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1. (+)-(r)-4-isopropenyl-1-methylcyclohexene
2. (+)-limonene
3. (-)-limonene
4. (4r)-1-methyl-4-(1-methylethenyl)cyclohexene
5. (4s)-1-methyl-4-isopropenylcyclohex-1-ene
6. (d)-limonene
7. (r)-(+)-limonene
8. (r)-4-isopropenyl-1-methylcyclohexene
9. 1-methyl-4-(1-methylethenyl)cyclohexene
10. 4 Mentha 1,8 Diene
11. 4-mentha-1,8-diene
12. Aisa 5203-l (+)limonene
13. Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (4r)-
14. D Limonene
15. Dipentene
16. Limonene
17. Limonene, (+)-
18. Limonene, (+-)-
19. Limonene, (+-)-isomer
20. Limonene, (r)-isomer
21. Limonene, (s)-isomer
1. (r)-(+)-limonene
2. (+)-limonene
3. 5989-27-5
4. (d)-limonene
5. (+)-(4r)-limonene
6. (+)-carvene
7. (4r)-limonene
8. D-(+)-limonene
9. (r)-limonene
10. Limonene, D-
11. (+)-dipentene
12. (r)-p-mentha-1,8-diene
13. Citrene
14. (+)-p-mentha-1,8-diene
15. D-limonen
16. Limonene, (+)-
17. (r)-4-isopropenyl-1-methyl-1-cyclohexene
18. Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (4r)-
19. (+)-r-limonene
20. Fema No. 2633
21. D-p-mentha-1,8-diene
22. (+)-4-isopropenyl-1-methylcyclohexene
23. R-(+)-limonene
24. (4r)-4-isopropenyl-1-methylcyclohexene
25. (r)-(+)-p-mentha-1,8-diene
26. (r)-1-methyl-4-(1-methylethenyl)cyclohexene
27. (+)-(r)-limonene
28. D-limonene [jan]
29. (r)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
30. (4r)-1-methyl-4-prop-1-en-2-ylcyclohexene
31. (4r)-1-methyl-4-(1-methylethenyl)cyclohexene
32. Mfcd00062991
33. Gfd7c86q1w
34. (4r)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
35. 4betah-p-mentha-1,8-diene
36. Chebi:15382
37. (+) Limonene
38. Nsc-757069
39. Carvene
40. Glidesafe
41. Glidsafe
42. Kautschiin
43. Refchole
44. (4r)-1-methyl-4-isopropenylcyclohex-1-ene
45. Orange X
46. Biogenic Se 374
47. (+)-alpha-limonene
48. D-limonene (natural)
49. D-limoneno [spanish]
50. D Limonene
51. D-limoneno
52. Hemo-sol
53. (4r)-(+)-limonene
54. Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (r)-
55. (4r)-4-isopropenyl-1-methyl-cyclohexene
56. Citrus Stripper Oil
57. Ccris 671
58. Ec 7
59. Hsdb 4186
60. D-1,8-p-menthadiene
61. Nci-c55572
62. Einecs 227-813-5
63. Unii-gfd7c86q1w
64. P-mentha-1,8-diene, (r)-(+)-
65. Sulfate Turpentine, Distilled
66. (+)-1,8-para-menthadiene
67. Dextro-limonene
68. Ai3-15191
69. 1-methyl-4-(1-methylethenyl)cyclohexene, (r)-
70. Einecs 266-034-5
71. (r)-4-isopropenyl-1-methylcyclohexene
72. Dipentene No. 122
73. (+)-(r)-4-isopropenyl-1-methylcyclohexene
74. D-limonene Reagent Grade
75. Dsstox_cid_778
76. D-limonene [iarc]
77. Ec 227-813-5
78. Dsstox_rid_75785
79. Orange Oil Distillate
80. (+)-limonene, Stabilized With 0.03% Tocopherol
81. Dsstox_gsid_20778
82. (d)-limonene [hsdb]
83. (+)-limonene [fcc]
84. Chembl449062
85. Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (theta)-
86. Dtxsid1020778
87. (r)-(+)-limonene, 95%
88. (r)-(+)-limonene, 97%
89. Zinc967513
90. Cs-m3273
91. (r)-(+)-limonene, >=93%
92. Tox21_200400
93. Limonene, (+)- [who-dd]
94. Akos015899935
95. Ccg-266134
96. Db08921
97. Lmpr0102090013
98. Nsc 757069
99. (r)-(+)-limonene, Analytical Standard
100. Ncgc00248591-01
101. Ncgc00248591-02
102. Ncgc00257954-01
103. Bs-22387
104. Cas-5989-27-5
105. (r)-(+)-4-isopropenyl-1-methylcyclohexene
106. L0047
107. L0105
108. (r)-limonene 2000 Microg/ml In Acetonitrile
109. C06099
110. D91245
111. (4r)-1-methyl-4-(prop-1-en-2-yl)cyclohexene
112. J-502148
113. W-105295
114. Q27888324
115. (r)-(+)-limonene, Primary Pharmaceutical Reference Standard
116. (r)-(+)-limonene, Purum, >=96.0% (sum Of Enantiomers, Gc)
117. (r)-(+)-limonene, Technical, ~90% (sum Of Enantiomers, Gc)
118. 68647-72-3
| Molecular Weight | 136.23 g/mol |
|---|---|
| Molecular Formula | C10H16 |
| XLogP3 | 3.4 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 0 |
| Rotatable Bond Count | 1 |
| Exact Mass | 136.125200510 g/mol |
| Monoisotopic Mass | 136.125200510 g/mol |
| Topological Polar Surface Area | 0 Ų |
| Heavy Atom Count | 10 |
| Formal Charge | 0 |
| Complexity | 163 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.
PMID:18072821 Sun J; Altern Med Rev 12 (3): 259-64 (2007)
d-Limonene infused directly into the bile system of human volunteers to dissolve gallstones caused pain in the upper abdomen, nausea, vomiting, and diarrhea, as well as increases in serum aminotransferases and alkaline phosphatase. The oral administration of 20 g d-limonene to volunteers resulted in diarrhea, painful constrictions, and proteinuria, but no biochemical changes (total protein, bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase) in the liver.
International Programme on Chemical Safety; Concise International Chemical Assessment Documents Number 5: Limonene p.14 (1998). Available from, as of February 3, 2006: https://www.inchem.org/pages/cicads.html
d-Limonene was a safe and effective gallstone solubilizer in animals and humans; side effects in humans were reported to be pain and tenderness radiating from the upper abdomen to the anterior chest, nausea and vomiting, and diarrhea.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additives Series 30: Limonene (1993). Available from, as of February 3, 2006: https://www.inchem.org/documents/jecfa/jecmono/v30je05.htm
The fate of dermally applied [(14)C]d-limonene was evaluated in humans and Long-Evans rats. In rats, 5 mg/kg body weight of [(14)C]d-limonene applied dermally to the shaved back under occlusion, resulted in the absorption of approximately 12% of the dose. The absorbed d-limonene was completely metabolized and excreted rapidly, primarily from the urine (80%) with a small fraction (20%) excreted in the feces. There was no long-term retention of the test material in body tissues. In humans, following dermal application of 12 mg of [(14)C]d-limonene in ethanol (1 mL) to the back under nonocclusive conditions (for 1 h after application to allow the material to dry, thereafter under occlusion), only 0.16% of the dose was absorbed and the radioactivity was recovered from the urine. Radioactivity in human feces was below the limit of detection. These results indicate that under conditions of simulated use of fragrances and cosmetics, d-limonene has a low potential for dermal absorption and tissue accumulation, and the d-limonene that is absorbed is rapidly excreted in the urine. Based upon these findings and the knowledge that d-limonene possesses a low-systemic toxicity profile, it is reasonable to conclude that dermal exposure to d-limonene from fragrance and cosmetic applications is highly unlikely to result in any clinically significant human toxicity.
PMID:23493903 Api AM et al; Int J Toxicol 32 (2): 130-5 (2013)
After oral administration of (14)C-labeled d-limonene to animals and humans, 75-95 and <10% of the radioactivity was excreted in the urine and feces respectively within 2-3 days.
PMID:969565 Kodama R et al; Xenobiotica 6 (6): 377 (1976)
The toxicokinetics of d-limonene were studied in human volunteers exposed by inhalation (2 hr, work load 50 W) in an exposure chamber on three different occasions. The exposure concentrations were approximately 10, 225, and 450 mg/cu m d-limonene. The relative pulmonary uptake was high, approximately 70% of the amount supplied. The blood clearance of d-limonene observed in this study, 1.1 L/kg/hr, indicates that d-limonene is metabolized readily. About 1% of the total uptake was eliminated unchanged in the expired air after the end of exposure, while approximately 0.003% was eliminated in the urine. A long half-time in blood was observed in the slow elimination phase, which indicates accumulation in adipose tissues.
PMID:8421324 Falk-Filipsson A et al; J Toxicol Environ Health 38 (1): 77-88 (1993)
Orally administered d-limonene is rapidly and almost completely taken up from the gastrointestinal tract in humans as well as in animals. Infusion of labelled d-limonene into the common bile duct of volunteers revealed that the chemical was very poorly absorbed from the biliary system.
International Programme on Chemical Safety; Concise International Chemical Assessment Documents Number 5: Limonene p.11 (1998). Available from, as of February 3, 2006: https://www.inchem.org/pages/cicads.html
For more Absorption, Distribution and Excretion (Complete) data for (D)-LIMONENE (10 total), please visit the HSDB record page.
Incubation of d-limonene with rat liver microsomes produced d-limonene-1,2-diol and d-limonene-8,9-diol as metabolites and d-limonene-1,2-epoxide and d-limonene-8,9-epoxide were identified as intermediates.
PMID:6992785 Watabe T et al; Biochem Pharmacol 29 (7): 1068 (1980)
After oral administration of (14)C-labeled d-limonene, 5 new metabolites were isolated from dog and rat urine: 2-hydroxy-p-menth-8-en-7-oic acid, perillylglycine, perillyl-beta-d-glucopyranosiduronic acid, p-mentha-1,8-dien-6-ol, and probably p-menth-1-ene-6,8,9-triol.
PMID:969565 Kodama R et al; Xenobiotica 6 (6): 377 (1976)
The major metabolite of d-limonene in urine was perillic acid 8,9-diol in rats and rabbits, perillyl-beta-d-glucopyranosiduronic acid in hamsters, p-menth-1-ene-8,9-diol in dogs, and 8-hydroxy-p-menth-1-ene-9-yl-beta-d-glucopyranosiduronic acid in guinea pigs and man.
PMID:969565 Kodama R et al; Xenobiotica 6 (6): 377 (1976)
Adult male and female Sprague Dawley rats were given single oral doses of 0, 0.1, 0.3, 1, or 3 mmol d-limonene/kg (0, 14, 41, 136, or 409 mg/kg) in corn oil. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a mol wt of approximately 20000. Using reverse phase HPLC, d-limonene was shown to be associated with alpha-2u-globulin which was identified by amino acid sequencing. The major metabolite associated with alpha-2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha-2u-globulin fraction.
PMID:2472019 Lehman-McKeeman LD et al; Toxicol Appl Pharmacol 99 (2): 250-9 (1989)
For more Metabolism/Metabolites (Complete) data for (D)-LIMONENE (8 total), please visit the HSDB record page.
(+)-limonene has known human metabolites that include Carveol and Limonen-10-ol.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
75-95% excreted within 2-3 days; [AIHA]
AIHA - Workplace Environmental Exposure Level Guides, Complete Set and Update Set. Fairfax, VA: AIHA, 2008.
Following the inhalation exposure of volunteers to d-limonene at 450 mg/cu m for 2 hours, three phases of elimination were observed in the blood, with half-lives of about 3, 33, and 750 minutes, respectively. ...
International Programme on Chemical Safety; Concise International Chemical Assessment Documents Number 5: Limonene p.11 (1998). Available from, as of February 3, 2006: https://www.inchem.org/pages/cicads.html
The sequence of events /in the spontaneously occurring nephropathy in mature male rats/ appears to be that: (1) protein accumulates in the lysosomes in the cytoplasm of epithelial cells of the P2 segment of the proximal convoluted tubules in the kidney cortex; (2) the accumulated material becomes so abundant that it crystallizes, forming the microscopically visible hyaline droplets; (3) the continued build-up of material eventually leads to the death of epithelial cells with a concomitant thinning of the epithelial layer (although some regeneration is usually seen); and (4) the dead cell debris becomes lodged in the outer strip of the outer medulla where the tubules narrow, forming granular casts and causing tubule dilation with pressure necrosis of the cells of the tubule walls. There is also an increase in the relative weight of the kidneys accompanying this phenomenon. ...Agents ...that appear to exacerbate this hyaline droplet formation and its consequences in mature male rats /include/ ...d-limonene.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additives Series 30: Limonene (1993). Available from, as of February 3, 2006: https://www.inchem.org/documents/jecfa/jecmono/v30je05.htm
The mechanism by which d-limonene causes alpha2u-globulin accumulation in the male rat kidney has been elucidated. The prerequisite step in the development of the nephropathy is the binding to alpha2u-globulin of an agent, which in the case of d-limonene is the 1,2-epoxide. This binding is specific for alpha2u-globulin and reversible, with a binding affinity (Kd) of approximately 5.6X10-7 mol/L. Binding of this ligand to alpha2u-globulin reduces the rate of its lysosomal degradation relative to that of native protein, thereby causing it to accumulate. Lysosomal cathepsin activity towards other protein substrates is not altered. Whereas accumulation of alpha2u-globulin can be observed after a single oral dose of d-limonene, continued treatment results in additional histological changes in the kidney. Phagolysosomes become enlarged, engorged with protein and show polyangular crystalloid inclusions. After 3-4 weeks of dosing, progressive renal injury, characterized by single-cell degeneration and necrosis in the P2 segment of the renal proximal tubule, is noted. Dead cells are sloughed into the lumen of the nephron, contributing to the development of granular casts at the cortico-medullary junction. Renal functional perturbations, including reduced uptake of organic anions, cations and amino acids and mild proteinuria resulting from a large increase in the amount of alpha2u-globulin excreted in urine, are observed. These functional changes occur only in male rats and only at doses that exacerbate the protein droplet formation. In response to the cell death and functional changes, there is a compensatory increase in cell proliferation in the kidney, most notably in the P2 segment of the proximal tubules, the site of protein accumulation. With continued treatment, the cell proliferation persists, but it does not restore renal function. The increase in cell proliferation is linked to the development of renal tubular tumors. alpha2u-Globulin nephropathy and renal-cell proliferation occur at doses consistent with those that produce renal tubular tumors.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V73 319 (1999)
In the male rat, the production of renal tumors by chemicals inducing alpha2u-globulin accumulation (CIGA) is preceded by the renal lesions ascribed to alpha2u-globulin-associated nephropathy. The involvement of hyaline droplet accumulation in the early nephrotoxicity associated with CIGA is a major difference from the sequence seen for classical carcinogens. The pathologic changes that precede the proliferative sequence for classical renal carcinogens also include a form of early nephrotoxicity, but no apparent hyaline droplet accumulation. Investigations performed in multiple laboratories ... have demonstrated a consistent association between hyaline droplets containing alpha2u-globulin and production of certain lesions in the male rat kidney. These renal lesions are not found in mice, female rats, or other laboratory species tested. The histopathological sequence in the male rat consists of the following: (1) an excessive accumulation of hyaline droplets containing alpha2u-globulin in renal proximal tubules; (2) subsequent cytotoxicity and single-cell necrosis of the tubule epithelium; (3) sustained regenerative tubule cell proliferation, providing exposure continues; (4) development of intralumenal granular casts from sloughed cell debris associated with tubule dilation, and papillary mineralization; (5) foci of tubule hyperplasia in the convoluted proximal tubules; and finally, (6) renal tubule tumors. Biochemical studies with model compounds show that CIGA or their metabolites bind specifically. but reversibly, to male rat alpha2u-globulin. The resulting alpha2u-globulin-CIGA complex appears to be more resistant to hydrolytic degradation by lysosomal enzyemes than native, unbound alpha2u-globulin. Inhibition of the catabolism of alpha2u-globulin, a protein only slowly hydrolyzed by renal lysosomal enzymes under normal physiological conditions, provides a plausible basis for the initial stage of protein overload in the nephropathy sequence.
EPA Risk Assessment Forum; Alpha2u-Globulin: Association with Chemically Induced Renal TOxicity and Neoplasia in the Male Rat. US Environmenal Protection Agency (1991) EPA/625/3-91/019F
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