View source for Salicylic acid

{{chembox
| Watchedfields = changed
| verifiedrevid = 266507429
|   Name = Salicylic acid
|   ImageFileL1 = Salicylic-acid-skeletal.svg
|   ImageSizeL1 = 120px
|   ImageFileR1 = Salicylic-acid-from-xtal-2006-3D-balls.png
|   ImageSizeR1 = 120px
|   IUPACName = 2-Hydroxybenzoic acid
| Section1 = {{Chembox Identifiers
|   CASNo = 69-72-7
|    CASNo_Ref = {{cascite}}
|   PubChem = 338
|   EINECS = 200-712-3
|   ChemSpiderID = 331
|   SMILES = OC(=O)c1ccccc1O
  }}
| Section2 = {{Chembox Properties
|   C = 7 | H = 6 | O = 3
|   MeltingPtC = 159.0
|   BoilingPt = 211 °C (20 mmHg)
|   pKa = 2.97 <ref>[http://www.drugbank.ca/drugs/DB00936 pKa from drugbank]</ref>
|   Density = 1.443 g/cm<sup>3</sup>
|   Solubility = 0.2 g/100 mL H<sub>2</sub>O (20 °C)
|   SolubleOther = Chloroform 0.19 M, ethanol 1.84 M, methanol 2.65 M <ref>[http://oru.edu/cccda/sl/solubility/allsolvents.php?solute=salicylic%20acid Solubility of salicylic acid in non-aqueous solvents]</ref>
|    Solvent = [[chloroform]], [[ethanol]], [[methanol]]
  }}
| Section8 = {{Chembox Related
|   OtherCpds = [[Methyl salicylate]],<br/>[[Benzoic acid]],<br/>[[Phenol]], [[Aspirin]],<br/>[[4-Hydroxybenzoic acid]],<br/> [[Magnesium salicylate]],<br/>[[Choline salicylate]],<br/>[[Bismuth subsalicylate]],<br/>[[Sulfosalicylic acid]]
  }}
| Section9 = {{Chembox Hazards
|   ExternalMSDS = [http://msds.chem.ox.ac.uk/SA/salicylic_acid.html Oxford MSDS]
|   EUClass = Harmful ('''Xn''')
|   EUIndex = 200-712-3
|   MainHazards =
|   NFPA-H = 2
|   NFPA-F = 1
|   NFPA-R = 0
|   NFPA-O =
|   RPhrases = [[R22]] [[R36]] [[R38]] [[R61]]
|   SPhrases = [[S22]] [[S26]] [[S36]] [[S37]] [[S39]]
|   RSPhrases =
|   FlashPt = 157 °C
|   Autoignition = 545 °C
|   ExploLimits =
|   PEL =
 }}
}}

'''Salicylic acid''' (from [[Latin]] ''[[salix]]'', ''willow tree'', from the bark of which the substance is obtained) is a [[beta hydroxy acid]]. This colorless crystalline organic [[acid]] is widely used in [[organic synthesis]] and functions as a [[plant hormone]]. It is derived from the metabolism of [[salicin]]. In addition to being a compound that is chemically similar to but not identical to the active component of [[aspirin]] (''acetylsalicylic acid''), it is probably best known for its use in anti-acne treatments.  The salts and [[ester]]s of salicylic acid are known as '''salicylates'''.

==Chemistry==
Salicylic acid has the [[chemical formula|formula]] C<sub>6</sub>H<sub>4</sub>(OH)COOH, where the OH group is ortho to the [[carboxylic acid|carboxyl group]]. It is also known as 2-hydroxybenzenecarboxcylic acid. It is poorly soluble in water (0.2 g/100 ml H<sub>2</sub>O at 20 °C).<ref>{{cite web |url=http://www.inchem.org/documents/icsc/icsc/eics0563.htm|title=Salicilyc acid |accessdate=2008-10-13 |work=}}</ref>  [[Aspirin]] (acetylsalicylic acid or ASA) can be prepared by the [[esterification]] of the [[phenol]]ic [[hydroxyl group]] of salicylic acid with the [[acetate]] ion from acetic acid.

==Plant hormone==
Salicylic acid (SA) is a [[phenol]]ic [[phytohormone]] and is found in plants with roles in plant growth and development, [[photosynthesis]], [[transpiration]], [[ion]] uptake and transport. SA also induces specific changes in leaf anatomy and [[chloroplast]] structure. SA is involved in [[endogenous]] signaling, mediating in plant defense against [[pathogens]].<ref>{{cite book | title = Salicylic acid - A Plant Hormone | author = S. Hayat, A. Ahmad | isbn = 1402051832| date = 2007 | publisher = [[Springer Science+Business Media|Springer]]}}</ref> It plays a role in the resistance to pathogens by inducing the production of pathogenesis-related proteins.<ref name="HOOFT VAN HUIJSDUIJNEN">{{cite journal|url=http://vir.sgmjournals.org/cgi/reprint/67/10/2135.pdf|title=Induction by Salicylic Acid of Pathogenesis-related Proteins and Resistance to Alfalfa Mosaic Virus Infection in Various Plant Species|last=HOOFT VAN HUIJSDUIJNEN|accessdate=2009-05-28}}</ref> It is involved in the [[systemic acquired resistance]] (SAR) in which a pathogenic attack on one part of the plant induces resistance in other parts. The signal can also move to nearby plants by salicyclic acid being converted to the volatile ester, [[methyl salicylate]].<ref>''Plant Physiology Third Edition'', Taiz and Zeiger, 2002, page 306</ref>

==Production==
Salicylic acid is [[biosynthesis|biosynthesize]]d from the amino acid [[phenylalanine]]. In ''[[Arabidopsis thaliana]]'' it can also be synthesized via a phenylalanine-independent pathway.

[[Sodium salicylate]] is commercially prepared by treating [[sodium phenolate]] (the sodium salt of [[phenol]]) with [[carbon dioxide]] at high pressure (100 atm) and high temperature (390K) -a method known as the [[Kolbe-Schmitt reaction]]. Acidification of the product with [[sulfuric acid]] gives salicylic acid:

:[[Image:Kolbe-Schmitt.png|left|400px]]<br clear=left/>

It can also be prepared by the [[hydrolysis]] of [[Aspirin]] (acetylsalicylic acid)<ref>{{cite web | title=Hydrolysis of ASA to SA | url=http://www.crscientific.com/article-aspirin.html | accessdate=July 31, 2007 }}</ref> or [[methyl salicylate]] (Oil of Wintergreen) with a strong acid or base.

==History==
{{Main|History of aspirin}}
[[Image:Thomé Salix alba clean.jpg|thumb|White willow (''[[Salix alba]]'') is a natural source of salicylic acid]]

The [[Hellenic civilization|Greek]] physician [[Hippocrates]] wrote in the 5th century BC about a bitter powder extracted from [[willow]] bark that could ease aches and pains and reduce fevers. This remedy was also mentioned in texts from ancient [[Sumer]], [[Lebanon]], and [[Assyria]]. The [[Cherokee]] and other Native Americans used an infusion of the bark for fever and other medicinal purposes for centuries.<ref>Paul B. Hemel and Mary U. Chiltoskey, ''Cherokee Plants and Their Uses -- A 400 Year History,'' Sylva, NC: Herald Publishing Co. (1975); cited in Dan Moerman, A Database of Foods, Drugs, Dyes and Fibers of Native American Peoples, Derived from Plants.[http://herb.umd.umich.edu/] A search of this database for "salix AND medicine" finds 63 entries.</ref> The medicinal part of the plant is the inner bark and was used as a pain reliever for a variety of ailments. The [[Edward Stone (clergyman)|Reverend Edward Stone]], a vicar from [[Chipping Norton, Oxfordshire]], [[England]], noted in 1763 that the bark of the willow was effective in reducing a fever.<ref name="RoyalSoc1763EdmundStone">{{cite journal | author=Stone, E | title=An Account of the Success of the Bark of the Willow in the Cure of Agues | journal=Philosophical Transactions | date=1763 | pages=195–200 | volume=53 | url=http://www.journals.royalsoc.ac.uk/openurl.asp?genre=article&issn=0260-7085&volume=53&spage=195 | doi=10.1098/rstl.1763.0033}}</ref>

The active extract of the bark, called ''[[salicin]]'', after the [[Latin]] name for the white willow (''[[Salix alba]]''), was isolated and named by the [[Germans|German]] chemist [[Johann Andreas Buchner]] in 1826. A larger amount of the substance was isolated in 1828 by [[Henri Leroux]] a [[France|French]] pharmacist. [[Raffaele Piria]], an [[Italy|Italian]] chemist was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.<ref>{{cite book | url = http://books.google.com/?id=x-sL4iNQOgcC&pg=PA38 | isbn = 9781582346007 | pages = 38&ndash;40 | author = Diarmuid Jeffreys. | date = 2005 | publisher = Bloomsbury | location = New York, NY | title = Aspirin : the remarkable story of a wonder drug}}</ref>

Salicylic acid was also isolated from the herb [[meadowsweet]] (''[[Filipendula|Filipendula ulmaria]]'', formerly classified as ''[[Spiraea|Spiraea ulmaria]]'') by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as [[gastric]] irritation, bleeding, [[diarrhea]], and even death when consumed in high doses.

==Medicinal and cosmetic uses==
Salicylic acid is known for its ability to ease aches and pains and reduce [[fever]]s.  These medicinal properties, particularly fever relief, have been known since ancient times, and it was used as an anti-inflammatory drug.<ref>{{cite journal|title=Brief History of Antipyretic Therapy|author=Philip A. Mackowiak|journal=Clinical Infectious Diseases,| volume= 31|date=2000 |pages= 154–156|doi= 10.1086/317510|pmid=11113017}}</ref> Some researchers believe that salicylate is an essential micronutrient in the human diet, potentially qualifying as a [[vitamin]], namely Vitamin S.<ref>{{cite journal|title=Rapid Responses to: Aspirin protects women at risk of pre-eclampsia without causing bleeding|author=Kamran Abbasi|journal=British Medical Journal|volume=327|date=2003|pages=7424|doi=10.1136/bmj.327.7424.0-h|url=http://www.bmj.com/cgi/eletters/327/7424/0-h}}</ref>

In modern medicine, salicylic acid and its derivatives are used as constituents of some [[rubefacient]] products.  For example, [[methyl salicylate]] is used as a [[liniment]] to soothe joint and muscle pain, and [[choline salicylate]] is used topically to relieve the pain of [[aphthous ulcer]]s.

[[Image:Salicylic acid pads.jpg|thumb|right|[[Cotton]] pads soaked in salicylic acid can be used to chemically [[Exfoliation (cosmetology)|exfoliate]] skin]]
As with other [[beta hydroxy acid]]s, salicylic acid is a key ingredient in many skin-care products for the treatment of [[Acne vulgaris|acne]], [[psoriasis]], [[callus]]es, [[callus|corns]], [[keratosis pilaris]], and [[wart]]s.<ref>http://www3.interscience.wiley.com/journal/119449119/abstract?CRETRY=1&SRETRY=0</ref> It works as both a [[keratolytic]] and [[comedolytic]] agent by causing the cells of the [[Epidermis (skin)|epidermis]] to shed more readily, opening clogged [[sebaceous gland|pores]] and neutralizing bacteria within, preventing [[sebaceous gland|pores]] from clogging up again by constricting pore diameter, and allowing room for new cell growth.<ref>[http://www.kaviskin.com/info/salicylicacid.html Salicylic Acid] ''Essential Actives'', KAVI.</ref> Because of its effect on skin cells, salicylic acid is used in several [[shampoo]]s used to treat [[dandruff]].  Use of concentrated solutions of salicylic acid may cause [[hyperpigmentation]] on unpretreated skin for those with darker skin types ([[Fitzpatrick scale|Fitzpatrick]] phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock.<ref>{{cite journal|title=The Safety and Efficacy of Salicylic Acid Chemical Peels in Darker Racial-ethnic Groups| author= Grimes P.E.|journal= Dermatologic Surgery| volume= 25|date= 1999| pages =18–22 | doi = 10.1046/j.1524-4725.1999.08145.x|pmid=9935087|issue=1}}</ref><ref>{{cite journal|title= Chemical peeling in ethnic/dark skin| author= Roberts W. E. |journal=Dermatologic Therapy |volume= 17|issue= 2| pages= 196|date= 2004|doi= 10.1111/j.1396-0296.2004.04020.x|pmid= 15113287}}</ref>

[[Bismuth subsalicylate]], a [[salt (chemistry)|salt]] of [[bismuth]] and salicyclic acid, is the active ingredient in stomach relief aids such as [[Pepto-Bismol]]. Bismuth subsalicylate helps control nausea, heartburn, indigestion, upset stomach, and [[diarrhea]].{{Reference necessary|date=April 2010}} It is also a very mild [[antibiotic]].

==Other uses==
* Although toxic in large quantities, salicylic acid is used as a [[food preservative]].{{Citation needed|date=August 2009}}  For some people with [[salicylate sensitivity]] even these small doses can be harmful.
* [[Sodium salicylate]] is a useful [[phosphor]] in the [[vacuum ultraviolet]] with nearly flat quantum efficiency for wavelengths between 10 to 100&nbsp;nm.<ref>JAR Samson ''Techniques of Vacuum Ultraviolet Spectroscopy''</ref> It fluoresces in the blue at 420&nbsp;nm. It is easily prepared on a clean surface by spraying a saturated solution of the salt in [[methanol]] followed by evaporation.

==Safety==
Salicylic acid has an [[ototoxic]] effect by inhibiting [[prestin]].<ref>{{cite journal |
journal = [[HNO]] | date = 2004 | volume = 52 | issue = 4 | pages = 347–51 | title = Reversible hearing loss in acute salicylate intoxication | author = Wecker, H.; Laubert, A. | language = German | pmid = 15143764 |
doi = 10.1007/s00106-004-1065-5}}</ref> It can induce transient hearing loss in [[zinc]]-deficient individuals.

This finding is based on clinical studies with [[rat]]s. An injection of salicylic acid induced hearing loss in zinc-deficient rats, while a simultaneous injection of zinc reversed the hearing loss. An injection of [[magnesium]] in the zinc-deficient rats did not reverse the salicylic acid-induced hearing loss.

Salicylic acid is used to treat acne, warts and other dermatological problems. There are no studies specifically looking at topical salicylic acid in pregnancy. Oral salicylic acid has not been associated with an increase in malformations if used during the first trimester, but use in late pregnancy has been associated with bleeding, especially intracranial bleeding.<ref>{{cite journal | pmid = 7312229 | date = 1981 | month = Nov | author = Rumack, Cm; Guggenheim, Ma; Rumack, Bh; Peterson, Rg; Johnson, Ml; Braithwaite, Wr | title = Neonatal intracranial hemorrhage and maternal use of aspirin. | volume = 58 | issue = 5 Suppl | pages = 52S–6S | issn = 0029-7844 | journal = Obstetrics and gynecology }}</ref> The risks of aspirin late in pregnancy are probably not relevant for a topical exposure to salicylic acid, even late in the pregnancy, because of its low systemic levels. Topical salicylic acid is common in many over-the-counter dermatological agents, and the lack of adverse reports suggests a low [[Teratology|teratogenic]] potential.<ref>[http://www.fetal-exposure.org/ACNE.html Acne and Pregnancy]</ref>

Salicylic acid overdose can lead to [[salicylate intoxication]], which often presents clinically in a state of [[metabolic acidosis]] with compensatory [[respiratory alkalosis]].  In patients presenting with an acute overdose, a 16% morbidity rate and a 1% mortality rate are observed.<ref>http://emedicine.medscape.com/article/818242-overview</ref>

Some people are [[Salicylate sensitivity|hypersensitive to salicylic acid]] and related compounds.

The United States [[Food and Drug Administration]] recommends the use of sun protection when using skincare products containing salicylic acid (or any other BHA) on sun-exposed skin areas.<ref>{{cite web |url=http://www.cfsan.fda.gov/~dms/cos-bha.html|title=Beta Hydroxy Acids in Cosmetics |accessdate=2007-11-23 |work=}}</ref>

There is data to support an association between exposure to salicylic acid and [[Reye's Syndrome]]. The National Reye's Syndrome Foundation cautions against the usage of these substances, and other substances similar to aspirin, on children and adolescents.

Epidemiological research has shown an association between the development of Reye's Syndrome and the use of aspirin (a salicylate compound) for treating the symptoms of influenza-like illnesses, chicken pox, colds, etc.

The U.S. Surgeon General, the Food and Drug Administration, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics recommend that aspirin and combination products containing aspirin not be given to children under 19 years of age during episodes of fever-causing illnesses.<ref>{{cite web|url=http://www.reyessyndrome.org/aspirin.html|title=Aspirin / Salicylates and Reye's Syndrome |accessdate=2009-05-22 |work=}}</ref>

==See also==
* [[Trolamine salicylate]]

==Footnotes==
{{Reflist}}

==External links==
* [http://msds.chem.ox.ac.uk/SA/salicylic_acid.html Safety MSDS data]

{{Acne Agents}}
{{Ancient anaesthesia-footer}}
{{Antifungals}}
{{NSAIDs}}
{{Analgesics}}
{{Plant hormones}}

{{Salicylates}}

{{DEFAULTSORT:Salicylic Acid}}
[[Category:Non-steroidal anti-inflammatory drugs]]
[[Category:Antiseptics]]
[[Category:Salicylic acids| ]]
[[Category:Plant hormones]]
[[Category:Acne treatments]]

[[ar:حمض الساليسيليك]]
[[bs:Salicilna kiselina]]
[[bg:Салицилова киселина]]
[[ca:Àcid salicílic]]
[[cs:Kyselina salicylová]]
[[da:Salicylsyre]]
[[de:Salicylsäure]]
[[es:Ácido salicílico]]
[[fa:اسید سالیسیلیک]]
[[fr:Acide salicylique]]
[[gv:Geayr salicylagh]]
[[ko:살리실산]]
[[id:Asam salisilat]]
[[it:Acido salicilico]]
[[he:חומצה סליצילית]]
[[lv:Salicilskābe]]
[[hu:Szalicilsav]]
[[ml:സാലിസിലിക് അമ്ലം]]
[[nl:Salicylzuur]]
[[ja:サリチル酸]]
[[no:Salicylsyre]]
[[pl:Kwas salicylowy]]
[[pt:Ácido salicílico]]
[[ru:Салициловая кислота]]
[[simple:Salicylic acid]]
[[sk:Kyselina salicylová]]
[[sv:Salicylsyra]]
[[th:กรดซาลิไซลิก]]
[[tr:Salisilik asit]]
[[ur:سالیسائلک تیزاب]]
[[zh-yue:水楊酸]]
[[zh:水楊酸]]
[[Category:2Fix]]