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Isophorone

PubChem CID
6544
Structure
Isophorone_small.png
Isophorone_3D_Structure.png
Molecular Formula
Synonyms
  • ISOPHORONE
  • 78-59-1
  • Isoacetophorone
  • 3,5,5-Trimethylcyclohex-2-en-1-one
  • Isoforone
Molecular Weight
138.21 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-01-11
Description
Isophorone is a clear liquid that smells like peppermint. It can be dissolved in water and evaporates somewhat faster than water. It is an industrial chemical used as a solvent in some printing inks, paints, lacquers, and adhesives. It is also used as an intermediate in the production of certain chemicals. Although isophorone is an industrial chemical, it also occurs naturally in cranberries.
Isophorone appears as a clear colorless liquid, with a camphor-like odor. Less dense than water and insoluble in water. Boiling point 420 °F. Flash point near 200 °F. Contact irritates skin and eyes. Toxic by ingestion. Used as a solvent and in pesticides.
Isophorone is a cyclic ketone, the structure of which is that of cyclohex-2-en-1-one substituted by methyl groups at positions 3, 5 and 5. It has a role as a solvent and a plant metabolite. It is a cyclic ketone and an enone.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Isophorone.png

1.2 3D Conformer

1.3 Crystal Structures

COD records with this CID as component

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

3,5,5-trimethylcyclohex-2-en-1-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C9H14O/c1-7-4-8(10)6-9(2,3)5-7/h4H,5-6H2,1-3H3
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

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

2.1.4 SMILES

CC1=CC(=O)CC(C1)(C)C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C9H14O
Computed by PubChem 2.2 (PubChem release 2021.10.14)
C9H14O

2.3 Other Identifiers

2.3.1 CAS

78-59-1

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 UN Number

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DSSTox Substance ID

2.3.8 FEMA Number

2.3.9 HMDB ID

2.3.10 ICSC Number

2.3.11 JECFA Number

1112

2.3.12 KEGG ID

2.3.13 Metabolomics Workbench ID

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 RTECS Number

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • diisophorone
  • isophorone

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
138.21 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
1.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
0
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
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
138.104465066 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
138.104465066 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
17.1 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
10
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
187
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
0
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

Isophorone appears as a clear colorless liquid, with a camphor-like odor. Less dense than water and insoluble in water. Boiling point 420 °F. Flash point near 200 °F. Contact irritates skin and eyes. Toxic by ingestion. Used as a solvent and in pesticides.
Liquid
Colorless to white liquid with a peppermint-like odor; [NIOSH]
COLOURLESS LIQUID WITH CHARACTERISTIC ODOUR.
Clear colourless liquid; peppermint-like odour
Colorless to white liquid with a camphor-like odor.
Colorless to white liquid with a peppermint-like odor.

3.2.2 Color / Form

Water-white liquid
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 631
Colorless to white-liquid.
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178
Clear liquid
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 887

3.2.3 Odor

Peppermint-like odor
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 887
Camphor-like
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

3.2.4 Boiling Point

419.4 °F at 760 mmHg (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
215.32 °C
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-131
213.00 to 215.00 °C. @ 760.00 mm Hg
The Good Scents Company Information System
215 °C
419.4 °F
419 °F

3.2.5 Melting Point

18 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
-8.1 °C
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-131
-8 °C
17 °F

3.2.6 Flash Point

184 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
84 °C
184 °F (84 °C) CLOSED CUP
Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-62
84 °C c.c.
184 °F

3.2.7 Solubility

0.1 to 1 mg/mL at 64 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Soluble in ether, acetone, alcohol
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 887
Has high solvent power for vinyl resins, cellulose esters, ether, and many substances soluble with difficulty in other solvents.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 631
In water, 12,000 mg/l @ 25 °C.
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V21(1983) 385
12 mg/mL at 25 °C
Solubility in water, g/100ml at 25 °C: 1.2
slightly soluble in water; soluble in ether and acetone
Miscible at room temperature (in ethanol)
1%

3.2.8 Density

0.921 at 77 °F (USCG, 1999) - Less dense than water; will float
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
0.9255 @ 20 °C
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-131
Bulk density: 7.7 lb/gal @ 20 °C
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 631
Relative density (water = 1): 0.92
0.919-0.927
0.92

3.2.9 Vapor Density

4.77 (NTP, 1992) - Heavier than air; will sink (Relative to Air)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
4.77 (Air= 1)
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1161
Relative vapor density (air = 1): 4.8
4.77

3.2.10 Vapor Pressure

0.2 mmHg at 68 °F ; 1 mmHg at 100 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.43 [mmHg]
0.438 mm Hg @ 25 °C
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.
Vapor pressure, Pa at 20 °C: 40
0.3 mmHg

3.2.11 LogP

log Kow = 1.70
Veith GD et al; pp. 116-29 in Aquatic Toxicology. Easton JG et al, eds. Amer Soc Test Mat ASTM STP 707 (1980)
1.70
1.67

3.2.12 Autoignition Temperature

864 °F (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
860 °F; 460 °C
Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-62
460 °C

3.2.13 Viscosity

2.62 cP @ 20 °C
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 631

3.2.14 Heat of Combustion

-16,170 BTU/lb= -8,980 cal/g= -376x10+5 J/kg
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

3.2.15 Heat of Vaporization

43.4 kJ/mol
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V14 (1995) 981

3.2.16 Surface Tension

32 dyn/cm @ 20 °C
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V14 (1995) 981

3.2.17 Ionization Potential

9.07 eV

3.2.18 Odor Threshold

Odor Threshold Low: 0.19 [mmHg]

Odor Threshold High: 0.53 [mmHg]

Detection odor threshold from AIHA (mean = 0.19 ppm)

Odor detection in air= 2.00 ppm. Purity not specified.
Fazzalari, F.A. (ed.). Compilation of Odor and Taste Threshold Values Data. ASTM Data Series DS 48A (Committee E-18). Philadelphia, PA: American Society for Testing and Materials, 1978., p. 136
Odor recognition in air= 5.40 ppm. Purity not specified.
Fazzalari, F.A. (ed.). Compilation of Odor and Taste Threshold Values Data. ASTM Data Series DS 48A (Committee E-18). Philadelphia, PA: American Society for Testing and Materials, 1978., p. 136
1 mg/cu m (odor low); 50 mg/cu m (odor high)
Ruth JH; Am Ind Hyg Assoc J 47: A-142-51 (1986)

3.2.19 Refractive Index

Index of refraction: 1.4766 @ 18 °C/D
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-131
1.474-1.481

3.2.20 Kovats Retention Index

Standard non-polar
1094 , 1086 , 1080.7 , 1090 , 1082 , 1086 , 1086 , 1107 , 1113.5 , 1089 , 1113 , 1097 , 1099 , 1074 , 1089 , 1099 , 1088 , 1088 , 1088 , 1084 , 1088 , 1102 , 1088 , 1089 , 1094 , 1097 , 187.34 , 187.71
Semi-standard non-polar
1118 , 1120 , 1117 , 1137 , 1138 , 1138 , 1144 , 1128.05 , 1080 , 1124 , 1126 , 1127 , 1117 , 1124 , 1122 , 1118 , 1111 , 1067 , 1120 , 1118 , 1130 , 1118 , 1137 , 1123 , 1125 , 1124 , 1124 , 1124 , 1126 , 1127 , 1124 , 1126 , 1138 , 1080 , 1134 , 1132 , 1135 , 1118 , 1135 , 1120.9 , 1118 , 1138 , 1117 , 1146 , 1141.6 , 1119 , 1116 , 1116 , 1117 , 1119 , 1121 , 186.6
Standard polar
1599 , 1544 , 1611 , 1576 , 1563 , 1591 , 1571 , 1577 , 1571 , 1563 , 1621 , 1541 , 1543 , 1595 , 1600 , 1600 , 1607 , 1607 , 1591 , 1559 , 1563 , 1600 , 1593 , 1615 , 1591 , 1607 , 1607 , 1569 , 1569 , 1577 , 1601

3.2.21 Other Experimental Properties

CONVERSION FACTORS: 1 PPM= 5.65 MG/CU M; 1 MG/L= 177 PPM
Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 455
1 mg/cu m = 0.18 ppm; 1 ppm = 5.65 mg/cu m
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 1340

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Other Classes -> Aliphatic Ketones, Other
Apocarotenoids(ε-)
S75 | CyanoMetDB | Comprehensive database of secondary metabolites from cyanobacteria | DOI:10.5281/zenodo.4551528 | DOI:10.1021/jf010722p
Volatile Organic Compound (VOC) and(or) Semi-Volatile Organic Compound (SVOC) and(or) Waste-water effluent contaminant

3.4.1 Food Additives

FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food

3.4.2 Fragrances

Fragrance substance (Isophorone) -> IFRA amendment 49

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
NMR: 7311 (Sadtler Research Laboratories Spectral Collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
BRUKER AC-300
Source of Sample
Fluka AG, Buchs, Switzerland
Copyright
Copyright © 1991-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Varian A-60
Source of Sample
Carbide & Carbon Chemicals Corporation, New York, New York
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Source of Sample
Fluka AG, Buchs, Switzerland
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
BRUKER AM-360
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. 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

82.0 99.99

54.0 14.80

138.0 12.20

53.0 6.90

67.0 5.30

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Notes
instrument=JEOL JMS-01-SG
2 of 14
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Spectra ID
Instrument Type
CI-B
Ionization Mode
positive
Top 5 Peaks

139.0 99.99

82.0 34.38

138.0 14.86

140.0 10.08

95.0 3.66

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Notes
instrument=HITACHI M-80

4.2.2 MS-MS

Spectra ID
Ionization Mode
Positive
Top 5 Peaks

139.1108 100

140.1136 9.85

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4.2.3 LC-MS

1 of 64
View All
Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
7.143 min
Precursor m/z
139.1117
Precursor Adduct
[M+H]+
Top 5 Peaks

139.1108 999

140.1136 98

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License
CC BY
2 of 64
View All
Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
Ramp 15.8-23.7 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
7.172 min
Precursor m/z
139.1117
Precursor Adduct
[M+H]+
Top 5 Peaks

139.1105 999

69.0329 586

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License
CC BY

4.2.4 Other MS

1 of 5
View All
Other MS
MASS: 57756 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 5
View All
Authors
KOGA M, UNIV. OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
Instrument
JEOL JMS-01-SG
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

82 999

54 148

138 122

53 69

67 53

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License
CC BY-NC-SA

4.3 UV Spectra

UV max (MeOH): 235.5 nm (e 14300)
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 887
MAXIMUM ABSORPTION (ALCOHOL): 236 NM (LOG E= 4.09); SADTLER REF NUMBER: 122 (IR, PRISM)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-354
UV: 6-247 (Phillip et al., Organic Electronic Spectral Data, John Wiley & Sons, New York)
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 2317

4.3.1 UV-VIS Spectra

Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 IR Spectra

IR Spectra
PERCENT IN SATURATED AIR: 0.06
IR Spectra
IR: 36 (Sadtler Research Laboratories IR Grating Collection)

4.4.1 FTIR Spectra

1 of 2
Technique
NEAT
Source of Sample
Aldrich Chemical Company, Inc., Milwaukee, Wisconsin
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
CAPILLARY CELL: NEAT
Source of Sample
Union Carbide Corporation, New York, New York
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.2 ATR-IR Spectra

1 of 2
Technique
ATR-Cylindrical Internal Reflectance (CIR)
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Alfa Aesar, Thermo Fisher Scientific
Catalog Number
A14844
Lot Number
10196411
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.3 Near IR Spectra

1 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR Spectrometer= INSTRUMENT PARAMETERS=INST=BRUKER,RSN=8211,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=8211,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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4.4.4 Vapor Phase IR Spectra

1 of 2
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 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
Alfa Aesar, Thermo Fisher Scientific
Catalog Number
A14844
Lot Number
10196411
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
I18709
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

Intense mass spectral peaks: 82 m/z (100%), 138 m/z (17%), 54 m/z (13%), 41 m/z (13%)
Hites, R.A. Handbook of Mass Spectra of Environmental Contaminants. Boca Raton, FL: CRC Press Inc., 1985., p. 379

6 Chemical Vendors

7 Food Additives and Ingredients

7.1 Food Additive Classes

Flavoring Agents
JECFA Functional Classes
Flavouring Agent -> FLAVOURING_AGENT;

7.2 FEMA Flavor Profile

Cedarwood, Spice

7.3 FDA Substances Added to Food

Substance
Used for (Technical Effect)
FLAVORING AGENT OR ADJUVANT
Document Number (21 eCFR)
FEMA Number
3553
GRAS Number
11
JECFA Flavor Number
1112

7.4 Associated Foods

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

1 of 4
Chemical Name
1,3,3-TRIMETHYLCYLOHEXEN-5-ONE
Evaluation Year
2002
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
2 of 4
Chemical Name
ISOPHORONE
Evaluation Year
2002
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
3 of 4
Chemical Name
ISOACETOPHORON
Evaluation Year
2002
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
4 of 4
Chemical Name
1,5,5-TRIMETHYL-3-OXOCYCLOHEXENE
Evaluation Year
2002
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph

8 Pharmacology and Biochemistry

8.1 Absorption, Distribution and Excretion

The demonstrated toxicity of isophorone by oral, inhalation, and dermal exposures indicates that it is capable of passage across epithelial membranes.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-5 (1980) EPA 440/5-80-056
Rabbits and rats treated orally with isophorone excreted unchanged isophorone in the expired air and in the urine.
DHHS/ATSDR; Toxicological Profile for Isophorone p.46-7 PB90-180225 (1989)
Preliminary results of a pharmacokinetic study indicate that rats treated orally with 14C-isophorone excreted 93% of the radiolabel in the urine, expired air & feces in 24 hr. The majority was found in the urine indicating that isophorone was well absorbed. The wide distribution of isophorone in the organs of rats & a rabbit 1-5 hr after dosing by gavage with 4000 mg/kg indicates rapid GI absorption. In two rabbits given a gavage dose of 1000 mg/kg isophorone, a blood level of isophorone of 102 ug/L was found within 10 min. The level increased to 141 ug/L in 30 min & declined to < or = 0.05 ug/L in 21 hr. The results indicate rapid absorption & elimination. The detection of unchanged isophorone & its metabolites in the urine & the observations of systemic toxicity & carcinogenicity in animals exposed orally to isophorone provide qualitative evidence that isophorone is absorbed after oral exposure.
DHHS/ATSDR; Toxicological Profile for Isophorone p.45 TP-89/15 (1989)
In rats exposed to 400 ppm isophorone for 4 hr & sacrificed immediately after exposure or 1.5 or 3 hr after exposure, levels of isophorone were highest in all tissues examined (brain, lungs, heart, stomach, liver, spleen, pancreas, kidney, adrenals, testicles, & ovaries) immediately after exposure. Levels ranged from 1.5-74 ug/g tissue wet weight. The levels declined rapidly in males but declined very little in females by 3 hr after exposure.
DHHS/ATSDR; Toxicological Profile for Isophorone p.45 TP-89/15 (1989)
Radiolabel was widely distributed in male rats 24 hr after an oral dose of 14C-isophorone in corn oil, with highest levels in the liver, kidney, preputial gland, testes, brain, & lungs. Isophorone was widely distributed to the tissues of rats & a rabbit following treatment with isophorone at a gavage dose of 4000 mg/kg. The rats died within 1-5 hr & the rabbit died within an hr after dosing at which times the tissues were sampled for analysis. in rats, tissue levels of isophorone in ug/g tissue wet weight were as follows: stomach-6213, pancreas-2388, adrenals-1513, spleen-1038, liver-613, brain-378, lung-383, heart-387, kidney-465, testes-275, & ovaries-471. In the rabbit, tissue levels were as follows: stomach-5395, adrenals-1145, ovaries-3000, spleen-545, liver-515, kidney-295, heart-260, & lungs-50.
DHHS/ATSDR; Toxicological Profile for Isophorone p.46 TP-89/15 (1989)

8.2 Metabolism / Metabolites

... ISOPHORONE IS METABOLIZED IN RABBITS INTO 5,5-DIMETHYLCYCLOHEX-1-EN-3-ONE-1-CARBOXYLIC ACID, WHICH IS EXCRETED IN URINE AS ESTER GLUCURONIDE.
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 316
AFTER ORAL ADMIN OF 1 G/KG ALPHA-ISOPHORONE, RABBIT & RAT URINE CONTAINED ALPHA-ISOPHORONE, ISOPHOROL, CIS-3,5,5-TRIMETHYLCYCLOHEXANOL, TRANS-3,5,5-TRIMETHYLCYCLOHEXANOL, DIHYDROISOPHORONE, 5,5-DIMETHYLCYCLOHEX-1-EN-3-ONE-1-CARBOXYLIC ACID, & DIHYDROISOPHORONE GLUCURONIDE.
DUTERTRE CATELLA H ET AL; TOXICOL EUR RES 1 (4): 209-16 (1978)
The allylic methyl group of isophorone was oxidized to a carboxylic acid group when industrial isophorone was administered orally to rabbits. The product was detected in urine and no other products were identified.
Truhaut RH et al; CR Acad Sci Ser D 271 (15): 1333-6 (1970)
Rabbits & rats treated orally with isophorone excreted unchanged isophorone in the expired air & in the urine. The urine also contained 3-carboxy-5,5-dimethyl-2-cyclohexene-1-one & glucuronic conjugates of 3,3,5-trimethyl-2-cyclohexene-1-ol (isophorol), 3,5,5,-trimethylcyclohexanone (dihydroisophorone), & cis- & trans-3,5,5-trimethylcyclohexanols. Rat urine contained more dihydroisophorone & less isophorol than did rabbit urine. ... /It was/ proposed that metab of isophorone involves methyloxidation to 3-carboxy-5,5-dimethyl-2-cyclohexene-1-one, reduction of the ketone group to isophorol, reduction of the ring double bond to dihydroisophorone, & dismutation of dihydroisophorone to cis- & trans-3,5,5-trimethylcyclohexanols.
DHHS/ATSDR; Toxicological Profile for Isophorone p.46 TP-89/15 (1989)

8.3 Human Metabolite Information

8.3.1 Cellular Locations

  • Cytoplasm
  • Extracellular

9 Use and Manufacturing

9.1 Uses

Isophorone is used mainly as a solvent for concentrated vinyl chloride/acetate-based coating systems for metal cans, other metal paints, nitrocellulose finishes, and printing inks for plastics. Isophorone is an intermediate in the synthesis of 3,5-xylenol, 3,3,5-trimethylcyclohexanol, and plant growth retardants.
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
Sources/Uses
Used as a solvent for coatings, especially vinyl resins applied by roller; also used as a chemical intermediate and a solvent for other materials; [ACGIH]
ACGIH - Documentation of the TLVs and BEIs, 7th Ed. Cincinnati: ACGIH Worldwide, 2020.
Industrial Processes with risk of exposure
Painting (Solvents) [Category: Paint]
For Isophorone (USEPA/OPP Pesticide Code: 047401) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
U.S. Environmental Protection Agency/Office of Pesticide Program's Chemical Ingredients Database on Isophorone (78-59-1). Available from, as of September 26, 2001: https://npirspublic.ceris.purdue.edu/ppis/
SOLVENT FOR LACQUERS & PLASTICS
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-184
SOLVENT FOR MANY OILS, FATS, GUMS, RESINS, NITROCELLULOSE, & VINYL-RESIN COPOLYMERS
Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1763
CHEM INT FOR 3,3,5-TRIMETHYLCYCLOHEXANOL, & 3,5-XYLENOL; SPECIALTY SOLVENT
SRI
For more Uses (Complete) data for ISOPHORONE (9 total), please visit the HSDB record page.

9.1.1 Use Classification

Hazardous Air Pollutants (HAPs)
Food additives -> Flavoring Agents
Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes
Flavoring Agents -> JECFA Flavorings Index
Hazard Classes and Categories -> Carcinogens, Flammable - 2nd degree, Reactive - 1st degree

9.1.2 Industry Uses

  • Solvents (which become part of product formulation or mixture)
  • Other (specify)
  • Intermediates
  • Not Known or Reasonably Ascertainable

9.1.3 Consumer Uses

  • Not Known or Reasonably Ascertainable
  • Solvents (which become part of product formulation or mixture)

9.2 Methods of Manufacturing

ACETONE ... IS PASSED OVER CALCIUM OXIDE, HYDROXIDE OR CARBIDE OR THEIR MIXT AT 350 °C AND ATMOSPHERIC PRESSURE, OR IT IS HEATED @ 200-250 °C UNDER PRESSURE. ISOPHORONE IS SEPARATED FROM RESULTANT PRODUCTS BY DISTILLATION.
Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1763
Produced by the condensation of acetone in the liquid phase at ca. 200 °C and 3.6 Mpa in the presence of an aqueous potassium hydroxide solution (ca. 1%). The process steps condensation, separation of unreacted acetone, and hydrolysis of byproducts can be carried out in a single reactor. Reaction in the gas phase at 350 °C over calcium-aluminum oxide has also been reported.
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA15 (1990) 88
Review of preparation and purification: G.S. Salvapati, M. Janardanarao, J. Sci. Ind. Res. 42, 261-267 (1983).
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 887

9.3 IFRA Fragrance Standards

IFRA Substance
Isophorone
Synonyms
2-Cyclohexen-1-one, 3,5,5-trimethyl-; Isoacetophorone; 3,5,5-Trimethyl-2-cyclohexen-1-one
Amendment
49
IFRA Standard type
Prohibition: This material should not be used as a fragrance ingredient_Restriction: This material should be used only in the limited quantity as stated in the Standard
Intrinsic property driving the risk management measure
INSUFFICIENT DATA
Flavor use consideration
Due to the possible ingestion of small amounts of fragrance ingredients from their use in products in Categories 1 and 6, materials must not only comply with IFRA Standards but must also be recognized as safe as a flavoring ingredient as defined by the IOFI Code of Practice (www.iofi.org). For more details see chapter 1 of the Guidance for the use of IFRA Standards.
Prohibited fragrance ingredients: notes

Isophorone as such should not be used as fragrance ingredient.

Natural extracts containing Isophorone should not be used as substitutes for this substance.

Restricted ingredients: notes
On the basis of established maximum concentration levels of this substance in commercially available natural sources (like essential oils and extracts), exposure to this substance from the use of these oils and extracts is not significant and the use of these oils is authorized as long as the level of Isophorone in the finished product does not exceed 0.0013%.

9.4 Impurities

It usually contains 1-3% of the isomeric beta-isophorone (3,5,5-trimethyl-3-cyclohexen-1-one).
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA15 (1990) 88
COMMERCIAL ISOPHORONE USUALLY CONTAINS SOME UNCONJUGATED ISOMER (UP TO 5%) AND SMALL AMOUNTS (<1%) OF XYLITONE
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 13(81) 920
Beta-isophorone 2-4%, mesitylene (1,3,5-trimethylbenzene) trace, mesityl oxide (2-methyl-2 pentene-4-one) trace, phorone (2,6-dimethyl-2, 5-heptadiene-4-one) trace, isoxylitones trace, water trace.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.A-2 (1980) EPA 440/5-80-056

9.5 Formulations / Preparations

Purity: 98.0% by wt., min.
Flick, E.W. (ed.). Industrial Solvents Handbook 4 th ed. Noyes Data Corporation., Park Ridge, NJ., 1991., p. 668

9.6 U.S. Production

Aggregated Product Volume

2019: 10,000,000 - <50,000,000 lb

2018: 10,000,000 - <50,000,000 lb

2017: 10,000,000 - <50,000,000 lb

2016: 10,000,000 - <50,000,000 lb

(1972) GREATER THAN 4.54X10+5 G
SRI
(1976) GREATER THAN 2.27X10+6 G
SRI
Worldwide production capacity for isophorone currently stands at ca. 50,000 tons annually.
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA15 (1990) 88

9.7 U.S. Imports

(1984) 9.81X10+8 g
BUREAU OF THE CENSUS US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1984 p.1-359
(1986) 7.44X10+5 lb
BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1986 P.1-526

9.8 General Manufacturing Information

Industry Processing Sectors
  • Printing Ink Manufacturing
  • Plastics Material and Resin Manufacturing
  • Not Known or Reasonably Ascertainable
  • All Other Basic Organic Chemical Manufacturing
  • Paint and Coating Manufacturing
  • Pesticide, Fertilizer, and Other Agricultural Chemical Manufacturing
EPA TSCA Commercial Activity Status
2-Cyclohexen-1-one, 3,5,5-trimethyl-: ACTIVE
It is the most powerful solvent for nitrocellulose and "Vinylite" resins.
Flick, E.W. (ed.). Industrial Solvents Handbook 4 th ed. Noyes Data Corporation., Park Ridge, NJ., 1991., p. 6668

9.9 Sampling Procedures

Activated charcoal, Ambersorb XE-348, and Amberlites XAD-2, XAD-4, and XAD-7 were evaluated as solid adsorbents for work-room air sampling of acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl n-butyl ketone, cyclohexanone, and isophorone. Activated charcoal had good capacity for the compounds investigated, but most ketones decomposed on this adsorbent during storage. Ambersorb XE-348 also showed good capacity for most of the ketones and decomposition was insignificant.
Levin JO, Carleborg L; Ann Occup Hyg 31 (1): 31-8 (1987)
NIOSH Method 2508. Analyte: isophorone; sampler: solid sorbent tube (petroleum-based charcoal, 100 mg/50 mg); flow rate: 0.01-1 l/min; vol: -min: 2 l, -max: 25 l; sample stability: at least 7 days @ 25 °C.
U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods. 4th ed. Methods A-Z & Supplements. Washington, DC: U.S. Government Printing Office, Aug 1994.

10 Identification

10.1 Analytic Laboratory Methods

NIOSH Method 2508. Isophorone. Technique: Gas chromatography, FID. The working range for this method is 0.35 to 70 ppm (2 to 400 mg/cu m) for a 12-L air sample. Estimated limit of detection: 0.02 mg per sample.
U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods. 4th ed. Methods A-Z & Supplements. Washington, DC: U.S. Government Printing Office, Aug 1994.
Isophorone has been determined in water by gas chromatography and mass spectrometry.
Eichelberger JW et al; Anal Chem 55 (9): 1471-9 (1983)
EPA Method 609-A. Nitroaromatics and Isophorone in Wastewater by Gas Chromatography with Electron Capture Detection. Detection limit = 16.000 ug/l.
USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)
EPA Method 609-B. Nitroaromatics and Isophorone in Wastewater by Gas Chromatography with Flame Ionization Detection. Detection limit = 5.7 ug/l.
USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)
For more Analytic Laboratory Methods (Complete) data for ISOPHORONE (10 total), please visit the HSDB record page.

10.2 NIOSH Analytical Methods

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

1 of 6
View All
Note
Pictograms displayed are for > 99.9% (2245 of 2246) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for < 0.1% (1 of 2246) of reports.
Pictogram(s)
Irritant
Health Hazard
Signal
Warning
GHS Hazard Statements

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

H312 (> 99.9%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H319 (96.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (> 99.9%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H351 (> 99.9%): Suspected of causing cancer [Warning Carcinogenicity]

Precautionary Statement Codes

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, 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 2246 reports by companies from 28 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 2246 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 27 notifications provided by 2245 of 2246 reports by companies with hazard statement code(s).

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.

11.1.2 Hazard Classes and Categories

Acute Tox. 4 (> 99.9%)

Acute Tox. 4 (> 99.9%)

Eye Irrit. 2A (96.1%)

STOT SE 3 (> 99.9%)

Carc. 2 (> 99.9%)

Carcinogenicity - category 2

Acute toxicity - category 4

Acute toxicity - category 4

Eye irritation - category 2A

Specific target organ toxicity (single exposure) - category 3

11.1.3 NFPA Hazard Classification

1 of 2
View All
NFPA 704 Diamond
2-2-0
NFPA Health Rating
2 - Materials that, under emergency conditions, can cause temporary incapacitation or residual injury.
NFPA Fire Rating
2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.
NFPA Instability Rating
0 - Materials that in themselves are normally stable, even under fire conditions.

11.1.4 Health Hazards

LIQUID: Irritating to skin and eyes. Harmful if swallowed. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.

11.1.5 Fire Hazards

Combustible. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Combustible. Above 84 °C explosive vapour/air mixtures may be formed.

11.1.6 Hazards Summary

Isophorone is a clear liquid that smells like peppermint. It can be dissolved in water and evaporates somewhat faster than water. It is an industrial chemical used as a solvent in some printing inks, paints, lacquers, and adhesives. It is also used as an intermediate in the production of certain chemicals. Although isophorone is an industrial chemical, it also occurs naturally in cranberries.
Isophorone is a widely used solvent and chemical intermediate. The acute (short-term) effects of isophorone in humans from inhalation exposure include eye, nose, and throat irritation. Chronic (long- term) exposure to isophorone in humans can cause dizziness, fatigue, and depression. Animal studies indicate that long-term inhalation of high concentrations of isophorone causes central nervous system effects. Limited evidence in animal studies suggests that isophorone may cause birth defects such as fetal malformations and growth retardation from inhalation exposure to isophorone during pregnancy. No information is available on the reproductive, developmental, or carcinogenic effects of isophorone in humans. EPA has classified isophorone as a Group C, possible human carcinogen.
Liquid causes first degree burns on short exposure. [CHRIS] Isophorone is a skin irritant. [Quick CPC]
Quick CPC - Forsberg K, Mansdorf SZ. Quick Selection Guide to Chemical Protective Clothing, 5th Ed. Hoboken, NJ: Wiley-Interscience, 2007.

11.1.7 Fire Potential

Flammable & explosive when exposed to heat or flame.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1971

11.1.8 Skin, Eye, and Respiratory Irritations

... HUMAN VOLUNTEERS EXPOSED AT 40, 85, 200 & 400 PPM ISOPHORONE EXPERIENCED EYE, NOSE, & THROAT IRRITATION.
American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 819
Irritates and burns eyes, nose, mucous membranes, respiratory tract.
Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 273
Isophorone vapor (25 ppm) produced irritation to the eyes, nose, and throats of unacclimatized volunteers.
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1850

11.2 Safety and Hazard Properties

11.2.1 Flammable Limits

Lower 0.8% by vol; upper 3.8%
Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 272
Flammability
Class IIIA Combustible Liquid: Fl.P. at or above 140 °F and below 200 °F.

11.2.2 Lower Explosive Limit (LEL)

0.8 % (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.8%

11.2.3 Upper Explosive Limit (UEL)

3.8 % (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
3.8%

11.2.4 Explosive Limits and Potential

Flammable & explosive when exposed to heat or flame.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1971
lower explosive limit: 0.8% upper explosive limit: 3.8%
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1971
Explosive limits , vol% in air: 0.8-3.8

11.2.5 OSHA Standards

Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 25 ppm (140 mg/cu m).
29 CFR 1910.1000 (7/1/2001)

11.2.6 NIOSH Recommendations

Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 4 ppm (23 mg/cu m).
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178

11.3 First Aid Measures

Inhalation First Aid
Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.
Skin First Aid
Remove contaminated clothes. Rinse and then wash skin with water and soap.
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Ingestion First Aid
Rinse mouth. Give a slurry of activated charcoal in water to drink. Do NOT induce vomiting.

11.3.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

(See general first aid procedures)

Eye: Irrigate immediately - If this chemical contacts the eyes, immediately wash (irrigate) the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately.

Skin: Soap wash promptly - If this chemical contacts the skin, promptly wash the contaminated skin with soap and water. If this chemical penetrates the clothing, promptly remove the clothing and wash the skin with soap and water. Get medical attention promptly.

Breathing: Respiratory support

Swallow: Medical attention immediately - If this chemical has been swallowed, get medical attention immediately.

11.4 Fire Fighting

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

CAUTION: The majority of these products have a very low flash point. Use of water spray when fighting fire may be inefficient. CAUTION: For mixtures containing alcohol or polar solvent, alcohol-resistant foam may be more effective.

SMALL FIRE: Dry chemical, CO2, water spray or regular foam. If regular foam is ineffective or unavailable, use alcohol-resistant foam.

LARGE FIRE: Water spray, fog or regular foam. If regular foam is ineffective or unavailable, use alcohol-resistant foam. Avoid aiming straight or solid streams directly onto the product. If it can be done safely, move undamaged containers away from the area around the fire.

FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Cool containers with flooding quantities of water until well after fire is out. For petroleum crude oil, do not spray water directly into a breached tank car. This can lead to a dangerous boil over. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2024)

Use water spray, powder, foam, carbon dioxide.

11.4.1 Fire Fighting Procedures

Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical or carbon dioxide.
Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 273
If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped or safely confined. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical or carbon dioxide.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 615
Use water spray to keep fire exposed containers cool. Use flooding quantities of water as fog or spray, dry chemical, foam, or carbon dioxide.
Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-80

11.5 Accidental Release Measures

11.5.1 Isolation and Evacuation

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area for at least 50 meters (150 feet) in all directions.

LARGE SPILL: Consider initial downwind evacuation for at least 300 meters (1000 feet).

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

11.5.2 Spillage Disposal

Personal protection: filter respirator for organic gases and vapours adapted to the airborne concentration of the substance. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

11.5.3 Cleanup Methods

If leak or spill has not ignited, use water spray to disperse vapors & to protect men attempting to stop leak.
Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 273
Environmental considerations: Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surfact flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder, or comercial sorbents.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 615
Environmental considerations: Water spill: Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction hoses.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 615
Environmental considerations: Air spill: Apply water spray or mist ot knock kown vapors.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 615

11.5.4 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
The following wastewater treatment technologies have been investigated for Isophorone. Concentration process: Biological treatment.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-35 (1982)
The following wastewater treatment technologies have been investigated for Isophorone. Concentration process: Solvent extraction.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-110 (1982)
The following wastewater treatment technologies have been investigated for Isophorone. Concentration process: Activated carbon.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-146 (1982)
Spray into incinerator or burn in paper packaging. Additional flammable solvent may be added.
Prager, J.C. Environmental Contaminant Reference Databook Volume 2. New York, NY: Van Nostrand Reinhold, 1996., p. 274

11.5.5 Preventive Measures

Irrigate eyes with water. Wash skin with abundant quantities of water.
ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1982., p. 228
SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.
Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 615
For more Preventive Measures (Complete) data for ISOPHORONE (7 total), please visit the HSDB record page.

11.6 Handling and Storage

11.6.1 Nonfire Spill Response

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. All equipment used when handling the product must be grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. A vapor-suppressing foam may be used to reduce vapors. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. Use clean, non-sparking tools to collect absorbed material.

LARGE SPILL: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor, but may not prevent ignition in closed spaces. (ERG, 2024)

11.6.2 Safe Storage

Separated from strong oxidants, strong bases and amines.

11.6.3 Storage Conditions

store in a cool, dry, well-ventilated location. Outside or detached storage is preferred. Separate from oxidizing materials.
Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-80

11.7 Exposure Control and Personal Protection

RD50 (Exposure concentration producing a 50% respiratory rate decrease)
27.0 [mmHg]
Maximum Allowable Concentration (MAK)
2.0 [ppm]

11.7.2 Permissible Exposure Limit (PEL)

25.0 [ppm]
PEL-TWA (8-Hour Time Weighted Average)
25 ppm (140 mg/m³)
TWA 25 ppm (140 mg/m3) See Appendix G

11.7.3 Immediately Dangerous to Life or Health (IDLH)

200 ppm (NIOSH, 2024)

200.0 [ppm]

Excerpts from Documentation for IDLHs: Basis for original (SCP) IDLH: The chosen IDLH is based on the UCC [1971] report that exposure of animals for 1 hour to 880 ppm caused serious organ damage; only 1 of 6 animals died from an 8­hour exposure to air saturated with isophorone (approximately 525 ppm at 77°F). . . . Human data: A few of the 11 or 12 volunteers exposed for a few minutes to 200 or 400 ppm complained of nausea, headache, dizziness, faintness, inebriation, and a feeling of suffocation [Smyth and Seaton 1940].

200 ppm
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178

200 ppm

See: 78591

11.7.4 Threshold Limit Values (TLV)

TLV-Ceiling
5.0 [ppm]
Ceiling Limit: 5 ppm.
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, p. 35
A3; Confirmed animal carcinogen with unknown relevance to humans.
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, p. 35
5 ppm as STEL; A3 (confirmed animal carcinogen with unknown relevance to humans).
TLV-C (Ceiling)
5 ppm [1992]

11.7.5 Occupational Exposure Limits (OEL)

MAK (Maximale Arbeitsplatz Konzentration)
11 mg/m

11.7.6 Inhalation Risk

A harmful contamination of the air will be reached rather slowly on evaporation of this substance at 20 °C.

11.7.7 Effects of Short Term Exposure

The substance and the vapour are irritating to the eyes and respiratory tract. The substance may cause effects on the central nervous system.

11.7.8 Allowable Tolerances

Isophorone is exempted from the requirement of a tolerance when used as a solvent or cosolvent in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only.
40 CFR 180.1001(d) (7/1/2001)

11.7.9 Personal Protective Equipment (PPE)

Excerpt from NIOSH Pocket Guide for Isophorone:

Skin: PREVENT SKIN CONTACT - Wear appropriate personal protective clothing to prevent skin contact.

Eyes: PREVENT EYE CONTACT - Wear appropriate eye protection to prevent eye contact.

Wash skin: WHEN CONTAMINATED - The worker should immediately wash the skin when it becomes contaminated.

Remove: WHEN WET OR CONTAMINATED - Work clothing that becomes wet or significantly contaminated should be removed and replaced.

Change: No recommendation is made specifying the need for the worker to change clothing after the workshift.

Provide: EYEWASH - Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substances; this is irrespective of the recommendation involving the wearing of eye protection. (NIOSH, 2024)

... Wear appropriate chemical protective gloves, boots and goggles.
Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, D.C.: Assoc. of American Railroads, Hazardous Materials Systems (BOE), 1987., p. 397
Wear appropriate personal protective clothing to prevent skin contact.
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178
Wear appropriate eye protection to prevent eye contact.
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178
Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178
For more Personal Protective Equipment (PPE) (Complete) data for ISOPHORONE (9 total), please visit the HSDB record page.

(See personal protection and sanitation codes)

Skin: Prevent skin contact - Wear appropriate personal protective clothing to prevent skin contact.

Eyes: Prevent eye contact - Wear appropriate eye protection to prevent eye contact.

Wash skin: When contaminated

Remove: When wet or contaminated

Change: No recommendation

Provide: Eyewash - Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substances; this is irrespective of the recommendation involving the wearing of eye protection.

11.7.10 Respirator Recommendations

NIOSH

Up to 40 ppm:

(APF = 10) Any chemical cartridge respirator with organic vapor cartridge(s)*

(APF = 10) Any supplied-air respirator*

Up to 100 ppm:

(APF = 25) Any supplied-air respirator operated in a continuous-flow mode*

(APF = 25) Any powered, air-purifying respirator with organic vapor cartridge(s)*

Up to 200 ppm:

(APF = 50) Any chemical cartridge respirator with a full facepiece and organic vapor cartridge(s)

(APF = 50) Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister

(APF = 50) Any powered, air-purifying respirator with a tight-fitting facepiece and organic vapor cartridge(s)*

(APF = 50) Any supplied-air respirator that has a tight-fitting facepiece and is operated in a continuous-flow mode*

(APF = 50) Any self-contained breathing apparatus with a full facepiece

(APF = 50) Any supplied-air respirator with a full facepiece

Emergency or planned entry into unknown concentrations or IDLH conditions:

(APF = 10,000) Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode

(APF = 10,000) Any supplied-air respirator that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained positive-pressure breathing apparatus

Escape:

(APF = 50) Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister

Any appropriate escape-type, self-contained breathing apparatus

Important additional information about respirator selection

11.7.11 Preventions

Fire Prevention
NO open flames. Above 84 °C use a closed system and ventilation.
Exposure Prevention
PREVENT GENERATION OF MISTS!
Inhalation Prevention
Use ventilation, local exhaust or breathing protection.
Skin Prevention
Protective gloves.
Eye Prevention
Wear safety spectacles.
Ingestion Prevention
Do not eat, drink, or smoke during work.

11.8 Stability and Reactivity

11.8.1 Air and Water Reactions

Insoluble in water.

11.8.2 Reactive Group

Ketones

Hydrocarbons, Aliphatic Unsaturated

11.8.3 Reactivity Alerts

Peroxidizable Compound

11.8.4 Reactivity Profile

Ketones, such as ISOPHORONE, are reactive with many acids and bases liberating heat and flammable gases (e.g., H2). The amount of heat may be sufficient to start a fire in the unreacted portion of the ketone. Ketones react with reducing agents such as hydrides, alkali metals, and nitrides to produce flammable gas (H2) and heat. Ketones are incompatible with isocyanates, aldehydes, cyanides, peroxides, and anhydrides. They react violently with aldehydes, HNO3, HNO3 + H2O2, and HClO4. Forms explosive peroxides

11.8.5 Hazardous Reactivities and Incompatibilities

Incompatible with strong oxidizers
Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 529
Oxidizers, strong alkalis, amines.
NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 178

11.8.6 Peroxide Forming Chemical

Chemical
Isophorone
Class (* = UMN Designation)
D: Other compounds that may form peroxides
Reference(s)

11.9 Transport Information

11.9.1 DOT ID and Guide

11.9.2 Standard Transportation Number

49 152 78; Isophorone (combustible liquid, not otherwise specified)

11.9.3 DOT Label

Combustible Liquid

11.9.4 EC Classification

Symbol: Xn; R: 21/22-36/37-40; S: (2)-13-23-36/37/39-46

11.10 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 2-Cyclohexen-1-one, 3,5,5-trimethyl-
California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Carcinogenicity; Dermatotoxicity; Developmental Toxicity; Hepatotoxicity and Digestive System Toxicity; Neurotoxicity; Respiratory Toxicity

Authoritative List - CA TACs; CWA 303(c); CWA 303(d); IARC Carcinogens - 2B; OEHHA RELs

Report - regardless of intended function of ingredient in the product

REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
2-Cyclohexen-1-one, 3,5,5-trimethyl-: HSNO Approval: HSR001178 Approved with controls

11.10.1 Atmospheric Standards

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Isophorone is produced, as an intermediate or a final product, by process units covered under this subpart.
40 CFR 60.489 (7/1/2001)
Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Isophorone is included on this list.
Clean Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990

11.10.2 Federal Drinking Water Guidelines

EPA 100 ug/l
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present

11.10.3 State Drinking Water Guidelines

(FL) FLORIDA 37 ug/L
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present
(ME) MAINE 370 ug/l
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present
(MN) MINNESOTA 100 ug/l
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present
(NH) NEW HAMPSHIRE 100 ug/l
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present

11.10.4 Clean Water Act Requirements

Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent limitations.
40 CFR 401.15 (7/1/2001)

11.10.5 CERCLA Reportable Quantities

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
40 CFR 302.4 (7/1/2001)

11.10.6 TSCA Requirements

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Isophorone is included on this list.
40 CFR 716.120 (7/1/2001)
Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.
40 CFR 712.30 (7/1/2001)

11.10.7 FIFRA Requirements

Isophorone is exempted from the requirement of a tolerance when used as a solvent or cosolvent in accordance with good agricultural practice as inert (or occasionally active) ingredents in pesticide formulations applied to growing crops only.
40 CFR 180.1001(d) (7/1/2001)

11.10.8 FDA Requirements

Isophorone is listed as an indirect food additive for use only as a component of adhesives.
21 CFR 175.105 (4/1/2001)

11.11 Other Safety Information

Chemical Assessment

IMAP assessments - 2-Cyclohexen-1-one, 3,5,5-trimethyl-: Human health tier II assessment

IMAP assessments - 2-Cyclohexen-1-one, 3,5,5-trimethyl-: Environment tier I assessment

11.11.1 Special Reports

USEPA; Ambient Water Quality Criteria Doc: Isophorone (1980) EPA 440/5-80-056
USEPA; Health and Environmental Effects Profile for Isophorone (1986) ECAO-CIN-P162
DHHS/ATSDR; Toxicological Profile for Isophorone (1989) ATSDR/TP-89/15
DHHS/NTP; Toxicology & Carcinogenesis Studies of Isophorone in F344/N Rats and B6C3F1 Mice (Gavage Studies) Technical Report Series No. 291 (1986) NIH Publication No. 86-2547

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Isophorone is a colorless liquid with a peppermint like odor. It is soluble in water and miscible with most organic solvents. HUMAN EXPOSURE: The odor of isophorone can be detected at low concentrations. Eye, nose and throat irritation has been observed along with nausea, headache, dizziness, faintness and inebriation. Dermal and inhalation exposure may occur along with oral exposure from drinking water. ANIMAL STUDIES: Distribution studies in rats using (14)C isophorone showed that 93% of orally administered radioactivity appeared mainly in the urine and expired air within 24 hr. The tissues retaining the highest concentration after this period were the liver, kidney and preputial glands. The metabolites from oral administration of isophorone identified in rabbit urine resulted from the oxidation of the 3-methyl group, reduction of the keto group and hydrogenation of the double bond of the cyclohexene ring, and were eliminated as such or as glucuronide derivatives in the case of the alcohols. In animal studies, data indicate that isophorone is rapidly absorbed through the skin. Acute effects from dermal exposure in rats and rabbits ranged from mild erythema to scabs. Conjunctivitis and corneal damage have been reported following direct application to the eye or exposure to high concentrations of isophorone. In acute and short-term oral studies on rodents at high doses degenerative effects were seen in the liver and CNS depression and some deaths. In a 90 day oral study in beagle dogs (with limited numbers) no effects were seen at doses up to 150 mg/kg body weight per day. Isophorone does not induce gene mutations in bacteria, chromosomal aberrations in vitro, DNA repair in primary rat hepatocytes, or bone marrow micronuclei in mice. Positive effects were observed only in the absence of an exogenous metabolic system in L5178YTK +/- mouse mutagenesis assays as well as in a sister chromatid exchange assay. Isophorone induced morphological transformation in vitro in the absence of an exogenous metabolism system. It did not induce sex linked recessive lethal mutations in Drosophilia. In long term oral toxicity studies in mice and rats, male rats showed several lesions of the kidney, including nephropathy, tubular cell hyperplasia and low incidence of tubular cell adenomas and adenocarcinomas. Isophorone exposure was associated with some neoplastic lesions of the liver, and the integumentary and lymphoreticular systems of male mice, as well non-neoplastic liver and adrenal cortex lesions, but this was not observed in female mice. In /one/ long term inhalation study in rats and rabbits, irritation to eye and nasal mucosa, and lung and liver changes were observed. Very limited studies in rats and mice indicate that isophorone does not affect fertility nor does it cause developmental toxicity in experimental animals. The fact that central nervous system depression occurs in experimental animals could indicate a positive neurotoxic effect. Isophorone also elicited a positive effect in the behavioral despair swimming test. No data on terrestrial animals were available. The available data suggest that isophorone has a low toxicity to aquatic organisms.
Environmental Health Criteria 174 Isophorone. pp.1-22 (1995) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.

12.1.2 EPA IRIS Information

Substance
Toxicity Summary
EPA IRIS Summary PDF (Update: Oct-01-1992 )
Cancer Sites
Reproductive
Critical Effect Systems
Urinary
Reference Dose (RfD), chronic
2 x 10 ^-1 mg/kg-day

12.1.3 RAIS Toxicity Values

Inhalation Chronic Reference Concentration (RfC) (mg/m^3)
2
Inhalation Chronic Reference Concentration Reference
CALEPA
Oral Chronic Reference Dose (RfDoc) (mg/kg-day)
0.2
Oral Chronic Reference Dose Reference
IRIS Current
Oral Subchronic Chronic Reference Dose (RfDos) (mg/kg-day)
3
Oral Subchronic Chronic Reference Dose Reference
ATSDR Final
Short-term Oral Reference Dose (RfDot) (mg/kg-day)
3
Short-term Oral Reference Dose Reference
ATSDR Final
Oral Slope Factor (CSFo)(mg/kg-day)^-1
0.00095
Oral Slope Factor Reference
IRIS Current

12.1.4 USGS Health-Based Screening Levels for Evaluating Water-Quality

Chemical
Isophorone
USGS Parameter Code
34408
Chemical Classes
Volatile Organic Compound (VOC) and(or) Semi-Volatile Organic Compound (SVOC) and(or) Waste-water effluent contaminant
Noncancer HBSL (Health-Based Screening Level)[μg/L]
900
Cancer HBSL [μg/L]
50−5000
Reference
Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

12.1.5 NIOSH Toxicity Data

12.1.6 Evidence for Carcinogenicity

Cancer Classification: Group C Possible Human Carcinogen
USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for Carcinogenic Potential" (April 2006)
CLASSIFICATION: C; possible human carcinogen. BASIS FOR CLASSIFICATION: Based on no data in humans; limited evidence of carcinogenicity of one tumor type in one sex of one animal species as shown by an increase of preputial gland carcinomas in male rats. The apparent renal tubular cell tumor in the male rat is associated with alpha-2u-globulin, considered to be of questionable relevance to humans. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Limited.
U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS). Summary on Isophorone (78-59-1). Available from, as of March 15, 2000: https://www.epa.gov/iris/
A3; Confirmed animal carcinogen with unknown relevance to humans.
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2010, p. 36

12.1.7 Carcinogen Classification

1 of 2
IARC Carcinogenic Agent
Isophorone
IARC Carcinogenic Classes
Group 2B: Possibly carcinogenic to humans
IARC Monographs
Volume 130: (2022) 1,1,1-Trichloroethane and Four Other Industrial Chemicals
2 of 2
Substance
NTP Technical Report
TR-291: Toxicology and Carcinogenesis Studies of Isophorone (CASRN 78-59-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies) (1986 )
Peer Review Date
Conclusion for Male Rat
Some Evidence Some Evidence
Conclusion for Female Rat
No Evidence No Evidence
Conclusion for Male Mice
Equivocal Evidence Equivocal Evidence
Conclusion for Female Mice
No Evidence No Evidence
Summary
Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenicity of isophorone in male F344/N rats as shown by the occurrence of renal tubular cell adenomas and adenocarcinomas in animals given 250 or 500 mg/kg per day; carcinomas of the preputial gland were also observed at increased incidence in male rats given 500 mg/kg. There was no evidence of carcinogenicity in female F344/N rats given 250 or 500 mg/kg per day. For male B6C3F1 mice, there was equivocal evidence of carcinogenicity of isophorone as shown by an increased incidence of hepatocellular adenomas or carcinomas (combined) and of mesenchymal tumors in the integumentary system in animals given 500 mg/kg per day and by an increase in malignant lymphomas in animals given 250 mg/kg per day. There was no evidence of carcinogenicity of isophorone in female B6C3F1 mice given 250 or 500 mg/kg per day.

12.1.8 Exposure Routes

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
inhalation, ingestion, skin and/or eye contact

12.1.9 Symptoms

Inhalation Exposure
Burning sensation. Sore throat. Cough. Dizziness. Headache. Nausea. Shortness of breath.
Eye Exposure
Redness. Pain. Blurred vision.
Ingestion Exposure
Abdominal pain. Further see Inhalation.
irritation eyes, nose, throat; headache, nausea, dizziness, lassitude (weakness, exhaustion), malaise (vague feeling of discomfort), narcosis; dermatitis; In Animals: kidney, liver damage

12.1.10 Target Organs

Dermal (Skin), Hepatic (Liver), Neurological (Nervous System), Ocular (Eyes), Respiratory (From the Nose to the Lungs)
Urinary
Eyes, skin, respiratory system, central nervous system, liver, kidneys

12.1.11 Cancer Sites

Reproductive

12.1.12 Adverse Effects

Neurotoxin - Acute solvent syndrome

Dermatotoxin - Skin burns.

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

ACGIH Carcinogen - Confirmed Animal.

12.1.13 Acute Effects

12.1.14 Toxicity Data

LC50 (rat) = 7,000 mg/m3/4h

12.1.15 Interactions

Joint toxic action of isophorone with 26 industrial liquid chemicals was examined based on acute LD50 data from oral intubations of female albino rats. ... LD50s were determined for each of the cmpds. Based on the assumption of simple similar action, isophorone exhibited >additive toxicity in combination with 9 cmpds & additive toxicity. An equitoxic mixture was defined as a mixture of chemicals in volumes directly proportional to their respective rat oral LD50 values, so that each component contributed the same degree of toxicity to the mixture.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-16 (1980) EPA 440/5-80-056
... /It was/ reported that inhalation of isophorone for 4 hr by mice increased the threshold for onset of seizures produced by iv admin of pentrazole ... .
DHHS/ATSDR; Toxicological Profile for Isophorone p.20 TP-89/15 (1989)

12.1.16 Antidote and Emergency Treatment

Basic treatment: Establish a patent airway. 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 ... . For contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline 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. Administer activated charcoal ... . /Ketones and related compounds/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 237
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Ketones and related compounds/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 237-8

12.1.17 Medical Surveillance

Consider the points of attack (respiratory system, skin) in preplacement and periodic physical examinations.
Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 529

12.1.18 Human Toxicity Excerpts

... HUMAN VOLUNTEERS EXPOSED AT 40, 85, 200, & 400 PPM ISOPHORONE EXPERIENCED EYE, NOSE, & THROAT IRRITATION. A FEW COMPLAINTS OF NAUSEA, HEADACHE, DIZZINESS, FAINTNESS, INEBRIATION, & A FEELING OF SUFFOCATION RESULTED FROM 200 & 400 PPM. SYMPTOMS OF IRRITATION & ... /CNS DEPRESSION/ ACTION DECREASED @ CONCNS OF 40 & 85 PPM.
American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 819
In a sensory threshold study ... twelve unconditioned subjects of both sexes were exposed to the vapors of several industrial solvents including isophorone for 15 min periods in a 1,200 cu ft chamber. They found that exposure to isophorone at 25 ppm produced irritation of the eyes, nose, & throat, & that isophorone vapor was considered by the subjects to be the most irritating of all the ketonic solvents tested. The highest tolerable level for an 8 hr isophorone exposure was judged to be 10 ppm by a majority of the subjects.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-15 (1980) EPA 440/5-80-056
... One min exposures to 200 ppm isophorone are intolerable for humans. A concn of 40 ppm was intolerable to half of an unspecified number of human volunteers after 4 min. ... Isophorone did not cause allergic contact sensitization in any of the ten human volunteers.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-16 (1980) EPA 440/5-80-056
NO REPORT OF SYSTEMIC POISONING ... BUT THE VAPOR IS KNOWN TO IRRITATE MUCOUS MEMBRANES.
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-184
For more Human Toxicity Excerpts (Complete) data for ISOPHORONE (7 total), please visit the HSDB record page.

12.1.19 Non-Human Toxicity Excerpts

... /FROM WORK ON/ EXPERIMENTAL ANIMALS ... NO EFFECT WHATEVER RESULTED FROM EXPOSURE AT 25 PPM OF ISOPHORONE OF VAPOR. ... 10 RATS & 10 GUINEA PIGS, WERE EXPOSED 8 HR/DAY FOR 30 DAYS @ CONCN RANGING FROM 25-500 PPM. AT THE HIGHER CONCN THE CHIEF EFFECTS WERE ON THE KIDNEYS.
American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 819
ISOPHORONE TESTED BY APPLICATION OF DROP TO RABBIT CORNEAS CAUSES MILD TRANSIENT INJURY, GRADED 4 ON SCALE OF 1 TO 10 AFTER 24 HR.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 770
BY SC INJECTION, SINGLE INJECTION OF 0.3 G /TO RABBITS/ CAUSED ONLY DIARRHEA, FECES HAVING UNPLEASANT ODOR; AFTER 4 INJECTIONS PRONE POSITION & LOSS OF REFLEXES, & DEATH AFTER 8 HR.
Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 457
FROM ORAL OR SC ADMIN, PUNCTATE HEMORRHAGES IN STOMACH & REDDENING OF INTESTINAL MUCOUS MEMBRANE. A TRACE OF ALBUMINURIA WAS FOUND AFTER SC INJECTION OF 0.3 G ... .
Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 457
For more Non-Human Toxicity Excerpts (Complete) data for ISOPHORONE (26 total), please visit the HSDB record page.

12.1.20 Non-Human Toxicity Values

LD50 Rat oral 1000-3450 mg/kg.
USEPA; Health and Environmental Effects Profile for Isophorone; p.30 (1986) ECAO-CIN-P162
LC50 Rabbit dermal 1380 mg/kg
USEPA; Health and Environmental Effects Profile for Isophorone; p.30 (1986) ECAO-CIN-P162
LC50 Rat inhalation 7000 mg/cu m/4 hr
USEPA; Health and Environmental Effects Profile for Isophorone; p.30 (1986) ECAO-CIN-P162
LD50 Mouse oral 2.0 g/kg
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1848
For more Non-Human Toxicity Values (Complete) data for ISOPHORONE (10 total), please visit the HSDB record page.

12.1.21 Ongoing Test Status

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=78-59-1]

12.1.22 National Toxicology Program Studies

Toxicology and carcinogenesis studies of isophorone > 94% pure, a widely used solvent and chem intermediate, were conducted by administering 0, 250, or 500 mg isophorone/kg/day by gavage in corn oil to groups of 50 rats and 50 mice of each sex, 5 days/wk for 103 wk. Doses selected for the 2 yr studies were based on 16 day studies in which rats and mice of each sex received doses of 0-2000 mg/kg/day and on 13 wk studies in which rats and mice of each sex received doses ranging from 0 to 1000 mg/kg/day by gavage in corn oil. No chemically related gross or histopathologic effects were observed in the 16 day or 13 wk studied, but 1/5 high-dose male rats, 4/5 high-dose female rats, and all high-dose female mice died. The high dose for the 2 yr studies was set at 500 mg/kg/day for each sex of rats and mice, based mainly on the deaths in the 13 wk studies. Throughout the 2 yr study, the mean body weights of the high-dose male rats averaged 5% lower than those of the vehicle controls. During the second year, the mean body wts of the female high-dose rats averaged 8% lower than those of the vehicle controls, and the high-dose female mice averaged 5% lower. The survival of male mice was also low (16/50; 16/50; 19/50), but there was a significant trend toward increased survival of dosed female mice relative to that of the vehicle controls (26/50; 35/50; 34/50). Dosed male rats showed a variety of proliferative lesions of the kidney ... . Dosed male rats also exhibited increased mineralization of the medullary collecting ducts ... and low-dose male rats showed a more severe nephropathy than is commonly seen in aging rats. Carcinomas of the preputial gland were increased in high-dose male rats ... . With the exception of a moderate increase in nephropathy, ... female rats did not show chem related increased incidences of neoplastic or nonneoplastic lesions. In high-dose male mice, isophorone exposure was associated with increased incidences of hepatocellular adenomas and carcinomas. An increased incidence of lymphomas or leukemias was noted in low-dose male mice.
NTP; Toxicology and Carcinogenesis Studies of Isophorone p 11 Report# 291 NIH Pub# 86-2547

12.1.23 TSCA Test Submissions

An inhalation teratology study was conducted with pregnant Fisher 344 rats and CD-1 mice receiving whole body exposure to isophorone at nominal concentrations of 0, 25, 50 or 115ppm in a dynamic air flow chamber. At each concentration, 22 rats and 22 mice were exposed for 6hrs/day on days 6-15 of gestation. There was no effect of treatment for all animals as indicated by mortality, gross necropsy observations and uterine implantation data. Maternal toxicity was evident by statistical differences between dosed groups and controls for: mean body weight and food consumption (115ppm group, rats and mice). No statistically significant differences (ANOVA) among control and treatment groups were found for any of the fetal external, visceral or skeletal parameters.[Bio/dynamics Inc.; Inhalation Teratology Study in Rats and Mice, Final Report. (1984), EPA Document No. 40-8555049, Fiche No. OTS0507224]
The ability of isophorone to induce specific locus mutations at the TK locus in cultured L5178Y mouse lymphoma cells (Mouse Lymphoma Mutagenesis Assay) was evaluated in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Based on preliminary toxicity tests, nine nonactivated cultures treated with 1.3, 1.0, 0.75, 0.56, 0.42, 0.32, 0.24, 0.18 or 0.13 ul/ml were cloned, producing a range of 12 - 111% total growth. Ten S9-activated cultures treated with 0.89, 0.67, 0.50, 0.38, 0.28, 0.21, 0.16, 0.12, 0.089 or 0.067 ul/ml were cloned, producing a range of 9 - 86% total growth. None of the cultures that were cloned produced mutant frequencies which were significantly greater than the mean mutant frequency of the solvent controls (DMSO,acetone).[Microbiological Associates; L5178Y TK+/- Mouse Lymphoma Mutagenicity Assay, (1984), EPA Document No. 40-8455047, Fiche No. OTS0507222]
Isophorone was evaluated for the ability to increase the incidence of micronucleated polychromatic erthrocytes in bone marrow of male and female CD-1 mice treated by single i.p. injection (Micronucleus Test). Groups of 10 mice (5 male, 5 female) were sacrificed 12, 24 and 48 hours following injection of isophorone in corn oil at a dose of 0.54 ml/kg body weight (calculated LD20 dose). The incidence of micronucleated polychromatic erythrocytes and the ratio of normochromatic to polychromatic erythrocytes were not significantly different (p > 0.05.ANOVA) in the treatment groups compared with the vehicle controls, regardless of sacrifice time.[Microbiological Associates, Inc.; Activity of Isophorone in the Micronucleus Cytogenetic Assay in Mice, Final Report, (1984), EPA Document No. 40-8455047, Fiche No. OTS0507222]
The effect of isophorone was examined in the rat hepatocyte primary culture/DNA repair assay. Based on preliminary toxicity tests, isophorone was tested at concentrations of 0.40 (cytotoxic), 0.20, 0.10, 0.50, 0.01 or 0.0005 ul/ml (no toxic effect). None of the tested concetrations caused a significant increase in the unscheduled DNA synthesis over the solvent control (ethanol).[Microbiological Associates; Unscheduled DNA Synthesis in the Rat Primary Hepatocytes, Final Report, (1984), EPA Document No. 40-8455047, Fiche No. OTS0507222]
For more TSCA Test Submissions (Complete) data for ISOPHORONE (15 total), please visit the HSDB record page.

12.2 Ecological Information

12.2.1 Ecotoxicity Values

LC50 Cyprinodon variegatus (sheepshead minnow) 166,000-295,000 ug/l/96 hr. /Conditions of bioassay not specified/
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.B-8 (1980) EPA 440/5-80-056
EC50 Selenastrum capricornutum (alga) 122,000 ug/l/96 hr, Toxic Effect: cell number reduced. /Conditions of bioassay not specified/
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.B-6 (1980) EPA 440/5-80-056
EC50 Selenastrum capricornutum (alga) 126,000 ug/l/96 hr, Toxic Effect: Chlorophyll a synthesis inhibited. /Conditions of bioassay not specified/
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.B-6 (1980) EPA 440/5-80-056
EC50 Skeletonema costatum (alga) 105,000 ug/l/96 hr, Toxic Effect: cell number reduced. /Conditions of bioassay not specified/
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.B-6 (1980) EPA 440/5-80-056
For more Ecotoxicity Values (Complete) data for ISOPHORONE (9 total), please visit the HSDB record page.

12.2.2 US EPA Regional Screening Levels for Chemical Contaminants

1 of 2
Resident Soil (mg/kg)
7.80e+03
Industrial Soil (mg/kg)
4.30e+04
Resident Air (ug/m3)
4.20e+02
Industrial Air (ug/m3)
1.80e+03
Tapwater (ug/L)
7.30e+02
MCL (ug/L)
5.00e+01
Risk-based SSL (mg/kg)
1.50e-01
Chronic Oral Reference Dose (mg/kg-day)
3.00e-01
Chronic Inhalation Reference Concentration (mg/m3)
4.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Soil Saturation Concentration (mg/kg)
1.00e+04
2 of 2
Resident Soil (mg/kg)
5.70e+02
Industrial Soil (mg/kg)
2.40e+03
Resident Air (ug/m3)
2.10e+03
Industrial Air (ug/m3)
8.80e+03
Tapwater (ug/L)
7.80e+01
MCL (ug/L)
5.00e+01
Risk-based SSL (mg/kg)
2.60e-02
Oral Slope Factor (mg/kg-day)-1
9.50e-04
Chronic Oral Reference Dose (mg/kg-day)
2.00e-01
Chronic Inhalation Reference Concentration (mg/m3)
2.00e+00
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

12.2.3 US EPA Regional Removal Management Levels for Chemical Contaminants

1 of 2
Resident Soil (mg/kg)
2.30e+04
Industrial Soil (mg/kg)
1.30e+05
Resident Air (ug/m3)
1.30e+03
Industrial Air (ug/m3)
5.30e+03
Tapwater (ug/L)
2.20e+03
MCL (ug/L)
5.00e+01
Chronic Oral Reference Dose (mg/kg-day)
3.00e-01
Chronic Inhalation Reference Concentration (mg/m3)
4.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Soil Saturation Concentration (mg/kg)
1.00e+04
2 of 2
Resident Soil (mg/kg)
3.80e+04
Industrial Soil (mg/kg)
2.40e+05
Resident Air (ug/m3)
6.30e+03
Industrial Air (ug/m3)
2.60e+04
Tapwater (ug/L)
7.80e+03
MCL (ug/L)
5.00e+01
Oral Slope Factor (mg/kg-day)-1
9.50e-04
Chronic Oral Reference Dose (mg/kg-day)
2.00e-01
Chronic Inhalation Reference Concentration (mg/m3)
2.00e+00
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

12.2.4 Environmental Fate / Exposure Summary

Isophorone's production and use as a solvent for printing inks, lacquers, adhesives, and use as a chemical intermediate may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.438 mm Hg at 25 °C indicates isophorone will exist solely as a vapor in the ambient atmosphere. Vapor-phase isophorone will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 5 hrs. If released to soil, isophorone is expected to have moderate mobility based upon an estimated Koc of 200. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 6.6X10-6 atm-cu m/mole. This compound is not expected to biodegrade rapidly in the environment based upon a 3% theoretical BOD in 2 weeks using an activated sludge inoculum and the Japanese MITI test. If released into water, isophorone is expected to adsorb moderately to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 7 and 52 days, respectively. A BCF of 7 suggests that bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to isophorone may occur through inhalation and dermal contact with this compound at workplaces where isophorone is produced or used. Monitoring data indicate that the general population may be exposed to isophorone via ingestion of contaminated drinking water. (SRC)

12.2.5 Natural Pollution Sources

There are no known natural sources of isophorone(1).
(1) Abrams EF et al; Identification of Organic Compounds in Effluents from Industrial Sources. Washington, DC: USEPA-560/3-75-002 (1975)

12.2.6 Artificial Pollution Sources

Isophorone's production and use as a solvent for printing inks, lacquers, adhesives(1), and use as a chemical intermediate(2) may result in its release to the environment through various waste streams(SRC).
(1) Budavari S, ed; The Merck Index. 12th ed. Whitehouse Station, NJ: Merck and Co., Inc. p. 887 (1996)
(2) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. NY, NY: John Wiley & Sons p. 1340 (2001)

12.2.7 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.70(2), indicates that isophorone is expected to have moderate mobility in soil(SRC). Volatilization of isophorone from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.6X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.438 mm Hg(3), and water solubility, 12,000 mg/l(4). Isophorone is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Biodegradation is not expected to be an important environmental fate process in soil based upon a 3% theoretical BOD in 2 weeks using an activated sludge inoculum and the Japanese MITI test(5).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Veith GD et al; pp. 116-29 in Aquatic Toxicology. Easton JG et al, eds. Amer Soc Test Mat ASTM STP 707 (1980)
(3) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(4) Parrish CF; Kirk-Othmer Encycl Chem Tech 3rd. NY, NY: Wiley-Intrsci 21: 377-401 (1983)
(5) Chemicals Inspection and Testing Insitute Japan is available on the web at <https://www.cerij.or.jp/ceri_en/index_e.shtml> as of Aug, 2001.
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.70(2), indicates that isophorone is not expected to adsorb strongly to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 6.6X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.438 mm Hg(4), and water solubility, 12,000 mg/l(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 7 and 52 days, respectively(SRC). According to a classification scheme(6), a BCF of 7(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation is not expected to be an important environmental fate process in water based upon a 3% theoretical BOD in 2 weeks using an activated sludge inoculum and the Japanese MITI test(7).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Veith GD et al; pp. 116-29 in Aquatic Toxicology. Easton JG et al, eds. Amer Soc Test Mat ASTM STP 707 (1980)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(5) Parrish CF; Kirk-Othmer Encycl Chem Tech 3rd. NY, NY: Wiley-Intrsci 21: 377-401 (1983)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Chemicals Inspection and Testing Insitute Japan is available on the web at <https://www.cerij.or.jp/ceri_en/index_e.shtml> as of Aug, 2001.
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isophorone, which has a vapor pressure of 0.438 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase isophorone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 5 hrs(SRC), calculated from its rate constant of 8.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)

12.2.8 Environmental Biodegradation

AEROBIC: Isophorone, present at 100 mg/l, reached 3% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(1). Removal of isophorone from unacclimated fresh and salt water seeded with settled domestic wastewater was 42 and 9%, respectively, after 20 days(3). Removal of isophorone from wastewater treated by various different biological treatment processes: trickling filter, activated sludge, aerated lagoon, and facultative lagoon was 19, 98, 24, and 30%, respectively(4); therefore this compound is not expected to biodegrade rapidly(SRC). A 100% loss was observed when 5 and 10 mg/l isophorone underwent a 7-day static incubation in the dark at 25 °C under aerobic conditions using settled domestic wastewater as inoculum(2). Using a multi-level respirometric test protocol employing a sludge microbiota, a half-life of 25 days for 100 mg test compound was determined(5).
(1) Chemicals Inspection and Testing Insitute Japan is available on the web at <https://www.cerij.or.jp/ceri_en/index_e.shtml> as of Aug, 2001.
(2) Tabak HH et al; J Water Pollut Control Fed 53: 1503-18 (1981)
(3) Price KS et al; J Water Pollut Control Fed 46: 63-77 (1974)
(4) Hannah SA et al; J Water Pollut Control Fed 58: 27 (1986)
(5) Tabak HH et al; Respirometric methods for determination of biodegradability and biodegradation kinetics for hazardous organic pollutant compounds. Cincinnati, OH: USEPA/600/A-92/174. NTIS PB92-217108 (1992)

12.2.9 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of isophorone with photochemically-produced hydroxyl radicals has been estimated as 8.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Isophorone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2-4) nor to undergo direct photolysis due to the lack of absorption in the environmental UV spectrum (>290 nm)(5). The rate constant for the vapor-phase reaction of isophorone with ozone has been estimated as 7.4X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(6).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(3) Callahan MA et al; Water-related Environmental Fate of 129 Priority Pollutants. USEPA-440-4-79-029a (1979)
(4) Mabey WR et al; Aquatic Fate Process Data for Organic Priority Pollutants. p. 434 USEPA-440/4-81-014 (1981)
(5) Sadtler; Sadtler Standard UV Spectra (1966)
(6) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)

12.2.10 Environmental Bioconcentration

A BCF of 7 was measured for isophorone in bluegill sunfish(1). The half-life of isophorone in fish tissue was found to be 1 day(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Veith GD et al; pp. 116-29 in Aquatic Toxicology. Easton JG et al, eds. Amer Soc Test Mat ASTM STP 707 (1980)
(2) Franke C et al; Chemosphere 29: 1501-14 (1994)

12.2.11 Soil Adsorption / Mobility

The Koc of isophorone is estimated as 200(SRC), using a log Kow of 1.7(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that isophorone is expected to have moderate mobility in soil.
(1) Veith GD et al; pp. 116-29 in Aquatic Toxicology. Easton JG et al, eds. Amer Soc Test Mat ASTM STP 707 (1980)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)

12.2.12 Volatilization from Water / Soil

The Henry's Law constant for isophorone is estimated as 6.6X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 0.438 mm Hg(1), and water solubility, 12,000 mg/l(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)(3) is estimated as 7 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)(3) is estimated as 52 days(SRC). Isophorone's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Isophorone is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
(1) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(2) Parrish CF; Kirk-Othmer Encycl Chem Tech 3rd; NY, NY: Wiley-Intrsci 21: 377-401 (1983)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

12.2.13 Environmental Water Concentrations

... EPA maintains an inventory of organic compounds that have been isolated and identified in drinking water in the USA. ... Isophorone was ... detected at concentrations as high as 9.5 ug/l.
USEPA; Report to Congress (1975) as cited in USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-1 (1980) EPA 440/5-80-056
GROUNDWATER: Isophorone was detected in groundwater samples collected from the Netherlands at a maximum concn of 10 ug/l(1).
(1) Zoeteman BCJ et al; Sci Total Environ 21: 187-202 (1981)
DRINKING WATER: Isophorone was identified in finished drinking water from: Cincinnati, OH - Oct 1978 and Jan 1980; Philadelphia, PA - Feb 1976; Ottumwa, IA - Sept 1976; and Seattle, WA - Nov 1976(1). During the USEPA 1974 National Organics Reconnaissance Survey (NORS) isophorone was detected in 1 of 10 finished drinking water supplies(2). Approximately 0.02 ug/l was found in drinking water from Cincinnati, OH(2). Trace levels were detected in Philadelpha, PA drinking water during Aug 1977(3). The compound was detected in drinking water from New Orleans, LA during 1974, with a max concn of 2.9 ug/l(4).
(1) Lucas SV; GC/MS Analysis of Organics in Drinking Water Concentrates and Advanced Water Treatment Concentrates Vol 3. USEPA-600/1-84-020 NTIS PB85 128221 p. 186 (1984)
(2) USEPA; Ambient Water Quality Criteria for Isophorone. USEPA 440/5-80-056 NTIS PB81 11767j (1980)
(3) Sheldon LS, Hites RA; Environ Sci Technol 13: 574-9 (1979)
(4) Cole RH et al; J Water Pollut Control Fed 56: 898-908 (1984)
SURFACE WATER: Data from the USEPA STORET Data Base indicates that of 795 water samples, 1% tested positive for isophorone with a median concn of <10 ug/l(1). During Aug 1977 in the Delaware River, Pennsylvania at river mile 106, 108, and 110, isophorone concentrations were found to be 3, 0.6 and <0.01 ug/l, respectively(2). Isophorone was detected in the St. Joseph River, Michigan and not detected in the Cuyahoga River, Ohio(3). USEPA National Urban Runoff Program (NURP) results as of July 1982 indicate that isophorone was found in runoff in 1 of 19 cities across USA(4). 10 ug/l was detected in urban runoff of Washington, DC(4). Samples collected on the St. Lawrence River in the region of Quebec, Canada in June, 1987 contained isophorone at a conc of 69 ng/l(5).
(1) Hauser TR, Bromberg SM; Environ Monit Assess 2: 249-72 (1982)
(2) Sheldon LS, Hites RA; Environ Sci Tech 13: 574-9 (1979)
(3) Great Lakes Quality Board; An Inventory of Chemical Substances Identified in the Great Lakes Ecosystem Vol 1 summary. p.195 (1983)
(4) Cole RH et al; JWCPF 56: 898-908 (1984)
(5) Germain A, Langlois C; Water Poll Res J Canada 23: 602-14 (1988)

12.2.14 Effluent Concentrations

According to the USEPA STORET Data Base, of 1272 effluent samples, 1.6% tested positive for isophorone, with a median concn of <10.0 ug/l(1). Isophorone has been found in the treated wastewater from the following industries: iron and steel mfg, 1 of 5 samples pos, concn 170 ug/l; coil coating, 5 of 31 samples pos, max concn 560 ug/l, mean concn 120 ug/l; foundries, 7 of 7 samples pos, max concn 28 ug/l, mean concn 12 ug/l; photographic equipment and supplies, 2/4 samples pos, max concn 10 ug/l, mean concn 10 ug/l; paint and ink formulation, 1 of 1 samples pos, concn <7 ug/l; automobile tire plant, 40 ug/l; and oil shale retorting, 340-5800 ug/l(2-4). The influent and effluent of the Philadelphia (PA) Northeast Sewage Treatment plant during Aug 1977 were 100 and 10 ug/l, respectively(5). Isophorone was tested for but not detected (detection limit of 1.0 ug/l) in tire leachates from tire plugs soaked 31 days in fresh water from Lake Mead, NV(6). Analysis of New York City municipal wastewaters was conducted from 1989 to 1993(7). Isophorone was detected once in 1989 and 1991 in influent samples at a concn of 5 ug/l (2% detection), and in a 1991 effluent sample at a concn of 8 ug/l (1% detection)(7). The compound was detected at a concn of 10.4 ug/l in leachate from a municipal landfill in Japan(8). According to a Danish study, isophorone was detected not quantified in waste exudate analysis of garden waste(9). Municipal landfill leachate concn of isphorone as reported in the literature range from a low of 3.18 pg/l to 16 mg/l, detected in 13 of 26 samples at a median concn of 76 ug/l(10). Isophorone has been detected in the effluents from latex and chemical plants in Alabama, but no levels were reported.
(1) Hauser TR, Bromberg SM; Environ Monit Assess 2: 249-72 (1982)
(2) USEPA; Treatability Manual I. USEPA-600/2-82-001a (1981)
(3) Jungclaus GA et al; Anal Chem 48: 1894-6 (1976)
(4) Hawthorne SB, Sievers RE; Environ Sci Tech 18: 483-90 (1984)
(5) Sheldon LS, Hites RA; Environ Sci Technol 13: 574-9 (1979)
(6) Nelson SM et al; Bull Environ Contam Toxicol 52: 574-81 (1994)
(7) Stubin AI et al; Water Environ Res 68: 1037-44 (1996)
(8) Yasuhara A et al; Kankyo Kagaku 3: 356-7 (1993)
(9) Wilkins K, Larsen K; Chemosphere 32: 2049-55 (1996)
(10) Roy WR; pp. 411-46 in Contaminated Groundwaters. Adriano DC et al, eds. Northwood, UK: Sci Rev (1994)
(11) Shackelford WM, Keith LH; Frequency of organic compounds identified in water. Athens, GA: USEPA 600/4-76-062 p. 626 (1976)

12.2.15 Sediment / Soil Concentrations

SEDIMENT: Isophorone was qualitatively identified in sediment/soil/water samples taken from Love Canal in Niagara Falls, NY during 1980(1). According to the USEPA STORET Data Base, of 318 sediment samples tested, 0% were positive for isophorone(2). The compound was detected in sediments taken from Lake Pontchartrain (LA), concn range 0.98-12 ng/g (ppb) dry wt(3).
(1) Hauser TR, Bromberg SM; Environ Monit Assess 2: 249-72 (1982)
(2) Staples CA et al. Environ Toxicol Chem 4: 131-42 (1985)
(3) McFall JA et al; Chemosphere 14: 1561-9 (1985)

12.2.16 Atmospheric Concentrations

SOURCE DOMINATED: Isophorone has been detected in coal fly ash at a concentration of 490 ug/g(1).
(1) Harrison FL et al; Environ Sci Tech 19: 186-93 (1985)

12.2.17 Food Survey Values

Isophorone was detected in apricots (Prunus armeniaca) and plums (Prunus salicina, Lindl.) at 17, 4, an 11 mg/kg in 3 of 3 apricots and at 1 mg/kg in 1 of 2 plums(1).
(1) Gomez E et al; J Agric Food Chem 41: 1669-76 (1993)

12.2.18 Fish / Seafood Concentrations

The USEPA STORET Data Base reports that of 123 samples of biota, 0% were positive for isophorone(1). Whole fish samples collected from nearshore tributaries and the Grand Traverse Bay on Lake Michigan in the fall of 1993 tested positive for isophorone, at a mean concn range of not detected to 3.61 mg/kg wet weight(2). Isophorone was not detected in Great Lakes fish collected from the Sheboygen (WI), Milwaukee (WI), Kinninkinnic (WI), Fox (WI), Black (OH), Menominnee (WI), Wolf (WI), Ashtabula (OH) rivers, and Chequamegon Bay (Lake Superior, WI)(3). Bottomfish collected in 1981 from Old Town Dock area, Commencement Bay in Tacoma WA tested positive for isophorone at a max concn of 0.92 ppm(4).
(1) Hauser TR, Bromberg SM; Environ Monit Assess 2: 249-72 (1982)
(2) Camanzo J et al; J Great Lakes Res 13: 296-309 (1987)
(3) DeVault DS; Arch Environ Contam 14: 587-594 (1985)
(4) Nicola RN et al; J Environ Health 49: 342-7 (1987)

12.2.19 Other Environmental Concentrations

Isophorone is present in printer's inks used for serigraphy, concn not specified(1).
(1) Rastogi SC; Arch Environ Contam Toxicol 20: 543-7 (1991)

12.2.20 Probable Routes of Human Exposure

Certain occupations (particularly individuals who are exposed to isophorone as a solvent) have elevated levels of exposure relative to the general population.
USEPA; Ambient Water Quality Criteria Doc: Isophorone p.C-16 (1980) EPA 440/5-80-056
NIOSH (NOES Survey 1981-1983) has statistically estimated that 47,097 workers (10,353 of these are female) are potentially exposed to isophorone in the US(1). Occupational exposure to isophorone may occur through inhalation and dermal contact with this compound at workplaces where isophorone is produced or used(SRC). Monitoring data indicate that the general population may be exposed to isophorone via ingestion of contaminated drinking water(SRC).
(1) NIOSH; National Occupational Exposure Survey (NOES) (1983)
Concentration of isophorone in breathing zone samples from an isophorone manufacturing plant (Exxon Chemical) were reported to range from 0.01-0.63 ppm, mean concn 0.07 ppm(1). Time-weighted average (TWA) concentration in breathing zones and workplace air of a screen printing plant ranged from 8.3-23 ppm and 3.5-14.5 ppm, respectively(2). Up to 25.7 ppm was detected in air of a silk screen printing plant in Pittsburgh, PA(3). Concentration of isophorone in breathing zone samples from a decal manufacturing plant in Ridgefield, NJ was 0.7-14 ppm(4).
(1) USEPA; Exxon Chemical Americas. Office of Toxic Substances Microfiche No. 206267 (1982)
(2) Samimi B; Amer Ind Hyg Assoc J 43: 858-62 (1982)
(3) Kominsky JR; National Institute of Occupational Safety and Health (NIOSH) Health Hazard. Report No. HE78-107-563 NTIS PB 81-14371 (1981)
(4) Lee SA, Frederick L; NIOSH Health Hazard. Report No. HHE80-103-827 NTIS PB82-189226 (1982)
The occupational exposures to isophorone occur by inhalation or dermal contact & mainly occur in the printing industry.
Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1121

13 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound

Solvents, acute toxic effect [Category: Acute Poisoning]

Encephalopathy, chronic solvent [Category: Chronic Poisoning]

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.2 Chemical-Target Interactions

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 ChEBI Ontology

19.3 ChemIDplus

19.4 CAMEO Chemicals

19.5 UN GHS Classification

19.6 EPA CPDat Classification

19.7 NORMAN Suspect List Exchange Classification

19.8 EPA DSSTox Classification

19.9 International Agency for Research on Cancer (IARC) Classification

19.10 The Natural Products Atlas Classification

19.11 EPA TSCA and CDR Classification

19.12 LOTUS Tree

19.13 EPA Substance Registry Services Tree

19.14 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Agency for Toxic Substances and Disease Registry (ATSDR)
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    2-Cyclohexen-1-one, 3,5,5-trimethyl-
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    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
  7. ChEBI
  8. LOTUS - the natural products occurrence database
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  9. Australian Industrial Chemicals Introduction Scheme (AICIS)
  10. CAS Common Chemistry
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  11. ChemIDplus
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  14. EPA Chemicals under the TSCA
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    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  15. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  16. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
    3,5,5-trimethylcyclohex-2-enone
    https://chem.echa.europa.eu/100.001.024
  17. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  18. Hazardous Substances Data Bank (HSDB)
  19. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
    3,5,5-Trimethyl-2-cyclohexen-1-one
    http://www.hmdb.ca/metabolites/HMDB0031195
  20. ILO-WHO International Chemical Safety Cards (ICSCs)
  21. New Zealand Environmental Protection Authority (EPA)
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  22. NJDOH RTK Hazardous Substance List
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  24. Risk Assessment Information System (RAIS)
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  30. EPA Chemical and Products Database (CPDat)
  31. EU Food Improvement Agents
  32. EPA Regional Screening Levels for Chemical Contaminants at Superfund Sites
  33. Hazardous Chemical Information System (HCIS), Safe Work Australia
  34. NITE-CMC
    2-Cyclohexen-1-one, 3,5,5-trimethyl- - FY2006 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/06-imcg-0644e.html
    Isophorone; alpha-Isophorone - FY2023 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/23-jniosh-2021e.html
  35. Regulation (EC) No 1272/2008 of the European Parliament and of the Council
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    3,5,5-trimethylcyclohex-2-enone; isophorone
    https://eur-lex.europa.eu/eli/reg/2008/1272/oj
  36. FDA Substances Added to Food
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  37. Flavor and Extract Manufacturers Association (FEMA)
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  40. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
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  45. SpectraBase
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  49. Japan Chemical Substance Dictionary (Nikkaji)
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  51. KNApSAcK Species-Metabolite Database
  52. Natural Product Activity and Species Source (NPASS)
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    Isophorone
  54. Metabolomics Workbench
  55. Nature Chemistry
  56. NIOSH Manual of Analytical Methods
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  58. Springer Nature
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  66. GHS Classification (UNECE)
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  68. EPA Substance Registry Services
  69. MolGenie
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  70. PATENTSCOPE (WIPO)
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CONTENTS