Methyl salicylate


Methyl salicylate
Accession Number

Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens. The compound was first extracted and isolated from plant species Gaultheria procumbens in 1843. It can be manufactured synthetically and it used as a fragrance, in foods, beverages, and liniments. It forms a colorless to yellow or reddish liquid and exhibits a characteristic odor and taste of wintergreen. For acute joint and muscular pain, methyl salicylate is used as a rubefacient and analgesic in deep heating liniments. It is used as a flavoring agent in chewing gums and mints in small concentrations and added as antiseptic in mouthwash solutions.

Small Molecule
Approved, Vet approved
Average: 152.1473
Monoisotopic: 152.047344122
Chemical Formula
  • 2-(Methoxycarbonyl)phenol
  • 2-Carbomethoxyphenol
  • 2-Hydroxybenzoic acid methyl ester
  • Betula oil
  • Gaultheria oil
  • Methyl 2-hydroxybenzoate
  • Methyl o-hydroxybenzoate
  • Methyl salicylate
  • Natural wintergreen oil
  • Oil of wintergreen
  • Spicewood Oil
  • Sweet birch oil
  • Teaberry oil



Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.

Associated Conditions
Contraindications & Blackbox Warnings
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Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth.

Mechanism of action

Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves 5. This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.


Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% 9.

Volume of distribution

After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier.

Protein binding

Degree of albumin binding depends on the plasma concentration of the compound


Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate. It is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes. Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites.

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Route of elimination

Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).


The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication.

Not Available
Adverse Effects
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Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination 7.

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AbciximabThe risk or severity of bleeding can be increased when Methyl salicylate is combined with Abciximab.
AcarboseMethyl salicylate may increase the hypoglycemic activities of Acarbose.
AceclofenacThe therapeutic efficacy of Methyl salicylate can be decreased when used in combination with Aceclofenac.
AcenocoumarolThe risk or severity of bleeding can be increased when Methyl salicylate is combined with Acenocoumarol.
AcetaminophenThe risk or severity of adverse effects can be increased when Acetaminophen is combined with Methyl salicylate.
AcetazolamideThe risk or severity of adverse effects can be increased when Methyl salicylate is combined with Acetazolamide.
AcetohexamideMethyl salicylate may increase the hypoglycemic activities of Acetohexamide.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be decreased when it is combined with Methyl salicylate.
Acetylsalicylic acidThe therapeutic efficacy of Methyl salicylate can be decreased when used in combination with Acetylsalicylic acid.
AlbiglutideMethyl salicylate may increase the hypoglycemic activities of Albiglutide.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
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  • Action

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Food Interactions
No interactions found.


Active Moieties
Salicylic acidunknownO414PZ4LPZ69-72-7YGSDEFSMJLZEOE-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aspi-Rub Pain RelieverSpray23 g/100gTopicalAspiRub Enterprises LLC2014-08-29Not applicableUS flag
Balsamo de Ubre MascuraOintment10.5 g/90gTopicalPharmalab Enterprises Inc.2011-05-102011-05-11US flag
Balsamo de Ubre MascuraOintment10.5 g/90gTopicalMENPER DISTRIBUTORS INC.2011-05-10Not applicableUS flag
Bumooly-SSolution3 g/100mLTransdermalScott Holdings Co., Ltd.2014-09-25Not applicableUS flag
Bumooly-SSolution3 g/100mLTransdermalScott Holdings Co., Ltd.2014-05-16Not applicableUS flag
Coats Aloe AnalgesicLotion10 g/1gTopicalTychasis Corporation2015-09-29Not applicableUS flag
Coats Aloe AnalgesicLotion10 g/100mLTopicalTychasis Corporation2015-11-02Not applicableUS flag
Foot Works Arthritis Achy Foot and MuscleCream250 mg/1mLTopicalNew Avon Llc2012-05-30Not applicableUS flag
Hot Pap CataplasmaPatch58.3 mg/13.4gTransdermalLydia Co., Ltd.2019-03-29Not applicableUS flag
Humco Wintergreen OilLiquid980 mg/1mLTopicalHumco Holding Group. Inc.1998-03-252021-10-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
1st Medxpatch With Lidocaine 4%Methyl salicylate (20 g/1) + Capsaicin (0.025 g/1) + Levomenthol (5 g/1) + Lidocaine (4 g/1)PatchTopical1ST MEDX LLC2018-03-15Not applicableUS flag
701 Dieda Zhengtong Yaogao MedicatedMethyl salicylate (10 g/1) + Levomenthol (8 g/1) + Synthetic camphor (3.1 g/1)PlasterTopical; TransdermalGUANGZHOU BAIYUNSHAN PHARMACEUTICAL CO., LTD. BAIYUNSHAN HEJIGONG PHARMACEUTICAL FACTORY2001-10-15Not applicableUS flag
AA Top MedicatedMethyl salicylate (0.05 g/1mL) + Levomenthol (0.1 g/1mL)OilTopicalAlbert Max, Inc.2018-02-01Not applicableUS flag
Advanced AntisepticMethyl salicylate (.060 kg/100L) + Eucalyptol (.092 kg/100L) + Levomenthol (.042 kg/100L) + Thymol (.064 kg/100L)MouthwashOralDemoulas Supermarkets, Inc.2010-07-22Not applicableUS flag
Advanced AntisepticMethyl salicylate (.060 mL/100L) + Eucalyptol (.042 mL/100L) + Levomenthol (.042 mL/100L) + Thymol (.064 mL/100L)MouthwashOralWakfern Food Corporation2010-11-24Not applicableUS flag
Advanced Antiseptic CitrusMethyl salicylate (.060 mL/100L) + Eucalyptol (.092 mL/100L) + Levomenthol (.042 mL/100L) + Thymol (.042 mL/100L)MouthwashOralDrug Mart1991-06-15Not applicableUS flag
Advanced Antiseptic CitrusMethyl salicylate (.060 mL/100L) + Eucalyptol (.092 mL/100L) + Levomenthol (.042 mL/100L) + Thymol (.042 mL/100L)MouthwashOralH.E.B.2010-10-15Not applicableUS flag
Advanced CitrusMethyl salicylate (.060 kg/100L) + Eucalyptol (.092 kg/100L) + Levomenthol (.042 kg/100L) + Thymol (.064 kg/100L)MouthwashOralWalmart Stores2010-07-22Not applicableUS flag
Advanced Citrus AntisepticMethyl salicylate (.060 mL/100L) + Eucalyptol (.092 mL/100L) + Levomenthol (.042 mL/100L) + Thymol (.064 mL/100L)MouthwashOralPublix Supermarkets, Inc.2001-05-03Not applicableUS flag
Ageless Pain ReliefMethyl salicylate (140 mg/1mL) + Levomenthol (70 mg/1mL)CreamTopicalIsagenix International, Llc2011-04-23Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
1st Medxpatch With Lidocaine 4%-rxMethyl salicylate (20 1/1) + Capsaicin (0.0375 1/1) + Levomenthol (5 1/1) + Lidocaine (4 1/1)PatchTopical1ST MEDX LLC2018-03-15Not applicableUS flag
AdazinMethyl salicylate (1 g/100g) + Benzocaine (2 g/100g) + Capsaicin (0.035 g/100g) + Lidocaine (2 g/100g)CreamTopicalSterling Knight Pharmaceuticals, Llc2014-12-032018-10-01US flag
Antiphlamine Coin PlasterMethyl salicylate (5.541 mg/0.2832g) + DL-alpha-Tocopherol (0.308 mg/0.2832g) + Diphenhydramine (0.246 mg/0.2832g) + Levomenthol (2.769 mg/0.2832g) + Nonivamide (0.046 mg/0.2832g) + Peppermint oil (0.693 mg/0.2832g) + Synthetic camphor (1.108 mg/0.2832g)PatchTopicalHanul Trading Co., Ltd.2016-10-10Not applicableUS flag
Antiseptic RinseMethyl salicylate (.060 kg/100L) + Eucalyptol (.092 kg/100L) + Levomenthol (.042 kg/100L) + Thymol (.064 kg/100L)MouthwashOralMeijer2006-08-08Not applicableUS flag
Comfort EZ Extra Strength Pain Relief PatchMethyl salicylate (20 g/100g) + Levomenthol (1 g/100g) + Lidocaine (4 g/100g)PatchTopicalSimple Diagnostics. Inc.2015-03-172015-03-17US flag
Comfort EZ Extra StrengthTransdermal PatchMethyl salicylate (2 g/100g) + Levomenthol (1 g/100g) + Lidocaine hydrochloride (4 g/100g)PatchTopicalSimple Diagnostics. Inc.2015-03-232015-03-24US flag
Comfort EZ Pain Relief PatchMethyl salicylate (16 g/100g) + Levomenthol (2 g/100g) + Lidocaine (4 g/100g)PatchTopicalSimple Diagnostics. Inc.2015-03-092015-03-09US flag
Dolor-parche With Lidocaine-RXMethyl salicylate (20 g/1) + Capsaicin (0.035 g/1) + Levomenthol (5 g/1) + Lidocaine (0.5 g/1)PatchTopicalTwo Hip Consulting, Llc2013-07-312016-05-31US flag
Doloracin RxMethyl salicylate (20 g/100mL) + Capsaicin (0.035 g/100mL) + Levomenthol (5 g/100mL)CreamTopicalTwo Hip Consulting, Llc2013-08-112016-04-11US flag
Doloracin/l Rx With LidocaineMethyl salicylate (20 g/100mL) + Capsaicin (0.035 g/100mL) + Levomenthol (5 g/100mL) + Lidocaine (4 g/100mL)CreamTopicalTwo Hip Consulting, Llc2013-07-312016-06-02US flag


Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as o-hydroxybenzoic acid esters. These are benzoic acid esters where the benzene ring is ortho-substituted with a hydroxy group.
Organic compounds
Super Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
o-Hydroxybenzoic acid esters
Alternative Parents
Salicylic acid and derivatives / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Methyl esters / Monocarboxylic acids and derivatives / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Aromatic homomonocyclic compound / Benzoyl / Carboxylic acid derivative / Carboxylic acid ester / Hydrocarbon derivative / Methyl ester / Monocarboxylic acid or derivatives / O-hydroxybenzoic acid ester
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
salicylates, benzoate ester (CHEBI:31832) / a small molecule (CPD-6442)

Chemical Identifiers

CAS number
InChI Key
methyl 2-hydroxybenzoate


General References
  1. He YY, Yan Y, Zhang HF, Lin YH, Chen YC, Yan Y, Wu P, Fang JS, Yang SH, Du GH: Methyl salicylate 2-O-beta-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction. Drug Des Devel Ther. 2016 Sep 29;10:3183-3196. eCollection 2016. [PubMed:27729775]
  2. Xin W, Huang C, Zhang X, Xin S, Zhou Y, Ma X, Zhang D, Li Y, Zhou S, Zhang D, Zhang T, Du G: Methyl salicylate lactoside inhibits inflammatory response of fibroblast-like synoviocytes and joint destruction in collagen-induced arthritis in mice. Br J Pharmacol. 2014 Jul;171(14):3526-38. doi: 10.1111/bph.12715. [PubMed:24712652]
  3. Mason L, Moore RA, Edwards JE, McQuay HJ, Derry S, Wiffen PJ: Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ. 2004 Apr 24;328(7446):995. Epub 2004 Mar 19. [PubMed:15033879]
  4. Higashi Y, Kiuchi T, Furuta K: Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin Ther. 2010 Jan;32(1):34-43. doi: 10.1016/j.clinthera.2010.01.016. [PubMed:20171409]
  5. Derry S, Matthews PR, Wiffen PJ, Moore RA: Salicylate-containing rubefacients for acute and chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2014 Nov 26;(11):CD007403. doi: 10.1002/14651858.CD007403.pub3. [PubMed:25425092]
  6. Moore RA, Derry S, McQuay HJ: Topical analgesics for acute and chronic pain in adults. Cochrane Database Syst Rev. 2010;(7). pii: CD008609. [PubMed:25411557]
  7. Thompson TM, Toerne T, Erickson TB: Salicylate Toxicity from Genital Exposure to a Methylsalicylate-Containing Rubefacient. West J Emerg Med. 2016 Mar;17(2):181-3. doi: 10.5811/westjem.2016.1.29262. Epub 2016 Mar 2. [PubMed:26973745]
  8. FDA SALONPAS® Pain Relief Patch Clinical Review [Link]
  9. Norwegian Food Safety Authority: Methyl salicylate risk review [Link]
Human Metabolome Database
KEGG Compound
PubChem Compound
PubChem Substance
ZINC000000000490 Drug Page
AHFS Codes
  • 28:08.04.24 — Salicylates
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Clinical Trials

Clinical Trials
4CompletedTreatmentBack Pain Lower Back Chronic1
4CompletedTreatmentSub-acute Back Pain1
4RecruitingTreatmentBack Pain Lower Back Chronic1
3Not Yet RecruitingTreatmentMigraine1
2WithdrawnTreatmentPain, Acute1
2, 3WithdrawnTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Immune Reconstitution Inflammatory Syndrome / Immune Reconstitution Syndrome / Tuberculosis (TB)1
Not AvailableCompletedTreatmentSoft Tissue Injury1
Not AvailableRecruitingTreatmentPeriodontitis / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusTreatmentInduction of Uterine contractions1


Not Available
Not Available
Dosage Forms
Aerosol, sprayPercutaneous; Topical; Transdermal
Aerosol, sprayCutaneous; Topical; Transdermal
OintmentTopical0.2025 g/15g
SprayTopical23 g/100g
OintmentTopical10.5 g/90g
OilPercutaneous; Topical; Transdermal
CreamTopical10 g
CreamTopical8 g
OintmentCutaneous15 %
SolutionTransdermal3 g/100mL
Ointment16.67 mg/g
LotionTopical10 g/100mL
LotionTopical10 g/1g
CreamTopical7 g
OintmentTopical6 g
OintmentTopical8 g
GelTopical10 g
KitOral; Topical
CreamTopical250 mg/1mL
PatchCutaneous; Topical; Transdermal
PatchTransdermal58.3 mg/13.4g
LiquidTopical980 mg/1mL
OilTopical60 g/100mL
OintmentTopical13.5 g/100g
OintmentTopical7.5 g
LiquidRespiratory (inhalation)
OintmentTopical10.5 g/100g
OintmentTopical15 g/100g
OintmentTopical12 g/100g
OintmentTopical15 g/113g
OintmentTopical12 g/113g
OilTopical105 mg/1mL
CreamTopical250 mg/1g
GelTopical105 mg/1g
LotionTopical20 g/100g
OintmentTopical3 %
LotionTopical6 g
PatchPercutaneous; Topical; Transdermal
LiquidTopical40 g/100mL
GelTopical10 %
GelPercutaneous; Topical; Transdermal
Aerosol, foamPercutaneous; Topical; Transdermal
OintmentPercutaneous; Topical; Transdermal
LiquidCutaneous; Topical; Transdermal
LiquidTopical10 g/100g
PatchTopical10 mg/100mg
PatchTopical10 g/100g
CreamTopical100 mg/1g
CreamTopical10 g/100g
GelTopical100 mg/1g
OintmentTopical4 g
OintmentTopical4.5 g
OintmentTopical15.75 g/150g
PlasterTopical; Transdermal
CreamTopical10 g/100mL
OintmentTopical7 g
PoulticeTransdermal160 mg/17g
PoulticeTransdermal105 mg/17.5g
LiquidTopical200 mg/1g
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8809615No2014-08-192030-01-03US flag
US9233184No2016-01-122027-08-01US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Experimental Properties
melting point (°C)-8.6MSDS
boiling point (°C)220-224MSDS
water solubilitySlightly solubleMSDS
Predicted Properties
Water Solubility5.73 mg/mLALOGPS
pKa (Strongest Acidic)9.72ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity40.06 m3·mol-1ChemAxon
Polarizability14.98 Å3ChemAxon
Number of Rings1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-00dl-9800000000-4c121b87ee97a30f4150
GC-MS Spectrum - EI-BGC-MSsplash10-00dl-9800000000-aeff759175e190d33827
GC-MS Spectrum - EI-BGC-MSsplash10-00dl-9700000000-8449a003796d4c61d429
Mass Spectrum (Electron Ionization)MSsplash10-00dl-9800000000-1d56d6cf07db519b50e2
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0900000000-eba52e49290e16ea60c0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uk9-0900000000-684f1c8a3cf324183257
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uk9-9300000000-a594ffaab84fc15a2edc
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0900000000-76d5fc81bafad7c2222c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0900000000-dae7a80af6333acd66fc
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0gb9-9600000000-09304803bc773495c704
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0fk9-3900000000-e2029bf3c75775175ff3
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Drug created on November 30, 2015 12:10 / Updated on September 27, 2020 08:17

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