Acetaldehyde#Carcinogenicity

Acetaldehyde was first observed by the Swedish pharmacist/chemist Carl Wilhelm Scheele (1774);Scheele, C. W. (1774) "Om Brunsten eller Magnesia nigra och dess egenskaper" (On brown-stone or black magnesia [i.e., manganese ore] and its properties), Kungliga Svenska vetenskapsakademiens handlingar (Proceedings of the Royal Swedish Academy of Sciences), 35 : 89–116; 177–194. On [https://books.google.com/books?id=5ME4AAAAMAAJ&pg=PA109 pages 109–110], Scheele mentions that refluxing ("digesting") ethanol (Alkohol vini) with manganese dioxide (Brunsten) and either hydrochloric acid (Spirtus salis) or sulfuric acid (Spiritus Vitrioli) produces a smell like "Aether nitri" (ethanol treated with nitric acid). Later investigators realized that Scheele had produced acetaldehyde. it was then investigated by the French chemists Antoine François, comte de Fourcroy and Louis Nicolas Vauquelin (1800),Note:

• Dabit, a pharmacist in Nantes, France, performed a series of experiments and concluded that acetaldehyde was formed when hydrogen in ethanol combined with oxygen in sulfuric acid to form water: {{cite journal |first= |last=Dabit |trans-title=Extract of the memoir by citizen Dabit on ether |title=Extrait du mémoire du cit. Dabit sur l'éther |journal=Annales de Chimie |volume=34 |pages=289–305 |date=1800 |url=https://books.google.com/books?id=PDZQAAAAcAAJ&pg=PA289}}
• Fourcroy and Vauquelin stated that sulfuric acid was not consumed in the production of acetaldehyde: {{cite journal |last=Fourcroy |last2=Vauquelin |trans-title=On the ether prepared in the way of citizen Dabit |title=Sur l'éther préparé à la manière du cit. Dabit |journal=Annales de Chimie |volume=34 |pages=318–332 |date=1800 |url=https://books.google.com/books?id=PDZQAAAAcAAJ&pg=PA318}} and the German chemists Johann Wolfgang Döbereiner (1821, 1822, 1832)See:
• {{cite journal |first=J.W. |last=Döbereiner |trans-title=New ethers |title=Neue Aether |journal=Journal für Chemie und Physik |volume=32 |pages=269–270 |date=1821 |url=http://babel.hathitrust.org/cgi/pt?q1=D%C3%B6bereiner;id=nyp.33433069069122;view=1up;seq=301;start=1;size=10;page=search;num=270#view=1up;seq=287}} Döbereiner named the new "ether" "Sauerstoffäther" (oxygen-ether).
• {{cite journal |first=J.W. |last=Döbereiner |trans-title=Döbereiner's apparatus for the preparation of oxygen-ether |title=Döbereiner's Apparat zur Darstellung des Sauerstoffaethers |journal=Journal für Chemie und Physik |volume=34 |pages=124–5 |date=1822 |url=http://babel.hathitrust.org/cgi/pt?num=124&u=1&seq=344&view=1up&size=100&id=nyp.33433069069148&q1=D%C3%B6bereiner#view=1up;seq=140}}
• {{cite journal |first=J.W. |last=Döbereiner |trans-title=Formation of oxy-ether by atmospheric oxidation of alcohol |title=Bildung des Sauerstoff-Aethers durch atmosphärische Oxidation des Alkohols |journal=Journal für Chemie und Physik |volume=64 |pages=466–8 |date=1832 |url=https://books.google.com/books?id=mAYAAAAAMAAJ&pg=PA466}} In this paper, Döbereiner made acetaldehyde by exposing ethanol vapor to air in the presence of platinum black. and Justus von Liebig (1835).{{cite journal |first=Justus |last=Liebig |trans-title=On the products of oxidation of alcohol [i.e., ethanol] |title=Ueber die Producte der Oxydation des Alkohols |journal=Annalen der Chemie |volume=14 |pages=133–167 |date=1835 |url=https://babel.hathitrust.org/cgi/pt?id=uva.x002457901;view=1up;seq=523}}{{cite book |first=William H. |last=Brock |title=Justus von Liebig: The Chemical Gatekeeper |publisher=Cambridge University Press |date=1997 |isbn=0-521-52473-3 |pages=[https://books.google.com/books?id=VugoemP2th0C&pg=PA83 pp. 83–84] }}

In 1835, Liebig named it "aldehyde",{{cite journal |first=J. |last=Liebig |trans-title=On the products of the oxidation of alcohol |title=Sur les produits de l'oxidation de l'alcool |journal=Annales de Chimie et de Physique |volume=59 |pages=289–327 See p. 290 |date=1835 |url=https://books.google.com/books?id=85c5AAAAcAAJ&pg=PA289 |quote=Je le décrirai dans ce mémoire sous le nom d'aldehyde; ce nom est formé de alcool dehydrogenatus. [I will describe it in this memoir by the name of aldehyde; this name is formed from alcohol dehydrogenatus.]}} and in the middle of the century the name was altered to "acetaldehyde".{{Cite book |last=Schlossberger |first=Julius Eugen |url=https://books.google.com/books?id=NWA3AAAAMAAJ&pg=PA234 |title=Lehrbuch der organischen Chemie mit besonderer Rücksicht auf Physiologie und Pathologie, auf Pharmacie, Technik und Landwirthschaft |date=1850 |publisher=Müller |language=de}}

In 2013, global production was about 438 thousand tons.{{cite news |last1=WMStrategy |title=The Global Acetaldehyde Market Projected to Drop to 406 Thousand Tons by 2023 |url=https://www.wm-strategy.com/news/the-global-production-of-acetaldehyde-is-expected-to-stabilize-in-the-upcoming-years |access-date=20 October 2024 |publisher=Williams & Marshall Strategy |date=May 20, 2019 |language=English |quote=The global acetaldehyde market was equal to 438 thousand tons in 2013.}} Before 1962, ethanol and acetylene were the major sources of acetaldehyde. Since then, ethylene is the dominant feedstock.

The main method of production is the oxidation of ethene by the Wacker process, which involves oxidation of ethene using a homogeneous palladium/copper catalyst system:

:{{chem2|2 CH2\dCH2 + O2 -> 2 CH3CH\dO}}

In the 1970s, the world capacity of the Wacker-Hoechst direct oxidation process exceeded 2 million tonnes annually.

Smaller quantities can be prepared by the partial oxidation of ethanol in an exothermic reaction. This process typically is conducted over a silver catalyst at about {{convert|500–650|C|F}}.

: {{chem2|2 CH3CH2OH + O2 -> 2 CH3CH\dO + 2 H2O}}

This method is one of the oldest routes for the industrial preparation of acetaldehyde.

Prior to the Wacker process and the availability of cheap ethylene, acetaldehyde was produced by the hydration of acetylene.{{Cite journal| title = Hydration of Acetylene: A 125th Anniversary |author1=Dmitry A. Ponomarev |author2=Sergey M. Shevchenko | journal = J. Chem. Educ. | volume = 84 | issue = 10 | year = 2007 | pages = 1725 | url = http://jchemed.chem.wisc.edu/HS/Journal/Issues/2007/OctACS/ACSSub/p1725.pdf | doi = 10.1021/ed084p1725| bibcode = 2007JChEd..84.1725P }} This reaction is catalyzed by mercury(II) salts:

:{{chem2|C2H2 + Hg^{2+} + H2O -> CH3CH\dO + Hg}}

The mechanism involves the intermediacy of vinyl alcohol, which tautomerizes to acetaldehyde. The reaction is conducted at {{convert|90–95|C|F}}, and the acetaldehyde formed is separated from water and mercury and cooled to {{convert|25–30|C|F}}. In the wet oxidation process, iron(III) sulfate is used to reoxidize the mercury back to the mercury(II) salt. The resulting iron(II) sulfate is oxidized in a separate reactor with nitric acid.

The enzyme Acetylene hydratase discovered in the strictly anaerobic bacterium Pelobacter acetylenicus can catalyze an analogous reaction without involving any compounds of mercury.{{cite journal | url=https://link.springer.com/article/10.1007/s00775-015-1330-y | doi=10.1007/s00775-015-1330-y | title=Acetylene hydratase: A non-redox enzyme with tungsten and iron–sulfur centers at the active site | date=2016 | last1=Kroneck | first1=Peter M. H. | journal=Journal of Biological Inorganic Chemistry | volume=21 | issue=1 | pages=29–38 | pmid=26790879 | s2cid=17179063 | url-access=subscription }} However, it has thus far not been brought to any large-scale or commercial use.

Traditionally, acetaldehyde was produced by the partial dehydrogenation of ethanol:

: {{chem2|CH3CH2OH -> CH3CH\dO + H2}}

In this endothermic process, ethanol vapor is passed at 260–290 °C over a copper-based catalyst. The process was once attractive because of the value of the hydrogen coproduct,Eckert, Marc et al. (2007) "Acetaldehyde" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim {{doi|10.1002/14356007.a01_031.pub2}} but in modern times is not economically viable.

The hydroformylation of methanol with catalysts like cobalt, nickel, or iron salts also produces acetaldehyde, although this process is of no industrial importance. Similarly noncompetitive, acetaldehyde arises from synthesis gas with modest selectivity.

File:Ethanal Ethenol Tautomerie.svg{{clear left}}

Like many other carbonyl compounds, acetaldehyde tautomerizes to give an enol (vinyl alcohol; IUPAC name: ethenol):

:{{chem2|CH3CH\dO <-> CH2\dCHOH}} {{spaces}} {{spaces}} {{spaces}} {{spaces}} {{spaces}} {{spaces}} {{spaces}} {{spaces}} ∆H_298,g = +42.7 kJ/mol

The equilibrium constant is 6{{e|−7}} at room temperature, thus that the relative amount of the enol form in a sample of acetaldehyde is very small.{{Cite journal | doi = 10.1021/ja00168a035| title = Keto-enol equilibrium constants of simple monofunctional aldehydes and ketones in aqueous solution| journal = Journal of the American Chemical Society| volume = 112| issue = 12| pages = 4862–8| year = 1990| last1 = Keeffe | first1 = J. R.| last2 = Kresge | first2 = A. J.| last3 = Schepp | first3 = N. P.}} At room temperature, acetaldehyde ({{chem2|CH3CH\dO}}) is more stable than vinyl alcohol ({{chem2|CH2\dCHOH}}) by 42.7 kJ/mol:Johnson, R.D. III "CCCBDB NIST Standard Reference Database". nist.gov Overall the keto-enol tautomerization occurs slowly but is catalyzed by acids.

Photo-induced keto-enol tautomerization is viable under atmospheric or stratospheric conditions. This photo-tautomerization is relevant to the Earth's atmosphere, because vinyl alcohol is thought to be a precursor to carboxylic acids in the atmosphere.{{Cite journal | doi = 10.1038/nchem.1052| pmid = 21602858| title = Near-threshold H/D exchange in CD₃CHO photodissociation| journal = Nature Chemistry| volume = 3| issue = 6| pages = 443–8| year = 2011| last1 = Heazlewood | first1 = B. R. | last2 = MacCarone | first2 = A. T. | last3 = Andrews | first3 = D. U. | last4 = Osborn | first4 = D. L. | last5 = Harding | first5 = L. B. | last6 = Klippenstein | first6 = S. J. | last7 = Jordan | first7 = M. J. T. | last8 = Kable | first8 = S. H. | bibcode = 2011NatCh...3..443H}}{{Cite journal | doi = 10.1126/science.1220712| pmid = 22903524| title = Photo-Tautomerization of Acetaldehyde to Vinyl Alcohol: A Potential Route to Tropospheric Acids| journal = Science| volume = 337| issue = 6099| pages = 1203–6| year = 2012| last1 = Andrews | first1 = D. U.| last2 = Heazlewood | first2 = B. R.| last3 = MacCarone | first3 = A. T.| last4 = Conroy | first4 = T.| last5 = Payne | first5 = R. J.| last6 = Jordan | first6 = M. J. T.| last7 = Kable | first7 = S. H.| bibcode = 2012Sci...337.1203A| s2cid = 42079807}}

Acetaldehyde is a common electrophile in organic synthesis.Sowin, T. J.; Melcher, L. M. (2004) "Acetaldehyde" in Encyclopedia of Reagents for Organic Synthesis (Ed: L. Paquette), J. Wiley & Sons, New York. {{doi|10.1002/047084289X}} In addition reactions acetaldehyde is prochiral. It is used primarily as a source of the "{{chem2|CH3C+H(OH)}}" synthon in aldol reactions and related condensation reactions.{{OrgSynth | author = Behrens, C. | authorlink2 = Leo Paquette | author2 = Paquette, L. A. | title = N-Benzyl-2,3-Azetidinedione (2,3-Azetidinedione, 1-(phenylmethyl)-)| collvol = 10 | collvolpages = 41 | year = 1998 | prep = V75P0106 | volume = 75 | pages = 106 | doi = 10.15227/orgsyn.075.0106}}. Grignard reagents and organolithium compounds react with MeCHO to give hydroxyethyl derivatives.{{OrgSynth | author = Walter, L. A. | title = 1-(α-Pyridyl)-2-Propanol (2-(β-Hydroxypropyl)pyridine) | collvol = 3 | collvolpages = 757 | year = 1943 | prep = cv3p0757 | volume = 23 | pages = 83 | doi = 10.15227/orgsyn.023.0083}} In one of the more spectacular addition reactions, formaldehyde in the presence of calcium hydroxide adds to MeCHO to give pentaerythritol, {{chem2|C(CH2OH)4}} and formate.{{OrgSynth | author = Schurink, H. B. J. | title = Pentaerythritol | collvol = 1 | collvolpages = 425 | year = 1925 | prep = CV1P0425 | volume = 4 | pages = 53 | doi = 10.15227/orgsyn.004.0053}}

In a Strecker reaction, acetaldehyde condenses with cyanide and ammonia to give, after hydrolysis, the amino acid alanine.{{OrgSynth | author1 = Kendall, E. C. | authorlink1 = Edward Calvin Kendall | author2 = McKenzie, B. F. | title = dl-Alanine | collvol = 1 | collvolpages = 21 | year = 1929 | prep = CV1P0021 | volume = 9 | pages = 4 | doi = 10.15227/orgsyn.009.0004}} Acetaldehyde can condense with amines to yield imines; for example, with cyclohexylamine to give N-ethylidenecyclohexylamine. These imines can be used to direct subsequent reactions like an aldol condensation.{{OrgSynth | authorlink1 = Georg Wittig | author1 = Wittig, G. | author2 = Hesse, A. | title = Directed Aldol Condensations: β-Phenylcinnamaldehyde (2-Propenal, 3,3-diphenyl-) | collvol = 6 | collvolpages = 901 | year = 1970 | prep = cv6p0901 | volume = 50 | pages = 66 | doi = 10.15227/orgsyn.050.0066}}

It is also a building block in the synthesis of heterocyclic compounds. In one example, it converts, upon treatment with ammonia, to 5-ethyl-2-methylpyridine ("aldehyde-collidine").{{OrgSynth | author1 = Frank, R. L. | author2 = Pilgrim, F. J. | author3 = Riener, E. F. | title = 5-Ethyl-2-Methylpyridine (2-Picoline, 5-ethyl-) | year = 1950 | volume = 30 | pages = 41 | doi = 10.15227/orgsyn.030.0041}}

{{multiple image|caption_align=left

| align = left

| direction = horizontal

| total_width = 320

| image1 = Paraldehyde structure.svg

| image2 = Metaldehyde.svg

| footer = Cyclic oligomers of acetaldehyde ({{chem2|CH3CHO)_{n}|}}: paraldehyde (n = 3, left) and metaldehyde (n = 4, right)

}}

Three molecules of acetaldehyde condense to form "paraldehyde", a cyclic trimer containing C-O single bonds. Similarly condensation of four molecules of acetaldehyde give the cyclic molecule metaldehyde. Paraldehyde can be produced in good yields, using a sulfuric acid catalyst. Metaldehyde is only obtained in a few percent yield and with cooling, often using HBr rather than {{chem2|H2SO4}} as the catalyst. At {{convert|−40|C|F}} in the presence of acid catalysts, polyacetaldehyde is produced. There are two stereomers of paraldehyde and four of metaldehyde.

The German chemist Valentin Hermann Weidenbusch (1821–1893) synthesized paraldehyde in 1848 by treating acetaldehyde with acid (either sulfuric or nitric acid) and cooling to {{convert|0|C|F}}. He found it quite remarkable that when paraldehyde was heated with a trace of the same acid, the reaction went the other way, recreating acetaldehyde.{{cite journal |first=H. |last=Weidenbusch |trans-title=On some products of the reaction of alkalies and acids with acetaldehyde |title=Ueber einige Producte der Einwirkung von Alkalien und Säuren auf den Aldehyd |journal=Annalen der Chemie |volume=66 |pages=152–165; see pp. 155–8 |date=1848 |url=https://babel.hathitrust.org/cgi/pt?id=chi.47401598;view=1up;seq=584}}

Although vinyl alcohol is a polymeric form of acetaldehyde ({{slink||Tautomerization to vinyl alcohol}}), polyvinyl alcohol cannot be produced from acetaldehyde.

File:Acetal formation 2.png, R¹={{chem2|CH3}} R²={{chem2|CH3CH2}}]]

Acetaldehyde forms a stable acetal upon reaction with ethanol under conditions that favor dehydration. The product, {{chem2|CH3CH(OCH2CH3)2}}, is formally named 1,1-diethoxyethane but is commonly referred to as "acetal".{{OrgSynth | author1 = Adkins, H. | authorlink1 = Homer Burton Adkins | author2 = Nissen, B. H. | title = Acetal | collvol = 1 | collvolpages = 1 | year = 1923 | prep = CV1P0001 | volume = 3 | pages = 1 | doi = 10.15227/orgsyn.003.0001}} This can cause confusion as "acetal" is more commonly used to describe compounds with the functional groups RCH(OR')₂ or RR'C(OR'')₂ rather than referring to this specific compound — in fact, 1,1-diethoxyethane is also described as the diethyl acetal of acetaldehyde.

Acetaldehyde is a precursor to vinylphosphonic acid, which is used to make adhesives and ion conductive membranes. The synthesis sequence begins with a reaction with phosphorus trichloride:{{cite journal | last1 = Lavinia | first1 = M. | last2 = Gheorghe | first2 = I. | year = 2010 | title = Poly(vinylphosphonic acid) and its derivatives | doi = 10.1016/j.progpolymsci.2010.04.001 | journal = Progress in Polymer Science | volume = 35 | issue = 8| pages = 1078–92 }}

1. {{chem2|PCl3 + CH3CHO -> CH3CH(O−)PCl3+}}
2. {{chem2|CH3CH(O−)PCl3+ + 2 CH3CO2H -> CH3CH(Cl)PO(OH)2 + 2 CH3COCl}}
3. {{chem2|CH3CH(Cl)PO(OH)2 -> CH2\dCHPO(OH)2 + HCl}}

In the liver, the enzyme, alcohol dehydrogenase oxidizes ethanol into acetaldehyde, which is then further oxidized into harmless acetic acid by acetaldehyde dehydrogenase. These two oxidation reactions are coupled with the reduction of {{chem2|NAD+}} to NADH.{{cite journal | author1 = Hipolito, L. | author2 = Sanchez, M. J. | author3 = Polache, A. | author4 = Granero, L. | title = Brain metabolism of ethanol and alcoholism: An update | journal = Curr. Drug Metab. | year = 2007 | volume = 8 | pages = 716–727 | doi = 10.2174/138920007782109797 | pmid = 17979660 | issue = 7}} In the brain, the enzyme catalase is primarily responsible for oxidizing ethanol to acetaldehyde, and alcohol dehydrogenase plays a minor role. The last steps of alcoholic fermentation in bacteria, plants, and yeast involve the conversion of pyruvate into acetaldehyde and carbon dioxide by the enzyme pyruvate decarboxylase, followed by the conversion of acetaldehyde into ethanol. The latter reaction is again catalyzed by an alcohol dehydrogenase, now operating in the opposite direction.

Many East Asian people have an ALDH2 mutation which makes them significantly less efficient at oxidizing acetaldehyde. On consuming alcohol, their bodies tend to accumulate excessive amounts of acetaldehyde, causing the so-called alcohol flush reaction.{{cite journal | vauthors = Lee H, Kim SS, You KS, Park W, Yang JH, Kim M, Hayman LL | title = Asian flushing: genetic and sociocultural factors of alcoholism among East asians | journal = Gastroenterology Nursing | volume = 37 | issue = 5 | pages = 327–36 | year = 2014 | pmid = 25271825 | doi = 10.1097/SGA.0000000000000062 | s2cid = 206059192 }} They develop a characteristic flush on the face and body, along with "nausea, headache and general physical discomfort".{{cite web | title=Esophageal Cancer and the 'Asian Glow'|publisher=Dartmouth Undergraduate Journal of Science| date=21 November 2009 | url=https://sites.dartmouth.edu/dujs/2009/11/21/esophageal-cancer-and-the-asian-glow/|archive-date=2016-01-12 |archive-url=https://web.archive.org/web/20160112231737/http://dujs.dartmouth.edu/fall-2009/esophageal-cancer-and-the-%e2%80%98asian-glow%e2%80%99 |url-status=live}} Ingestion of the drug disulfiram, which inhibits ALDH2, leads to a similar reaction {{crossreference|(see: {{slink||Aggravating factors}} below)}}.

Traditionally, acetaldehyde was mainly used as a precursor to acetic acid. This application has declined because acetic acid is produced more efficiently from methanol by the Monsanto and Cativa processes. Acetaldehyde is an important precursor to pyridine derivatives, pentaerythritol, and crotonaldehyde. Urea and acetaldehyde combine to give a useful resin. Acetic anhydride reacts with acetaldehyde to give ethylidene diacetate, a precursor to vinyl acetate, which is used to produce polyvinyl acetate.

The global market for acetaldehyde is declining. Demand has been impacted by changes in the production of plasticizer alcohols, which has shifted because n-butyraldehyde is less often produced from acetaldehyde, instead being generated by hydroformylation of propylene. Likewise, acetic acid, once produced from acetaldehyde, is made predominantly by the lower-cost methanol carbonylation process.[http://www.ihs.com/products/chemical/planning/ceh/acetaldehyde.aspx "Acetaldehyde"]. ihs.com. The impact on demand has led to increase in prices and thus slowdown in the market.

File:Production of acetaldehyde.JPG

China is the largest consumer of acetaldehyde in the world, accounting for almost half of global consumption in 2012. Major use has been the production of acetic acid. Other uses such as pyridines and pentaerythritol are expected to grow faster than acetic acid, but the volumes are not large enough to offset the decline in acetic acid. As a consequence, overall acetaldehyde consumption in China may grow slightly at 1.6% per year through 2018. Western Europe is the second-largest consumer of acetaldehyde worldwide, accounting for 20% of world consumption in 2012. As with China, the Western European acetaldehyde market is expected to increase only very slightly at 1% per year during 2012–2018. However, Japan could emerge as a potential consumer for acetaldehyde in the next five years due to newfound use in commercial production of butadiene. The supply of butadiene has been volatile in Japan and the rest of Asia. This should provide the much needed boost to the flat market, as of 2013.Research and Markets ltd. [http://www.researchandmarkets.com/research/lc8hz5/acetaldehyde "Acetaldehyde — Global Business Strategic Report"].

The threshold limit value is 25ppm (STEL/ceiling value) and the MAK (Maximum Workplace Concentration) is 50 ppm. At 50 ppm acetaldehyde, no irritation or local tissue damage in the nasal mucosa is observed. When taken up by the organism, acetaldehyde is metabolized rapidly in the liver to acetic acid. Only a small proportion is exhaled unchanged. After intravenous injection, the half-life in the blood is approximately 90 seconds.

Many serious cases of acute intoxication have been recorded. Acetaldehyde naturally breaks down in the human body.{{Cite journal

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| year = 1989

| last1 = Tsukamoto

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| title = Determinations of ethanol, acetaldehyde and acetate in blood and urine during alcohol oxidation in man

| journal = Alcohol and Alcoholism

| volume = 24

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}}

Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat, and respiratory tract. This occurs at concentrations as low as 1000 ppm. Symptoms of exposure to this compound include nausea, vomiting, and headache. These symptoms may not happen immediately. The perception threshold for acetaldehyde in air is in the range between 0.07 and 0.25 ppm. At such concentrations, the fruity odor of acetaldehyde is apparent. Conjunctival irritations have been observed after a 15-minute exposure to concentrations of 25 and 50 ppm, but transient conjunctivitis and irritation of the respiratory tract have been reported after exposure to 200 ppm acetaldehyde for 15 minutes.

Acetaldehyde is carcinogenic in humans.[http://www.epa.gov/chemfact/s_acetal.txt Chemical Summary For Acetaldehyde], US Environmental Protection Agency{{cite web |url= http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out275_en.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out275_en.pdf |archive-date=2022-10-09 |url-status=live|title= Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers Concerning Acetaldehyde |author= Scientific Committee on Cosmetic Products and Non-Food Products|date=2004-05-25 |page=11|access-date=2011-09-28}} In 1988 the International Agency for Research on Cancer stated, "There is sufficient evidence for the carcinogenicity of acetaldehyde (the major metabolite of ethanol) in experimental animals."{{Cite book |title=Alcohol drinking |publisher=World Health Organization, International Agency for Research on Cancer |location=Lyon |year=1988 |isbn=978-92-832-1244-7 |url=https://archive.org/details/alcoholdrinking0044iarc |author=International Agency for Rescarch on Cancer, World Health Organization. |url-access=registration }} p3 In October 2009 the International Agency for Research on Cancer updated the classification of acetaldehyde stating that acetaldehyde included in and generated endogenously from alcoholic beverages is a Group I human carcinogen.{{cite journal |vauthors=Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V |title=A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish |journal=Lancet Oncol |volume=10 |issue=11 |pages=1033–4 |date=November 2009 |pmid=19891056 |doi=10.1016/s1470-2045(09)70326-2 }} In addition, acetaldehyde is damaging to DNA{{Cite journal

| pmid = 3389666

| year = 1988

| last1 = Lambert

| first1 = B

| title = DNA and chromosome damage induced by acetaldehyde in human lymphocytes in vitro

| journal = Annals of the New York Academy of Sciences

| volume = 534

| issue = 1

| pages = 369–76

| last2 = He

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| bibcode = 1988NYASA.534..369L |doi = 10.1111/j.1749-6632.1988.tb30124.x | s2cid = 22732731

}} and causes abnormal muscle development as it binds to proteins.{{Cite journal | doi = 10.1093/alcalc/agh085| pmid = 15304379| title = Acetaldehyde-Induced Cardiac Contractile Dysfunction May Be Alleviated by Vitamin B1 but Not by Vitamins B6 or B12| journal = Alcohol and Alcoholism| volume = 39| issue = 5| pages = 450–4| year = 2004| last1 = Aberle | first1 = N. S.| last2 = Burd| first2 = L| last3 = Zhao| first3 = B. H.| last4 = Ren| first4 = J| doi-access = free}}

Acetaldehyde induces DNA interstrand crosslinks, a form of DNA damage. These can be repaired by either of two replication-coupled DNA repair pathways.{{cite journal |vauthors=Hodskinson MR, Bolner A, Sato K, Kamimae-Lanning AN, Rooijers K, Witte M, Mahesh M, Silhan J, Petek M, Williams DM, Kind J, Chin JW, Patel KJ, Knipscheer P |title=Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms |journal=Nature |volume=579 |issue=7800 |pages=603–8 |date=March 2020 |pmid=32132710 |pmc=7116288 |doi=10.1038/s41586-020-2059-5 }} The first is referred to as the FA pathway, because it employs gene products defective in Fanconi's anemia patients. This repair pathway results in increased mutation frequency and altered mutational spectrum. The second repair pathway requires replication fork convergence, breakage of the acetaldehyde crosslink, translesion synthesis by a Y-family DNA polymerase and homologous recombination.

People with a genetic deficiency for the enzyme responsible for the conversion of acetaldehyde into acetic acid may have a greater risk of Alzheimer's disease. "These results indicate that the ALDH2 deficiency is a risk factor for LOAD [late-onset Alzheimer's disease] ..."{{Cite journal|last= Ohta |first=S |author2=Ohsawa I|author3=Kamino K|author4=Ando F|author5= Shimokata H. |date=April 2004 |title=Mitochondrial ALDH2 Deficiency as an Oxidative Stress |journal=Annals of the New York Academy of Sciences |volume=1011 |issue=1 |pages=36–44 |doi= 10.1196/annals.1293.004 |pmid= 15126281|bibcode=2004NYASA1011...36O |s2cid=28571902 }}

A study of 818 heavy drinkers found that those exposed to more acetaldehyde than normal through a genetic variant of the gene encoding for ADH1C, ADH1C*1, are at greater risk of developing cancers of the upper gastrointestinal tract and liver.{{Cite journal | last1 = Homann | first1 = N. | last2 = Stickel | first2 = F. | last3 = König | first3 = I. R. | last4 = Jacobs | first4 = A. | last5 = Junghanns | first5 = K. | last6 = Benesova | first6 = M. | last7 = Schuppan | first7 = D. | last8 = Himsel | first8 = S. | last9 = Zuber-Jerger | first9 = I. | last10 = Hellerbrand | first10 = C. | last11 = Ludwig | first11 = D. | last12 = Caselmann | first12 = W. H. | last13 = Seitz | first13 = H. K. | title = Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers | doi = 10.1002/ijc.21583 | journal = International Journal of Cancer | volume = 118 | issue = 8 | pages = 1998–2002 | year = 2006 | pmid = 16287084| s2cid = 11716548 | doi-access = free }}

The drug disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase, an enzyme that oxidizes the compound into acetic acid. Metabolism of ethanol forms acetaldehyde before acetaldehyde dehydrogenase forms acetic acid, but with the enzyme inhibited, acetaldehyde accumulates. If one consumes ethanol while taking disulfiram, the hangover effect of ethanol is felt more rapidly and intensely (disulfiram-alcohol reaction). As such, disulfiram is sometimes used as a deterrent for alcoholics wishing to stay sober.{{cite journal |last1=Omran |first1=Z |title=Development of new disulfiram analogues as ALDH1a1-selective inhibitors. |journal=Bioorganic & Medicinal Chemistry Letters |date=15 May 2021 |volume=40 |pages=127958 |doi=10.1016/j.bmcl.2021.127958 |pmid=33744437|s2cid=232311209 }}

Acetaldehyde is a potential contaminant in workplace, indoors, and ambient environments. Moreover, the majority of humans spend more than 90% of their time in indoor environments, increasing any exposure and the risk to human health.{{Cite book |author=Spengler, John D. |author2=McCarthy, John F. |author3=Samet, Jonathan M. | date = 2000 | title = Indoor Air Quality Handbook |url=https://archive.org/details/indoorairquality00spen |url-access=limited | publisher = McGraw-Hill | isbn = 978-0-07-445549-4 |oclc=50566621 | page = [https://archive.org/details/indoorairquality00spen/page/n11 761]}}

In a study in France, the mean indoor concentration of acetaldehydes measured in 16 homes was approximately seven times higher than the outside acetaldehyde concentration. The living room had a mean of 18.1±17.5 μg m⁻³ and the bedroom was 18.2±16.9 μg m⁻³, whereas the outdoor air had a mean concentration of 2.3±2.6 μg m⁻³.{{citation needed|date=June 2018}}

It has been concluded that volatile organic compounds (VOC) such as benzene, formaldehyde, acetaldehyde, toluene, and xylenes have to be considered priority pollutants with respect to their health effects. It has been pointed that in renovated or completely new buildings, the VOCs concentration levels are often several orders of magnitude higher. The main sources of acetaldehydes in homes include building materials, laminate, PVC flooring, varnished wood flooring, and varnished cork/pine flooring (found in the varnish, not the wood). It is also found in plastics, oil-based and water-based paints, in composite wood ceilings, particle-board, plywood, treated pine wood, and laminated chipboard furniture.{{cite journal | author1 = Dafni A. Missia | author2 = E. Demetriou | author3 = N. Michael | author4= E.I. Tolis | author5 = J.G. Bartzis | title = Indoor exposure from building materials: A field study | journal = Atmospheric Environment | year = 2010 | volume = 44 | pages = 4388–95 | doi = 10.1016/j.atmosenv.2010.07.049 | issue = 35| bibcode = 2010AtmEn..44.4388M }}

The use of acetaldehyde is widespread in different industries, and it may be released into waste water or the air during production, use, transportation and storage. Sources of acetaldehyde include fuel combustion emissions from stationary internal combustion engines and power plants that burn fossil fuels, wood, or trash, oil and gas extraction, refineries, cement kilns, lumber and wood mills and paper mills.{{Cite journal|last1=Shrestha|first1=Krishna Prasad|last2=Giri|first2=Binod Raj|last3=Adil|first3=Mohammad|last4=Seidel|first4=Lars|last5=Zeuch|first5=Thomas|last6=Farooq|first6=Aamir|last7=Mauss|first7=Fabian|date=2021-09-16|title=Detailed Chemical Kinetic Study of Acetaldehyde Oxidation and Its Interaction with NOx|url=https://doi.org/10.1021/acs.energyfuels.1c01948|journal=Energy & Fuels|volume=35|issue=18|pages=14963–83|doi=10.1021/acs.energyfuels.1c01948|s2cid=239683740|issn=0887-0624|hdl=10754/670859|hdl-access=free}} Acetaldehyde is also present in automobile and diesel exhaust.{{Cite journal | last1 = Clements | first1 = A. L. | last2 = Jia | first2 = Y. | last3 = Denbleyker | first3 = A. | last4 = McDonald-Buller | first4 = E. | last5 = Fraser | first5 = M. P. | last6 = Allen | first6 = D. T. | last7 = Collins | first7 = D. R. | last8 = Michel | first8 = E. | last9 = Pudota | first9 = J. | last10 = Sullivan | first10 = D. | last11 = Zhu | first11 = Y. | doi = 10.1016/j.atmosenv.2009.06.044 | title = Air pollutant concentrations near three Texas roadways, part II: Chemical characterization and transformation of pollutants | journal = Atmospheric Environment | volume = 43 | issue = 30 | pages = 4523–34 | year = 2009 |bibcode = 2009AtmEn..43.4523C }} As a result, acetaldehyde is "one of the most frequently found air toxics with cancer risk greater than one in a million".

Natural tobacco polysaccharides, including cellulose, have been shown to be the primary precursors making acetaldehyde a significant constituent of tobacco smoke.{{cite journal | last1 = Talhout | first1 = R | last2 = Opperhuizen | first2 = A | last3 = van Amsterdam | first3 = JG | date = Oct 2007 | title = Role of acetaldehyde in tobacco smoke addiction | journal = Eur Neuropsychopharmacol | volume = 17 | issue = 10| pages = 627–36 | pmid = 17382522 | doi = 10.1016/j.euroneuro.2007.02.013 | s2cid = 25866206 }}{{cite journal|last1=Talhout|first1=Reinskje|last2=Schulz|first2=Thomas|last3=Florek|first3=Ewa|last4=Van Benthem|first4=Jan|last5=Wester|first5=Piet|last6=Opperhuizen|first6=Antoon|title=Hazardous Compounds in Tobacco Smoke|journal=International Journal of Environmental Research and Public Health|volume=8|issue=12|year=2011|pages=613–628|issn=1660-4601|doi=10.3390/ijerph8020613|pmid=21556207|pmc=3084482|doi-access=free}} It has been demonstrated to have a synergistic effect with nicotine in rodent studies of addiction.[http://drugabuse.gov/NIDA_notes/NNvol20N3/Study.html "NIDA — Publications — NIDA Notes — Vol. 20, No. 3"] {{Webarchive|url=https://web.archive.org/web/20090825223924/http://drugabuse.gov/NIDA_notes/NNvol20N3/Study.html |date=25 August 2009 }}. drugabuse.gov.[https://web.archive.org/web/20110209232332/http://www.universityofcalifornia.edu/news/article/6726 Nicotine's addictive hold increases when combined with other tobacco smoke chemicals, UCI study finds]. University of California. 2004-10-28 Acetaldehyde is also the most abundant carcinogen in tobacco smoke; it is dissolved into the saliva while smoking.

Acetaldehyde has been found in cannabis smoke. This finding emerged through the use of new chemical techniques that demonstrated the acetaldehyde present was causing DNA damage in laboratory settings.{{cite journal | last1 = Singh | first1 = R | year = 2009 | title = Evaluation of the DNA Damaging Potential of Cannabis Cigarette Smoke by the Determination of Acetaldehyde Derived N2-Ethyl-2'-deoxyguanosine Adducts | journal = Chem. Res. Toxicol. | volume = 22 | issue = 6| pages = 1181–8 | doi = 10.1021/tx900106y | pmid = 19449825 }}

Many microbes produce acetaldehyde from ethanol, but they have a lower capacity to eliminate the acetaldehyde, which can lead to the accumulation of acetaldehyde in saliva, stomach acid, and intestinal contents. Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans.{{cite journal | author = Salaspuro, M. | title = Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract cancers | year = 2009 | volume = 44 | issue = 8 | pages = 912–925 | doi = 10.1080/00365520902912563 | journal = Scandinavian Journal of Gastroenterology | pmid = 19396661| s2cid = 23291758 }} According to European Commission's Scientific Committee on Consumer Safety's (SCCS) "Opinion on Acetaldehyde" (2012) the cosmetic products special risk limit is 5 mg/L and acetaldehyde should not be used in mouth-washing products.[http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_104.pdf Scientific Committee on Consumer Safety SCCS OPINION ON Acetaldehyde]. European Commission. 18 September 2012

Acetaldehyde can be produced by the photo-oxidation of polyethylene terephthalate (PET), via a Type II Norrish reaction.{{cite journal |last1=Day |first1=M. |last2=Wiles |first2=D. M. |title=Photochemical degradation of poly(ethylene terephthalate). III. Determination of decomposition products and reaction mechanism |journal=Journal of Applied Polymer Science |date=January 1972 |volume=16 |issue=1 |pages=203–215 |doi=10.1002/app.1972.070160118}}

File:Poly(ethylene terephthalate) - Type II Norrish to acetaldehyde.png

Although the levels produced by this process are minute acetaldehyde has an exceedingly low taste/odor threshold of around 20–40 ppb and can cause an off-taste in bottled water.{{cite journal |last1=Nawrocki |first1=J |last2=Dąbrowska |first2=A |last3=Borcz |first3=A |title=Investigation of carbonyl compounds in bottled waters from Poland |journal=Water Research |date=November 2002 |volume=36 |issue=19 |pages=4893–4901 |doi=10.1016/S0043-1354(02)00201-4|pmid=12448533 |bibcode=2002WatRe..36.4893N }} The level at which an average consumer could detect acetaldehyde is still considerably lower than any toxicity.{{cite web|title=Do Acetaldehyde and Formaldehyde from Pet Bottles Result in Unacceptable Flavor or Aroma in Bottled Water?|url=http://www.petresin.org/pdf/PETRAACETALDEHYDE_AND_FORMALDEHYDE_FROM_PET_BOTTLES_August_2006.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.petresin.org/pdf/PETRAACETALDEHYDE_AND_FORMALDEHYDE_FROM_PET_BOTTLES_August_2006.pdf |archive-date=2022-10-09 |url-status=live|publisher=PET Resin Association|access-date=26 February 2015}}

Candida albicans in patients with potentially carcinogenic oral diseases has been shown to produce acetaldehyde in quantities sufficient to cause problems.{{cite journal|last1=Gainza-Cirauqui|first1=M.L.|last2=Nieminen|first2=M.T.|last3=Novak Frazer|first3=L.|last4=Aguirre-Urizar|first4=J.M.|last5=Moragues|first5=M.D.|last6=Rautemaa|first6=R.|title=Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders|journal=Journal of Oral Pathology and Medicine|date=March 2013|volume=42|issue=3|pages=243–9|doi=10.1111/j.1600-0714.2012.01203.x|pmid=22909057|url=https://www.um.edu.mt/library/oar//handle/123456789/16302 |url-access=subscription}}

• Alcohol dehydrogenase
• Disulfiram-like drug
• Formaldehyde
• Paraldehyde
• Wine fault

{{Reflist|30em}}

{{Commons category}}

• [http://www.inchem.org/documents/icsc/icsc/eics0009.htm International Chemical Safety Card 0009]
• [https://www.cdc.gov/niosh/npg/npgd0001.html NIOSH Pocket Guide to Chemical Hazards]
• {{cite book |chapter=ALIPHATIC ALDEHYDES: METHOD 2018 |chapter-url=https://web.archive.org/web/20081227035621/http://www.cdc.gov/niosh/nmam/pdfs/2018.pdf |title=NIOSH Manual of Analytical Methods (NMAM) |edition=4th |date=15 March 2003 |pages=1–10 }}
• {{cite book |chapter=ACETALDEHYDE |chapter-url=https://publications.iarc.fr/_publications/media/download/2291/c8544cbda9f596bef663eb54801042da1af73405.pdf |title=Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=71 |date=1999 |isbn=978-92-832-1271-3 |pages=319–334 |url=https://publications.iarc.fr/89}}
• Hal Kibbey, [http://www.indiana.edu/~rcapub/v17n3/p18.html Genetic Influences on Alcohol Drinking and Alcoholism], Indiana University Research and Creative Activity, Vol. 17 no. 3.
• [https://web.archive.org/web/20041009142826/http://www.grokfood.com/additives/2.htm United States Food and Drug Administration (FDA) information for acetaldehyde]
• [https://web.archive.org/web/20130601111815/http://www.inclusive-science-engineering.com/acetaldehyde-production-ethylene-oxidation-stage-process/ Acetaldehyde production process flow sheet by ethylene oxidation method]

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