked to cough syrup have risen to 70|url=https://www.reuters.com/world/africa/gambia-says-child-deaths-linked-cough-syrup-have-risen-70-2022-10-14/|newspaper=Reuters|date=15 October 2022|via=www.reuters.com}}</ref><ref>{{cite news|last1=BBC|title=Indonesia bans all syrup medicines after death of 99 children|url=https://www.bbc.com/news/world-asia-63324653/|newspaper=BBC|date=21 October 2022}}</ref>

== See also ==

*[[Ethylene]]

*[[Ethylene glycol poisoning]]

*[[Polyethylene glycol]]

*[[1985 diethylene glycol wine scandal]]

== References ==

;Sources

{{Authority control}}

[[Category:Mass poisoning]]

[[Category:Nephrotoxins]]

[[Category:Glycol ethers]]