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Chemistry

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Also known as: Cineole, 1,8-cineole, 470-82-6, 1,8-cineol, Cajeputol, 1,8-epoxy-p-menthane
Molecular Formula
C10H18O
Molecular Weight
154.25  g/mol
InChI Key
WEEGYLXZBRQIMU-UHFFFAOYSA-N
FDA UNII
RV6J6604TK

Eucalyptol
A monoterpene and cyclohexanol derivative that is the major component of EUCALYPTUS OIL. It is used in mouthwash, insect repellent, and as a cough suppressant, and also is widely used as a flavoring agent and solvent. It has antimicrobial properties.
1 2D Structure

Eucalyptol

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2.1.2 InChI
InChI=1S/C10H18O/c1-9(2)8-4-6-10(3,11-9)7-5-8/h8H,4-7H2,1-3H3
2.1.3 InChI Key
WEEGYLXZBRQIMU-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CC1(C2CCC(O1)(CC2)C)C
2.2 Other Identifiers
2.2.1 UNII
RV6J6604TK
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 1,8 Cineol

2. 1,8 Cineole

3. 1,8 Epoxy P Menthane

4. 1,8-cineol

5. 1,8-cineole

6. 1,8-epoxy-p-menthane

7. Cineole

8. Soledum

2.3.2 Depositor-Supplied Synonyms

1. Cineole

2. 1,8-cineole

3. 470-82-6

4. 1,8-cineol

5. Cajeputol

6. 1,8-epoxy-p-menthane

7. Eucalyptole

8. Eucapur

9. Zineol

10. Terpan

11. P-cineole

12. 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

13. Eukalyptol

14. 1,8-oxido-p-menthane

15. Eucalyptus Oil

16. Cineol

17. Cucalyptol

18. Soledum

19. P-menthane, 1,8-epoxy-

20. Eukalyptol [czech]

21. Eucalyptol (natural)

22. Fema No. 2465

23. Zedoary Oil

24. 2-oxabicyclo[2.2.2]octane, 1,3,3-trimethyl-

25. 8000-48-4

26. Cineole (van)

27. Nci-c56575

28. 2-oxabicyclo(2.2.2)octane, 1,3,3-trimethyl-

29. Eucaly

30. 1,3,3-trimethyl-2-oxabicyclo(2.2.2)octane

31. 2-oxa-1,3,3-trimethylbicyclo(2.2.2)octane

32. Nsc 6171

33. Nsc-6171

34. Nsc6171

35. 2,2,4-trimethyl-3-oxabicyclo[2.2.2]octane

36. 2-oxa-1,3,3-trimethylbicyclo[2.2.2]octane

37. Rv6j6604tk

38. Cnl

39. 4,7,7-trimethyl-8-oxabicyclo[2.2.2]octane

40. Chebi:27961

41. Eucalyptol [usan]

42. Ncgc00091666-01

43. Ncgc00091666-04

44. Dsstox_cid_616

45. Dsstox_rid_75692

46. Dsstox_gsid_20616

47. (1s,4s)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

48. Eucalyptus Citriodora Oil

49. Eucalyptol 1000 Microg/ml In Methanol

50. Unii-rv6j6604tk

51. Cas-470-82-6

52. Smr000471853

53. Ccris 3727

54. Hsdb 991

55. Eucalyptol [usan:usp]

56. Einecs 207-431-5

57. Mfcd00167977

58. Terpane

59. Cyneol

60. Bidd:er0481

61. Ai3-00578

62. Eucalyptol,(s)

63. Eucalyptol (usp)

64. 1.8-cineole

65. Eucalyptol, 99%

66. Eucalyptol, Ph Helv

67. P-menthane,8-epoxy-

68. Cineole (1,8-)

69. Eucalyptol [ii]

70. Eucalyptol [mi]

71. Wln: T66 A B Aotj B1 B1 F1

72. Cineole [inci]

73. Eucalyptol [fcc]

74. 1,8-cineol-[d3]

75. Cineole [mart.]

76. Spectrum2_000221

77. Spectrum3_000683

78. Spectrum4_001747

79. Spectrum5_000704

80. Eucalyptol [fhfi]

81. Eucalyptol [hpus]

82. Eucalyptol [hsdb]

83. Eucalyptol [inci]

84. Cineole [who-dd]

85. Eucalyptol [vandf]

86. Bmse000523

87. Ec 207-431-5

88. Eucalyptol [usp-rs]

89. Schembl19622

90. Schembl41020

91. Bspbio_002405

92. Kbiogr_002194

93. Mls001050089

94. Mls001066338

95. Divk1c_000333

96. Spectrum1500294

97. Spbio_000261

98. Cineole [ep Monograph]

99. Eucalyptol, Analytical Standard

100. Chembl485259

101. Gtpl2464

102. Chembl1231862

103. Chembl1397305

104. Dtxsid4020616

105. Schembl13554591

106. Schembl17836873

107. Hms501a15

108. Kbio1_000333

109. Kbio3_001625

110. Eucalyptol [usp Impurity]

111. Ninds_000333

112. Eucalyptol [usp Monograph]

113. Hms2271p04

114. Pharmakon1600-01500294

115. Zinc967566

116. Hy-n0066

117. Tox21_111161

118. Tox21_202090

119. Tox21_302902

120. Bdbm50459887

121. Ccg-36080

122. Nsc760388

123. Acylated Oxime Isatin Derivative, 19

124. Akos015903223

125. Akos016034339

126. Akos037514637

127. Tox21_111161_1

128. Ccg-266254

129. Cs-8146

130. Db03852

131. Lmpr0102090019

132. Nsc-760388

133. Idi1_000333

134. Eucalyptol, Tested According To Ph.eur.

135. Ncgc00091666-02

136. Ncgc00091666-03

137. Ncgc00091666-05

138. Ncgc00095774-01

139. Ncgc00178671-01

140. Ncgc00256479-01

141. Ncgc00259639-01

142. Ac-20234

143. Eucalyptol, Natural, >=99%, Fcc, Fg

144. Ls-13868

145. Nci60_005108

146. 1,3-trimethyl-2-oxabicyclo[2.2.2]octane

147. 2-oxa-1,3-trimethylbicyclo[2.2.2]octane

148. Db-070775

149. 2-oxabicyclo[2.2.2]octane,3,3-trimethyl-

150. Ft-0607033

151. Ft-0626369

152. 1,3,3-trimethyl-2-oxabicyclo[2,2,2]octane

153. A15662

154. C09844

155. D04115

156. Ab01563262_01

157. Q161572

158. Sr-01000763816

159. Sr-01000763816-2

160. W-106080

161. 1,8-cineole, Primary Pharmaceutical Reference Standard

162. Cineole, European Pharmacopoeia (ep) Reference Standard

163. Eucalyptol, Certified Reference Material, Tracecert(r)

164. F0001-1260

165. Eucalyptol, United States Pharmacopeia (usp) Reference Standard

166. Eucalyptol (cineole), Pharmaceutical Secondary Standard; Certified Reference Material

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 154.25 g/mol
Molecular Formula C10H18O
XLogP32.5
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count1
Rotatable Bond Count0
Exact Mass154.135765193 g/mol
Monoisotopic Mass154.135765193 g/mol
Topological Polar Surface Area9.2 Ų
Heavy Atom Count11
Formal Charge0
Complexity164
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

/EXPL THER/ Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole. As part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarizes the relevant symptoms of acute bronchitis. After 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p?=?0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p?=?0.0001 after 4 days. The effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. ...

PMID:24261680 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842692 Fischer J, Dethlefsen U; Cough 9 (1): 25 (2013)


/EXPL THER/ The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesized that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane.

PMID:19624838 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720945 Worth H et al; Respir Res 10: 69 (2009)


/EXPL THER/ The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesized that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane.

PMID:19624838 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720945 Worth H et al; Respir Res 10: 69 (2009)


4.2 Drug Indication

As an active agent, eucalyptus oil has been indicated for relief of the symptoms of catarrhal colds, and/or the relief of the symptoms of minor muscular sprains and cramps.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Lipophilic monoterpene formulations of eucalyptus oil appear to be readily absorbed orally, with a primarily oxidative metabolism that might necessitate induction of the cytochrome P450 enzyme system and subsequent urinary excretion. Gastrointestinal absorption of eucalyptus appears to be rapid and may be enhanced by the intake of lipids and milk. 1,8-cineole (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) has also been found in vitro and in animals to possess cytochrome P450 inducing activity.


5.2 MeSH Pharmacological Classification

Flavoring Agents

Substances added to foods and medicine to improve the taste. (See all compounds classified as Flavoring Agents.)


Insect Repellents

Substances causing insects to turn away from them or reject them as food. (See all compounds classified as Insect Repellents.)


Solvents

Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant and Hackh's Chemical Dictionary, 5th ed) (See all compounds classified as Solvents.)


Antitussive Agents

Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally. (See all compounds classified as Antitussive Agents.)


Anti-Infective Agents

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)


Mouthwashes

Solutions for rinsing the mouth, possessing cleansing, germicidal, or palliative properties. (From Boucher's Clinical Dental Terminology, 4th ed) (See all compounds classified as Mouthwashes.)


5.3 ATC Code

R - Respiratory system

R05 - Cough and cold preparations

R05C - Expectorants, excl. combinations with cough suppressants

R05CA - Expectorants

R05CA13 - Cineole


5.4 Absorption, Distribution and Excretion

Absorption

Common monoterpenoid compound preparations of eucalyptus oil have been observed to be readily absorbed after dermal application, likely due to their lipophilic character. Although maximal plasma levels were demonstrated in as short a time period as 10 minutes even with thicker preparations like eucalyptus oil ointments, like many other topically applied agents, the extent of absorption is also likely largely dependent upon additional factors like the size of treated skin area, patient skin condition(s), concentrations of the applied substance, and time of exposure to the substance. Currently, more data regarding the oral absorption of eucalyptus would be useful, given the relative lack of existing information. Lipophilic monoterpene compound formulations of eucalyptus oil seems to be readily absorbed orally. Regardless, there is some data that suggests that the upper part of the gastrointestinal tract has no particularly significant role in the absorption of cineole based eucalyptus oil. Pulmonary absorption of eucalyptus oil is also possible although little information exists regarding this element at the moment. Nevertheless, 1,8-cineol (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) appears to be well absorbed via inhalation with peak plasma levels observed reportedly at 18 minutes. Given the three main constituents from Eucalyptus globulus Labill fruits, the intestinal absorption of macrocarpal A (M-A), macrocarpal B (M-B), and cypellocarpa C (Cy-C) is predominantly via passive diffusion while Cy-C demonstrates some partly ATP-dependent absorption.


Route of Elimination

Studies suggest the route of elimination for cineole or eucalyptol (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) in brushtail possum (Trichosurus vulpecula), rats, and rabbit subjects as being in the urine.


Volume of Distribution

Studies have determined a large terminal volume of distribution for cineole or eucalyptol (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) of 27 l/kg in brushtail possum (Trichosurus vulpecula).


Clearance

Studies have determined a high clearance rate for cineole or eucalyptol (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) of 43 ml/min/kg in brushtail possum (Trichosurus vulpecula).


5.5 Metabolism/Metabolites

With in vivo models, eucalyptol or cineole (which make up to as much as 90% of most commonly used cineole-based eucalyptus oils), undergoes oxidation to form hydroxycineole which is excreted as glucuronide. In rats, 2-hydroxycineole, 3-hydroxycineole, and 1,8--dihydroxycineol-9-oic acid were identified as main urinary metabolites. After oral administration to brushtail possums, p-cresol, 9-hydroxycineole, and Cineole-9-oic acid were found in urine. Rabbits given eucalyptol by savage excreted 2-exo- and 2-endo-hydroxycineole in the urine. The monterpene bicyclic ketone verbenone is a known component in eucalyptus globules. In one study, this component was observed to be converted to 10-hydroxyverbenone by rat and human liver microsomal cytochrome P450 enzymes, and indicated that CYP2A6 is a principal enzyme in verbenone hydroxylation in humans.


The biotransformation of 1,8-cineole was investigated using human liver microsomes. The metabolite was established as 2-exo-hydroxy-1,8-cineole. 1,8-cineole 2-hydroxylation catalyzed by human liver microsomes was found to be efficiently conducted.

European Chemicals Agency (ECHA); Registered substances, Cineole (CAS Number: 470-82-6) (EC Number: 207-431-5) (Last modified: January 19, 2015). Available from, as of June 22, 2015: https://echa.europa.eu/


Cineole was administered to male rats once daily by gastric intubation for 20 days. Urine was collected and major metabolites identified as methyl ester of 1,8-dihydroxy-10-carboxy p-methane, 2-hydroxy cineole and 3-hydroxy cineole.

European Chemicals Agency (ECHA); Registered substances, Cineole (CAS Number: 470-82-6) (EC Number: 207-431-5) (Last modified: January 19, 2015). Available from, as of June 22, 2015: https://echa.europa.eu/


Nature of non-conjugated metabolites of 1,8-cineole in urine and feces of brushtail possum yield p-cresol, 9-hydroxycineole and cineol-9-oic acid.

Southwell IA et al; Xenobiotica 10(1) 17 (1980)


1,8-Cineole has known human metabolites that include 2alpha-hydroxy-1,8-cineole and 3alpha-hydroxy-1,8-cineole.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560


5.6 Biological Half-Life

Studies have determined a terminal half-life for cineole or eucalyptol (which makes up to as much as 90% of most commonly used cineole-based eucalyptus oils) of approximately 7h in brushtail possum (Trichosurus vulpecula).


5.7 Mechanism of Action

The general consensus is that the exact mechanism of action of eucalyptus oil is largely unknown at this time but comprises various hypotheses from various studies. Cineol containing preparations of eucalyptus oil may contain up to 80% (or more) 1,8-cineole and is one of the most common types of eucalyptus oil formulations used. As an active agent indicated for relieving certain cold symptoms and/or certain muscular sprains and cramps, it is believed that eucalyptus oil may possess some antimicrobial and anti-inflammatory activities. Some in vitro studies of human blood monocytes suggest a dose-dependent effect of eucalyptus oil to elicit significant inhibition of multiple cytokines, perhaps in the treatment of airway inflammation. Moreover, other studies in animal models discuss the possibility of eucalyptus oil demonstrating anti-inflammatory and anti-nociceptive effects that potentially account for inhibiting the formation of prostaglandins and cytokines by stimulated monocytes in vitro. Furthermore, additional studies have observed eucalyptus oil anti-viral activity against herpes simplex virus (HSV-1, HSV-2) in cell cultures as well as the demonstration of broad antimicrobial activity of eucalyptus medicinal plant extracts against Alicyclobacillus acidoterretris, Bacillus cereus, E. coli, Enterococcus faecalis, MRSA, Propionibacterium acnes, S. aureus, fungus including C. albicans isolates, Trichophyton mentagrophytes, and other Gram-positive bacteria. Specific activity against periodontopathic bacteria, such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sobrinus has also been observed.


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A 31, PHASE 1, MEPZ-SEZ,,","city":"CHENNAI,TAMIL NADU","supplier":"ERNESTO VENTOS S.A","supplierCountry":"SPAIN","foreign_port":"BARCELONA","customer":"QUINTESSENCE FRAGRANCES PRIVATE ","customerCountry":"INDIA","quantity":"50.00","actualQuantity":"50","unit":"KGS","unitRateFc":"15.9","totalValueFC":"802.5","currency":"USD","unitRateINR":"1346.3","date":"27-Aug-2024","totalValueINR":"67316","totalValueInUsd":"802.5","indian_port":"Madras-EPZ\/SEZ","hs_no":"29329990","bill_no":"1017222","productDescription":"API","marketType":"REGULATED MARKET","country":"SPAIN","selfForZScoreResived":"Pharma Grade","supplierPort":"BARCELONA","supplierAddress":"CARRETERA REIAL 120 B08960 SANT JUS T DESVERNES ESPANA SPAIN","customerAddress":"PLOT NO. A 31, PHASE 1, MEPZ-SEZ,,"}]
05-Jan-2021
27-Aug-2024
KGS
overview
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Average Price (USD/KGS)

Number of Transactions

Total Quantity (KGS)

Total Value (USD)

Quantity (KGS) & Unit rate (USD/KGS) over time

API Imports and Exports

Importing Country Total Quantity
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Average Price
(USD/KGS)
Number of Transactions

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