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Registry of Toxic Effects of Chemical Substances (RTECS)

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

RTECS #

GW6360000

CAS #

5989-27-5; 7705-13-7; 95327-98-3

Updated

July 2013

Molecular Weight

136.26

Molecular Formula

C10H16

Synonyms

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

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
skin /rabbit 10%/24H mildDRDED* 6,229,1990
skin /rat 100%/1HTOXID9 72,379,2003

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
DNA Damageliver/human1 mmol/l/48HMUREAV 696,21,2010
morphological transformfibroblast/mouse28 mg/L/10DMUREAV 702,100,2010
morphological transformfibroblast/mouse0.005 pph/21D (-enzymatic activation step)EMMUEG 37,231,2001

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
oral/rat 20083 mg/kg (9-15D 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/mouse 3546 mg/kg (7-12D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Effects on newborn: Physical
OYYAA2 13,863,1977
oral/mouse 14178 mg/kg (7-12D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)OYYAA2 13,863,1977
oral/rabbit 3250 mg/kg (6-18D pregnant)Reproductive: Effects on newborn: PhysicalOYYAA2 13,885,1977
oral/rat 20083 mg/kg (9-15D pregnant)Reproductive: Other effects on female

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
HPV304 -,-,2002
oral/rabbit 6500 mg/kg (6-18D pregnant)Reproductive: Other effects on femaleHPV304 -,-,2002
oral/mouse 14178 mg/kg (7-12D pregnant)Reproductive: Other effects on female

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
HPV304 -,-,2002

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 67 gm/kg/39W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Gastrointestinal: Tumors
JNCIAM 35,771,1965
oral/rat lowest published toxic dose: 38625 mg/kg/103W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors
NTIS** PB90-231416/AS
oral/rat lowest published toxic dose: 77250 mg/kg/103W- intermittentTumorigenic: Neoplastic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Tumorigenic: Increased incidence of tumors in susceptible strains
HPV304 -,-,2002
oral/rat lowest published toxic dose: 38625 mg/kg/2Y- continuousTumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors

Reproductive: Tumorigenic effects: Testicular tumors
NTPTR* NTP-TR-347,1990

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, colon tumor Inhibitor Concentration Low: 1523 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/Human, kidney tumor Inhibitor Concentration Low: >1836 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/Human, leukemia cells Inhibitor Concentration Low: 560 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/Human, lung tumor Inhibitor Concentration Low: 794 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/Human, melanoma Inhibitor Concentration Low: 1499 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/jrdInhibitor Concentration Low: 314 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/jtfInhibitor Concentration Low: 445 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
In Vitro/jtiInhibitor Concentration Low: 268 µmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisFCTOD7 49,1610,2011
inhalation/mouse lowest published toxic concentration: 570000 µg/m3/1MLung, Thorax, or Respiration: Respiratory depressionHPV304 -,-,2002
intraduodenal/mouse lowest published lethal dose: 1 gm/kgBehavioral: 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/kgBehavioral: 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): 3600 mg/kgBehavioral: 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/kgBehavioral: 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): 5600 mg/kgBehavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair
OYYAA2 9,387,1975
oral/mouse lethal dose (50 percent kill): 5600 mg/kgHPV304 -,-,2002
oral/rat lethal dose (50 percent kill): 4400 mg/kgBehavioral: 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): 4400 mg/kgHPV304 -,-,2002
skin/mammal (species unspecified) lethal dose (50 percent kill): >5 gm/kgFCTXAV 12,703,1974
skin/rabbit lethal dose (50 percent kill): >5000 mg/kgHPV304 -,-,2002
subcutaneous/mouse lethal dose (50 percent kill): 3170 mg/kgPeripheral Nerve and Sensation: Spastic paralysis with/without sensory changeSIZSAR 3,73,1952
subcutaneous/rat lowest published lethal dose: 30200 mg/kgBehavioral: Excitement

Lung, Thorax, or Respiration: Respiratory depression

Skin and Appendages: Other: Hair
OYYAA2 9,387,1975

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse lowest published toxic dose: 68.1 mg/kg/5D- intermittentBlood: Changes in bone marrow not included in above

Blood: Changes in leukocyte (WBC) count
BPBLEO 31,656,2008
oral/Dog lowest published toxic dose: 180 gm/kg/26W- intermittentKidney, Ureter, and Bladder: Changes in bladder weightFCTOD7 28,669,1990
oral/mouse lowest published toxic dose: 39600 mg/kg/16D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-347,1990
oral/mouse lowest published toxic dose: 32500 mg/kg/13W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-347,1990
oral/mouse lowest published toxic dose: 9900 mg/kg/3D- continuousRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldHPV304 -,,2002
oral/mouse lowest published toxic dose: 45 gm/kg/180D- intermittentGastrointestinal: Other changes

Kidney, Ureter, and Bladder: Interstitial nephritis

Related to Chronic Data: Changes in prostate weight
EVHPAZ 108,61,2000
oral/mouse lowest published toxic dose: 65000 mg/kg/13W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainHPV304 -,,2002
oral/mouse lowest published toxic dose: 130000 mg/kg/13W- continuousBehavioral: Somnolence (general depressed activity)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
HPV304 -,,2002
oral/mouse lowest published toxic dose: 515000 mg/kg/103W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainHPV304 -,,2002
oral/rat lowest published toxic dose: 1500 mg/kg/27D- continuousLiver: Changes in liver weight

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

Kidney, Ureter, and Bladder: Changes in kidney weight
HPV304 -,,2002
oral/rat lowest published toxic dose: 1950 mg/kg/13W- continuousKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Kidney, Ureter, and Bladder: Changes in kidney weight
HPV304 -,,2002
oral/rat lowest published toxic dose: 2925 mg/kg/13W- continuousLiver: Changes in liver weight

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

Kidney, Ureter, and Bladder: Changes in kidney weight
HPV304 -,,2002
oral/rat lowest published toxic dose: 83100 mg/kg/30D- continuousKidney, Ureter, and Bladder: Changes primarily in glomeruliHPV304 -,,2002
oral/rat lowest published toxic dose: 375 mg/kg/7D- continuousKidney, Ureter, and Bladder: Other changesEVHPAZ 110,363,2002
oral/rat lowest published toxic dose: 1500 mg/kg/28D- continuousKidney, 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: 9750 mg/kg/90D- continuousLiver: 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: 12000 mg/kg/28D- continuousLiver: 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: 3000 mg/kg/28D- intermittentKidney, Ureter, and Bladder: Other changesTXCYAC 180,233,2002
oral/rat lowest published toxic dose: 6600 mg/kg/3D- continuousRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldHPV304 -,,2002
oral/rat lowest published toxic dose: 39000 mg/kg/13W- continuousKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
HPV304 -,,2002
oral/rat lowest published toxic dose: 12000 mg/kg/1W- continuousKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
HPV304 -,,2002
oral/rat lowest published toxic dose: 21000 mg/kg/25W- continuousGastrointestinal: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent
CALEDQ 137,131,1999
oral/rat lowest published toxic dose: 11550 mg/kg/7D- intermittentKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)TOLED5 104,83,1999
oral/rat lowest published toxic dose: 39600 mg/kg/16D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTPTR* NTP-TR-347,1990
oral/rat lowest published toxic dose: 840 mg/kg/4W- continuousKidney, Ureter, and Bladder: Other changes in urine composition

Kidney, Ureter, and Bladder: Other changes
FCTOD7 31,125,1993
oral/rat lowest published toxic dose: 4875 mg/kg/91D- intermittentLiver: 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: 1500 mg/kg/5D- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight
FCTOD7 25,345,1987

Reviews

OrganizationStandardReference
International Agency for Research on Cancer (IARC)Cancer Review:Animal Limited EvidenceIMEMDT 56,135,1993
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 73,307,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human No Available DataIMEMDT 56,135,1993
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 73,307,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 73,307,1999
TOXICOLOGY REVIEWCTRRDO 60,1171,1976
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWEMMUEG 39,69,2002
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWTOLED5 180,75,2008
TOXICOLOGY REVIEWTOLED5 180,93,2008
TOXICOLOGY REVIEWMUREAV 590,1,2005
TOXICOLOGY REVIEWMUREAV 682,94,2009
TOXICOLOGY REVIEWMUREAV 653,99,2008
TOXICOLOGY REVIEWMUREAV 723,108,2011
TOXICOLOGY REVIEWFCTOD7 49,2471,2011

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit-FINLANDtime-weighted average 25 ppm (140 mg/m3), short term exposure limit 50 ppm (280 mg/m3), NOV2011
Occupational Exposure Limit-GERMANYMAK 5 ppm (28 mg/m3), skin, sen, 2011
Occupational Exposure Limit-SWITZERLANDMAK-week 20 ppm (110 mg/m3), KZG-week 40 ppm (220 mg/m3), sen, JAN2011

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code X9088; Number of Industries 87; Total Number of Facilities 8310; Number of Occupations 65; Total Number of Employees Exposed 138309; Total Number of Female Employees Exposed 35634

Status in Federal Agencies

OrganizationReference
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);clear evidence:rat
NCI Carcinogenesis Studies (gavage);no evidence:mouse
NIOSH Analytical Method, 1996: Volatile organic compound, 2549
On EPA IRIS database
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