The Registry of Toxic Effects of Chemical Substances

Cyclohexene, 1 - methyl - 4 - (1 - methylethenyl) - , (R) -

RTECS #: GW6360000

CAS #: 5989-27-5

UPDATE: November 2004 MW: 136.26 MF: C10H16


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. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

  1. (+) - 4 - Isopropenyl - 1 - methylcyclohexene
  2. (+) - R - Limonene
  3. (R) - 1 - Methyl - 4 - (1 - methylethenyl) cyclohexene
  4. 1 - Methyl - 4 - (1 - methylethenyl) cyclohexene
  5. Cajeputene
  6. Carvene
  7. Cinene
  8. Cyclohexene, 4 - isopropenyl - 1 - methyl -
  1. D - (+) - Limonene
  2. NCI - C55572
  3. Refchole
  4. d - Limonene
  5. d - Limoneno (Spanish)
  6. d - p - Mentha - 1,8 - diene
  7. p - Mentha - 1,8 - diene
  8. p - Mentha - 1,8 - diene, (R) - (+) -


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
skin
rat 		1,00%/1 hour TOXID9 72,379,2003
skin
rabbit 		10%/24 hour mild DRDED* 6,229,1990


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis oral
mouse 		0.5 ppb EMMUEG 39,69,2002
cytogenetic analysis oral
rat 		0.5 ppb EMMUEG 39,69,2002
morphological transform mouse fibroblast 0.5 pph/21 day (-enzymatic activation step) EMMUEG 37,231,2001
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
oral
mouse 		lowest published toxic dose: 3,546 mg/kg (7-12 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Effects on newborn: Physical 		OYYAA2 13,863,1977
oral
mouse 		lowest published toxic dose: 14,178 mg/kg (7-12 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) OYYAA2 13,863,1977
oral
rat 		lowest published toxic dose: 20,083 mg/kg (9-15 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Physical 		OYYAA2 10,179,1975
oral
rabbit 		lowest published toxic dose: 3,250 mg/kg (6-18 day pregnant) Reproductive: Effects on newborn: Physical OYYAA2 13,885,1977


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 67 gm/kg/39 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Gastrointestinal: Tumors 		JNCIAM 35,771,1965
oral
rat 		lowest published toxic dose: 38,625 mg/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Reproductive: Tumorigenic effects: Testicular tumors 		NTPTR* NTP-TR-347,1990
oral
rat 		lowest published toxic dose: 38,625 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors 		NTIS** PB90-231416/AS


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraduodenal
mouse 		lowest published lethal dose: 1 gm/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Somnolence (general depressed activity)

Nutritional and Gross Metabolic: Body temperature decrease 		OYYAA2 8,1439,1974
intraperitoneal
mouse 		lethal dose (50 percent kill): 600 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Somnolence (general depressed activity)

Nutritional and Gross Metabolic: Body temperature decrease 		OYYAA2 8,1439,1974
intraperitoneal
rat 		lethal dose (50 percent kill): 3,600 mg/kg Behavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair 		OYYAA2 9,387,1975
intravenous
rat 		lethal dose (50 percent kill): 110 mg/kg Behavioral: Convulsions or effect on seizure threshold

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair 		OYYAA2 9,387,1975
oral
mouse 		lethal dose (50 percent kill): 5,600 mg/kg Behavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair 		OYYAA2 9,387,1975
oral
rat 		lethal dose (50 percent kill): 4,400 mg/kg Behavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair 		OYYAA2 9,387,1975
subcutaneous
mouse 		lethal dose (50 percent kill): 3,170 mg/kg Peripheral Nerve and Sensation: Spastic paralysis with/without sensory change SIZSAR 3,73,1952
subcutaneous
rat 		lowest published lethal dose: 30,200 mg/kg Behavioral: Excitement

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair 		OYYAA2 9,387,1975
skin
mammal (species unspecified) 		lethal dose (50 percent kill): >5 gm/kg N/R FCTXAV 12,703,1974
skin
rabbit 		lethal dose (50 percent kill): >5 gm/kg N/R FCTXAV 13,825,1975


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
dog 		lowest published toxic dose: 180 gm/kg/26 week- intermittent Kidney, Ureter, and Bladder: Changes in bladder weight FCTOD7 28,669,1990
oral
mouse 		lowest published toxic dose: 39,600 mg/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-347,1990
oral
mouse 		lowest published toxic dose: 32,500 mg/kg/13 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-347,1990
oral
mouse 		lowest published toxic dose: 45 gm/kg/180 day- intermittent Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Interstitial nephritis

Related to Chronic Data: Changes in prostate weight 		EVHPAZ 108,61,2000
oral
rat 		lowest published toxic dose: 11,550 mg/kg/7 day- intermittent Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) TOLED5 104,83,1999
oral
rat 		lowest published toxic dose: 39,600 mg/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-347,1990
oral
rat 		lowest published toxic dose: 840 mg/kg/4 week- continuous Kidney, Ureter, and Bladder: Other changes in urine composition

Kidney, Ureter, and Bladder: Other changes 		FCTOD7 31,125,1993
oral
rat 		lowest published toxic dose: 4,875 mg/kg/91 day- intermittent Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight 		FCTOD7 27,639,1989
oral
rat 		lowest published toxic dose: 1,500 mg/kg/5 day- intermittent Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight 		FCTOD7 25,345,1987
oral
rat 		lowest published toxic dose: 21,000 mg/kg/25 week- continuous Gastrointestinal: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent 		CALEDQ 137,131,1999
oral
rat 		lowest published toxic dose: 375 mg/kg/7 day- continuous Kidney, Ureter, and Bladder: Other changes EVHPAZ 110,363,2002
oral
rat 		lowest published toxic dose: 1,500 mg/kg/28 day- continuous Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Kidney, Ureter, and Bladder: Other changes 		EVHPAZ 110,363,2002
oral
rat 		lowest published toxic dose: 9,750 mg/kg/90 day- continuous Liver: Other changes

Kidney, Ureter, and Bladder: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation) 		EVHPAZ 110,363,2002
oral
rat 		lowest published toxic dose: 12,000 mg/kg/28 day- continuous Liver: Other changes

Liver: Changes in liver weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation) 		EVHPAZ 110,363,2002
oral
rat 		lowest published toxic dose: 3,000 mg/kg/28 day- intermittent Kidney, Ureter, and Bladder: Other changes TXCYAC 180,233,2002


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Animal Limited Evidence IMEMDT 56,135,1993
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 73,307,1999
International Agency for Research on Cancer (IARC) Cancer Review Human No Available Data IMEMDT 56,135,1993
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 73,307,1999
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 73,307,1999
TOXICOLOGY REVIEW
CTRRDO 60,1171,1976
TOXICOLOGY REVIEW
MUREAV 543,201,2003


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X9088;
Number of Industries 87;
Total Number of Facilities 8,310;
Number of Occupations 65;
Total Number of Employees Exposed 138,309;
Total Number of Female Employees Exposed 35,634


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a food and feed additive, flavor and packaging material
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, 1996: Volatile organic compound, 2549
NCI Carcinogenesis Studies (gavage);clear evidence:rat
NCI Carcinogenesis Studies (gavage);no evidence:mouse


REFERENCES:

CODEN
REFERENCE
CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975-
CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ.
DRDED* Drug Design and Delivery (Chur Harwood Academic) V.1- 1986-
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
EVHPAZ EHP, Environmental Health Perspectives. (U.S. Government Printing Office, Supt of Documents, Washington, DC 20402) No.1- 1972-
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982-
FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7.
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8.
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
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-
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967-
SIZSAR Sapporo Igaku Zasshi. Sapporo Medical Journal. (Sapporo Igaku Daigaku, Nishi-17-chome, Minami-1-jo, Chuo-ku, Sapporo 060, Japan) V.3- 1952-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-

Used as a food and feed additive, flavor and packaging material

RTECS Compound Description:
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Natural Product
   Primary Irritant

ALT CAS #: 7705-13-7
ALT CAS #: 95327-98-3
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