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4-Terpineol, (+/-)-

PubChem CID
11230
Structure
4-Terpineol, (+/-)-_small.png
4-Terpineol, (+/-)-_3D_Structure.png
Molecular Formula
Synonyms
  • Terpinen-4-ol
  • 4-Carvomenthenol
  • 562-74-3
  • 4-Terpineol
  • p-Menth-1-en-4-ol
Molecular Weight
154.25 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-01-18
Description
4-terpineol is a terpineol that is 1-menthene carrying a hydroxy substituent at position 4. It has a role as a plant metabolite, an antibacterial agent, an antioxidant, an anti-inflammatory agent, an antiparasitic agent, an antineoplastic agent, an apoptosis inducer and a volatile oil component. It is a terpineol and a tertiary alcohol.
Terpinen-4-ol is under investigation in clinical trial NCT01647217 (Demodex Blepharitis Treatment Study).
4-Carvomenthenol has been reported in Anthriscus nitida, Tetradenia riparia, and other organisms with data available.
See also: Lavender Oil (part of); Juniper Berry Oil (part of); Peumus boldus leaf (part of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
4-Terpineol, (+/-)-.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-methyl-1-propan-2-ylcyclohex-3-en-1-ol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C10H18O/c1-8(2)10(11)6-4-9(3)5-7-10/h4,8,11H,5-7H2,1-3H3
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

WRYLYDPHFGVWKC-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=CCC(CC1)(C(C)C)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C10H18O
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

562-74-3

2.3.2 Deprecated CAS

1336-05-6, 28219-82-1
1336-05-6

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 FEMA Number

2.3.10 HMDB ID

2.3.11 JECFA Number

439

2.3.12 KEGG ID

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 RXCUI

2.3.16 Wikidata

2.3.17 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • (R)-1-isopropyl-4-methyl-3-cyclohexen-1-ol
  • terpinen-4-ol
  • terpinenol-4

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
154.25 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
2.2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
154.135765193 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
154.135765193 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
20.2 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
11
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
170
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Colourless to pale yellow, oily liquid; Warm-peppery, mildly earthy, musty-woody odour

3.2.2 Color / Form

Colorless to pale yellow liquid
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 261

3.2.3 Odor

Pine
Center for Disease Control and Prevention Agency for Toxic Substances and Disease Registry. Available from, as of July 22, 2015: https://www.atsdr.cdc.gov/odors/search_results.html

3.2.4 Taste

Herbal pepper flavoring
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 12th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2012., p. V5: 4151

3.2.5 Boiling Point

209 °C
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3: 2311
88.00 to 90.00 °C. @ 6.00 mm Hg
The Good Scents Company Information System

3.2.6 Flash Point

79 degrees C (174 degrees F) - closed cup
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

3.2.7 Solubility

Slightly soluble in water, soluble in oils
Soluble (in ethanol)

3.2.8 Density

0.926 g/cu cm at 20 °C
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3: 2311
0.928-0.934

3.2.9 LogP

log Kow = 3.26
Griffin S et al; J Chromatogr 864: 221-8 (1999)
3.26

3.2.10 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

3.2.11 Optical Rotation

Specific optical rotation: +24.5 deg at 11 °C/D
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3: 2311

3.2.12 Refractive Index

Index of refraction: 1.4785 ar 19 °C/D
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3: 2311
1.476-1.480

3.2.13 Kovats Retention Index

Standard non-polar
1161 , 1162 , 1177 , 1161 , 1164 , 1161 , 1161 , 1171 , 1154 , 1172 , 1161 , 1173 , 1156 , 1162 , 1161 , 1163 , 1172 , 1158 , 1225 , 1161 , 1158 , 1173 , 1153 , 1189 , 1178 , 1159 , 1149 , 1164 , 1164 , 1170 , 1181 , 1161 , 1164 , 1163 , 1177 , 1163 , 1145 , 1141 , 1161 , 1159 , 1178 , 1161 , 1167 , 1160 , 1158 , 1158 , 1148 , 1162 , 1158 , 1158 , 1177 , 1164 , 1157 , 1161 , 1163 , 1158 , 1160 , 1158 , 1162 , 1162 , 1162 , 1149 , 1148 , 1154 , 1153 , 1158 , 1166 , 1162 , 1158 , 1153 , 1157 , 1157 , 1162 , 1159.52 , 1163 , 1164 , 1160 , 1162 , 1178 , 1162 , 1162 , 1157 , 1157 , 1162 , 1161 , 1161 , 1163 , 1162 , 1175 , 1166 , 1166 , 1174.6 , 1167 , 1162 , 1162 , 1161 , 1168 , 1168 , 1159 , 1172 , 1167 , 1156 , 1167 , 1161 , 1164 , 1160 , 1163 , 1178 , 1173 , 1160 , 1182 , 1167 , 1169 , 1160 , 1169 , 1164 , 1161 , 1172 , 1155 , 1162 , 1165 , 1165 , 1163 , 1168 , 1184 , 1143.97 , 1147.52 , 1151.16 , 1154.87 , 1158.69 , 1162.62 , 1166.67 , 1170.83 , 1175.01 , 1179.37 , 1183.77 , 1188.31 , 1154 , 1165 , 1163 , 1168 , 1173 , 1167 , 1165 , 1165 , 1177 , 1177 , 1169 , 1157 , 1159 , 1165 , 1167 , 1167 , 1168 , 1170 , 1166 , 1165 , 1161 , 1155.67 , 1159.02 , 1162.62 , 1166.49 , 1170.68 , 1175.22 , 1180.15 , 1185.54 , 1176 , 1164 , 1156 , 1152 , 1157 , 1170 , 1161 , 1158 , 1152 , 1161 , 1165 , 1170 , 1170 , 1173 , 1175 , 1165 , 1155 , 1163 , 1165 , 1164 , 1171 , 1169.6 , 1166 , 1178 , 1169 , 1166 , 1170 , 1160 , 1164 , 1165 , 1178 , 1170 , 1171 , 1180 , 1186 , 1192 , 1197 , 1180 , 1186 , 1192 , 1197 , 1190 , 1170 , 1173 , 1182 , 1175 , 1148 , 1162 , 1160 , 1160 , 1164 , 1164 , 1157 , 1143 , 1175 , 1177 , 1186 , 1178 , 1166 , 1161 , 1164 , 1166 , 1166 , 1157 , 1157 , 1159 , 1175 , 1157 , 1175 , 1171 , 1148 , 1148 , 1164 , 1164 , 1159 , 1156 , 1148 , 1161 , 1176 , 1177 , 1182 , 1177 , 1168 , 1166 , 1148 , 1168 , 1154 , 1148 , 1166 , 1178 , 1180 , 1154 , 1175 , 1159 , 1168 , 1148 , 1162 , 1166 , 1176 , 1162 , 1164 , 1158 , 1158 , 1161 , 1161 , 1148 , 1162 , 1166 , 1177 , 1166 , 1176 , 1161 , 1162 , 1162 , 1177 , 1167 , 1165 , 1166 , 1171 , 1164 , 1157 , 1165 , 1175 , 1157 , 1158 , 1152 , 1160 , 1148 , 1163 , 1170 , 1175 , 1169 , 1148 , 1160 , 1148 , 1161 , 1153 , 1165 , 1177 , 1171 , 1153 , 1168 , 1165 , 1152 , 1166 , 1169 , 1161 , 1177 , 1175 , 1172 , 1155 , 1158 , 1181 , 1156 , 1178 , 1168 , 1161 , 1167 , 1148 , 1166 , 1166 , 1159 , 1154 , 1156 , 1156 , 1159 , 1166 , 1165 , 1170 , 1153 , 1175 , 1175 , 1160 , 1146 , 1177 , 1159 , 1164 , 1176 , 1158 , 1148 , 1169 , 1161 , 1161.1 , 1161 , 1158 , 1156 , 1171 , 1163 , 1164 , 1167 , 1155 , 1172 , 1173 , 1169.6 , 1171.9 , 1157 , 1141 , 1157 , 1169 , 1158 , 1166 , 1173 , 1181 , 1170 , 1167 , 1169 , 1196 , 1160 , 1155 , 1159 , 1158 , 1152 , 1158.3 , 1160 , 1162 , 1148 , 1165 , 1168 , 1162 , 1160 , 1160 , 1157 , 1161 , 1159 , 1151 , 1156 , 1167 , 1169 , 1167 , 1159 , 1171 , 1157 , 1180.6 , 1148 , 1205 , 1166 , 1151 , 1156 , 1157 , 1166 , 1177 , 1158 , 1148 , 1170 , 1161 , 1170 , 1168 , 1164 , 1170 , 1177 , 1170 , 1166 , 1160 , 1166 , 1173 , 1161 , 1158 , 1160 , 1152 , 1165 , 1175 , 1181 , 1175.6 , 1166 , 1167 , 1147 , 1164 , 1168 , 1169 , 1170 , 1166 , 1148 , 1166 , 1166 , 1166 , 1177 , 1163 , 1168 , 1160 , 1164 , 1167 , 1170 , 1154 , 1154 , 1154 , 1148 , 1148 , 1172 , 1148 , 1167 , 1168 , 1166 , 1158 , 1179 , 1162 , 1159 , 1166 , 1167 , 1158 , 1161 , 1175 , 1175 , 1178 , 1168 , 1170 , 1175 , 1167 , 1170 , 1167 , 1169 , 1161 , 1160 , 1155 , 1159 , 1161 , 1161 , 1168 , 1169 , 1159 , 1159 , 1160 , 1166 , 1163 , 1160 , 1163 , 1169 , 1166 , 1169 , 1158 , 1159 , 1161 , 1153 , 1153 , 1160 , 1175 , 1161 , 1159 , 1170 , 1183 , 1162 , 1164 , 1165 , 1156 , 1159 , 1170 , 1156
Semi-standard non-polar
1181 , 1174 , 1175 , 1193 , 1179 , 1179 , 1180 , 1178 , 1171 , 1180 , 1180 , 1173 , 1173 , 1178 , 1215 , 1176 , 1203 , 1184 , 1169 , 1175 , 1176 , 1175 , 1177 , 1176 , 1175 , 1175 , 1179 , 1182.2 , 1174 , 1174 , 1178 , 1177 , 1192 , 1197 , 1177 , 1176 , 1176 , 1176 , 1177 , 1181 , 1178 , 1180 , 1175 , 1185 , 1165 , 1157 , 1171 , 1179 , 1177 , 1174 , 1177 , 1177 , 1179 , 1173 , 1181.5 , 1186 , 1177 , 1168 , 1176 , 1177 , 1179 , 1178 , 1179 , 1178 , 1179 , 1155 , 1178 , 1177 , 1177 , 1175 , 1174 , 1177 , 1177 , 1174 , 1178 , 1177 , 1170 , 1165 , 1189 , 1178 , 1180 , 1174 , 1174 , 1176 , 1179 , 1177 , 1177 , 1182 , 1179 , 1179 , 1174 , 1175 , 1179 , 1176 , 1177 , 1178 , 1182 , 1184 , 1177 , 1178 , 1177 , 1180 , 1176 , 1179 , 1176 , 1158 , 1173 , 1185 , 1186 , 1184 , 1187 , 1178 , 1177 , 1178 , 1178 , 1179 , 1179 , 1179 , 1178 , 1180 , 1182 , 1179 , 1182 , 1179 , 1179 , 1176 , 1179 , 1193 , 1177 , 1178 , 1178 , 1180 , 1165 , 1179 , 1180 , 1181 , 1172 , 1179 , 1176 , 1177 , 1177 , 1177 , 1178 , 1177 , 1186 , 1176 , 1175 , 1179 , 1177 , 1177 , 1177 , 1165 , 1172 , 1178 , 1177 , 1145 , 1177 , 1179 , 1179 , 1182 , 1175 , 1174 , 1175 , 1177 , 1177 , 1173 , 1177 , 1177 , 1177 , 1179 , 1177 , 1177 , 1184 , 1178 , 1171 , 1177 , 1177 , 1180 , 1175 , 1171 , 1182 , 1180 , 1175 , 1185.54 , 1200 , 1182 , 1173 , 1174 , 1177 , 1183 , 1174 , 1183 , 1165 , 1165 , 1176 , 1174 , 1182 , 1184 , 1184 , 1217 , 1180 , 1180 , 1182 , 1182 , 1175 , 1187 , 1206 , 1177 , 1180 , 1177 , 1179 , 1184 , 1173 , 1171 , 1172 , 1172 , 1177 , 1177 , 1178 , 1181 , 1184 , 1180 , 1177 , 1177 , 1177 , 1182 , 1190 , 1185 , 1179 , 1181 , 1176 , 1175 , 1179 , 1177 , 1180 , 1191 , 1174 , 1192 , 1177 , 1170 , 1178 , 1160 , 1172 , 1177 , 1177 , 1179 , 1178 , 1185 , 1178 , 1175 , 1180 , 1177 , 1181 , 1176 , 1177 , 1177 , 1177 , 1177 , 1178 , 1177 , 1175 , 1177 , 1181 , 1177 , 1174 , 1177 , 1175 , 1141 , 1171 , 1178 , 1177 , 1153 , 1176 , 1141 , 1178 , 1175 , 1141 , 1177 , 1177 , 1175 , 1176 , 1167 , 1176 , 1176 , 1182 , 1182 , 1177 , 1177 , 1183 , 1179 , 1180 , 1188 , 1177 , 1193 , 1213 , 1194 , 1174 , 1174 , 1174 , 1177 , 1177 , 1177 , 1179 , 1181 , 1177 , 1179 , 1192 , 1171 , 1177 , 1178 , 1182 , 1184 , 1196 , 1176 , 1185 , 1182 , 1185 , 1182 , 1183 , 1178 , 1174 , 1177 , 1170 , 1179 , 1184 , 1182 , 1172 , 1177 , 1182 , 1179 , 1179 , 1178 , 1179 , 1176 , 1179 , 1182 , 1184 , 1184 , 1179 , 1180 , 1182 , 1160 , 1177 , 1186 , 1188 , 1174 , 1177 , 1174 , 1211 , 1182 , 1191 , 1203 , 1177 , 1186 , 1173 , 1172 , 1177 , 1175 , 1178 , 1177 , 1181 , 1179 , 1183 , 1176 , 1176 , 1178 , 1179 , 1184 , 1167 , 1179 , 1177 , 1178 , 1178 , 1185 , 1178 , 1182 , 1181 , 1183 , 1179 , 1177 , 1182 , 1174 , 1180 , 1180 , 1191 , 1220 , 1177 , 1177 , 1181 , 1186 , 1177 , 1179 , 1185 , 1179 , 1172 , 1180 , 1206 , 1179 , 1179 , 1180 , 1185 , 1177 , 1178 , 1175 , 1177 , 1185 , 1177 , 1179 , 1179 , 1167 , 1168 , 1177 , 1176 , 1174 , 1177 , 1141 , 1192 , 1177 , 1174 , 1177 , 1168 , 1178 , 1191 , 1170 , 1176 , 1191 , 1177 , 1175 , 1153 , 1180 , 1168 , 1175 , 1177 , 1175 , 1174 , 1146 , 1177 , 1178 , 1147 , 1177 , 1177 , 1180 , 1186 , 1172 , 1176 , 1177 , 1212 , 1178 , 1173 , 1175 , 1192 , 1153 , 1177 , 1177 , 1187 , 1176 , 1176 , 1179 , 1166 , 1177 , 1140 , 1177 , 1175 , 1174 , 1178 , 1175 , 1177 , 1175.3 , 1177 , 1178 , 1173 , 1184 , 1191 , 1177 , 1177 , 1174 , 1176 , 1177 , 1177 , 1182 , 1180 , 1177 , 1177 , 1184 , 1176 , 1177 , 1177 , 1193 , 1177 , 1177 , 1174 , 1220 , 1177 , 1172 , 1220 , 1179 , 1179 , 1179 , 1179 , 1180 , 1180 , 1185 , 1180 , 1179 , 1172 , 1180 , 1177 , 1177 , 1177 , 1177 , 1177 , 1142 , 1179 , 1179 , 1182 , 1180 , 1173 , 1191 , 1177 , 1181 , 1177 , 1175 , 1177 , 1184 , 1179 , 1147 , 1177 , 1177 , 1177 , 1179 , 1180 , 1186 , 1184 , 1169 , 1175 , 1175 , 1165 , 1177 , 1177 , 1179 , 1174 , 1182 , 1194 , 1177 , 1184 , 1179 , 1182 , 1177 , 1175 , 1177 , 1173 , 1175 , 1180 , 1178.1 , 1171 , 1177 , 1179 , 1177 , 1182 , 1172 , 1177 , 1179 , 1179 , 1185 , 1177 , 1178 , 1164 , 1177 , 1183 , 1177 , 1178 , 1182 , 1175 , 1175 , 1177 , 1175 , 1174 , 1177 , 1171 , 1177 , 1168 , 1177 , 1183 , 1179 , 1207 , 1177 , 1140 , 1150 , 1177 , 1175 , 1175 , 1175 , 1161 , 1168 , 1177 , 1165 , 1183 , 1179 , 1171 , 1177 , 1177 , 1177 , 1193 , 1175 , 1175 , 1177 , 1143 , 1178 , 1172 , 1176 , 1143 , 1181 , 1176 , 1176 , 1177 , 1177 , 1144 , 1177 , 1170 , 1174 , 1177 , 1177 , 1177 , 1176 , 1184 , 1177 , 1177 , 1177 , 1220 , 1175 , 1177 , 1177 , 1203 , 1186 , 1172 , 1160 , 1177 , 1168 , 1166 , 1172 , 1183 , 1189 , 1189 , 1182 , 1176 , 1177 , 1177 , 1178 , 1169 , 1175 , 1182 , 1220 , 1174 , 1188 , 1178 , 1179 , 1168 , 1180 , 1177 , 1177 , 1177 , 1178.8 , 1177 , 1177 , 1162 , 1178 , 1180 , 1177 , 1177 , 1177 , 1177 , 1174 , 1174 , 1177 , 1179 , 1180 , 1180 , 1178 , 1177 , 1168 , 1177 , 1177 , 1177 , 1177 , 1178 , 1180 , 1174 , 1177 , 1183.3 , 1173 , 1172 , 1182 , 1178 , 1191 , 1176 , 1181 , 1171 , 1177 , 1184 , 1170 , 1174 , 1179 , 1177 , 1177 , 1177 , 1179 , 1183 , 1177 , 1175 , 1173 , 1178 , 1177 , 1177 , 1175 , 1175 , 1176 , 1171 , 1178 , 1172 , 1179 , 1179 , 1177 , 1172 , 1174.3 , 1178.5 , 1190 , 1154 , 1154 , 1173 , 1176 , 1177 , 1176 , 1177 , 1177 , 1170 , 1178 , 1174 , 1175 , 1176 , 1177 , 1178 , 1148 , 1177 , 1177 , 1192 , 1177 , 1174 , 1179 , 1179 , 1178 , 1179 , 1179 , 1179 , 1177 , 1176 , 1175.6 , 1178 , 1176 , 1176 , 1177 , 1174 , 1182 , 1172 , 1175
Standard polar
1600 , 1598 , 1599 , 1612 , 1597 , 1552 , 1576 , 1563 , 1604 , 1606 , 1594 , 1588 , 1589 , 1601 , 1592 , 1599 , 1625 , 1597 , 1607 , 1598 , 1605 , 1606 , 1578 , 1597 , 1619 , 1599 , 1559 , 1577 , 1574 , 1598 , 1612 , 1581 , 1591 , 1578 , 1595 , 1619 , 1591 , 1583 , 1602 , 1554 , 1602 , 1577 , 1575 , 1621 , 1645 , 1589 , 1591 , 1640 , 1603 , 1595 , 1574 , 1581 , 1607 , 1630 , 1630 , 1600 , 1630 , 1595 , 1559 , 1591 , 1585 , 1595 , 1587 , 1590 , 1586 , 1589 , 1603 , 1630 , 1597 , 1599 , 1572 , 1588 , 1621 , 1623 , 1616 , 1607 , 1593 , 1568 , 1583 , 1585 , 1612 , 1587 , 1594 , 1592 , 1575 , 1605 , 1633 , 1584 , 1556 , 1595 , 1582 , 1571 , 1593 , 1581 , 1592 , 1597 , 1604 , 1592 , 1618 , 1569 , 1592 , 1595 , 1559 , 1585 , 1571 , 1593 , 1577 , 1600 , 1603 , 1603 , 1609 , 1599 , 1613 , 1593 , 1593 , 1595 , 1557 , 1575 , 1603 , 1588 , 1588 , 1588 , 1609 , 1564 , 1595 , 1595 , 1598 , 1636 , 1630 , 1630 , 1609 , 1600 , 1603 , 1603 , 1603 , 1617 , 1603 , 1603 , 1600 , 1591 , 1593 , 1610 , 1621 , 1592 , 1626 , 1602 , 1579 , 1642 , 1602 , 1596 , 1570 , 1572 , 1601 , 1573 , 1574 , 1594 , 1595 , 1591 , 1613 , 1635 , 1624 , 1594 , 1590 , 1616 , 1592 , 1609 , 1628 , 1600 , 1602 , 1589 , 1591 , 1601 , 1612 , 1584 , 1600 , 1605 , 1627 , 1587 , 1585 , 1628 , 1601 , 1601 , 1611 , 1563 , 1602 , 1608 , 1596 , 1611 , 1614 , 1617 , 1611 , 1611 , 1611 , 1606 , 1586 , 1597 , 1602 , 1598 , 1611 , 1611 , 1611 , 1597 , 1572 , 1583 , 1611 , 1570 , 1610 , 1611 , 1611 , 1595 , 1602 , 1600 , 1586 , 1610 , 1618 , 1604 , 1633 , 1591 , 1571 , 1601 , 1601 , 1606 , 1590 , 1574 , 1611 , 1618 , 1607 , 1607 , 1611 , 1608 , 1609 , 1593 , 1608 , 1603 , 1599 , 1604 , 1610 , 1617 , 1600 , 1604 , 1611 , 1611 , 1593 , 1612 , 1586 , 1601 , 1613 , 1616 , 1628 , 1599 , 1597 , 1612 , 1610 , 1611 , 1600 , 1600 , 1555 , 1600 , 1608 , 1611 , 1642 , 1586 , 1611 , 1601 , 1603 , 1560 , 1614 , 1571 , 1571 , 1604 , 1605 , 1611 , 1611 , 1594 , 1602 , 1581 , 1628 , 1559 , 1611 , 1611 , 1577 , 1601 , 1636 , 1599 , 1608 , 1592 , 1611 , 1597 , 1607 , 1607 , 1614 , 1580 , 1579 , 1611 , 1593 , 1624 , 1588 , 1589 , 1602 , 1643 , 1590 , 1610 , 1603 , 1567 , 1599 , 1599 , 1611 , 1611 , 1610 , 1592 , 1593 , 1602 , 1592 , 1622 , 1622 , 1611 , 1600.6 , 1600 , 1628 , 1611 , 1622 , 1587 , 1611 , 1611 , 1620 , 1564 , 1611 , 1611 , 1568 , 1642 , 1607 , 1591 , 1630 , 1611 , 1594 , 1611 , 1638 , 1618.2 , 1611 , 1613 , 1611 , 1611 , 1611 , 1611 , 1631 , 1588 , 1606.5 , 1611 , 1628 , 1623 , 1642 , 1603 , 1611 , 1590 , 1611 , 1559 , 1603 , 1611 , 1609 , 1611 , 1611 , 1605 , 1590 , 1595 , 1610.3 , 1605 , 1596 , 1593 , 1611 , 1611 , 1617 , 1607 , 1611 , 1597 , 1637 , 1605 , 1611 , 1611 , 1611 , 1574 , 1589 , 1561 , 1564 , 1607 , 1602 , 1559 , 1613 , 1601 , 1589 , 1611 , 1603 , 1611 , 1611 , 1611 , 1611 , 1622 , 1628 , 1605 , 1634 , 1637 , 1619 , 1607 , 1617 , 1622 , 1557 , 1561 , 1615 , 1621 , 1592 , 1636 , 1607 , 1616 , 1614 , 1617 , 1617 , 1617 , 1617 , 1617 , 1617 , 1622 , 1622 , 1603 , 1581 , 1583 , 1596 , 1605 , 1622 , 1634 , 1610 , 1595 , 1638 , 1628 , 1598 , 1598 , 1600 , 1602 , 1604.9 , 1602 , 1603 , 1594 , 1583 , 1600 , 1595 , 1611 , 1598 , 1600 , 1600 , 1626 , 1628 , 1595 , 1557 , 1581 , 1628 , 1628 , 1629 , 1597.9

3.3 Chemical Classes

3.3.1 Food Additives

FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food

3.3.2 Fragrances

Fragrance Ingredient (4-Carvomenthenol) -> IFRA transparency List

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
1.92:79.00, 1.91:91.00, 1.57:103.00, 1.51:39.00, 2.14:119.00, 1.68:631.00, 1.92:82.00, 5.30:107.00, 1.64:143.00, 0.95:915.00, 5.29:114.00, 5.30:42.00, 1.54:68.00, 1.92:80.00, 1.67:315.00, 1.90:81.00, 0.93:1000.00, 1.65:223.00, 1.53:46.00, 1.59:74.00, 1.91:90.00, 1.56:95.00, 5.29:115.00, 1.93:87.00, 1.54:67.00, 0.91:973.00, 5.29:116.00, 1.54:57.00, 5.28:108.00, 1.56:55.00, 0.94:904.00
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
218383
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 3
View All
Spectra ID
Instrument Type
Varian
Frequency
25.16 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
23.28:595.00, 36.84:835.00, 71.71:750.00, 16.85:870.00, 133.80:850.00, 27.15:795.00, 16.89:905.00, 30.93:800.00, 34.60:765.00, 118.54:1000.00
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Source of Sample
F. Bohlmann, R. Zeisberg Org. Magn. Resonance 7, 426(1975)
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 14
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

71.0 99.99

111.0 52.64

43.0 44.78

93.0 43.32

41.0 32.84

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Notes
instrument=HITACHI M-80B
2 of 14
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

71.0 99.99

111.0 61.07

93.0 59.60

86.0 48.75

69.0 38.56

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Notes
instrument=HITACHI M-80

4.2.2 MS-MS

1 of 3
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

54.01098 100

151.11385 26.50

57.03397 21.60

69.03412 10.50

80.0256 9.90

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View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

153.1307 100

54.01161 18.50

151.11431 10.80

68.00077 3.30

78.24482 2.70

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4.2.3 LC-MS

1 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
153.1284892
Instrument
Agilent qTOF 6545
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Collision Energy
20 eV
Top 5 Peaks

54.01098 100

151.11385 26.50

57.03397 21.60

69.03412 10.50

80.0256 9.90

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2 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
153.1284892
Instrument
Agilent qTOF 6545
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Collision Energy
40 eV
Top 5 Peaks

31.71729 100

41.24386 46.20

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4.2.4 Other MS

1 of 3
View All
Other MS
MASS: 36604 (NIST/EPA/MSDC Mass Spectral Database, 1990 version); 205 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
2 of 3
View All
Authors
TAJIMA S, GUNMA COLLEGE OF TECHNOLOGY
Instrument
HITACHI M-80B
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

71 999

111 526

43 448

93 433

41 328

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License
CC BY-NC-SA

4.3 IR Spectra

4.3.1 FTIR Spectra

1 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
Neat
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
TCI Chemicals India Pvt. Ltd.
Catalog Number
T1993
Lot Number
GL01-HTIL
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
Between salts
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
W224820
Lot Number
12817BD
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.2 ATR-IR Spectra

1 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
TCI Chemicals India Pvt. Ltd.
Catalog Number
T1993
Lot Number
GL01-HTIL
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
218383
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.3 Near IR Spectra

1 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR Spectrometer= INSTRUMENT PARAMETERS=INST=BRUKER,RSN=8932,REO=2,CNM=HEI,ZFF=2
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR Spectrometer= INSTRUMENT PARAMETERS=INST=BRUKER,RSN=8932,REO=2,CNM=HEI,ZFF=2
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.3.4 Vapor Phase IR Spectra

1 of 2
Technique
Vapor Phase
Source of Spectrum
Sigma-Aldrich Co. LLC.
Catalog Number
218383
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
218383
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

1 of 2
Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Technique
FT-Raman
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
TCI Chemicals India Pvt. Ltd.
Catalog Number
T1993
Lot Number
GL01-HTIL
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
218383
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Clinical Trials

7.1.1 ClinicalTrials.gov

7.2 Therapeutic Uses

EXPL THER To evaluate potential antiinflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia. The ability of tea tree oil to reduce the production in vitro of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-8, IL-10 and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-activated human peripheral blood monocytes was examined. Tea tree oil emulsified by sonication in a glass tube into culture medium containing 10% fetal calf serum (FCS) was toxic for monocytes at a concentration of 0.016% v/v. However, the water soluble components of tea tree oil at concentrations equivalent to 0.125% significantly suppressed LPS-induced production of TNFalpha, IL-1beta and IL-10 (by approximately 50%) and PGE2 (by approximately 30%) after 40 h. Gas chromatography/mass spectrometry identified terpinen-4-ol (42 %), a-terpineol (3 %) and 1,8-cineole (2%, respectively, of tea tree oil) as the water soluble components of tea tree oil. When these components were examined individually, only terpinen-4-ol suppressed the production after 40 h of TNFalpha, IL-1beta, IL-8, IL-10 and PGE2 by LPS-activated monocytes. The water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes.
Hart PH et al; Inflamm Res 49(11): 619-26 (2000)
EXPL THER To evaluate the regulatory properties of the essential oil of Melaleuca alternifolia (tea tree oil) on the production of oxygen derived reactive species by human peripheral blood leukocytes activated in vitro. The ability of tea tree oil to reduce superoxide production by neutrophils and monocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) was examined. The water-soluble fraction of tea tree oil had no significant effect on agonist-stimulated superoxide production by neutrophils, but significantly and dose-dependently suppressed agonist-stimulated superoxide production by monocytes. This suppression was not due to cell death. Chemical analysis identified the water-soluble components to be terpinen-4-ol, alpha-terpineol and 1,8-cineole. When examined individually, terpinen-4-ol significantly suppressed fMLP- and LPS- but not PMA-stimulated superoxide production; alpha-terpineol significantly suppressed fMLP-, LPS- and PMA-stimulated superoxide production; 1,8-cineole was without effect. Tea tree oil components suppress the production of superoxide by monocytes, but not neutrophils, suggesting the potential for selective regulation of cell types by these components during inflammation.
Brand C et al; Inflamm Res 50(4): 213-19 (2001)
EXPL THER The aim of this study was to compare both the antimicrobial activity of terpinen-4-ol and tea tree oil (TTO) against clinical skin isolates of meticillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CoNS) and their toxicity against human fibroblast cells. Antimicrobial activity was compared by using broth microdilution and quantitative in vitro time-kill test methods. Terpinen-4-ol exhibited significantly greater bacteriostatic and bactericidal activity, as measured by minimum inhibitory and bactericidal concentrations, respectively, than TTO against both MRSA and CoNS isolates. Although not statistically significant, time-kill studies also clearly showed that terpinen-4-ol exhibited greater antimicrobial activity than TTO. Comparison of the toxicity of terpinen-4-ol and TTO against human fibroblasts revealed that neither agent, at the concentrations tested, were toxic over the 24-hr test period. Terpinen-4-ol is a more potent antibacterial agent against MRSA and CoNS isolates than TTO with neither agent exhibiting toxicity to fibroblast cells at the concentrations tested. Terpinen-4-ol should be considered for inclusion as a single agent in products formulated for topical treatment of MRSA infection.
Loughlin R et al; Lett Appl Microbiol 46(4): 428-33 (2008)
EXPL THER To examine the in vitro anticancer activity of Melaleuca alternifolia (tea tree) oil (TTO), and its major active terpene component, terpinen-4-ol, against two aggressive murine tumour cell lines, AE17 mesothelioma and B16 melanoma. Effects of TTO and terpinen-4-ol on the cellular viability of two tumour cell lines and fibroblast cells were assessed by MTT assay. Induction of apoptotic and necrotic cell death was visualised by fluorescent microscopy and quantified by flow cytometry. Tumour cell ultrastructural changes were examined by transmission electron microscopy and changes in cell cycle distribution were assessed by flow cytometry, with changes in cellular morphology monitored by video time lapse microscopy. TTO and terpinen-4-ol significantly inhibited the growth of two murine tumour cell lines in a dose- and time-dependent manner. Interestingly, cytotoxic doses of TTO and terpinen-4-ol were significantly less efficacious against non-tumour fibroblast cells. TTO and terpinen-4-ol induced necrotic cell death coupled with low level apoptotic cell death in both tumour cell lines. This primary necrosis was clarified by video time lapse microscopy and also by transmission electron microscopy which revealed ultrastructural features including cell and organelle swelling following treatment with TTO. In addition, both TTO and terpinen-4-ol induced their inhibitory effect by eliciting G1 cell cycle arrest. TTO and terpinen-4-ol had significant anti-proliferative activity against two tumour cell lines. Moreover, the identification of primary necrotic cell death and cell cycle arrest of the aggressive tumour cells highlights the potential anticancer activity of TTO and terpinen-4-ol.
Greay SJ et al; Cancer Chemother Pharmacol 65(5): 877-88 (2010)
For more Therapeutic Uses (Complete) data for 4-Terpineol (6 total), please visit the HSDB record page.

8 Food Additives and Ingredients

8.1 Food Additive Classes

Flavoring Agents
JECFA Functional Classes
Flavouring Agent -> FLAVOURING_AGENT;

8.2 FEMA Flavor Profile

Earth, Must, Nutmeg, Wood

8.3 FDA Substances Added to Food

Used for (Technical Effect)
FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT
Document Number (21 eCFR)
FEMA Number
2248
GRAS Number
3, 25
JECFA Flavor Number
439

8.4 Associated Foods

8.5 Evaluations of the Joint FAO / WHO Expert Committee on Food Additives - JECFA

1 of 2
Chemical Name
4-CARVOMENTHENOL
Evaluation Year
1998
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
2 of 2
Chemical Name
ORIGANOL
Evaluation Year
1998
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph

9 Pharmacology and Biochemistry

9.1 Absorption, Distribution and Excretion

The terpenes disturb lipid arrangement in the intercellular region of the stratum corneum (SC) that leads to the increased permeability of the skin. This effect is used in technology of transdermal drug forms and depends on physicochemical properties of terpenes and their amounts penetrated to the stratum corneum; however terpenes do not need penetrate into viable skin tissue and this event is not even desired. To correlate skin absorption and elimination kinetics of four cyclic terpenes, namely alpha-pinene, beta-pinene, eucalyptol and terpinen-4-ol, applied as neat substance with their physicochemical properties. The terpenes were applied onto the human skin in vitro, and after 1-4 h their content in the separated by a tape-stripping method stratum corneum layers and in the epidermis/dermis was determined using GC. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1 h absorption. The fastest and progressive penetration into all skin layers was observed for terpinen-4-ol. All studied terpenes are absorbed in the viable epidermis/dermis, however penetration into this layers is time-dependent process, constantly increasing during 4 h. Like for stratum corneum, the largest cumulation in epidermis/dermis was observed for terpinen-4-ol. The elimination of terpenes from the stratum corneum was fast, especially in deeper layers, and much faster if the initial cumulation was small. Investigated cyclic terpenes represent different penetration and elimination characteristics and do not permeate across the skin to the acceptor medium due to large cumulation in the skin tissue. The penetration of terpenes into stratum corneum is greater if their log P-value is close to 3.
Cal K et al; J Dermatol Sci 41(2): 137-42 (2005).
The purpose of this study was to evaluate the in vitro cutaneous penetration of five terpenes--linalool, linalyl acetate, terpinen-4-ol, citronellol and alpha-pinene--applied in pure essential oils or in dermatological formulations (o/w emulsion, oily solution or hydrogel) containing 0.75 % w/w of the essential oils. Different skin absorption was observed depending on the type of the vehicle and terpenes' log P values. Cutaneous accumulation of terpenes is several times higher when they are applied in pure essential oils than in topical vehicles. Penetration of terpinen-4-ol to the skin was better from an oily solution (approximately 90 ug/cm (2)) than from an emulsion (60 ug/cm (2)). No penetration of linalyl acetate from topical vehicles into viable skin was observed, but also for this terpene penetration to the upper layers of the stratum corneum was 2-times higher when an oily solution was used. In contrast, the cutaneous absorption of linalool was the same from both vehicles (50-60 ug/cm (2)). The skin penetration of alpha-pinene was not traceable when it was applied in an oily solution. Only a small amount (approximately 5 ug/cm (2)) of this terpene was determined in viable skin after application as a hydrogel. Citronellol applied in a hydrogel penetrated into all skin layers in a total amount of 25 ug/cm (2), while no penetration into viable skin layers after application of an oily solution was noted. Only citronellol permeated into the acceptor medium.
Cal K; Planta Med 72(4): 311-16 (2006)
This work aimed to evaluate the effect induced by excipients conventionally used for topical dosage forms, namely isopropyl myristate (IPM) or oleic acid (OA) or polyethylene glycol 400 (PEG400) or Transcutol (TR), on the human skin permeability of terpinen-4-ol (T4OL) contained in the pure Tea tree oil. The effect of such excipients was determined by evaluating the absorption of T4OL using human epidermis and the perturbation of the organization of stratum corneum by ATR-FTIR. Among the tested excipients OA enhanced the absorption of T4OL by perturbing the stratum corneum lipid barrier. Other excipients caused a weak enhancement effect and their use should be carefully monitored.
Casiraghi A et al; Pharm Dev Technol 15(5): 545-52 (2010)
The purpose of this study was to investigate dermal pharmacokinetics of terpinen-4-ol in rats following topical administration of plai oil derived from the rhizomes of Zingiber cassumunar Roxb. Unbound terpinen-4-ol concentrations in dermal tissue were measured by microdialysis. The dermal pharmacokinetic study of terpinen-4-ol was performed under non-occlusive conditions. The oil was topically applied at a dose of 2, 4, and 8 mg/square cm plai oil corresponding to the amount of 1.0, 1.9, and 3.8 mg/square cm terpinen-4-ol, respectively. Following topical application of the oil, terpinen-4-ol rapidly distributed into the dermis and demonstrated linear pharmacokinetics with no changes in the dose-normalized area under the concentration-time curves across the investigated dosage range. The mean percentages of free terpinen-4-ol distributed in the dermis per amount of administered were 0.39 +/- 0.06 %, 0.41 +/- 0.08 %, and 0.30 +/- 0.03 % for 2, 4, and 8 mg/square cm doses, respectively. The dermal pharmacokinetics of terpinen-4-ol could provide information for its further formulation development and therapy schedules.
Chooluck K et al; Planta Med 78(16): 1761-66 (2012)

9.2 Metabolism / Metabolites

(R)-Terpinen-4-ol was mixed in an artificial diet at a concentration of 1 mg/g of diet, and the diet was fed to the last instar larvae of common cutworm (Spodoptera litura). Metabolites were recovered from frass and analyzed spectroscopically. (R)-Terpinen-4-ol was transformed mainly to (R)-p-menth-1-en-4,7-diol. Similarly, (S)-terpinen-4-ol was transformed mainly to (S)-p-menth-1-en-4,7-diol. The C-7 position (allylic methyl group) of (R)- and (S)-terpinen-4-ol was preferentially oxidized.
Miyazawa M et al; J Agric Food Chem 49(9): 4312-4 (2001)
We examined the in vitro metabolism of (+)-terpinen-4-ol by human liver microsomes and recombinant enzymes. The biotransformation of (+)-terpinen-4-ol was investigated by gas chromatography-mass spectrometry (GC-MS). (+)-Terpinen-4-ol was found to be oxidized to (+)-(1R,2S,4S)-1,2-epoxy-p-menthan-4-ol, (+)-(1S,2R,4S)-1,2-epoxy-p-menthan-4-ol, and (4S)-p-menth-1-en-4,8-diol by human liver microsomal P450 enzymes. The identities of (+)-terpinen-4-ol metabolites were determined through the relative abundance of mass fragments and retention times on GC-MS. Of 11 recombinant human P450 enzymes tested, CYP1A2, CYP2A6, and CYP3A4 were found to catalyze the oxidation of (+)-terpinen-4-ol. Based on several lines of evidence, CYP2A6 and CYP3A4 were determined to be major enzymes involved in the oxidation of (+)-terpinen-4-ol by human liver microsomes. First, of the 11 recombinant human P450 enzymes tested, CYP1A2, CYP2A6 and CYP3A4 catalyzed oxidation of (+)-terpinen-4-ol. Second, oxidation of (+)-terpinen-4-ol was inhibited by (+)-menthofuran and ketoconazole, inhibitors known to be specific for these enzymes. Finally, there was a good correlation between CYP2A6 and CYP3A4 activities and (+)-terpinen-4-ol oxidation activities in the 10 human liver microsomes.
Haigou R et al; J Oleo Sci 61(1): 35-43 (2012)

9.3 Human Metabolite Information

9.3.1 Cellular Locations

  • Extracellular
  • Membrane

9.4 Biochemical Reactions

10 Use and Manufacturing

10.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
It is used ... in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes.
Fahlbusch K-G et al; Flavors and Fragrances. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2015). NY, NY: John Wiley & Sons. Online Posting Date: January 15, 2003
In public use since the 1890's. In the United States, use in fragrances amounts for about 1 million lbs/ year.
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695

Reported uses (ppm):

Table: Reported uses (ppm): (Flavor and Extract Manufacturers' Association, 1994)

Food Category
Baked goods
Usual
6.85
Max.
40.66
Food Category
Chewing gum
Usual
0.25
Max.
0.25
Food Category
Frozen dairy
Usual
3.47
Max.
11.02
Food Category
Gelatins, puddings
Usual
3.79
Max.
10.11
Food Category
Gravies
Usual
3.00
Max.
6.00
Food Category
Meat products
Usual
10.00
Max.
20.00
Food Category
Nonalcoholic beverages
Usual
1.49
Max.
2.67
Food Category
Soft candy
Usual
3.68
Max.
5.63

Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 261
MEDICATION

10.1.1 Use Classification

Food additives -> Flavoring Agents
Fragrance Ingredients
Flavoring Agents -> JECFA Flavorings Index
Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes

10.1.2 Household Products

Household & Commercial/Institutional Products

Information on 10 consumer products that contain 4-Terpineol in the following categories is provided:

• Auto Products

• Inside the Home

10.2 Methods of Manufacturing

1-Terpinen-4-ol is a byproduct in the synthesis of terpineol from terpin hydrate, and occurs in commercial terpineol. Pure 1-terpinen-4-ol can be prepared from terpinolene by photosensitized oxidation, reduction of the resulting 1-methyl-4-isopropenyl-1-cyclohexene-4-hydroperoxide, and selective hydrogenation of the corresponding alcohol.
Fahlbusch K-G et al; Flavors and Fragrances. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2015). NY, NY: John Wiley & Sons. Online Posting Date: January 15, 2003
Prepared from terpin hydrate by the splitting off the elements of water.
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695
One of several terpinenol isomers, depending on the position of the double bond and that of the hydroxyl group, this terpene ... can be isolated by fractional distillation.
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 261

10.3 U.S. Production

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-. National Production Volume: 29,751 lb/yr.
USEPA/Pollution Prevention and Toxics; 2012 Chemical Data Reporting Database. 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)- (562-74-3). Available from, as of June 9, 2015: https://java.epa.gov/oppt_chemical_search/

10.4 General Manufacturing Information

EPA TSCA Commercial Activity Status
3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-: ACTIVE
Found in more than 200 derivatives from leaves, herbs, and flowers.
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695

11 Identification

11.1 Analytic Laboratory Methods

Cell integrity in Saccharomyces cerevisiae is ensured by a rigid cell wall whose synthesis is controlled by a highly conserved MAP kinase signal transduction cascade. Stress at the cell surface is detected by a set of sensors and ultimately transmitted through this cascade to the transcription factor Rlm1, which governs expression of many genes encoding enzymes of cell wall biosynthesis. We here report on a number of versatile reporter constructs which link activation of a hybrid, Rlm1-lexA, by the MAP kinase Mpk1/Slt2 to the expression of the bacterial lacZ gene. This system was adapted to automated microwell screening and shown to be activated by a number of compounds inhibiting cell wall biosynthesis or interfering with plasma membrane function.
Straede A et al; Yeast 24(4): 321-34 (2007)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 2
View All
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H302 (> 99.9%): Harmful if swallowed [Warning Acute toxicity, oral]

H315 (98.4%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (12.4%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (96.6%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H336 (13.9%): May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 1985 reports by companies from 27 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Acute Tox. 4 (> 99.9%)

Skin Irrit. 2 (98.4%)

Skin Sens. 1 (12.4%)

Eye Irrit. 2 (96.6%)

STOT SE 3 (13.9%)

12.1.3 Skin, Eye, and Respiratory Irritations

A skin irritant.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3363
/Skin/ Terpineol applied at full strength ...produced moderate irritation.
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695

12.2 Fire Fighting

12.2.1 Fire Fighting Procedures

Use water spray to cool unopened containers.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-ol, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-ol, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-ol, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.3 Accidental Release Measures

12.3.1 Cleanup Methods

Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.3.2 Disposal Methods

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.
Product: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product. Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.3.3 Preventive Measures

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.4 Handling and Storage

12.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Combustible liquids.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.5 Exposure Control and Personal Protection

12.5.1 Personal Protective Equipment (PPE)

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.6 Stability and Reactivity

12.6.1 Hazardous Reactivities and Incompatibilities

Incompatible materials: Strong oxidizing agents, strong oxidizing agents, acid chlorides, and acid anhydrides.
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html

12.7 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Terpinen-4-ol: Does not have an individual approval but may be used under an appropriate group standard

12.7.1 FDA Requirements

4-Carvomenthenol is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.
21 CFR 172.515 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 3, 2015: https://www.ecfr.gov

12.8 Other Safety Information

12.8.1 Toxic Combustion Products

Carbon oxides
Sigma-Aldrich; Material Safety Data Sheet for Terpinen 4-oll, Product Number: 03900590, Version 5.4 (Revision Date 02/03/2015). Available from, as of July 15, 2015. https://www.sigmaaldrich.com/safety-center.html
When heated to decomposition it emits acrid smoke and irritating fumes.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3363

13 Toxicity

13.1 Toxicological Information

13.1.1 Toxicity Summary

IDENTIFICATION AND USE: 1-Terpinen-4-ol is colorless to pale yellow liquid with pine odor. It is found in more than 200 derivatives from leaves, herbs, and flowers. It is used in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes. It is also used as experimental medication and topical antimicrobial. HUMAN EXPOSURE AND TOXICITY: Terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways. It suppress the production of superoxide by monocytes, but not neutrophils, suggesting the potential for selective regulation of cell types by these components during inflammation. In addition, the water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes. ANIMAL STUDIES: Oral LD50's range from 1.0 to 4.3 g/kg in rodents. A single study of dermal toxicity in rabbits reported a LD50 of >3 g/kg.

13.1.2 Acute Effects

13.1.3 Interactions

This study compared the antimicrobial activity of Melaleuca alternifolia (tea tree) oil with that of some of its components, both individually and in two-component combinations. Minimum inhibitory concentration and time-kill assays revealed that terpinen-4-ol, the principal active component of tea tree oil, was more active on its own than when present in tea tree oil. Combinations of terpinen-4-ol and either gamma-terpinene or p-cymene produced similar activities to tea tree oil. Concentration-dependent reductions in terpinen-4-ol activity and solubility also occurred in the presence of gamma-terpinene. Non-oxygenated terpenes in tea tree oil appear to reduce terpinen-4-ol efficacy by lowering its aqueous solubility. These findings explain why tea tree oil can be less active in vitro than terpinen-4-ol alone and further suggest that the presence of a non-aqueous phase in tea tree oil formulations may limit the microbial availability of its active components.
Cox SD et al; J Appl Microbiol 91(3): 492-7 (2001)
Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 uL. For in vitro experiments, 4TRP concentrations were 0.1mM and 1.0mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.
Nobrega FF et al; Oxid Med Cell Longev (2014)
Artemisia phaeolepis, a perennial herb with a strong volatile odor, grows on the grasslands of Mediterranean region. Essential oil obtained from Artemisia phaeolepis was analyzed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. A total of 79 components representing 98.19% of the total oil were identified, and the main compounds in the oil were found to be eucalyptol (11.30%), camphor (8.21%), terpine-4-ol (7.32%), germacrene D (6.39), caryophyllene oxide (6.34%), and caryophyllene (5.37%). The essential oil showed definite inhibitory activity against 10 strains of test microorganisms. Eucalyptol, camphor, terpine-4-ol, caryophyllene, germacrene D and caryophyllene oxide were also examined as the major components of the oil. Camphor showed the strongest antimicrobial activity; terpine-4-ol, eucalyptol, caryophyllene and germacrene D were moderately active and caryophyllene oxide was weakly active. The study revealed that the antimicrobial properties of the essential oil can be attributed to the synergistic effects of its diverse major and minor components.
Ben Hsouna A et al; J Oleo Sci 62(12): 973-80 (2013)
The combined effect of terpinen-4-ol, the main component of tea tree oil, and capric acid against mycelial growth of Candida albicans and murine oral candidiasis was evaluated in vitro and in vivo. Mycelial growth of C. albicans was estimated by the Cristal violet method. Combination of these compounds revealed a potent synergistic inhibition of growth. Therapeutic efficacy of the combination was evaluated microbiologically in murine oral candidiasis, and its application of the compounds clearly demonstrated therapeutic activity. Based on these results, the combined agent of terpinen-4-ol and capric acid was discussed as a possible candidate for oral candidiasis therapy.
Ninomiya K et al; Yakugaku Zasshi 133(1): 133-40 (2013)
The present study investigated the hypotensive responses to intravenous (i.v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) and its main constituent, terpinen-4-ol (Trp-4-ol), in the experimental model of deoxycorticosterone-acetate (DOCA)-salt hypertensive rat. In both DOCA-salt hypertensive and uninephrectomized, normotensive rats, i.v. bolus injections of EOAZ (1-20 mg/kg) or Trp-4-ol (1-10 mg/kg) decreased mean aortic pressure (MAP) in a dose-related manner. However, hypotensive responses to Trp-4-ol were significantly greater than those evoked by the same doses of EOAZ (1-10 mg/kg). Treatment with DOCA-salt significantly enhanced the maximal percentage decreases in MAP evoked by EOAZ or Trp-4-ol. Likewise, both maximal percentage and absolute decreases in MAP elicited by i.v. injection of the ganglion blocker, hexamethonium (30 mg/kg), were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, neither hexamethonium (30 mg/kg, i.v.) nor methylatropine (1 mg/kg, i.v.) pretreatment affected the enhancement of EOAZ-induced hypotension. These results show that i.v. treatment with either EOAZ or Trp-4-ol dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement could be related mainly to an increase in EOAZ-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. The data further support our previous hypothesis that hypotensive effects of EOAZ are partially attributed to the actions of Trp-4-ol.
Lahlou S et al; Fundam Clin Pharmacol 17(3): 323-30 (2003)

13.1.4 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Turpentine, terpenes, and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 244
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. /Turpentine, terpenes, and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 244
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive- pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Turpentine, Terpenes, and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 245

13.1.5 Human Toxicity Excerpts

/ALTERNATIVE and IN VITRO TESTS/ Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.
Khaw-on P et al; Asian Pac J Cancer Prev 13(7): 3073-76 (2012)
/ALTERNATIVE and IN VITRO TESTS/ To evaluate the regulatory properties of the essential oil of Melaleuca alternifolia (tea tree oil) on the production of oxygen derived reactive species by human peripheral blood leukocytes activated in vitro. The ability of tea tree oil to reduce superoxide production by neutrophils and monocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) was examined. The water-soluble fraction of tea tree oil had no significant effect on agonist-stimulated superoxide production by neutrophils, but significantly and dose-dependently suppressed agonist-stimulated superoxide production by monocytes. This suppression was not due to cell death. Chemical analysis identified the water-soluble components to be terpinen-4-ol, alpha-terpineol and 1,8-cineole. When examined individually, terpinen-4-ol significantly suppressed fMLP- and LPS- but not PMA-stimulated superoxide production; alpha-terpineol significantly suppressed fMLP-, LPS- and PMA-stimulated superoxide production; 1,8-cineole was without effect. Tea tree oil components suppress the production of superoxide by monocytes, but not neutrophils, suggesting the potential for selective regulation of cell types by these components during inflammation.
Brand C et al; Inflamm Res 50(4): 213-19 (2001)
/ALTERNATIVE and IN VITRO TESTS/ To evaluate potential antiinflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia. The ability of tea tree oil to reduce the production in vitro of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-8, IL-10 and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-activated human peripheral blood monocytes was examined. Tea tree oil emulsified by sonication in a glass tube into culture medium containing 10% fetal calf serum (FCS) was toxic for monocytes at a concentration of 0.016% v/v. However, the water soluble components of tea tree oil at concentrations equivalent to 0.125% significantly suppressed LPS-induced production of TNFalpha, IL-1beta and IL-10 (by approximately 50%) and PGE2 (by approximately 30%) after 40 h. Gas chromatography/mass spectrometry identified terpinen-4-ol (42 %), a-terpineol (3 %) and 1,8-cineole (2%, respectively, of tea tree oil) as the water soluble components of tea tree oil. When these components were examined individually, only terpinen-4-ol suppressed the production after 40 h of TNFalpha, IL-1beta, IL-8, IL-10 and PGE2 by LPS-activated monocytes. The water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes. /Tea tree oil/
Hart PH et al; Inflamm Res 49(11): 619-26 (2000)

13.1.6 Non-Human Toxicity Excerpts

/OTHER TOXICITY INFORMATION/ Cell integrity in Saccharomyces cerevisiae is ensured by a rigid cell wall whose synthesis is controlled by a highly conserved MAP kinase signal transduction cascade. Stress at the cell surface is detected by a set of sensors and ultimately transmitted through this cascade to the transcription factor Rlm1, which governs expression of many genes encoding enzymes of cell wall biosynthesis. We here report on a number of versatile reporter constructs which link activation of a hybrid, Rlm1-lexA, by the MAP kinase Mpk1/Slt2 to the expression of the bacterial lacZ gene. This system was adapted to automated microwell screening and shown to be activated by a number of compounds inhibiting cell wall biosynthesis or interfering with plasma membrane function. In addition, we tested tea tree oil and two of its purified constituents (alpha-terpineol, terpinen-4-ol) for their effects on growth and on cell integrity signalling using such reporter strains. Tea tree oil was found to inhibit growth of wild-type and slg1/wsc1 mutant cells at a threshold of approximately 0.1% v/v, with the purified compounds acting already at half these concentrations. A mid2 deletion displayed hyper-resistance. Tea tree oil also induces the signalling pathway in a dose-dependent manner.
Straede A et al; Yeast 24(4): 321-34 (2007)

13.1.7 Non-Human Toxicity Values

LD50 Rabbit Dermal >3 g/kg
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695
LD50 Rat Oral 4.3 g/kg
Opdyke, D.L.J. (ed.). Monographs on Fragrance Raw Materials. New York: Pergamon Press, 1979., p. 695
LD50 rat oral 1300 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3363
LD50 Mice oral 1016 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3363

13.2 Ecological Information

13.2.1 Environmental Fate / Exposure Summary

4-Terpineol's production, extraction and use as a food and beverage additive and in perfumery may result in its release to the environment through various waste streams. 4-Terpineol occurs naturally in many plants and plant volatiles including; guava, big sagebrush and choke cherry trees, ginger root, Artemisia phaeolepis, lavender, Eucalyptus, apple, apricots, orange, lemon, grapefruit, tangerines, anise, cinnamon and nutmeg. If released to air, an estimated vapor pressure of 0.04 mm Hg at 25 °C indicates 4-terpineol will exist solely as a vapor in the atmosphere. Vapor-phase 4-terpineol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone; the half-lives for these reactions in air are estimated to be 3.7 hours and 38 minutes, respectively. 4-Terpineol does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, 4-terpineol is expected to have high mobility based upon an estimated Koc of 80. Volatilization from moist soil surfaces is expected based upon an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole. 4-Terpineol is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Aerobic degradation studies done using batch and continuous digesters resulting in 96% 4-terpineol removal suggest that biodegradation is an important environmental fate process in soil and water. If released into water, 4-terpineol is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 15 and 110 days, respectively. An estimated BCF of 66 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to 4-terpineol may occur through inhalation and dermal contact with this compound at workplaces where 4-terpineol is produced or used. Monitoring data indicate that the general population may be exposed to 4-terpineol via ingestion of food and beverages containing it. (SRC)

13.2.2 Natural Pollution Sources

4-Terpineol occurs naturally in many plants and plant volatiles including; guava(1), big sagebrush and choke cherry trees(2), ginger root(3), Artemisia phaeolepis(4), lavender(5), Eucalyptus(5), apple(5), apricots(5), orange(5), lemon(5), grapefruit(5), tangerines(5), anise(5), cinnamon(5) and nutmeg(5).
(1) Binder RG, Flath RA; J Agric Food Chem 37: 734-6 (1989)
(2) Helmig D et al; Chemosphere 38: 2163-87 (1999)
(3) Nishimura O; J Agric Food Chem 43: 2941-5 (1995)
(4) BenHsouna A et al; J Oleo Sci 62: 973-80 (2013)
(5) Burdock GA, ed; Fenaroli's Handbook of Flavor Ingredients. 6th ed., Boca Raton, FL: CRC Press p. 621 (2009)

13.2.3 Artificial Pollution Sources

4-Terpineol's production, extraction and use as a food and beverage additive(1,2) and in perfumery(2) may result in its release to the environment through various waste streams(SRC).
(1) Burdock GA, ed; Fenaroli's Handbook of Flavor Ingredients. 6th ed., Boca Raton, FL: CRC Press p. 621 (2009)
(2) Fahlbusch K-G et al; Flavors and Fragrances. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2015). New York, NY: John Wiley & Sons. Online Posting Date: 15 Jan 2003

13.2.4 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that 4-terpineol is expected to have high mobility in soil(SRC). Volatilization of 4-terpineol from moist soil surfaces is expected(SRC) given an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). 4-Terpineol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.04 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Aerobic degradation studies done using batch and continuous digesters resulting in 96% 4-terpineol removal(3) suggest that biodegradation may be an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Hrutfiord BF et al; Tappi 58: 98-100 (1975)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that 4-terpineol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 15 and 110 days, respectively(SRC). 4-Terpineol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 66(SRC), from its log Kow of 3.26(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Aerobic degradation studies done using batch and continuous digesters resulting in 96% 4-terpineol removal(6) suggest that biodegradation may be an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) Griffin S et al; J Chromatogr 864: 221-8 (1999)
(6) Hrutfiord BF et al; Tappi 58: 98-100 (1975)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-terpineol, which has a estimated vapor pressure of 0.04 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-terpineol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone(SRC); the half-lives for these reactions in air are estimated to be 3.7 hours and 38 minutes(SRC), calculated from respective rate constants of 1.0X10-10 and 4.3X10-16 cu cm/molecule-sec at 25 °C(SRC) that were derived using a structure estimation method(2). 4-Terpineol does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

13.2.5 Environmental Biodegradation

AEROBIC: Utilizing both batch and continuous digesters, 96% removal of 4-terpineol (initial concentration of 0.50 ppm) was reported when it was incubated for 168-192 hr under aerobic conditions using sewage inoculum in a biological treatment study(1).
(1) Hrutfiord BF et al; Tappi 58: 98-100 (1975)

13.2.6 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of 4-terpineol with photochemically-produced hydroxyl radicals has been estimated as 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 4-terpineol with ozone is estimated as 4.3X10-16 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of 38 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). 4-Terpineol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 4-Terpineol does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12, 8-13 (1990)

13.2.7 Environmental Bioconcentration

An estimated BCF of 66 was calculated in fish for 4-terpineol(SRC), using a log Kow of 3.26(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).
(1) Griffin S et al; J Chromatogr 864: 221-8 (1999)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.8 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-terpineol can be estimated to be 80(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-terpineol is expected to have high mobility in soil.
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)

13.2.9 Volatilization from Water / Soil

The Henry's Law constant for 4-terpineol is estimated as 3.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-terpineol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 15 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 110 days(SRC). 4-Terpineol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 4-Terpineol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.04 mm Hg(SRC), determined from a fragment constant method(1).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of July 22, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

13.2.10 Environmental Water Concentrations

SURFACE WATER: 4-Terpineol was identified, not quantified, in water samples collected from Black Warrior River, Tuscaloosa, AL(1). Water collected from 6 of 8 small rivers flowing into Lake Constance, Germany, contained 4-terpineol at unreported concentrations(2).
(1) Bertsch W et al; J Chromatogr 112: 701-18 (1075)
(2) Juttner F; Wat Sci Tech 25: 155-64 (1992)

13.2.11 Effluent Concentrations

4-Terpineol was detected in wastewater effluent at unreported concentrations from plastics and synthetics industries(1). 4-Terpineol was detected in a final effluent sample collected Apr 17, 1980 from a publicly owned water treatment plant in Addison, IL at an unreported concentration; grab samples from 9 other sites in Illinois did not contain detectable concentrations of 4-terpineol(2). 4-Terpineol was detected in effluent from two kraft pulp mill waste waters receiving secondary treatment in aerated lagoons(3). 4-Terpineol was detected at unreported concentrations in head space analyses of kitchen waste exudate(4) and garden waste exudate(5) collected in Denmark. 4-Terpineol was detected in the primary clarifier effluent from a Finnish bleached kraft pulp mill(6). 4-Terpineol was detected in 4 of 9 aerated lagoon discharge samples at a mean and range of 50 and 10-100 ug/L, respectively; samples were collected from softwood bleached kraft pulp mills located across Canada during winter 1980-1981(7).
(1) Bursey JT, Pellizzari ED; Analysis of Industrial Wastewater for Organic Pollutants in Consent Degree Survey. Contract No. 68-03-2867. Athens, GA: USEPA Environ Res Lab pp. 162 (1982)
(2) Ellis DD et al; Arch Environ Contam Toxicol 11: 373-82 (1982)
(3) Wilson D, Hrutfiord B; Pulp Pap Canada 76: 91 (1975)
(4) Wilkins CK, Larsen K; J High Resol Chromatogr 18: 373-77 (1995)
(5) Wilkins K, Larsen K; Chemosphere 32: 2049-55 (1996)
(6) Koistinen J et al; Chemosphere 37: 219-35 (1998)
(7) Voss RH; Environ Sci Technol 18: 938-46 (1984)

13.2.12 Atmospheric Concentrations

RURAL/REMOTE: 4-Terpineol was detected in Balbina, Amazonia tropical forest atomospheric samples at concentrations of <0.1 ppb(1).
(1) Kesselmeier J et al; Atmos Environ 34: 4063-72 (2000)

13.2.13 Food Survey Values

4-Terpineol was identified, not quantified, in the volatile emissions of raw earth almonds(1), Frankfurter sausages(2), edible Korean chamchwi (Aster scaber Thunb)(3), apricots(4), pine needle tea(5), roasted filberts(6), and nectarines(7). 4-Terpineol was detected in fresh-squeezed unpasteurized orange juice from five of six different cultivars at 0.071-0.20 ppm(8). 4-Terpineol has been detected in beer, wine and spirits(9).
(1) Cantalejo MH; J Agric Food Chem 45: 1853-60 (1997)
(2) Chevance FV, Farmer LJ; J Agric Food Chem 47: 5161-8 (1999)
(3) Chung TY et al; J Agric Food Chem 41: 1693-7 (1993)
(4) Gomez E et al; J Agric Food Chem 1: 1669-76 (1993)
(5) Kim KY, Chung HJ; J Agric Food Chem 48: 1269-72 (2000)
(6) Kinlin TE et al; J Agric Food Chem 20: 1021-8 (1972)
(7) Takeoka GR et al; J Agric Food Chem 36: 553-60 (1988)
(8) Moshonas MG, Shaw PE; J Agric Food Chem 42: 1525-8 (1994)
(9) IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Alcohol Drinking. Volume 44. Available from, as of July 22, 2015: https://monographs.iarc.fr/ENG/Monographs/vol44/index.php

13.2.14 Plant Concentrations

Pineapple guava contained 4-terpineol at 0.03 ug/g(1). 4-Terpineol has been identified as a volatile emission from big sagebrush and choke cherry trees(2). 4-Terpineol was identified as a volatile component of fresh ginger root(3). 4-Terpineol was found to be 7.32% of the essential oil of the perennial herb Artemisia phaeolepis; plants were collected from Qassim, Saudi Arabia(4). 4-Terpineol has been reported in the oil of Cupressus macrocarpa lavender, Spanish origanum, Ledum palustre, Eucalyptus australiana, Eucalyptus dives, Xanthoxylum rhetsa and camphor oil(5). It has been found in fresh apple, apricots, orange juice, peel oils of orange, lemon, grapefruit, tangerines, anise, cinnamon, ginger and nutmeg(5).
(1) Binder RG, Flath RA; J Agric Food Chem 37: 734-6 (1989)
(2) Helmig D et al; Chemosphere 38: 2163-87 (1999)
(3) Nishimura O; J Agric Food Chem 43: 2941-5 (1995)
(4) BenHsouna A et al; J Oleo Sci 62: 973-80 (2013)
(5) Burdock GA, ed; Fenaroli's Handbook of Flavor Ingredients. 6th ed., Boca Raton, FL: CRC Press p. 621 (2009)
4-Terpineol detections in plants(1).
Genus species
Thymus vularis
Family
Lamiaceae
Common name
common thyme
Part
plant
Concn (ppm)
8320
Genus species
Origanum onites
Family
Lamiaceae
Common name
pot marjoram
Part
shoot
Concn (ppm)
0-525
Genus species
Satureja thymbra
Family
Lamiaceae
Common name
goat oregano
Part
shoot
Concn (ppm)
0-185
Genus species
Coridothymus capitatus
Family
Lamiaceae
Common name
Spanish oregano
Part
shoot
Concn (ppm)
0-155
Genus species
Origanum vulgare (subsp. hirtum)
Family
Lamiaceae
Common name
Turkish, Greek, wild oregano
Part
shoot
Concn (ppm)
0-90
Genus species
Agathosma betulina
Family
Rutaceae
Common name
Buchu, Honey Buchu, Mountain Buchu
Part
Leaf
Concn (ppm)
not reported
Genus species
Barosma betulina
Family
Rutaceae
Common name
Buchu
Part
Leaf
Concn (ppm)
not reported
Genus species
Camellia sinensis
Family
Theaceae
Common name
Tea
Part
Leaf
Concn (ppm)
not reported
Genus species
Carica papaya
Family
Cariaceae
Common name
Papaya
Part
Fruit
Concn (ppm)
not reported
Genus species
Citrus aurantium
Family
Rutaceae
Common name
Bitter Orange, Petitgrain
Part
Plant
Concn (ppm)
not reported
Genus species
Psoralea corylifolia
Family
Fabaceae
Common name
Babchi, Black Dot, Malaya Tea
Part
Seed
Concn (ppm)
not reported
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. 4-Terpineol. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of July 22, 2015: https://www.ars-grin.gov/duke/

13.2.15 Other Environmental Concentrations

4-Terpineol was detected in liquid floor wax at unreported concentrations(1).
(1) Knoeppel H, Schauenburg H; Environ Int 15: 413-8 (1989)

13.2.16 Probable Routes of Human Exposure

According to the 2012 TSCA Inventory Update Reporting data, one reporting facility estimates the number of persons reasonably likely to be exposed in the manufacturing, processing, or use of 4-terpineol in the United States may be 50-99 workers; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).
(1) US EPA; Chemical Data Reporting (CDR). Non-confidential 2012 Chemical Data Reporting information on chemical production and use in the United States. Available from, as of July 22, 2015: https://www.epa.gov/cdr/pubs/guidance/cdr_factsheets.html
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1167 workers (51 of these are female) were potentially exposed to 4-terpineol in the US(1). Occupational exposure to 4-terpineol may occur through inhalation and dermal contact with this compound at workplaces where 4-terpineol is produced or used. Monitoring data indicate that the general population may be exposed to 4-terpineol via ingestion of food and beverages containing 4-terpineol(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of July 22, 2015: https://www.cdc.gov/noes/

14 Associated Disorders and Diseases

Disease
Nonalcoholic fatty liver disease
References
PubMed: 23454028

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Chemical Co-Occurrences in Literature

15.6 Chemical-Gene Co-Occurrences in Literature

15.7 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Chemical-Target Interactions

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106
S29 | PHYTOTOXINS | Toxic Plant Phytotoxin (TPPT) Database | DOI:10.5281/zenodo.2652993

20 Classification

20.1 MeSH Tree

20.2 ChEBI Ontology

20.3 KEGG: Lipid

20.4 ChemIDplus

20.5 ChEMBL Target Tree

20.6 UN GHS Classification

20.7 EPA CPDat Classification

20.8 NORMAN Suspect List Exchange Classification

20.9 EPA DSSTox Classification

20.10 Consumer Product Information Database Classification

20.11 EPA TSCA and CDR Classification

20.12 LOTUS Tree

20.13 EPA Substance Registry Services Tree

20.14 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
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    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
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  5. DTP/NCI
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    https://www.cancer.gov/policies/copyright-reuse
  6. EPA Chemicals under the TSCA
    3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  7. EPA DSSTox
    4-Methyl-1-(1-methylethyl)-3-cyclohexen-1-ol
    https://comptox.epa.gov/dashboard/DTXSID4044824
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. European Chemicals Agency (ECHA)
    LICENSE
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    https://echa.europa.eu/web/guest/legal-notice
  9. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. Hazardous Substances Data Bank (HSDB)
  11. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  12. International Fragrance Association (IFRA)
    LICENSE
    (c) The International Fragrance Association, 2007-2021. All rights reserved.
    https://ifrafragrance.org/links/copyright
  13. New Zealand Environmental Protection Authority (EPA)
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    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  14. ChEBI
  15. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  16. Yeast Metabolome Database (YMDB)
    LICENSE
    YMDB is offered to the public as a freely available resource.
    http://www.ymdb.ca/downloads
  17. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  18. ClinicalTrials.gov
    LICENSE
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  19. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  20. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  21. EPA Chemical and Products Database (CPDat)
    4-Methyl-1-(propan-2-yl)cyclohex-3-en-1-ol
    https://comptox.epa.gov/dashboard/DTXSID4044824#exposure
  22. EU Food Improvement Agents
  23. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) licence.
    https://www.who.int/about/policies/publishing/copyright
  24. FDA Substances Added to Food
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  25. Flavor and Extract Manufacturers Association (FEMA)
  26. FooDB
    LICENSE
    FooDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (FooDB) and the original publication.
    https://foodb.ca/about
  27. MassBank Europe
  28. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  29. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
    3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-, (R)-
    http://www.nist.gov/srd/nist1a.cfm
  30. SpectraBase
    3-CYCLOHEXEN-1-OL, 4-METHYL-1-(1-METHYLETHYL)-
    https://spectrabase.com/spectrum/DnHbJ4pA4gs
    3-CYCLOHEXEN-1-OL, 4-METHYL-1-(1-METHYLETHYL)-
    https://spectrabase.com/spectrum/60A0nu45s4b
    3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-
    https://spectrabase.com/spectrum/EfEfaYFgo6B
    3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-
    https://spectrabase.com/spectrum/I8wnWnTLK7K
  31. Japan Chemical Substance Dictionary (Nikkaji)
  32. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  33. Natural Product Activity and Species Source (NPASS)
  34. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Terpinen-4-ol
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  35. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
    4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol
    https://rxnav.nlm.nih.gov/id/rxnorm/1314261
  36. Rhea - Annotated Reactions Database
    LICENSE
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    https://www.rhea-db.org/help/license-disclaimer
  37. Springer Nature
  38. Thieme Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  39. Wikidata
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  41. PubChem
  42. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  43. GHS Classification (UNECE)
  44. EPA Substance Registry Services
  45. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  46. PATENTSCOPE (WIPO)
CONTENTS