Editing Antioxidant (section)

== Uses ==

=== Food preservatives ===
{{See also|E number#E300–E399 (antioxidants, acidity regulators)}}

Antioxidants are added to food to prevent deterioration. Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers. However, as oxygen is also important for plant [[Respiration (physiology)|respiration]], storing plant materials in [[Anaerobic organism#Metabolism|anaerobic]] conditions produces unpleasant flavors and unappealing colors.<ref>{{Cite journal |vauthors=Kader AA, Zagory D, Kerbel EL |year=1989 |title=Modified atmosphere packaging of fruits and vegetables |journal=Critical Reviews in Food Science and Nutrition |volume=28 |issue=1 |pages=1–30 |doi=10.1080/10408398909527490 |pmid=2647417}}</ref> Consequently, packaging of fresh fruits and vegetables contains an ≈8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or [[fungus|fungal]] spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.<ref>{{Cite journal |vauthors=Zallen EM, Hitchcock MJ, Goertz GE |date=December 1975 |title=Chilled food systems. Effects of chilled holding on quality of beef loaves |journal=Journal of the American Dietetic Association |volume=67 |issue=6 |pages=552–7 |doi=10.1016/S0002-8223(21)14836-9 |pmid=1184900}}</ref> These preservatives include natural antioxidants such as ascorbic acid (AA, E300) and tocopherols (E306), as well as synthetic antioxidants such as [[propyl gallate]] (PG, E310), [[tert-Butylhydroquinone|tertiary butylhydroquinone]] (TBHQ), [[butylated hydroxyanisole]] (BHA, E320) and [[butylated hydroxytoluene]] (BHT, E321).<ref>{{Cite journal |vauthors=Iverson F |date=June 1995 |title=Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole |journal=Cancer Letters |volume=93 |issue=1 |pages=49–54 |doi=10.1016/0304-3835(95)03787-W |pmid=7600543}}</ref><ref>{{Cite web |title=E number index |url=http://www.ukfoodguide.net/enumeric.htm#antioxidants |url-status=usurped |archive-url=https://web.archive.org/web/20070304151341/http://www.ukfoodguide.net/enumeric.htm |archive-date=4 March 2007 |access-date=5 March 2007 |publisher=UK food guide}}</ref>

Unsaturated fats can be highly susceptible to oxidation, causing [[rancidification]].<ref>{{Cite journal |vauthors=Robards K, Kerr AF, Patsalides E |date=February 1988 |title=Rancidity and its Measurement in Edible Oils and Snack Foods. A review |journal=The Analyst |volume=113 |issue=2 |pages=213–24 |bibcode=1988Ana...113..213R |doi=10.1039/an9881300213 |pmid=3288002}}</ref> Oxidized lipids are often discolored and can impart unpleasant tastes and flavors. Thus, these foods are rarely preserved by drying; instead, they are preserved by [[Smoking (cooking technique)|smoking]], [[salting (food)|salting]], or [[fermentation (food)|fermenting]]. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Metals catalyse oxidation.{{Citation needed|date=April 2025}} Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants. Fatty foods are sensitive to photooxidation,<ref>{{Cite journal |vauthors=Del Carlo M, Sacchetti G, Di Mattia C, Compagnone D, Mastrocola D, Liberatore L, Cichelli A |date=June 2004 |title=Contribution of the phenolic fraction to the antioxidant activity and oxidative stability of olive oil |journal=Journal of Agricultural and Food Chemistry |volume=52 |issue=13 |pages=4072–9 |doi=10.1021/jf049806z |pmid=15212450|bibcode=2004JAFC...52.4072D }}</ref> which forms [[hydroperoxide]]s by oxidizing unsaturated fatty acids and [[ester]].<ref name=":1">{{Citation |last=Frankel |first=Edwin N. |title=Chapter 3 - Photooxidation of unsaturated fats |date=2012-01-01 |work=Lipid Oxidation (Second Edition) |pages=51–66 |editor-last=Frankel |editor-first=Edwin N. |url=https://www.sciencedirect.com/science/article/pii/B9780953194988500047 |access-date=2023-04-15 |series=Oily Press Lipid Library Series |publisher=Woodhead Publishing |language=en |isbn=978-0-9531949-8-8}}</ref> Exposure to [[Ultraviolet|ultraviolet (UV)]] radiation can cause direct photooxidation and decompose peroxides and [[Carbonyl group|carbonyl]] molecules. These molecules undergo free radical chain reactions, but antioxidants inhibit them by preventing the oxidation processes.<ref name=":1" />

=== Pharmaceutical excipients ===
Some pharmaceutical products require protection from oxidation. A number of antioxidants can be used as [[excipient]]s. [[Sequestrant]]s{{Citation needed|date=April 2025}} such as [[disodium EDTA]] can also be used to prevent metal-catalyzed oxidation.<ref>{{cite web |title=Excipients in the dossier for application for marketing authorisation of a medicinal product - Scientific guideline {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/excipients-dossier-application-marketing-authorisation-medicinal-product-scientific-guideline |website=www.ema.europa.eu |language=en |date=1 January 2008}}</ref>

=== Cosmetics preservatives ===
Antioxidant stabilizers are also added to fat-based cosmetics such as lipstick and [[moisturizer]]s to prevent rancidity.<ref>{{Cite journal |date=2007 |title=Final report on the amended safety assessment of Propyl Gallate. |journal=International Journal of Toxicology |volume=26 |issue=3_suppl |pages=89–118 |doi=10.1080/10915810701663176 |pmid=18080874 |s2cid=39562131 |quote=Propyl Gallate is a generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat-containing food from rancidity that results from the formation of peroxides.}}</ref> Antioxidants in cosmetic products prevent oxidation of active ingredients and lipid content. For example, phenolic antioxidants such as [[(E)-Stilbene|stilbenes]], [[flavonoid]]s, and [[hydroxycinnamic acid]] strongly absorb UV radiation due to the presence of [[chromophore]]s. They reduce oxidative stress from sun exposure by absorbing UV light.<ref>{{Cite journal |last1=Débora |first1=Jackeline |last2=Cleide |first2=Viviane |last3=Luciana |first3=Oliveira |last4=Rosemeire |first4=Aparecida |date=August 7, 2019 |title=Polyphenols as natural antioxidants in cosmetics applications |journal=Journal of Cosmetic Dermatology |volume=19 |issue=1 |pages=33–37 |doi=10.1111/jocd.13093 |pmid=31389656 |s2cid=201156301}}</ref>

=== Industrial uses ===
{{more citations needed section|date=February 2025}}
[[Image:Antioxidant.png|thumb|right|250px|class=skin-invert-image|Substituted [[phenols]] and derivatives of [[p-Phenylenediamine|phenylenediamine]] are common antioxidants used to inhibit gum formation in gasoline (petrol).]]
[[File:Polymer auto-oxidation.png|250px|right|thumb|The cyclic mechanism of autoxidation, which antioxidants aim to break]]

Antioxidants may be added to industrial products, such as [[Gasoline additive|stabilizers]] in [[fuel]]s and [[Oil additive|additives]] in [[lubricant]]s, to prevent oxidation and polymerization that leads to the formation of engine-fouling residues.<ref>{{Cite journal |vauthors=Boozer CE, Hammond GS, Hamilton CE, Sen JN |year=1955 |title=Air Oxidation of Hydrocarbons.1II. The Stoichiometry and Fate of Inhibitors in Benzene and Chlorobenzene |journal=Journal of the American Chemical Society |volume=77 |issue=12 |pages=3233–7 |doi=10.1021/ja01617a026|bibcode=1955JAChS..77.3233B }}</ref>

{| class="wikitable" style="margin-left: auto; margin-right: auto; text-align:center;"
|-
!Fuel additive (Innospec)
!Components<ref name="innospec">{{Cite web |title=Fuel antioxidants |url=http://www.innospecinc.com/americas/products/fuel_antitoxidants.cfm |archive-url=https://web.archive.org/web/20061015202259/http://www.innospecinc.com/americas/products/fuel_antitoxidants.cfm |archive-date=15 October 2006 |access-date=27 February 2007 |publisher=Innospec Chemicals}} [https://innospec.com/fuel-additives/refinery-pipeline/antioxidants/ newer version, less details]</ref>
!Applications<ref name="innospec" />
|-
|AO-22
|[[N,N'-di-2-butyl-1,4-phenylenediamine]]
||Turbine oils, [[transformer oil]]s, [[hydraulic fluid]]s, [[wax]]es, and [[grease (lubricant)|greases]]
|-
||AO-24
||50% active ingredient, principally N,N'-di-2-butyl-1,4-phenylenediamine
||Low-temperature oils
|-
||AO-29
||principally [[2,6-di-tert-butyl-4-methylphenol]] (BHT)
||Turbine oils, transformer oils, hydraulic fluids, waxes, greases, and gasolines
|-
||AO-30
||&gt; 97% [[2,4-dimethyl-6-tert-butylphenol]] 
||[[Jet fuel]]s and gasolines, including aviation gasolines
|-
||AO-31
||&gt; 72% 2,4-dimethyl-6-tert-butylphenol
||Jet fuels and gasolines, including aviation gasolines
|-
||AO-32
||&gt;&nbsp;55%&nbsp;2,4-dimethyl-6-tert-butylphenol&nbsp;and &gt;&nbsp;15%&nbsp;2,6-di-tert-butyl-4-methylphenol
||Jet fuels and gasolines, including aviation gasolines
|-
|AO-36
|principally propylated and butylated phenols
|gasolines, low temperature
|-
||AO-37
||principally [[2,6-di-tert-butylphenol]]
||Jet fuels and gasolines, widely approved for [[aviation fuel]]s
|}

Antioxidant [[polymer stabilizers]] are widely used to prevent the degradation of [[polymer]]s, such as rubbers, plastics and [[adhesive]]s, that causes a loss of strength and flexibility in these materials.<ref>{{Cite web |title=Why use Antioxidants? |url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id= |url-status=dead |archive-url=https://web.archive.org/web/20070211063739/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id= |archive-date=11 February 2007 |access-date=27 February 2007 |publisher=SpecialChem Adhesives}}</ref> Polymers containing [[double bond]]s in their main chains, such as [[natural rubber]] and [[polybutadiene]], are especially susceptible to [[oxidation]] and [[ozonolysis]]. They can be protected by [[antiozonant]]s. Oxidation can be accelerated by [[UV radiation]] in natural sunlight to cause [[Photo-oxidation of polymers|photo-oxidation]]. Various specialised light stabilisers, such as [[hindered amine light stabilizers|HALS]] may be added to plastics to prevent this. Antioxidants for polymer materials are:

* Primary antioxidants scavenge free radicals formed during the initial (thermal) oxidation process (ROO•), thus preventing chain reactions that lead to polymer degradation. 
** Phenolics: They are more specifically "hindered phenols", which means a bulky group (typically a tert-butyl) is put near the phenol OH.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hinderedphenols | archive-url=https://web.archive.org/web/20060529051925/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hinderedphenols | archive-date=29 May 2006 | title=Antioxidants Center - Hindered Phenols }}</ref> Examples: [[butylated hydroxytoluene]], [[2,4-Dimethyl-6-tert-butylphenol|2,4-dimethyl-6-''tert''-butylphenol]], [[para tertiary butyl phenol]], [[2,6-Di-tert-butylphenol|2,6-di-tert-butylphenol]], [[1,3,5-Tris(4-(tert-butyl)-3-hydroxy-2,6-dimethylbenzyl)-1,3,5-triazinane-2,4,6-trione]]
** Secondary aromatic amines: Not as hindered, which make them more active. Very few FDA approvals.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=aromaticamines | archive-url=https://web.archive.org/web/20060529051933/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=aromaticamines | archive-date=29 May 2006 | title=Antioxidants Center - Secondary Aromatic Amines }}</ref>
** Hindered amine light stabilizers (HALS): Unlike other primary antioxidants, HALS scavenges free radicals generated during photo-oxidation, thus preventing the polymer material from UV radiation.<ref>{{Cite journal |last1=Costa |first1=Tiago |last2=Sampaio-Marques |first2=Belém |last3=Neves |first3=Nuno M. |last4=Aguilar |first4=Helena |last5=Fraga |first5=Alexandra G. |date=2024-06-24 |title=Antimicrobial properties of hindered amine light stabilizers in polymer coating materials and their mechanism of action |journal=Frontiers in Bioengineering and Biotechnology |language=English |volume=12 |doi=10.3389/fbioe.2024.1390513|doi-access=free |pmid=38978720 |issn=2296-4185|pmc=11229053 }}</ref>{{better source needed|date=February 2025}}
* Secondary antioxidants act to decompose peroxides (ROOH) into non-radical products, thus preventing further generation of free radicals, and contributing to the overall oxidate stability of the polymer. Often used in combination with phenolic antioxidants for syngeristic effects.
** Phosphites: Example: [[tris(2,4-di-tert-butylphenyl)phosphite]].<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=organophosphorus | archive-url=https://web.archive.org/web/20060529051829/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=organophosphorus | archive-date=29 May 2006 | title=Antioxidants Center - Organophosphorus Compounds }}</ref>
** Thiosynergists: Most of this class are "thio-esters" (not to be confused with [[thioester]]s): an ester of 3,3-thiodipropionic acid.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=thiosynergists | archive-url=https://web.archive.org/web/20060529051844/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=thiosynergists | archive-date=29 May 2006 | title=Antioxidants Center - Thiosynergists }}</ref> Other [[organic sulfide]] (R1-S-R2) compounds also have a similar effect.<ref name=chap5/>
* Multifunctional antioxidants: an antioxidant can have both primary and secondary functional groups to act as both. Having multiple functional groups is what "multifunctional" means in chemistry.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=multiao | archive-url=https://web.archive.org/web/20060510232735/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=multiao | archive-date=10 May 2006 | title=Multifunctional Antioxidants - Antioxidants Center - SpecialChem4Adhesives }}</ref> The hydroxylamine functional group on its own can act as both.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hydroxylamine | archive-url=https://web.archive.org/web/20060510233253/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=hydroxylamine | archive-date=10 May 2006 | title=Hydroxylamine - Antioxidants Center - SpecialChem4Adhesives }}</ref>
* Radical scavengers: scavenges free radicals to halt the chain reaction. This can be any radical in the oxidation cycle (R•, ROO•, RO•, •OH), though in practice RO• and •OH are too reactive to "trap". Common types include lactones (esp. substituted benzofuranone) and acrylated bis-phenols.<ref>{{cite web | url=http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=acrylatebphenols | archive-url=https://web.archive.org/web/20050419003511/http://www.specialchem4adhesives.com/tc/antioxidants/index.aspx?id=acrylatebphenols | archive-date=19 April 2005 | title=Antioxidants Center - Acrylated Bis-Phenols }}</ref><ref name=chap5>{{cite journal |last1=Marturano |first1=Valentina |last2=Cerruti |first2=Pierfrancesco |last3=Ambrogi |first3=Veronica |title=Polymer additives |journal=Physical Sciences Reviews |date=27 June 2017 |volume=2 |issue=6 |page=130 |doi=10.1515/psr-2016-0130 |doi-access=free|bibcode=2017PhSRv...2..130M }}</ref>

=== Use as pharmaceutical ===
[[File:Probucol.svg|thumb|right|Probucol, which has 2 hindered phenols and 2 sulfides.]]
[[Probucol]] was originally designed as an antioxidant polymer stabilizer for rubber tires. It was later found to reduce [[LDL-C]] levels independently of the [[LDL receptor]] and became a prescription drug. Its approval predated statins by a decade.<ref name="pmid32507832">{{cite journal |vauthors=Yamashita S, Masuda D, Matsuzawa Y |title=New Horizons for Probucol, an Old, Mysterious Drug |journal=Journal of Atherosclerosis and Thrombosis |volume=28 |issue=2 |pages=100–102 |date=February 2021 |pmid=32507832 |pmc=7957029 |doi=10.5551/jat.ED132 |quote=Probucol was developed as an anti-oxidative compound to prevent the degradation of tire rubber and later applied to reduce serum LDL-C levels in patients with hypercholesterolemia.}}</ref>

=== Environmental and health hazards ===
Synthetic phenolic antioxidants (SPAs)<ref>{{Cite journal |last1=Liu |first1=Runzeng |last2=Mabury |first2=Scott A. |date=6 October 2020 |title=Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity |journal=Environmental Science & Technology |volume=54 |issue=19 |pages=11706–11719 |bibcode=2020EnST...5411706L |doi=10.1021/acs.est.0c05077 |pmid=32915564 |s2cid=221637214}}</ref> and aminic antioxidants<ref>{{Cite journal |last1=Xu |first1=Jing |last2=Hao |first2=Yanfen |last3=Yang |first3=Zhiruo |last4=Li |first4=Wenjuan |last5=Xie |first5=Wenjing |last6=Huang |first6=Yani |last7=Wang |first7=Deliang |last8=He |first8=Yuqing |last9=Liang |first9=Yong |last10=Matsiko |first10=Julius |last11=Wang |first11=Pu |date=7 November 2022 |title=Rubber Antioxidants and Their Transformation Products: Environmental Occurrence and Potential Impact |journal=International Journal of Environmental Research and Public Health |volume=19 |issue=21 |pages=14595 |doi=10.3390/ijerph192114595 |pmc=9657274 |pmid=36361475 |doi-access=free}}</ref> have potential human and environmental health hazards. SPAs are common in indoor dust, small air particles, sediment, sewage, river water and wastewater.<ref name=":0">{{Cite journal |last1=Li |first1=Chao |last2=Cui |first2=Xinyi |last3=Chen |first3=Yi |last4=Liao |first4=Chunyang |last5=Ma |first5=Lena Q |date=February 2019 |title=Synthetic phenolic antioxidants and their major metabolites in human fingernail |url=https://www.sciencedirect.com/science/article/pii/S0013935118306029 |journal=Environmental Research |volume=169 |pages=308–314 |bibcode=2019ER....169..308L |doi=10.1016/j.envres.2018.11.020 |pmid=30500685 |s2cid=56486425}}</ref> They are synthesized from phenolic compounds and include [[Butylated hydroxytoluene|2,6-di-tert-butyl-4-methylphenol]] (BHT), [[2,6-di-tert-butyl-p-benzoquinone]] (BHT-Q), [[2,6-Di-tert-butylphenol|2,4-di-tert-butyl-phenol]] (DBP) and [[Butylated hydroxyanisole|3-''tert''-butyl-4-hydroxyanisole]] (BHA). BHT can cause [[hepatotoxicity]] and damage to the [[endocrine system]] and may increase the carcinogenicity of [[Unsymmetrical dimethylhydrazine|1,1-dimethylhydrazine]] exposure.<ref>{{Cite journal |last1=Liu |first1=Runzeng |last2=Mabury |first2=Scott A. |date=September 11, 2020 |title=Synthetic Phenolic Antioxidants: A Review of Environmental Occurrence, Fate, Human Exposure, and Toxicity |url=https://pubs.acs.org/doi/full/10.1021/acs.est.0c05077 |journal=Environ. Sci. Technol. |volume=54 |issue=19 |pages=11706–11719 |bibcode=2020EnST...5411706L |doi=10.1021/acs.est.0c05077 |pmid=32915564 |s2cid=221637214}}</ref> BHT-Q can cause DNA damage and mismatches<ref>{{Cite journal |last1=Wang |first1=Wanyi |last2=Xiong |first2=Ping |last3=Zhang |first3=He |last4=Zhu |first4=Qingqing |last5=Liao |first5=Chunyang |last6=Jiang |first6=Guibin |date=2021-10-01 |title=Analysis, occurrence, toxicity and environmental health risks of synthetic phenolic antioxidants: A review |url=https://www.sciencedirect.com/science/article/pii/S0013935121008252 |journal=Environmental Research |language=en |volume=201 |pages=111531 |bibcode=2021ER....20111531W |doi=10.1016/j.envres.2021.111531 |issn=0013-9351 |pmid=34146526}}</ref> through the cleavage process, generating [[superoxide]] radicals.<ref name=":0" /> DBP is toxic to marine life if exposed long-term. Phenolic antioxidants have low biodegradability, but they do not have severe toxicity toward aquatic organisms at low concentrations. Another type of antioxidant, [[diphenylamine]] (DPA), is commonly used in the production of commercial, industrial lubricants and rubber products and it also acts as a supplement for automotive engine oils.<ref>{{Cite journal |last1=Zhang |first1=Zi-Feng |last2=Zhang |first2=Xue |last3=Sverko |first3=Ed |last4=Marvin |first4=Christopher H. |last5=Jobst |first5=Karl J. |last6=Smyth |first6=Shirley Anne |last7=Li |first7=Yi-Fan |date=2020-02-11 |title=Determination of Diphenylamine Antioxidants in Wastewater/Biosolids and Sediment |url=https://pubs.acs.org/doi/10.1021/acs.estlett.9b00796 |journal=Environmental Science & Technology Letters |language=en |volume=7 |issue=2 |pages=102–110 |bibcode=2020EnSTL...7..102Z |doi=10.1021/acs.estlett.9b00796 |issn=2328-8930 |s2cid=213719260}}</ref>