Methyl salicylate: Difference between revisions

Methyl salicylate
Names
	Preferred IUPAC name Methyl 2-hydroxybenzoate
	Other names Salicylic acid methyl ester; Oil of wintergreen; Betula oil;
Identifiers
CAS Number	119-36-8 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:31832;
ChEMBL	ChEMBL108545 ;
ChemSpider	13848808 ;
ECHA InfoCard	100.003.925
EC Number	204-317-7;
IUPHAR/BPS	2431;
KEGG	D01087 ;
PubChem CID	4133;
RTECS number	VO4725000;
UNII	LAV5U5022Y ;
CompTox Dashboard (EPA)	DTXSID5025659 ;
	InChI InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3 Key: OSWPMRLSEDHDFF-UHFFFAOYSA-N ; InChI=1/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3 Key: OSWPMRLSEDHDFF-UHFFFAOYAD;
	SMILES O=C(OC)c1ccccc1O;
Properties
Chemical formula	C8H8O3
Molar mass	152.149 g/mol
Appearance	Colorless liquid
Odor	Sweet, rooty
Density	1.174 g/cm3
Melting point	−8.6 °C (16.5 °F; 264.5 K)
Boiling point	222 °C (432 °F; 495 K); Decomposes at 340–350 °C
Solubility in water	0.639 g/L (21 °C); 0.697 g/L (30 °C)
Solubility	Miscible in organic solvents
Solubility in acetone	10.1 g/g (30 °C)
Vapor pressure	1 mmHg (54 °C)
Acidity (pKa)	9.8
Magnetic susceptibility (χ)	−8.630×10−5 cm3/mol
Refractive index (nD)	1.538
Hazards
	Occupational safety and health (OHS/OSH):
Main hazards	Harmful
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302
Precautionary statements	P264, P270, P280, P301+P312, P302+P352, P305+P351+P338, P321, P330, P332+P313, P337+P313, P362, P501
NFPA 704 (fire diamond)	2 1 0
Flash point	96 °C (205 °F; 369 K)
Autoignition; temperature	452.7 °C (846.9 °F; 725.8 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

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Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic compound with the formula C₈H₈O₃. It is the methyl ester of salicylic acid. It is a colorless, viscous liquid with a sweet, fruity odor reminiscent of root beer (in which it is used as a flavoring),^[4] but often associatively called "minty", as it is an ingredient in mint candies.^[5] It is produced by many species of plants, particularly wintergreens. It is also produced synthetically, used as a fragrance and as a flavoring agent.

Biosynthesis and occurrence

Methyl salicylate was first isolated (from the plant Gaultheria procumbens) in 1843 by the French chemist Auguste André Thomas Cahours (1813–1891), who identified it as an ester of salicylic acid and methanol.^[6]^[7]

The biosynthesis of methyl salicylate arises via the hydroxylation of benzoic acid by a cytochrome P450 followed by reaction with a methyltransferase enzyme.^[8]

Methyl salicylate as a plant metabolite

Many plants produce methyl salicylate in small quantities. Methyl salicylate levels are often upregulated in response to biotic stress, especially infection by pathogens, where it plays a role in the induction of resistance. Methyl salicylate is believed to function by being metabolized to the plant hormone salicylic acid. Since methyl salicylate is volatile, these signals can spread through the air to distal parts of the same plant or even to neighboring plants, whereupon they can function as a mechanism of plant-to-plant communication, "warning" neighbors of danger.^[9] Methyl salicylate is also released in some plants when they are damaged by herbivorous insects, where they may function as a cue aiding in the recruitment of predators, notably hoverflies, lacewings, and lady beetles.^[10] ^[11]

Some plants produce methyl salicylate in larger quantities, where it likely involved in direct defense against predators or pathogens. Examples of this latter class include: some species of the genus Gaultheria in the family Ericaceae, including Gaultheria procumbens, the wintergreen or eastern teaberry; some species of the genus Betula in the family Betulaceae, particularly those in the subgenus Betulenta such as B. lenta, the black birch; all species of the genus Spiraea in the family Rosaceae, also called the meadowsweets; species of the genus Polygala in the family Polygalaceae. Methyl salicylate can also be a component of floral scents, especially in plants dependent on nocturnal pollinators like moths,^[12] scarab beetles, and (nocturnal) bees.^[13]

Commercial production

Methyl salicylate can be produced by esterifying salicylic acid with methanol.^[14] Commercial methyl salicylate is now synthesized, but in the past, it was commonly distilled from the twigs of Betula lenta (sweet birch) and Gaultheria procumbens (eastern teaberry or wintergreen).

Uses

Methyl salicylate is used in high concentrations as a rubefacient and analgesic in deep heating liniments (such as Bengay) to treat joint and muscular pain. Randomised double blind trials report that evidence of its effectiveness is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to counterirritation. However, in the body it metabolizes into salicylates, including salicylic acid, a known NSAID.^[15]^[16]^[17]

Methyl salicylate is used in low concentrations (0.04% and under)^[18] as a flavoring agent in root beer,^[4] chewing gum, mints and medicine such as Pepto-Bismol. When mixed with sugar and dried, it is a potentially entertaining source of triboluminescence, for example by crushing Wint-O-Green Life Savers in a dark room. When crushed, sugar crystals emit light; methyl salicylate amplifies the spark because it fluoresces, absorbing ultraviolet light and re-emitting it in the visible spectrum.^[19]^[20] It is used as an antiseptic in Listerine mouthwash produced by the Johnson & Johnson company.^[21] It provides fragrance to various products and as an odor-masking agent for some organophosphate pesticides.^{[citation needed]}

Methyl salicylate is also used as a bait for attracting male orchid bees for study, which apparently gather the chemical to synthesize pheromones,^[22] and to clear plant or animal tissue samples of color, and as such is useful for microscopy and immunohistochemistry when excess pigments obscure structures or block light in the tissue being examined. This clearing generally only takes a few minutes, but the tissue must first be dehydrated in alcohol.^[23] It has also been discovered that methyl salicylate works as a kairomone that attracts some insects, such as the spotted lanternfly. Unlike some other kairomone's, Methyl Salicylate attracts all stages of the spotted lanternflies life. ^[24]

Additional applications include: used as a simulant or surrogate for the research of chemical warfare agent sulfur mustard, due to its similar chemical and physical properties,^[25] in restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers,^[26] as a transfer agent in printmaking (to release toner from photocopied images and apply them to other surfaces),^[27] and as a penetrating oil to loosen rusted parts.

Safety and toxicity

Methyl salicylate is potentially deadly, especially for young children who may accidentally ingest preparations containing methyl salicylate, such as an essential oil solution. A single teaspoon (5 mL) of methyl salicylate contains approximately 6 g of salicylate,^[28] which is equivalent to almost twenty 300 mg aspirin tablets (5 mL × 1.174 g/mL = 5.87 g). Toxic ingestions of salicylates typically occur with doses of approximately 150 mg/kg body weight. This can be achieved with 1 mL of oil of wintergreen, which equates to 140 mg/kg of salicylates for a 10 kg child (22 lbs).^[29] The lowest published lethal dose is 101 mg/kg body weight in adult humans,^[30]^[31] (or 7.07 grams for a 70 kg adult). It has proven fatal to small children in doses as small as 4 mL.^[18] A seventeen-year-old cross-country runner at Notre Dame Academy on Staten Island died in April 2007 after her body absorbed methyl salicylate through excessive use of topical muscle-pain relief products (using multiple patches against the manufacturer's instructions).^[32]

Most instances of human toxicity due to methyl salicylate are a result of overapplication of topical analgesics, especially involving children. Salicylate, the major metabolite of methyl salicylate, may accumulate in blood, plasma or serum which may help professionals to confirm a diagnosis of poisoning in hospitalized patients or to assist in an autopsy.^[33]

Compendial status

References

^ ^a ^b ^c "Methyl salicylate". chemister.ru. Archived from the original on 2014-05-24. Retrieved 2014-05-23.
^ ^a ^b ^c ^d ^e ^f Sigma-Aldrich Co., Methyl salicylate.
^ Scully, F. E.; Hoigné, J. (January 1987). "Rate constants for reactions of singlet oxygen with phenols and other compounds in water". Chemosphere. 16 (4): 681–694. Bibcode:1987Chmsp..16..681S. doi:10.1016/0045-6535(87)90004-X.
^ ^a ^b Markus, John R. (13 February 2020). "Determination of Methyl Salicylate in Root Beer". Journal of AOAC International. 57 (4): 1002–1004. doi:10.1093/jaoac/57.4.1002.
^ "The Good Scents Company - Aromatic/Hydrocarbon/Inorganic Ingredients Catalog information". Archived from the original on 2019-12-06. Retrieved 2019-12-03.
^ Cahours, A. A. T. (1843). "Recherches sur l'huile de Gaultheria procumbens" [Investigations into the oil of Gaultheria procumbens]. Comptes Rendus. 16: 853–856. Archived from the original on 2015-11-24. Retrieved 2013-11-19.
^ Cahours, A. A. T. (1843). "Sur quelques réactions du salicylate de méthylène" [On some reactions of methyl salicylate]. Comptes Rendus. 17: 43–47. Archived from the original on 2015-11-25. Retrieved 2013-11-19.
^ Vogt, T. (2010). "Phenylpropanoid Biosynthesis". Molecular Plant. 3: 2–20. doi:10.1093/mp/ssp106. PMID 20035037.
^ Shulaev, V.; Silverman, P.; Raskin, I. (1997). "Airborne signalling by methyl salicylate in plant pathogen resistance". Nature. 385 (6618): 718–721. Bibcode:1997Natur.385..718S. doi:10.1038/385718a0. S2CID 4370291.
^ James, D. G.; Price, T. S. (2004). "Field-testing of methyl salicylate for recruitment and retention of beneficial insects in grapes and hops". Journal of Chemical Ecology. 30 (8): 1613–1628. doi:10.1023/B:JOEC.0000042072.18151.6f. PMID 15537163. S2CID 36124603.
^ Rodriguez-Saona, C., Kaplan, I., Braasch, J., Chinnasamy, D., & Williams, L. (2011). Field responses of predaceous arthropods to methyl salicylate: A meta-analysis and case study in cranberries. Biological Control, 59(2), 394-303. https://doi.org/10.1016/j.biocontrol.2011.06.017
^ Knudsen, J. T.; Tollsten, L. (1993). "Trends in floral scent chemistry in pollination syndromes: floral scent composition in moth-pollinated taxa". Botanical Journal of the Linnean Society. 113 (3). Oxford Academic: 263–284. doi:10.1111/j.1095-8339.1993.tb00340.x.
^ Cordeiro, G. D.; Fernandes dos Santos, I. G.; da Silva, C. I.; Schlindwein, C.; Alves-dos-Santos, I.; Dötterl, S. (2019). "Nocturnal floral scent profiles of Myrtaceae fruit crops". Phytochemistry. 162: 193–198. doi:10.1016/j.phytochem.2019.03.011. PMID 30939396. S2CID 92997657.
^ Boullard, Olivier; Leblanc, Henri; Besson, Bernard (2012). "Salicylic Acid". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a23_477. ISBN 3527306730.
^ "Topical analgesics introduction". Medicine.ox.ac.uk. 2003-05-26. Archived from the original on 2012-08-04. Retrieved 2012-11-07.
^ Mason, L.; Moore, R. A.; Edwards, J. E.; McQuay, H. J.; Derry, S.; Wiffen, P. J. (2004). "Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain". British Medical Journal. 328 (7446): 995. doi:10.1136/bmj.38040.607141.EE. PMC 404501. PMID 15033879.
^ Tramer, M. R. (2004). "It's not just about rubbing—topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment". British Medical Journal. 328 (7446): 998. doi:10.1136/bmj.328.7446.998. PMC 404503. PMID 15105325.
^ ^a ^b Wintergreen Archived 2018-03-19 at the Wayback Machine at Drugs.com
^ Harvey, E. N. (1939). "The luminescence of sugar wafers". Science. 90 (2324): 35–36. Bibcode:1939Sci....90...35N. doi:10.1126/science.90.2324.35. PMID 17798129.
^ "Why do Wint-O-Green Life Savers spark in the dark?". HowStuffWorks. Archived from the original on 2007-08-17. Retrieved 2008-04-27.
^ Listerine. "Original Listerine Antiseptic Mouthwash". Archived from the original on 17 February 2015. Retrieved 25 March 2015.
^ Schiestl, F. P.; Roubik, D. W. (2004). "Odor Compound Detection in Male Euglossine Bees". Journal of Chemical Ecology. 29 (1): 253–257. doi:10.1023/A:1021932131526. hdl:20.500.11850/57276. PMID 12647866. S2CID 2845587.
^ Altman, J. S.; Tyrer, N. M. (1980). "Filling selected neurons with cobalt through cut axons". In Strausfeld, N. J.; Miller, T. A. (eds.). Neuroanatomical Techniques. Springer-Verlag. pp. 373–402.
^ Cooperband, Miriam F.; Wickham, Jacob; Cleary, Kaitlin; Spichiger, Sven-Erik; Zhang, Longwa; Baker, John; Canlas, Isaiah; Derstine, Nathan; Carrillo, Daniel (2019-03-21). "Discovery of three kairomones in relation to trap and lure development for spotted lanternfly (Hemiptera: Fulgoridae)". Journal of Economic Entomology. 112 (2): 671–682. doi:10.1093/jee/toy412. ISSN 0022-0493. PMID 30753676.
^ Bartlet-Hunt, S. L.; Knappe, D. R. U.; Barlaz, M. A. (2008). "A Review of Chemical Warfare Agent Simulants for the Study of Environmental Behaviour". Critical Reviews in Environmental Science and Technology. 38 (2): 112–136. doi:10.1080/10643380701643650. S2CID 97484598.
^ "MG Chemicals – Rubber Renue Safety Data Sheet" (PDF). Archived from the original (PDF) on 2015-06-26.
^ Modrak, Rebekah and Bill Anthes. "Image Transfer & Rubbing Techniques – Reframing Photography". www.reframingphotography.com. Retrieved 2021-09-07.
^ "Salicylate Poisoning – Patient UK". Patient.info. 2011-04-20. Archived from the original on 2015-08-18. Retrieved 2013-07-01.
^ Hoffman, R. (2015). Goldfrank's Toxicologic Emergencies (10th ed.). New York, NY: McGraw-Hill. pp. 915–922. ISBN 978-0-07-180184-3.
^ "Safety (MSDS) data for methyl salicylate". University of Oxford Department of Chemistry MSDS. 2010-09-15. Archived from the original on 2011-06-07. Retrieved 2023-04-24.
^ "Methyl Salicyclate" (PDF). CAMEO Chemicals. June 1999. Archived (PDF) from the original on 29 Dec 2016. Retrieved 24 Apr 2023.
^ "Muscle-Pain Reliever Is Blamed For Staten Island Runner's Death". New York Times. 10 June 2007. Archived from the original on 18 January 2018. Retrieved 22 February 2017.
^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1012–1014. ISBN 978-0-9626523-7-0.
^ The British Pharmacopoeia Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on 11 April 2009. Retrieved 5 July 2009.
^ "NIHS Japan". Moldb.nihs.go.jp. Archived from the original on 2013-02-17. Retrieved 2013-07-01.

External links

[chemister-1] "Methyl salicylate". chemister.ru. Archived from the original on 2014-05-24. Retrieved 2014-05-23.

[sigma-2] ^ ^a ^b ^c ^d ^e ^f Sigma-Aldrich Co., Methyl salicylate.

[3] Scully, F. E.; Hoigné, J. (January 1987). "Rate constants for reactions of singlet oxygen with phenols and other compounds in water". Chemosphere. 16 (4): 681–694. Bibcode:1987Chmsp..16..681S. doi:10.1016/0045-6535(87)90004-X.

[rootbeer-4] Markus, John R. (13 February 2020). "Determination of Methyl Salicylate in Root Beer". Journal of AOAC International. 57 (4): 1002–1004. doi:10.1093/jaoac/57.4.1002.

[5] "The Good Scents Company - Aromatic/Hydrocarbon/Inorganic Ingredients Catalog information". Archived from the original on 2019-12-06. Retrieved 2019-12-03.

[6] Cahours, A. A. T. (1843). "Recherches sur l'huile de Gaultheria procumbens" [Investigations into the oil of Gaultheria procumbens]. Comptes Rendus. 16: 853–856. Archived from the original on 2015-11-24. Retrieved 2013-11-19.

[7] Cahours, A. A. T. (1843). "Sur quelques réactions du salicylate de méthylène" [On some reactions of methyl salicylate]. Comptes Rendus. 17: 43–47. Archived from the original on 2015-11-25. Retrieved 2013-11-19.

[8] Vogt, T. (2010). "Phenylpropanoid Biosynthesis". Molecular Plant. 3: 2–20. doi:10.1093/mp/ssp106. PMID 20035037.

[9] Shulaev, V.; Silverman, P.; Raskin, I. (1997). "Airborne signalling by methyl salicylate in plant pathogen resistance". Nature. 385 (6618): 718–721. Bibcode:1997Natur.385..718S. doi:10.1038/385718a0. S2CID 4370291.

[10] James, D. G.; Price, T. S. (2004). "Field-testing of methyl salicylate for recruitment and retention of beneficial insects in grapes and hops". Journal of Chemical Ecology. 30 (8): 1613–1628. doi:10.1023/B:JOEC.0000042072.18151.6f. PMID 15537163. S2CID 36124603.

[11] Rodriguez-Saona, C., Kaplan, I., Braasch, J., Chinnasamy, D., & Williams, L. (2011). Field responses of predaceous arthropods to methyl salicylate: A meta-analysis and case study in cranberries. Biological Control, 59(2), 394-303. https://doi.org/10.1016/j.biocontrol.2011.06.017

[12] Knudsen, J. T.; Tollsten, L. (1993). "Trends in floral scent chemistry in pollination syndromes: floral scent composition in moth-pollinated taxa". Botanical Journal of the Linnean Society. 113 (3). Oxford Academic: 263–284. doi:10.1111/j.1095-8339.1993.tb00340.x.

[13] Cordeiro, G. D.; Fernandes dos Santos, I. G.; da Silva, C. I.; Schlindwein, C.; Alves-dos-Santos, I.; Dötterl, S. (2019). "Nocturnal floral scent profiles of Myrtaceae fruit crops". Phytochemistry. 162: 193–198. doi:10.1016/j.phytochem.2019.03.011. PMID 30939396. S2CID 92997657.

[14] Boullard, Olivier; Leblanc, Henri; Besson, Bernard (2012). "Salicylic Acid". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a23_477. ISBN 3527306730.

[15] "Topical analgesics introduction". Medicine.ox.ac.uk. 2003-05-26. Archived from the original on 2012-08-04. Retrieved 2012-11-07.

[16] Mason, L.; Moore, R. A.; Edwards, J. E.; McQuay, H. J.; Derry, S.; Wiffen, P. J. (2004). "Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain". British Medical Journal. 328 (7446): 995. doi:10.1136/bmj.38040.607141.EE. PMC 404501. PMID 15033879.

[17] Tramer, M. R. (2004). "It's not just about rubbing—topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment". British Medical Journal. 328 (7446): 998. doi:10.1136/bmj.328.7446.998. PMC 404503. PMID 15105325.

[Wintergreen-18] Wintergreen Archived 2018-03-19 at the Wayback Machine at Drugs.com

[19] Harvey, E. N. (1939). "The luminescence of sugar wafers". Science. 90 (2324): 35–36. Bibcode:1939Sci....90...35N. doi:10.1126/science.90.2324.35. PMID 17798129.

[20] "Why do Wint-O-Green Life Savers spark in the dark?". HowStuffWorks. Archived from the original on 2007-08-17. Retrieved 2008-04-27.

[21] Listerine. "Original Listerine Antiseptic Mouthwash". Archived from the original on 17 February 2015. Retrieved 25 March 2015.

[22] Schiestl, F. P.; Roubik, D. W. (2004). "Odor Compound Detection in Male Euglossine Bees". Journal of Chemical Ecology. 29 (1): 253–257. doi:10.1023/A:1021932131526. hdl:20.500.11850/57276. PMID 12647866. S2CID 2845587.

[23] Altman, J. S.; Tyrer, N. M. (1980). "Filling selected neurons with cobalt through cut axons". In Strausfeld, N. J.; Miller, T. A. (eds.). Neuroanatomical Techniques. Springer-Verlag. pp. 373–402.

[24] Cooperband, Miriam F.; Wickham, Jacob; Cleary, Kaitlin; Spichiger, Sven-Erik; Zhang, Longwa; Baker, John; Canlas, Isaiah; Derstine, Nathan; Carrillo, Daniel (2019-03-21). "Discovery of three kairomones in relation to trap and lure development for spotted lanternfly (Hemiptera: Fulgoridae)". Journal of Economic Entomology. 112 (2): 671–682. doi:10.1093/jee/toy412. ISSN 0022-0493. PMID 30753676.

[25] Bartlet-Hunt, S. L.; Knappe, D. R. U.; Barlaz, M. A. (2008). "A Review of Chemical Warfare Agent Simulants for the Study of Environmental Behaviour". Critical Reviews in Environmental Science and Technology. 38 (2): 112–136. doi:10.1080/10643380701643650. S2CID 97484598.

[26] "MG Chemicals – Rubber Renue Safety Data Sheet" (PDF). Archived from the original (PDF) on 2015-06-26.

[27] Modrak, Rebekah and Bill Anthes. "Image Transfer & Rubbing Techniques – Reframing Photography". www.reframingphotography.com. Retrieved 2021-09-07.

[28] "Salicylate Poisoning – Patient UK". Patient.info. 2011-04-20. Archived from the original on 2015-08-18. Retrieved 2013-07-01.

[29] Hoffman, R. (2015). Goldfrank's Toxicologic Emergencies (10th ed.). New York, NY: McGraw-Hill. pp. 915–922. ISBN 978-0-07-180184-3.

[30] "Safety (MSDS) data for methyl salicylate". University of Oxford Department of Chemistry MSDS. 2010-09-15. Archived from the original on 2011-06-07. Retrieved 2023-04-24.

[31] "Methyl Salicyclate" (PDF). CAMEO Chemicals. June 1999. Archived (PDF) from the original on 29 Dec 2016. Retrieved 24 Apr 2023.

[32] "Muscle-Pain Reliever Is Blamed For Staten Island Runner's Death". New York Times. 10 June 2007. Archived from the original on 18 January 2018. Retrieved 22 February 2017.

[33] Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1012–1014. ISBN 978-0-9626523-7-0.

[ib29-34] The British Pharmacopoeia Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on 11 April 2009. Retrieved 5 July 2009.

[35] "NIHS Japan". Moldb.nihs.go.jp. Archived from the original on 2013-02-17. Retrieved 2013-07-01.

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@@ Line 49: / Line 49: @@
 | MeltingPtC = −8.6
 | BoilingPtC = 222
-| BoilingPt_notes = <ref name="sigma" /><br> Decomposes at 340–350&nbsp;°C<ref name=chemister />
+| BoilingPt_ref = <ref name="sigma" /><br> Decomposes at 340–350{{nbsp}}°C<ref name=chemister />
 | RefractIndex = 1.538
 | Solubility = 0.639{{nbsp}}g/L (21{{nbsp}}°C)<br> 0.697{{nbsp}}g/L (30{{nbsp}}°C)<ref name=chemister>{{cite web|url=http://chemister.ru/Database/properties-en.php?dbid=1&id=2994|title=Methyl salicylate|work=chemister.ru|access-date=2014-05-23|archive-date=2014-05-24|archive-url=https://web.archive.org/web/20140524024109/http://chemister.ru/Database/properties-en.php?dbid=1&id=2994|url-status=live}}</ref>
@@ Line 65: / Line 65: @@
 | PPhrases = {{P-phrases|264|270|280|301+312|302+352|305+351+338|321|330|332+313|337+313|362|501}}
 | FlashPtC = 96
-| FlashPt_notes = <ref name="sigma" />
+| FlashPt_ref = <ref name="sigma" />
 | MainHazards = Harmful
 | NFPA-H = 2
@@ Line 76: / Line 76: @@
 }}
-'''Methyl salicylate''' ('''oil of wintergreen''' or '''wintergreen oil''') is an [[organic compound]] with the formula C<sub>8</sub>H<sub>8</sub>O<sub>3</sub>.  It is the methyl [[ester]] of [[salicylic acid]]. It is a colorless, [[viscous]] liquid with a sweet, fruity odor reminiscent of [[root beer]], but often [[association (psychology)|associatively]] called "minty", as it is an ingredient in mint candies.<ref>{{Cite web |url=http://www.thegoodscentscompany.com/data/rw1008472.html |title=Archived copy |access-date=2019-12-03 |archive-date=2019-12-06 |archive-url=https://web.archive.org/web/20191206205053/http://www.thegoodscentscompany.com/data/rw1008472.html |url-status=live }}</ref> It is produced by many species of [[plant]]s, particularly [[wintergreen]]s. It is also produced synthetically, used as a [[fragrance]] and as a flavoring agent.
+'''Methyl salicylate''' ('''oil of wintergreen''' or '''wintergreen oil''') is an [[organic compound]] with the formula C<sub>8</sub>H<sub>8</sub>O<sub>3</sub>.  It is the methyl [[ester]] of [[salicylic acid]]. It is a colorless, [[viscous]] liquid with a sweet, fruity odor reminiscent of [[root beer]] (in which it is used as a flavoring),<ref name="rootbeer"/> but often [[association (psychology)|associatively]] called "minty", as it is an ingredient in mint candies.<ref>{{Cite web |url=http://www.thegoodscentscompany.com/data/rw1008472.html |title=The Good Scents Company - Aromatic/Hydrocarbon/Inorganic Ingredients Catalog information |access-date=2019-12-03 |archive-date=2019-12-06 |archive-url=https://web.archive.org/web/20191206205053/http://www.thegoodscentscompany.com/data/rw1008472.html |url-status=live }}</ref> It is produced by many species of [[plant]]s, particularly [[wintergreen]]s. It is also produced synthetically, used as a [[fragrance]] and as a flavoring agent.
 ==Biosynthesis and occurrence==
 Methyl salicylate was first isolated (from the plant ''[[Gaultheria procumbens]]'') in 1843 by the French chemist [[Auguste André Thomas Cahours]] (1813–1891), who identified it as an [[ester]] of [[salicylic acid]] and [[methanol]].<ref>{{cite journal|last=Cahours|first=A. A. T.|author-link=Auguste André Thomas Cahours|date=1843|url=http://gallica.bnf.fr/ark:/12148/bpt6k29751/f853.image.langEN|title=Recherches sur l'huile de ''Gaultheria procumbens''|trans-title=Investigations into the oil of ''Gaultheria procumbens''|journal=Comptes Rendus|volume=16|pages=853–856|access-date=2013-11-19|archive-date=2015-11-24|archive-url=https://web.archive.org/web/20151124225104/http://gallica.bnf.fr/ark:/12148/bpt6k29751/f853.image.langEN|url-status=live}}</ref><ref>{{cite journal|last=Cahours|first=A. A. T.|author-link=Auguste André Thomas Cahours|date=1843|url=http://gallica.bnf.fr/ark:/12148/bpt6k2976b/f47.image.langEN|title=Sur quelques réactions du salicylate de méthylène|trans-title=On some reactions of methyl salicylate|journal=Comptes Rendus|volume=17|pages=43–47|access-date=2013-11-19|archive-date=2015-11-25|archive-url=https://web.archive.org/web/20151125200032/http://gallica.bnf.fr/ark:/12148/bpt6k2976b/f47.image.langEN|url-status=live}}</ref>
-The biosynthesis of methyl salicylate arises via the [[hydroxylation]] of [[benzoic acid]] by a [[cytochrome P450]] followed by methylation by a [[methylase]] enzyme.<ref>{{cite journal|journal=Molecular Plant|year=2010|pages=2–20|doi=10.1093/mp/ssp106|title=Phenylpropanoid Biosynthesis|last=Vogt|first=T.|pmid=20035037|volume=3|doi-access=free}}</ref>
+The biosynthesis of methyl salicylate arises via the [[hydroxylation]] of [[benzoic acid]] by a [[cytochrome P450]] followed by reaction with a [[methyltransferase]] enzyme.<ref>{{cite journal|journal=Molecular Plant|year=2010|pages=2–20|doi=10.1093/mp/ssp106|title=Phenylpropanoid Biosynthesis|last=Vogt|first=T.|pmid=20035037|volume=3|doi-access=free}}</ref>
 == Methyl salicylate as a plant metabolite ==
 [[File:Gaultheria procumbens.JPG|thumb|left|Wintergreen plants (''[[Gaultheria procumbens]]'')]]
-Many plants produce methyl salicylate in small quantities. Methyl salicylate levels are often upregulated in response to biotic stress, especially infection by pathogens, where it plays a role in the induction of [[systemic acquired resistance|resistance]]. Methyl salicylate is believed to function by being metabolized to the plant hormone salicylic acid. Since methyl salicylate is volatile, these signals can spread through the air to distal parts of the same plant or even to neighboring plants, whereupon they can function as a mechanism of [[plant communication|plant-plant communication]], "warning" neighbors of danger.<ref>{{cite journal|journal=Nature|title=Airborne signalling by methyl salicylate in plant pathogen resistance|first1=V. |last1=Shulaev |first2=P. |last2=Silverman |first3=I. |last3=Raskin |volume=385|pages=718–721|date=1997|doi=10.1038/385718a0|issue=6618|bibcode = 1997Natur.385..718S |s2cid=4370291|url=https://www.semanticscholar.org/paper/f15449f2dc41e396059aafd1bdc0b04413f7a7e7}}</ref> Methyl salicylate is also released in some plants when they are damaged by herbivorous insects, where they may function as a cue aiding in the recruitment of predators.<ref>{{cite journal|first1=D. G.|last1=James |first2=T. S.|last2=Price |title=Field-testing of methyl salicylate for recruitment and retention of beneficial insects in grapes and hops|journal=Journal of Chemical Ecology|date=2004|volume=30|issue=8|pages=1613–1628|pmid=15537163|doi=10.1023/B:JOEC.0000042072.18151.6f|s2cid=36124603 |url=https://www.semanticscholar.org/paper/6105c8db44b20da17b95fe2d4a62b7eae8644623 }}</ref>
+Many plants produce methyl salicylate in small quantities. Methyl salicylate levels are often upregulated in response to biotic stress, especially infection by pathogens, where it plays a role in the induction of [[systemic acquired resistance|resistance]]. Methyl salicylate is believed to function by being metabolized to the plant hormone salicylic acid. Since methyl salicylate is volatile, these signals can spread through the air to distal parts of the same plant or even to neighboring plants, whereupon they can function as a mechanism of [[plant communication|plant-to-plant communication]], "warning" neighbors of danger.<ref>{{cite journal|journal=Nature|title=Airborne signalling by methyl salicylate in plant pathogen resistance|first1=V. |last1=Shulaev |first2=P. |last2=Silverman |first3=I. |last3=Raskin |volume=385|pages=718–721|date=1997|doi=10.1038/385718a0|issue=6618|bibcode = 1997Natur.385..718S |s2cid=4370291}}</ref> Methyl salicylate is also released in some plants when they are damaged by herbivorous insects, where they may function as a cue aiding in the recruitment of predators, notably [[hoverflies]], [[lacewings]], and [[lady beetles]].<ref>{{cite journal|first1=D. G.|last1=James |first2=T. S.|last2=Price |title=Field-testing of methyl salicylate for recruitment and retention of beneficial insects in grapes and hops|journal=Journal of Chemical Ecology|date=2004|volume=30|issue=8|pages=1613–1628|pmid=15537163|doi=10.1023/B:JOEC.0000042072.18151.6f|s2cid=36124603 }}</ref> <ref>Rodriguez-Saona, C., Kaplan, I., Braasch, J., Chinnasamy, D., & Williams, L. (2011). Field responses of predaceous arthropods to methyl salicylate: A meta-analysis and case study in cranberries. Biological Control, 59(2), 394-303. https://doi.org/10.1016/j.biocontrol.2011.06.017</ref>
-Some plants produce methyl salicylate in larger quantities, where it likely involved in direct defense against predators or pathogens. Examples of this latter class include: some species of the genus ''[[Gaultheria]]'' in the family [[Ericaceae]], including ''[[Gaultheria procumbens]]'', the wintergreen or eastern teaberry; some species of the genus ''[[Birch|Betula]]'' in the family [[Betulaceae]], particularly those in the subgenus [[Betula subgenus Betulenta|''Betulenta'']] such as [[Betula lenta|''B. lenta'']], the black birch; all species of the genus ''[[Spiraea]]'' in the family [[Rosaceae]], also called the meadowsweets; species of the genus ''[[Polygala]]'' in the family [[Polygalaceae]]. Methyl salicylate can also be a component of [[floral scent]]s, especially in plants dependent on nocturnal pollinators like moths,<ref>Knudsen, J. T., and L. Tollsten. 1993. Trends in floral scent chemistry in pollination syndromes: floral scent composition in moth-pollinated taxa. Bot J Linn Soc 113:263–284. Oxford Academic.</ref> scarab beetles, and (nocturnal) bees.<ref>Cordeiro, G. D., I. G. Fernandes dos Santos, C. I. da Silva, C. Schlindwein, I. Alves-dos-Santos, and S. Dötterl. 2019. Nocturnal floral scent profiles of Myrtaceae fruit crops. Phytochemistry 162:193–198.</ref>
+Some plants produce methyl salicylate in larger quantities, where it likely involved in direct defense against predators or pathogens. Examples of this latter class include: some species of the genus ''[[Gaultheria]]'' in the family [[Ericaceae]], including ''[[Gaultheria procumbens]]'', the wintergreen or eastern teaberry; some species of the genus ''[[Birch|Betula]]'' in the family [[Betulaceae]], particularly those in the subgenus [[Betula subgenus Betulenta|''Betulenta'']] such as [[Betula lenta|''B. lenta'']], the black birch; all species of the genus ''[[Spiraea]]'' in the family [[Rosaceae]], also called the meadowsweets; species of the genus ''[[Polygala]]'' in the family [[Polygalaceae]]. Methyl salicylate can also be a component of [[floral scent]]s, especially in plants dependent on nocturnal pollinators like moths,<ref>{{cite journal|last1=Knudsen |first1=J. T. |first2=L. |last2=Tollsten |date=1993 |title=Trends in floral scent chemistry in pollination syndromes: floral scent composition in moth-pollinated taxa |journal=Botanical Journal of the Linnean Society |volume=113 |issue=3 |pages=263–284 |publisher=Oxford Academic|doi=10.1111/j.1095-8339.1993.tb00340.x }}</ref> scarab beetles, and (nocturnal) bees.<ref>{{cite journal|last1=Cordeiro |first1=G. D. |first2=I. G. |last2=Fernandes dos Santos |first3=C. I. |last3=da Silva |first4=C. |last4=Schlindwein |first5=I. |last5=Alves-dos-Santos |first6=S. |last6=Dötterl |date=2019 |title=Nocturnal floral scent profiles of Myrtaceae fruit crops |journal=Phytochemistry |volume=162 |pages=193–198|doi=10.1016/j.phytochem.2019.03.011 |pmid=30939396 |s2cid=92997657 }}</ref>
 ==Commercial production==
@@ Line 94: / Line 94: @@
 ==Uses==
 [[File:Chick embryo in methyl salicylate.jpg|thumb|left|200px|[[Chicken|Chick]] [[embryo]] that was treated with [[methylene blue]] to stain the skeleton, then cleansed with two or three [[ethanol]] washes, and treated with methyl salicylate to make the surrounding [[Tissue (biology)|tissues]] transparent]]
-Methyl salicylate is used in high concentrations as a [[rubefacient]] and [[analgesic]] in deep heating [[liniment]]s (such as [[Bengay]]) to treat joint and muscular pain. Randomised double blind trials report that evidence of its effectiveness is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to [[counterirritant|counterirritation]].  However, in the body it metabolizes into salicylates, including salicylic acid, a known [[NSAID]].<ref>{{cite web |url=http://www.medicine.ox.ac.uk/bandolier/booth/painpag/topical/Topintro.html |archive-url=https://archive.today/20120804155624/http://www.medicine.ox.ac.uk/bandolier/booth/painpag/topical/Topintro.html |url-status=dead |archive-date=2012-08-04 |title=Topical analgesics introduction |publisher=Medicine.ox.ac.uk |date=2003-05-26 |access-date=2012-11-07 }}</ref><ref>{{cite journal | journal = British Medical Journal | doi = 10.1136/bmj.38040.607141.EE | title = Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain | year = 2004 | last1 = Mason | first1 = L. | volume = 328 | issue = 7446 | page = 995 | pmid = 15033879 | last2 = Moore | first2 = R. A. | last3 = Edwards | first3 = J. E. | last4 = McQuay | first4 = H. J. | last5 = Derry | first5 = S. | last6 = Wiffen | first6 = P. J. | pmc = 404501 }}</ref><ref>{{cite journal | journal = British Medical Journal | pmc =404503 | doi =10.1136/bmj.328.7446.998 | title = It's not just about rubbing--topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment | year = 2004 | last1 = Tramer | first1 = M. R. | volume = 328 | issue = 7446 | page = 998 | pmid = 15105325}}</ref>
+Methyl salicylate is used in high concentrations as a [[rubefacient]] and [[analgesic]] in deep heating [[liniment]]s (such as [[Bengay]]) to treat joint and muscular pain. Randomised double blind trials report that evidence of its effectiveness is weak, but stronger for acute pain than chronic pain, and that effectiveness may be due entirely to [[counterirritant|counterirritation]].  However, in the body it metabolizes into salicylates, including salicylic acid, a known [[NSAID]].<ref>{{cite web |url=http://www.medicine.ox.ac.uk/bandolier/booth/painpag/topical/Topintro.html |archive-url=https://archive.today/20120804155624/http://www.medicine.ox.ac.uk/bandolier/booth/painpag/topical/Topintro.html |url-status=dead |archive-date=2012-08-04 |title=Topical analgesics introduction |publisher=Medicine.ox.ac.uk |date=2003-05-26 |access-date=2012-11-07 }}</ref><ref>{{cite journal | journal = British Medical Journal | doi = 10.1136/bmj.38040.607141.EE | title = Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain | year = 2004 | last1 = Mason | first1 = L. | volume = 328 | issue = 7446 | page = 995 | pmid = 15033879 | last2 = Moore | first2 = R. A. | last3 = Edwards | first3 = J. E. | last4 = McQuay | first4 = H. J. | last5 = Derry | first5 = S. | last6 = Wiffen | first6 = P. J. | pmc = 404501 }}</ref><ref>{{cite journal | journal = British Medical Journal | pmc =404503 | doi =10.1136/bmj.328.7446.998 | title = It's not just about rubbing—topical capsaicin and topical salicylates may be useful as adjuvants to conventional pain treatment | year = 2004 | last1 = Tramer | first1 = M. R. | volume = 328 | issue = 7446 | page = 998 | pmid = 15105325}}</ref>
-Methyl salicylate is used in low concentrations (0.04% and under)<ref name="Wintergreen">[https://www.drugs.com/npp/wintergreen.html Wintergreen] {{Webarchive|url=https://web.archive.org/web/20180319173538/https://www.drugs.com/npp/wintergreen.html |date=2018-03-19 }} at Drugs.com</ref> as a [[flavoring]] agent in [[chewing gum]] and [[mints (candy)|mints]]. When mixed with sugar and dried, it is a potentially entertaining source of [[triboluminescence]], for example by crushing Wint-O-Green [[Life Savers]] in a dark room. When crushed, sugar crystals emit light; methyl salicylate amplifies the spark because it [[Fluorescence|fluoresces]], absorbing [[ultraviolet]] light and re-emitting it in the visible spectrum.<ref>{{cite journal |first=E. N. |last=Harvey |title=The luminescence of sugar wafers |journal=Science |year=1939 |volume=90 |issue=2324 |pages=35–36 |doi=10.1126/science.90.2324.35 |pmid=17798129 |bibcode=1939Sci....90...35N }}</ref><ref>{{cite news | url = http://home.howstuffworks.com/question505.htm | title = Why do Wint-O-Green Life Savers spark in the dark? | publisher = [[HowStuffWorks]] | access-date = 2008-04-27 | archive-date = 2007-08-17 | archive-url = https://web.archive.org/web/20070817182812/http://home.howstuffworks.com/question505.htm | url-status = live }}</ref> It is used as an antiseptic in [[Listerine]] mouthwash produced by the [[Johnson & Johnson]] company.<ref>{{cite web|url=https://www.listerine.com/mouthwash/antiseptic/listerine-original-mouthwash#active-ingredients|title=Original Listerine Antiseptic Mouthwash|author=Listerine|access-date=25 March 2015|author-link=Listerine|archive-date=17 February 2015|archive-url=https://web.archive.org/web/20150217045317/https://www.listerine.com/mouthwash/antiseptic/listerine-original-mouthwash#active-ingredients|url-status=live}}</ref> It provides [[fragrance]] to various products and as an odor-masking agent for some [[organophosphate]] [[pesticides]].{{Citation needed|date=March 2012}}
+Methyl salicylate is used in low concentrations (0.04% and under)<ref name="Wintergreen">[https://www.drugs.com/npp/wintergreen.html Wintergreen] {{Webarchive|url=https://web.archive.org/web/20180319173538/https://www.drugs.com/npp/wintergreen.html |date=2018-03-19 }} at Drugs.com</ref> as a [[flavoring]] agent in [[root beer]],<ref name="rootbeer">{{cite journal |last=Markus |first=John R. |date=13 February 2020 |title=Determination of Methyl Salicylate in Root Beer |journal=[[Journal of AOAC International]] |volume=57 |issue=4 |pages=1002–1004 |doi=10.1093/jaoac/57.4.1002 |doi-access=free }}</ref> [[chewing gum]], [[Mint (candy)|mints]] and [[medicine]] such as [[Bismuth subsalicylate|Pepto-Bismol]].  When mixed with sugar and dried, it is a potentially entertaining source of [[triboluminescence]], for example by crushing Wint-O-Green [[Life Savers]] in a dark room. When crushed, sugar crystals emit light; methyl salicylate amplifies the spark because it [[Fluorescence|fluoresces]], absorbing [[ultraviolet]] light and re-emitting it in the visible spectrum.<ref>{{cite journal |first=E. N. |last=Harvey |title=The luminescence of sugar wafers |journal=Science |year=1939 |volume=90 |issue=2324 |pages=35–36 |doi=10.1126/science.90.2324.35 |pmid=17798129 |bibcode=1939Sci....90...35N }}</ref><ref>{{cite news | url = http://home.howstuffworks.com/question505.htm | title = Why do Wint-O-Green Life Savers spark in the dark? | publisher = [[HowStuffWorks]] | access-date = 2008-04-27 | archive-date = 2007-08-17 | archive-url = https://web.archive.org/web/20070817182812/http://home.howstuffworks.com/question505.htm | url-status = live }}</ref> It is used as an antiseptic in [[Listerine]] mouthwash produced by the [[Johnson & Johnson]] company.<ref>{{cite web|url=https://www.listerine.com/mouthwash/antiseptic/listerine-original-mouthwash#active-ingredients|title=Original Listerine Antiseptic Mouthwash|author=Listerine|access-date=25 March 2015|author-link=Listerine|archive-date=17 February 2015|archive-url=https://web.archive.org/web/20150217045317/https://www.listerine.com/mouthwash/antiseptic/listerine-original-mouthwash#active-ingredients|url-status=live}}</ref> It provides [[fragrance]] to various products and as an odor-masking agent for some [[organophosphate]] [[pesticides]].{{Citation needed|date=March 2012}}
-Methyl salicylate is also used as a bait for attracting male [[orchid bee]]s for study, which apparently gather the chemical to synthesize pheromones,<ref>{{cite journal | doi = 10.1023/A:1021932131526 |last1=Schiestl |first1=F. P. |last2=Roubik |first2=D. W. | year = 2004 | title = Odor Compound Detection in Male Euglossine Bees | journal = Journal of Chemical Ecology | volume = 29 | pages = 253–257 | pmid=12647866 | issue = 1|s2cid=2845587 |url=https://www.semanticscholar.org/paper/610ddeac2158a616a509252771ccb1f2f4537769 }}</ref> and to clear plant or animal tissue samples of color, and as such is useful for microscopy and [[immunohistochemistry]] when excess pigments obscure structures or block light in the tissue being examined. This clearing generally only takes a few minutes, but the tissue must first be dehydrated in alcohol.<ref>{{cite book |last1=Altman |first1=J. S. |last2=Tyrer |first2=N. M. | year = 1980 | chapter = Filling selected neurons with cobalt through cut axons | title = Neuroanatomical Techniques | pages = 373–402 |editor1=Strausfeld |editor1-first=N. J. |editor2=Miller |editor2-first=T. A. | publisher = Springer-Verlag}}</ref> It has also been discovered that methyl salicylate works as a [[kairomone]] that attracts some insects, such as the [[spotted lanternfly]].<ref>{{Cite journal|last1=Cooperband|first1=Miriam F.|last2=Wickham|first2=Jacob|last3=Cleary|first3=Kaitlin|last4=Spichiger|first4=Sven-Erik|last5=Zhang|first5=Longwa|last6=Baker|first6=John|last7=Canlas|first7=Isaiah|last8=Derstine|first8=Nathan|last9=Carrillo|first9=Daniel|date=2019-03-21|title=Discovery of three kairomones in relation to trap and lure development for spotted lanternfly (Hemiptera: Fulgoridae)|journal=Journal of Economic Entomology|language=en|volume=112|issue=2|pages=671–682|doi=10.1093/jee/toy412|pmid=30753676|issn=0022-0493|doi-access=free}}</ref>
+Methyl salicylate is also used as a bait for attracting male [[orchid bee]]s for study, which apparently gather the chemical to synthesize pheromones,<ref>{{cite journal | doi = 10.1023/A:1021932131526 |last1=Schiestl |first1=F. P. |last2=Roubik |first2=D. W. | year = 2004 | title = Odor Compound Detection in Male Euglossine Bees | journal = Journal of Chemical Ecology | volume = 29 | pages = 253–257 | pmid=12647866 | issue = 1|s2cid=2845587 | hdl = 20.500.11850/57276 | hdl-access = free }}</ref> and to clear plant or animal tissue samples of color, and as such is useful for microscopy and [[immunohistochemistry]] when excess pigments obscure structures or block light in the tissue being examined. This clearing generally only takes a few minutes, but the tissue must first be dehydrated in alcohol.<ref>{{cite book |last1=Altman |first1=J. S. |last2=Tyrer |first2=N. M. | year = 1980 | chapter = Filling selected neurons with cobalt through cut axons | title = Neuroanatomical Techniques | pages = 373–402 |editor1=Strausfeld |editor1-first=N. J. |editor2=Miller |editor2-first=T. A. | publisher = Springer-Verlag}}</ref> It has also been discovered that methyl salicylate works as a [[kairomone]] that attracts some insects, such as the [[spotted lanternfly]]. Unlike some other kairomone's, Methyl Salicylate attracts all stages of the spotted lanternflies life. <ref>{{Cite journal|last1=Cooperband|first1=Miriam F.|last2=Wickham|first2=Jacob|last3=Cleary|first3=Kaitlin|last4=Spichiger|first4=Sven-Erik|last5=Zhang|first5=Longwa|last6=Baker|first6=John|last7=Canlas|first7=Isaiah|last8=Derstine|first8=Nathan|last9=Carrillo|first9=Daniel|date=2019-03-21|title=Discovery of three kairomones in relation to trap and lure development for spotted lanternfly (Hemiptera: Fulgoridae)|journal=Journal of Economic Entomology|language=en|volume=112|issue=2|pages=671–682|doi=10.1093/jee/toy412|pmid=30753676|issn=0022-0493|doi-access=free}}</ref>
-Additional applications include: used as a simulant or surrogate for the research of chemical warfare agent [[sulfur mustard]], due to its similar chemical and physical properties,<ref>{{cite journal |first1=S. L. |last1=Bartlet-Hunt |title=A Review of Chemical Warfare Agent Simulants for the Study of Environmental Behaviour |journal=Critical Reviews in Environmental Science and Technology |year=2008 |volume=38 |issue=2 |pages=112–136 |doi=10.1080/10643380701643650 |last2=Knappe |first2=D. R. U. |last3=Barlaz |first3=M. A. |s2cid=97484598 }}</ref> in restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers,<ref>{{cite web|url=http://www.mgchemicals.com/downloads/msds/english/sds-408a-l.pdf|title=MG Chemicals – Rubber Renue Safety Data Sheet|url-status=dead|archive-url=https://web.archive.org/web/20150626182545/http://www.mgchemicals.com/downloads/msds/english/sds-408a-l.pdf|archive-date=2015-06-26}}</ref> as a transfer agent in printmaking (to release toner from photocopied images and apply them to other surfaces),<ref>{{Cite web|last=Modrak|first=Rebekah and Bill Anthes|title=Image Transfer & Rubbing Techniques {{!}} Reframing Photography|url=https://www.reframingphotography.com/content/image-transfer-rubbing-techniques|url-status=live|access-date=2021-09-07|website=www.reframingphotography.com|language=en}}</ref> and as a penetrating oil to loosen rusted parts.
+Additional applications include: used as a simulant or surrogate for the research of chemical warfare agent [[sulfur mustard]], due to its similar chemical and physical properties,<ref>{{cite journal |first1=S. L. |last1=Bartlet-Hunt |title=A Review of Chemical Warfare Agent Simulants for the Study of Environmental Behaviour |journal=Critical Reviews in Environmental Science and Technology |year=2008 |volume=38 |issue=2 |pages=112–136 |doi=10.1080/10643380701643650 |last2=Knappe |first2=D. R. U. |last3=Barlaz |first3=M. A. |s2cid=97484598 }}</ref> in restoring (at least temporarily) the elastomeric properties of old rubber rollers, especially in printers,<ref>{{cite web|url=http://www.mgchemicals.com/downloads/msds/english/sds-408a-l.pdf|title=MG Chemicals – Rubber Renue Safety Data Sheet|url-status=dead|archive-url=https://web.archive.org/web/20150626182545/http://www.mgchemicals.com/downloads/msds/english/sds-408a-l.pdf|archive-date=2015-06-26}}</ref> as a transfer agent in printmaking (to release toner from photocopied images and apply them to other surfaces),<ref>{{Cite web|last=Modrak|first=Rebekah and Bill Anthes|title=Image Transfer & Rubbing Techniques – Reframing Photography|url=https://www.reframingphotography.com/content/image-transfer-rubbing-techniques|access-date=2021-09-07|website=www.reframingphotography.com|language=en}}</ref> and as a penetrating oil to loosen rusted parts.
 ==Safety and toxicity==
-Methyl salicylate is potentially deadly, especially for young children who may accidentally ingest preparations containing methyl salicylate such as an [[essential oil]] solution. A single teaspoon (5&nbsp;ml) of methyl salicylate contains approximately 6&nbsp;g of salicylate,<ref>{{cite web|url = http://patient.info/doctor/salicylate-poisoning|title = Salicylate Poisoning – Patient UK|publisher = Patient.info|date = 2011-04-20|access-date = 2013-07-01|archive-date = 2015-08-18|archive-url = https://web.archive.org/web/20150818165207/http://patient.info/doctor/salicylate-poisoning|url-status = live}}</ref> which is equivalent to almost twenty 300&nbsp;mg [[aspirin]] tablets (5{{nbsp}}ml × 1.174{{nbsp}}g/ml = 5.87{{nbsp}}g). Toxic ingestions of salicylates typically occur with doses of approximately 150&nbsp;mg/kg body weight. This can be achieved with 1 ml of oil of wintergreen, which equates to 140{{nbsp}}mg/kg of salicylates for a 10{{nbsp}}kg child (22{{nbsp}}lbs).<ref>{{cite book |first=R. |last=Hoffman |title=Goldfrank's Toxicologic Emergencies |edition=10th |publisher=McGraw-Hill |location=New York, NY |year=2015 |pages=915–922 |isbn=978-0-07-180184-3 }}</ref> The lowest published lethal dose is 101&nbsp;mg/kg body weight in adult humans,<ref>[http://physchem.ox.ac.uk/MSDS/ME/methyl_salicylate.html Safety data for methyl salicylate] {{Webarchive|url=https://web.archive.org/web/20071013225653/http://physchem.ox.ac.uk/MSDS/ME/methyl_salicylate.html |date=2007-10-13 }}, Physical & Theoretical Chemistry Laboratory, Oxford University</ref> (or 7.07&nbsp;grams for a 70&nbsp;kg adult).  It has proven fatal to small children in doses as small as 4&nbsp;ml.<ref name="Wintergreen"/>  A seventeen-year-old [[cross-country running|cross-country runner]] at [[Notre Dame Academy (Staten Island)|Notre Dame Academy]] on [[Staten Island]] died in April 2007 after her body absorbed methyl salicylate through excessive use of topical muscle-pain relief products (using multiple patches against the manufacturer's instructions).<ref>{{cite news |title=Muscle-Pain Reliever Is Blamed For Staten Island Runner's Death |url=https://www.nytimes.com/2007/06/10/nyregion/10cream.html?_r=1&ref=nyregion&oref=slogin |work=New York Times |date=10 June 2007 |access-date=22 February 2017 |archive-date=18 January 2018 |archive-url=https://web.archive.org/web/20180118011031/http://www.nytimes.com/2007/06/10/nyregion/10cream.html?_r=1&ref=nyregion&oref=slogin |url-status=live }}</ref>
+Methyl salicylate is potentially deadly, especially for young children who may accidentally ingest preparations containing methyl salicylate, such as an [[essential oil]] solution. A single teaspoon (5&nbsp;mL) of methyl salicylate contains approximately 6&nbsp;g of salicylate,<ref>{{cite web|url = http://patient.info/doctor/salicylate-poisoning|title = Salicylate Poisoning – Patient UK|publisher = Patient.info|date = 2011-04-20|access-date = 2013-07-01|archive-date = 2015-08-18|archive-url = https://web.archive.org/web/20150818165207/http://patient.info/doctor/salicylate-poisoning|url-status = live}}</ref> which is equivalent to almost twenty 300&nbsp;mg [[aspirin]] tablets (5{{nbsp}}mL × 1.174{{nbsp}}g/mL = 5.87{{nbsp}}g). Toxic ingestions of salicylates typically occur with doses of approximately 150&nbsp;mg/kg body weight. This can be achieved with 1 mL of oil of wintergreen, which equates to 140{{nbsp}}mg/kg of salicylates for a 10{{nbsp}}kg child (22{{nbsp}}lbs).<ref>{{cite book |first=R. |last=Hoffman |title=Goldfrank's Toxicologic Emergencies |edition=10th |publisher=McGraw-Hill |location=New York, NY |year=2015 |pages=915–922 |isbn=978-0-07-180184-3 }}</ref> The lowest published lethal dose is 101&nbsp;mg/kg body weight in adult humans,<ref>{{Cite web |date=2010-09-15 |archive-date=2011-06-07 |title=Safety (MSDS) data for methyl salicylate |url=http://msds.chem.ox.ac.uk/ME/methyl_salicylate.html |url-status=dead |archive-url=https://web.archive.org/web/20110607225158/http://msds.chem.ox.ac.uk/ME/methyl_salicylate.html |access-date=2023-04-24 |website=University of Oxford Department of Chemistry MSDS}}</ref><ref>{{Cite web |date=June 1999 |title=Methyl Salicyclate |url=https://cameochemicals.noaa.gov/chris/MES.pdf |url-status=live |archive-url=https://web.archive.org/web/20161229181651/https://cameochemicals.noaa.gov/chris/MES.pdf |archive-date=29 Dec 2016 |access-date=24 Apr 2023 |website=CAMEO Chemicals}}</ref> (or 7.07&nbsp;grams for a 70&nbsp;kg adult).  It has proven fatal to small children in doses as small as 4&nbsp;mL.<ref name="Wintergreen"/>  A seventeen-year-old [[cross-country running|cross-country runner]] at [[Notre Dame Academy (Staten Island)|Notre Dame Academy]] on [[Staten Island]] died in April 2007 after her body absorbed methyl salicylate through excessive use of topical muscle-pain relief products (using multiple patches against the manufacturer's instructions).<ref>{{cite news |title=Muscle-Pain Reliever Is Blamed For Staten Island Runner's Death |url=https://www.nytimes.com/2007/06/10/nyregion/10cream.html?_r=1&ref=nyregion&oref=slogin |work=New York Times |date=10 June 2007 |access-date=22 February 2017 |archive-date=18 January 2018 |archive-url=https://web.archive.org/web/20180118011031/http://www.nytimes.com/2007/06/10/nyregion/10cream.html?_r=1&ref=nyregion&oref=slogin |url-status=live }}</ref>
-Most instances of human toxicity due to methyl salicylate are a result of over-application of topical analgesics, especially involving children. Salicylate, the major metabolite of methyl salicylate, may accumulate in [[blood]], [[blood plasma|plasma]] or [[blood serum|serum]] to confirm a diagnosis of poisoning in hospitalized patients or to assist in an [[autopsy]].<ref>{{cite book |first=R. |last=Baselt |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications |location=Foster City, CA |year=2008 |pages=1012–1014 |isbn=978-0-9626523-7-0 }}</ref>
+Most instances of human toxicity due to methyl salicylate are a result of overapplication of topical analgesics, especially involving children. Salicylate, the major metabolite of methyl salicylate, may accumulate in [[blood]], [[blood plasma|plasma]] or [[blood serum|serum]] which may help professionals to confirm a diagnosis of poisoning in hospitalized patients or to assist in an [[autopsy]].<ref>{{cite book |first=R. |last=Baselt |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications |location=Foster City, CA |year=2008 |pages=1012–1014 |isbn=978-0-9626523-7-0 }}</ref>
 ==Compendial status==
@@ Line 145: / Line 145: @@
 [[Category:3-Hydroxypropenals]]
 [[Category:Sweet-smelling chemicals]]
+[[Category:Substances discovered in the 19th century]]

v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
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