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Registry of Toxic Effects of Chemical Substances (RTECS)

2-Cyclohexen-1-one, 3,5,5-trimethyl-

RTECS #

GW7700000

CAS #

78-59-1

Updated

June 2017

Molecular Weight

138.23

Molecular Formula

C9H14O

Synonyms

1,1,3-Trimethyl-3-cyclohexene-5-one
3,3,5-Trimethyl-5-cyclohexen-1-one
3,5,5-Trimethyl-2-cyclohexen-1-on (German, Dutch)
3,5,5-Trimethyl-2-cyclohexen-1-one
3,5,5-Trimethyl-2-cyclohexene-1-one
3,5,5-Trimethylcyclohex-2-ene-1-one
3,5,5-Trimetil-2-cicloesen-1-one (Italian)
Isoacetophorone
Isoforon
Isoforone (Italian)
Isophoron
Isophorone
Isophorone (ACGIH:OSHA)
Izoforon (Polish)
NCI-C55618

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /guinea pig 840 ppm/4H severeJIHTAB 22,477,1940
eye /human 25 ppm/15MJIHTAB 28,262,1946
eye /rabbit 920 µg severeUCDS** 11/15/1971
eye /rabbit 100 mg/24H moderate85JCAE -,290,1986
skin /rabbit 100 mg/24H mildJETOAS 5,31,1972
skin /rabbit 0.5 mL/24H moderateVCVGK* -,460,1994

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysislung/hamster1250 mg/LMUREAV 369,243,1996
mutation in mammalian somatic cellslymphocyte/mouse400 mg/LEMMUEG 12,85,1988
sister chromatid exchangeovary/hamster1 gm/LNTPTR* NTP-TR-291,1986
specific locus testother cell types/mouse1500 mg/L/24H (-enzymatic activation step)MUTAEX 14,23,1999
Unscheduled DNA Synthesisliver/rat5 mmol/LMUREAV 315,147,1994

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
inhalation/rat 115 ppm/6H (6-15D pregnant)Reproductive: Other effects on femaleNTIS** OTS0546532
inhalation/mouse 115 ppm/6H (6-15D pregnant)Reproductive: Other effects on femaleNTIS** OTS0546532
inhalation/rat 115 ppm (6-15D pregnant)Reproductive: Other effects on femaleHPV275 -,-,2003
inhalation/mouse 115 ppm (6-15D pregnant)Reproductive: Other effects on femaleHPV275 -,-,2003

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 258 gm/kg/2Y- intermittentTumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors
TXCYAC 39,207,1986
oral/mouse lowest published toxic dose: 257500 mg/kg/103W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors
NTIS** PB86-181823/AS
oral/mouse lowest published toxic dose: 128750 mg/kg/103W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Blood: Lymphoma including Hodgkin's disease
NTIS** PB86-181823/AS
oral/rat lowest published toxic dose: 128750 mg/kg/103W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Tumorigenic: Increased incidence of tumors in susceptible strains
HPV275 -,-,2003
oral/rat lowest published toxic dose: 128750 mg/kg/103W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Reproductive: Other reproductive system tumors
NTIS** PB86-181823/AS
oral/rat lowest published toxic dose: 180 gm/kg/2Y- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors
NTIS** OTS0571092

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 5000 mg/m3Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Cough
VCVGK* -,459,1994
inhalation/guinea pig lowest published toxic concentration: 5000 mg/m3/150MBehavioral: Alteration of classical conditioningVCVGK* -,459,1994
inhalation/guinea pig lowest published toxic concentration: 5000 mg/m3/6HLung, Thorax, or Respiration: Respiratory depressionVCVGK* -,459,1994
inhalation/guinea pig lowest published toxic concentration: 5000 mg/m3/10HBehavioral: General anesthetic

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes
VCVGK* -,459,1994
inhalation/guinea pig lethal concentration (50 percent kill): 4600 ppm/8H85JCAE -,290,1986
inhalation/human lowest published toxic concentration: 141 mg/m3/10MOlfaction: Other olfaction effects

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Cough
VCVGK* -,459,1994
inhalation/human lowest published toxic concentration: 1100 mg/m3/15MBehavioral: Headache

Gastrointestinal: Nausea or vomiting
VCVGK* -,459,1994
inhalation/human lowest published toxic concentration: 25 ppmOlfaction: Other olfaction effects

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Other changes
JIHTAB 28,262,1946
inhalation/mammal (species unspecified) lethal concentration (50 percent kill): >7000 mg/m3/4HFEREAC 70,21767,2005
inhalation/mouse lowest published toxic concentration: 4 ppm/6MLung, Thorax, or Respiration: Respiratory depressionTOLED5 9,137,1981
inhalation/mouse Lethal concentration: >3500 mg/kg/6HLung, Thorax, or Respiration: Acute pulmonary edemaNTIS** OTS0535380
inhalation/rat lethal concentration (50 percent kill): 7 gm/m3Behavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Dyspnea

Skin and Appendages: Other: Hair
NTIS** OTS0572861
inhalation/rat Lowest published lethal concentration: 10000 mg/m3/4HGastrointestinal: Gastritis

Liver: Other changes
VCVGK* -,459,1994
inhalation/rat lethal concentration (50 percent kill): 1281 ppm/4HBehavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Dyspnea
HPV275 -,-,2003
intravenous/Dog Lethal dose: >10 mg/kgBehavioral: Convulsions or effect on seizure threshold

Cardiac: Pulse rate decreased with fall in BP

Lung, Thorax, or Respiration: Respiratory stimulation
NTIS** OTS0535380
oral/guinea pig lethal dose (50 percent kill): 700 mg/kgNTIS** OTS0535380
oral/mammal (species unspecified) lethal dose (50 percent kill): 1500 mg/kgFEREAC 70,21767,2005
oral/mouse lethal dose (50 percent kill): 2690 mg/kgTXAPA9 17,498,1970
oral/rabbit lethal dose (50 percent kill): 1420 mg/kgNTIS** OTS0535380
oral/rat lethal dose (50 percent kill): 1870 mg/kgUCDS** 11/15/1971
oral/rat lethal dose (50 percent kill): 3450 mg/kgBehavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Acute pulmonary edema

Gastrointestinal: Gastritis
HPV275 -,-,2003
skin/mammal (species unspecified) lethal dose (50 percent kill): 1200 mg/kgFEREAC 70,21767,2005
skin/rabbit lethal dose (50 percent kill): 1500 µL/kgUCDS** 11/15/1971
skin/rat lethal dose (50 percent kill): 1390 mg/kgNTIS** OTS0526403

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 500 ppm/8H/6W- intermittentLung, Thorax, or Respiration: Other changes

Kidney, Ureter, and Bladder: Changes in both tubules and glomeruli

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
JIHTAB 24,46,1942
inhalation/guinea pig lowest published toxic concentration: 500 ppm/8H/6W- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Blood: Changes in other cell count (unspecified)
NTIS** OTS0535380
inhalation/guinea pig lowest published toxic concentration: 2800 mg/m3/8H/6W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldVCVGK* -,459,1994
inhalation/guinea pig lowest published toxic concentration: 280 mg/m3/8H/6W- intermittentKidney, Ureter, and Bladder: Other changesVCVGK* -,459,1994
inhalation/human lowest published toxic concentration: 5 ppm/30D- intermittentBehavioral: Somnolence (general depressed activity)VCVGK* -,460,1994
inhalation/rat lowest published toxic concentration: 280 mg/m3/8H/6W- intermittentKidney, Ureter, and Bladder: Other changesVCVGK* -,459,1994
inhalation/rat lowest published toxic concentration: 2800 mg/m3/8H/6W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldVCVGK* -,459,1994
inhalation/rat lowest published toxic concentration: 500 ppm/8H/6W- intermittentLung, Thorax, or Respiration: Other changes

Kidney, Ureter, and Bladder: Changes in both tubules and glomeruli

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
JIHTAB 24,46,1942
inhalation/rat lowest published toxic concentration: 500 ppm/8H/6W- intermittentEye: Other eye effects

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes in urine composition
NTIS** OTS0535380
inhalation/rat lowest published toxic concentration: 208 mg/m3/6H/4W- intermittentLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** OTS0535380
oral/mouse lowest published toxic dose: 24 gm/kg/16D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-291,1986
oral/mouse lowest published toxic dose: 65 gm/kg/13W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-291,1986
oral/rat lowest published toxic dose: 24 gm/kg/16D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-291,1986
oral/rat lowest published toxic dose: 65 gm/kg/13W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-291,1986
oral/rat lowest published toxic dose: 128750 mg/kg/103W- intermittentKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Related to Chronic Data: Changes in ovarian weight
HPV275 -,-,2003

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-ceiling concentration 5 ppmDTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Confirmed animal carcinogenDTLVS* TLV/BEI,2013
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWMUTAEX 14,5,1999
TOXICOLOGY REVIEWEMMUEG 39,69,2002
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWFEREAC 71,45403,2006
TOXICOLOGY REVIEWFCTOD7 47,1287,2009
TOXICOLOGY REVIEWMUREAV 721,27,2011
TOXICOLOGY REVIEWMUREAV 763,36,2014
TOXICOLOGY REVIEWMUREAV 769,34,2014
TOXICOLOGY REVIEWMUREAV 802,1,2016

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARD-airtime-weighted average 25 ppm (140 mg/m3)DTLVS* 3,140,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIAceiling concentration 5 ppm (28 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 2 ppm (11 mg/m3);KZW 2 ppm (11 mg/m3), 2007
Occupational Exposure Limit-BELGIUMshort term exposure limit 5 ppm (28 mg/m3), MAR2002
Occupational Exposure Limit-DENMARKceiling concentration 5 ppm (25 mg/m3), carc, MAY2011
Occupational Exposure Limit-FINLANDtime-weighted average 1 ppm (5.7 mg/m3), NOV2011
Occupational Exposure Limit-FRANCEVLE 5 ppm (25 mg/m3), C3 Carcinogen, FEB2006
Occupational Exposure Limit-GERMANYMAK 2 ppm (11 mg/m3), 2011
Occupational Exposure Limit-ICELANDshort term exposure limit 5 ppm (30 mg/m3), NOV2011
Occupational Exposure Limit-KOREAceiling concentration 5 ppm (25 mg/m3), 2006
Occupational Exposure Limit-MEXICOpeak 5 ppm (25 mg/m3), 2004
Occupational Exposure Limit-NEW ZEALANDceiling concentration 5 ppm (28 mg/m3), JAN2002
Occupational Exposure Limit-PERUshort term exposure limit 5 ppm (28 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 5 mg/m3, MAC(C) 25 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 1 mg/m3, JUN2003
Occupational Exposure Limit-SWEDENceiling concentration 5 ppm (30 mg/m3), JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 2 ppm (11 mg/m3), KZG-week 4 ppm (22 mg/m3), carc 3, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-C 25 mg/m3, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 25 ppm (140 mg/m3), JAN1993
Occupational Exposure Limit-TURKEYtime-weighted average 25 ppm (149 mg/m3), JAN1993
Occupational Exposure Limit-UNITED KINGDOMshort term exposure limit 5 ppm (29 mg/m3), OCT2007
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)8H time-weighted average 25 ppm (140 mg/m3)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)8H time-weighted average 25 ppm (140 mg/m3)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)8H time-weighted average 25 ppm (140 mg/m3)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)8H time-weighted average 25 ppm (140 mg/m3)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO ISOPHORONE-air10H time-weighted average 4 ppmNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 40910; Number of Industries 43; Total Number of Facilities 3593; Number of Occupations 47; Total Number of Employees Exposed 47097; Total Number of Female Employees Exposed 10353
National Occupational Hazard Survey 1974Hazard Code 40910; Number of Industries 44; Total Number of Facilities 2934; Number of Occupations 40; Total Number of Employees Exposed 26825

Status in Federal Agencies

OrganizationReference
ATSDR TOXICOLOGY PROFILE (NTIS** PB/90/180225/AS)
EPA TSCA 8(a) PRELIMINARY ASSESSMENT INFORMATION, FINAL RULEFEREAC 47,26992,82
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Studies (gavage);equivocal evidence:mouse,rat
NIOSH Analytical Method, 1994: Isophorone, 2508
NTP Carcinogenesis Studies (gavage);some evidence:rat NTPTR* NTP-TR-291,1986
On EPA IRIS database
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