The Registry of Toxic Effects of Chemical Substances

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

RTECS #: GW7700000

CAS #: 78-59-1

UPDATE: November 2004 MW: 138.23 MF: C9H14O


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. TUMORIGENIC DATA:
  6. ACUTE TOXICITY DATA:
  7. OTHER MULTIPLE DOSE DATA:
  8. REVIEWS:
  9. STANDARDS AND REGULATIONS:
  10. NIOSH DOCUMENTATION AND SURVEILLANCE:
  11. STATUS IN FEDERAL AGENCIES:
  12. REFERENCES:

SYNONYMS:

  1. 1,1,3 - Trimethyl - 3 - cyclohexene - 5 - one
  2. 3,3,5 - Trimethyl - 5 - cyclohexen - 1 - one
  3. 3,5,5 - Trimethyl - 2 - cyclohexen - 1 - on (German, Dutch)
  4. 3,5,5 - Trimethyl - 2 - cyclohexen - 1 - one
  5. 3,5,5 - Trimethyl - 2 - cyclohexene - 1 - one
  6. 3,5,5 - Trimethylcyclohex - 2 - ene - 1 - one
  7. 3,5,5 - Trimetil - 2 - cicloesen - 1 - one (Italian)
  8. Isoacetophorone
  1. Isoforon
  2. Isoforone (Italian)
  3. Isophoron
  4. Isophorone
  5. Isophorone (ACGIH:OSHA)
  6. Izoforon (Polish)
  7. NCI - C55618


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
guinea pig 		840 ppm/4 hour severe JIHTAB 22,477,1940
eye
human 		25 ppm/15 minute severe JIHTAB 28,262,1946
eye
rabbit 		920 µg severe UCDS** 11/15/1971
eye
rabbit 		100 mg/24 hour moderate 85JCAE -,290,1986
skin
rabbit 		100 mg/24 hour mild JETOAS 5,31,1972
skin
rabbit 		0.5 mL/24 hour moderate VCVGK* -,460,1994


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis hamster lung 1,250 mg/L MUREAV 369,243,1996
cytogenetic analysis oral
mouse 		0.5 ppb EMMUEG 39,69,2002
cytogenetic analysis oral
rat 		0.5 ppb EMMUEG 39,69,2002
unscheduled DNA synthesis rat liver 5 mmol/L MUREAV 315,147,1994
mutation in mammalian somatic cells mouse lymphocyte 400 mg/L EMMUEG 12,85,1988
sister chromatid exchange hamster ovary 1 gm/L NTPTR* NTP-TR-291,1986
specific locus test oral
mouse 		0.5 ppb EMMUEG 39,69,2002
specific locus test oral
rat 		0.5 ppb EMMUEG 39,69,2002


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 115 ppm/6 hour (6-15 day pregnant) Reproductive: Other effects on female NTIS** OTS0546532
inhalation
rat 		lowest published toxic concentration: 115 ppm/6 hour (6-15 day pregnant) Reproductive: Other effects on female NTIS** OTS0546532


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 258 gm/kg/2 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors 		TXCYAC 39,207,1986
oral
mouse 		lowest published toxic dose: 257,500 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		NTIS** PB86-181823/AS
oral
mouse 		lowest published toxic dose: 128,750 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Lymphoma including Hodgkin's disease 		NTIS** PB86-181823/AS
oral
rat 		lowest published toxic dose: 180 gm/kg/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		NTIS** OTS0571092
oral
rat 		lowest published toxic dose: 128,750 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Reproductive: Other reproductive system tumors 		NTIS** PB86-181823/AS


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
guinea pig 		lethal concentration (50 percent kill): 4,600 ppm/8 hour N/R 85JCAE -,290,1986
inhalation
guinea pig 		lowest published toxic concentration: 5,000 mg/m3 Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Cough 		VCVGK* -,459,1994
inhalation
guinea pig 		lowest published toxic concentration: 5,000 mg/m3/150 minute Behavioral: Alteration of classical conditioning VCVGK* -,459,1994
inhalation
guinea pig 		lowest published toxic concentration: 5,000 mg/m3/6 hour Lung, Thorax, or Respiration: Respiratory depression VCVGK* -,459,1994
inhalation
guinea pig 		lowest published toxic concentration: 5,000 mg/m3/10 hour Behavioral: General anesthetic

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes 		VCVGK* -,459,1994
inhalation
human 		lowest published toxic concentration: 25 ppm Olfaction: Other olfaction effects

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Other changes 		JIHTAB 28,262,1946
inhalation
human 		lowest published toxic concentration: 141 mg/m3/10 minute Olfaction: Other olfaction effects

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Cough 		VCVGK* -,459,1994
inhalation
human 		lowest published toxic concentration: 1,100 mg/m3/15 minute Behavioral: Headache

Gastrointestinal: Nausea or vomiting 		VCVGK* -,459,1994
inhalation
mouse 		lethal concentration : >3,500 mg/kg/6 hour Lung, Thorax, or Respiration: Acute pulmonary edema NTIS** OTS0535380
inhalation
mouse 		lowest published toxic concentration: 4 ppm/6 minute Lung, Thorax, or Respiration: Respiratory depression TOLED5 9,137,1981
inhalation
rat 		lethal concentration (50 percent kill): 7 gm/m3 Behavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Dyspnea

Skin and Appendages: Other: Hair 		NTIS** OTS0572861
inhalation
rat 		lowest published lethal concentration: 10,000 mg/m3/4 hour Gastrointestinal: Gastritis

Liver: Other changes 		VCVGK* -,459,1994
intravenous
dog 		lethal dose : >10 mg/kg Behavioral: 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/kg N/R NTIS** OTS0535380
oral
mouse 		lethal dose (50 percent kill): 2,690 mg/kg N/R TXAPA9 17,498,1970
oral
rat 		lethal dose (50 percent kill): 1,870 mg/kg N/R UCDS** 11/15/1971
oral
rabbit 		lethal dose (50 percent kill): 1,420 mg/kg N/R NTIS** OTS0535380
skin
rat 		lethal dose (50 percent kill): 1,390 mg/kg N/R NTIS** OTS0526403
skin
rabbit 		lethal dose (50 percent kill): 1,500 µL/kg N/R UCDS** 11/15/1971


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
guinea pig 		lowest published toxic concentration: 500 ppm/8 hour/6 week- intermittent Lung, 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/8 hour/6 week- intermittent Liver: 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: 2,800 mg/m3/8 hour/6 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field VCVGK* -,459,1994
inhalation
guinea pig 		lowest published toxic concentration: 280 mg/m3/8 hour/6 week- intermittent Kidney, Ureter, and Bladder: Other changes VCVGK* -,459,1994
inhalation
human 		lowest published toxic concentration: 5 ppm/30 day- intermittent Behavioral: Somnolence (general depressed activity) VCVGK* -,460,1994
inhalation
rat 		lowest published toxic concentration: 500 ppm/8 hour/6 week- intermittent Lung, 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/8 hour/6 week- intermittent Eye: 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/m3/6 hour/4 week- intermittent Liver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTIS** OTS0535380
inhalation
rat 		lowest published toxic concentration: 2,800 mg/m3/8 hour/6 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field VCVGK* -,459,1994
inhalation
rat 		lowest published toxic concentration: 280 mg/m3/8 hour/6 week- intermittent Kidney, Ureter, and Bladder: Other changes VCVGK* -,459,1994
oral
mouse 		lowest published toxic dose: 24 gm/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-291,1986
oral
mouse 		lowest published toxic dose: 65 gm/kg/13 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-291,1986
oral
rat 		lowest published toxic dose: 24 gm/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-291,1986
oral
rat 		lowest published toxic dose: 65 gm/kg/13 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-291,1986


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Confirmed Animal Carcinogen with Unknown DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value ceiling concentration 5 ppm DTLVS* TLV/BEI,2003
TOXICOLOGY REVIEW
MUREAV 543,201,2003


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD - air time-weighted average 25 ppm (140 mg/m3) DTLVS* 3,140,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) 8 hour time-weighted average 25 ppm (140 mg/m3) CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) 8 hour time-weighted average 25 ppm (140 mg/m3) CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) 8 hour time-weighted average 25 ppm (140 mg/m3) CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) 8 hour time-weighted average 25 ppm (140 mg/m3) CFRGBR 41,50-204.50,1994
Occupational Exposure Limit - AUSTRALIA time-weighted average 5 ppm (25 mg/m3), JAN1993
Occupational Exposure Limit - AUSTRIA MAK 5 ppm (28 mg/m3), JAN1999
Occupational Exposure Limit - BELGIUM short term exposure limit 5 ppm (28 mg/m3), JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 5 ppm (25 mg/m3), JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 5 ppm (28 mg/m3), short term exposure limit 10 ppm (56 mg/m3), JAN1999
Occupational Exposure Limit - FRANCE VLE 5 ppm (25 mg/m3), JAN1999
Occupational Exposure Limit - GERMANY MAK 5 ppm (28 mg/m3), JAN1999
Occupational Exposure Limit - THE NETHERLANDS MAC- continuous 25 mg/m3, 2003
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 25 ppm (140 mg/m3), JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 5 mg/m3, MAC( continuous) 25 mg/m3, JAN1999
Occupational Exposure Limit - RUSSIA short term exposure limit 1 mg/m3, JAN1993
Occupational Exposure Limit - SWEDEN KTV 5 ppm (30 mg/m3), JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 5 ppm (28 mg/m3), JAN1999
Occupational Exposure Limit - TURKEY time-weighted average 25 ppm (149 mg/m3), JAN1993
Occupational Exposure Limit - UNITED KINGDOM short term exposure limit 5 ppm (29 mg/m3), SEP2000
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

ceiling concentration 5 ppm
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
ceiling concentration 5 ppm


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO ISOPHORONE-air 10 hour time-weighted average 4 ppm NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 40910;
Number of Industries 44;
Total Number of Facilities 2,934;
Number of Occupations 40;
Total Number of Employees Exposed 26,825
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 40910;
Number of Industries 43;
Total Number of Facilities 3,593;
Number of Occupations 47;
Total Number of Employees Exposed 47,097;
Total Number of Female Employees Exposed 10,353


STATUS IN FEDERAL AGENCIES:

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


REFERENCES:

CODEN
REFERENCE
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936-
JETOAS Journal Europeen de Toxicologie. (Paris, France) V.1-6, 1968-72. For publisher information, see TOERD9.
JIHTAB Journal of Industrial Hygiene and Toxicology. (Cambridge, MA) V.18-31, 1936-49. For publisher information, see AEHLAU.
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-
UCDS** Union Carbide Data Sheet. (Union Carbide Corp., 39 Old Ridgebury Rd., Danbury, CT 06817)
VCVGK* "Vrednie chemichescie veshestva, galogen I kislorod sodergashie organicheskie soedinenia". (Hazardous substances. Galogen and oxygen containing substances), Bandman A.L. et al., Chimia, 1994.

Used as a solvent and emulsifier

RTECS Compound Description:
   Tumorigen
   Mutagen
   Reproductive Effector
   Human Data
   Hormone
   Primary Irritant

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