Absorption, Distribution and Excretion
In humans, this study investigated the pharmacokinetics of D-carvone in 15 male volunteers. After a 10-hour fast, participants took five immediate-release capsules containing 20 mg of carvone seed oil. Plasma carvone concentrations were determined using gas chromatography-mass spectrometry (GC/MS), with a limit of quantitation of 0.5 ng/mL. The determined pharmacokinetic parameters included: area under the plasma concentration-time curve (AUC) of 28.9 ± 20.0 ng·mL/hr, peak plasma concentration (Cmax) of 14.8 ± 10.4 ng/mL, time to peak concentration (Tmax) of 1.3 h, and half-life of 2.4 h. The inter-individual coefficients of variation for AUC, Cmax, and t1/2 were 69%, 74%, and 50%, respectively. /D-Carvone/

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Metabolism/Metabolites
As part of a project aimed at screening yeast strains that may serve as sources of natural flavorings, we investigated the bioreduction of (4R)-(-)-carvone and (1R)-(-)-myrtaldehyde by whole cells of unconventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazakhstans yeast, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma, and Wickerhamomyces. Volatile compounds were sampled using headspace solid-phase microextraction (SPME) and analyzed and identified using gas chromatography-mass spectrometry (GC-MS). Yields (expressed as a percentage of bioconversion) varied by strain. The reduction reactions of (4R)-(-)-carvone and (1R)-(-)-myrtaldehyde were both catalyzed by certain olefin reductases (ER) and/or carbonyl reductases (CR) to produce (1R,4R)-dihydrocarvone and (1R)-myrtol, respectively, as the main fragrance products. This paper explores the potential of NCY as a novel whole-cell biocatalyst for the selective bioconversion of electron-deficient olefins to produce industrially valuable fragrances and flavorings. Ketones (e.g., carvone and menthone) are reduced to secondary alcohols and then excreted as glucuronides. The cyclic monoterpene ketone (-)-carvone can be metabolized by the plant pathogenic fungus Absidia glauca. After 4 days of incubation, diol 10-hydroxy-(+)-neodihydrocarvone was generated. The absolute configuration and structure of this crystalline substance were identified using X-ray diffraction and spectroscopic techniques (mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance). The antimicrobial activity of the substrate and metabolites was determined using human pathogenic microorganisms. D-carvone exhibits rapid elimination in humans with a half-life of 2.4 hours; data for L-carvone are currently unavailable. Toxicokinetic data for carvone in animals are also lacking. Evidence from in vivo, in vitro, and computer simulation assessments suggests that the metabolism of carvone may differ between humans and rats, and possibly between male and female rats. Furthermore, its metabolites may not show significant differences in gastrointestinal absorption or in vivo half-life compared to carvone itself. Toxicokinetic data for other monoterpenoids (such as menthol) in rats indicate that their metabolism involves glucuronic acid binding, which occurs in the enterohepatic circulation in rats but not in humans. Given the molecular weight of glucuronidated carvone metabolites, they likely undergo enterohepatic circulation in rats but not in humans, making rats more sensitive to these compounds than humans. /D-Carvone and L-Carvone/
This study collected urine samples from six healthy volunteers (three men and three women) 24 hours before and after oral administration of D-carvone and L-carvone (1 mg/kg body weight) and investigated their in vivo metabolism. The chemical structures of the metabolites were elucidated using mass spectrometry combined with metabolite synthesis and nuclear magnetic resonance analysis. For this purpose, urine samples were treated with sulfatase and glucuronidase, assuming phase I metabolite binding. However, this study did not report quantitative data on the excretion of the bound metabolites. Three side-chain oxidation products were identified as the major unbound metabolites of D- and L-carvone: dihydrocarvate, carvate acid, and urinary terpene alcohol ketone, and 10-hydroxycarvone was hypothesized to be an intermediate metabolic step. However, unlike in other species, 10-hydroxycarvone was not detected in humans, presumably due to its more efficient oxidation to carvonic acid. According to this study, there was no difference in the metabolism of D- and L-carvone. However, although volunteers clearly ingested both carvone enantiomers in independent trials, the results presented only refer to "after carvone ingestion." According to the authors, all metabolites were identical after using either D- or L-carvone. However, the conformation of the metabolites was not determined, and chromatographic analysis was performed only on a non-chiral stationary phase. This experimental setup could not distinguish the stereoselective metabolism of D- and L-carvone. /D-Carvone and L-Carvone/

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Biological Half-Life
D-carvone exhibits rapid elimination toxicokinetics in humans with a half-life of 2.4 hours; data for L-carvone are currently unavailable. /D-Carvone/

Toxicity Summary
Identification and Uses: Carvone is a pale yellow or colorless liquid. Uses of carvone include: insecticides, feed additives, veterinary drugs, flavorings and natural food ingredients, and personal care products. D-carvone and L-carvone are used in a variety of non-food consumer products, including cosmetics and personal care products. Some of these products, such as toothpaste and mouthwash, may result in oral carvone ingestion. It is also used as a natural insect repellent. Human Exposure and Toxicity: L-carvone is considered to have low sensitization potential, but it occasionally causes contact sensitization in users of spearmint toothpaste and chewing gum. L-carvone inhibits the proliferation of MCF 7 and MDA MB 231 cells and suppresses the migration of breast cancer cell lines. L-carvone induces apoptosis, manifested as nucleoid fragmentation and the appearance of apoptotic bodies in DAPI, Annexin V/propidium iodide, and TUNEL staining. L-carvone exposure can arrest MCF 7 cells in the S phase of the cell cycle. Increased comet tail moments in comet assays indicate that L-carvone causes DNA damage, likely due to elevated levels of reactive oxygen species (ROS), detectable by fluorescent probes. Animal studies: Clinical symptoms following acute exposure to L-carvone in mice and rats varied depending on the route of exposure. Acute oral administration resulted in arched backs, lethargy, and occasional body tremors in mice and rats, but no abnormalities were observed upon necropsy. No systemic or skin effects were observed after acute skin exposure, while inhalation of carvone resulted in respiratory effects, hair loss, and limited weight gain. Carvone caused transient inhibition of central nervous system activity in mice. In developmental studies, rats were administered 0, 3, 10, or 30 mg/kg body weight of D-carvone (95%) daily from 10 weeks prior to mating until the end of the experiment. There were no differences between the treatment and control groups in all reproductive performance parameters and sperm morphology and motility assays. F0 generation male rats administered a dose of 30 mg/kg body weight/day showed an increase in relative kidney weight. Histopathological examination of male kidneys in all dose groups showed typical changes of α2u globulin nephropathy. No other histopathological changes were observed, nor were similar changes observed in female rats. In F1 generation male rats, administration of doses of 30 and 90 mg/kg body weight/day resulted in an increase in the mean relative weight of the liver and kidneys. Histopathological examination of male kidneys in all dose groups showed typical changes of α2u globulin nephropathy. No differences were observed in female rats, nor were any other histopathological changes observed. The mutagenicity of carvone was unclear in sister chromatid exchange studies and Chinese hamster ovary cell chromosomal aberration studies. In vivo UDS and micronucleus assays of the liver were negative, and in vitro chromosomal aberration assays were also inconclusive. Therefore, carvone was concluded to be non-genotoxic. Fifty male mice and fifty female mice were administered D-carvone (dissolved in corn oil) by gavage at doses of 0, 375, or 750 mg/kg, respectively, five days a week for 103 weeks. In the past two years of gavage studies, there has been no evidence that D-carvone has carcinogenic activity in male or female mice.

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Interactions
This study aimed to investigate the differences in the promoting effects of R-carvone, S-carvone, and RS-carvone on transdermal drug penetration in vitro. In vitro penetration studies used neonatal rat epidermis, employing a 2% w/v hydroxypropyl methylcellulose (HPMC) gel containing 4% w/v nicorandil (a model drug), with selected concentrations (12% w/v) of R-carvone, S-carvone, or RS-carvone added, with a control group serving as a control. The rat stratum corneum (SC) was treated with excipients (70% v/v ethanol-water solution) or an ethanol solution of 12% w/v R-carvone, S-carvone, or RS-carvone. Compared with the control group, the enhancement ratios (ERs) of R-carvone, S-carvone, and RS-carvone were approximately 37.1, 31.2, and 29.9, respectively, indicating that the carvone enantiomers have an enantioselective permeation-enhancing effect. Furthermore, compared with R-carvone and RS-carvone, S-carvone significantly shortened the lag time required for nicorandil to reach steady-state flux. DSC and FT-IR studies showed that the studied carvone enantiomers differed in their influence on the cellular structure of stratum corneum lipids and proteins, thus exhibiting enantioselective transdermal drug permeation. The study concluded that R-carvone has a higher promoting effect on the transdermal absorption of nicorandil compared with the S-isomer or racemic mixture. The study also investigated the ability of the two natural compounds to inhibit N-nitrosodiethylamine-induced carcinogenesis in A/J female mice. One class of compounds consists of organosulfur compounds found in Allium species (such as garlic, onion, leek, and scallion), while the other class comprises two monoterpenoids: D-limonene and D-carvone. Experimental results showed that D-limonene and D-carvone reduced forestomach tumor formation by more than 60% and lung adenoma formation by approximately 35%. These findings indicate that an increasing number of natural compounds possess the ability to inhibit the carcinogenic effects of nitrosamines. Carvone is a monoterpenoid found in the essential oils of Mentha spicata and Carum carvi, and has been shown to have anticonvulsant effects (possibly through blocking voltage-gated sodium channels) and anxiolytic-like effects. Considering that some anticonvulsant drugs that block voltage-gated sodium channels (such as sodium valproate and carbamazepine) have clinical antimanic effects, this study aimed to evaluate the effects of (R)-(-)-carvone and (S)-(+)-carvone in a manic animal model (i.e., methylphenidate and sleep deprivation-induced hyperactivity). Mice treated with methylphenidate (5 mg/kg) or deprived of sleep for 24 hours using a multi-platform protocol exhibited increased motor activity in an automated activity chamber. Pre-administration of acute (R)-(-)-carvone (50–100 mg/kg), (S)-(+)-carvone (50–100 mg/kg), and lithium (100 mg/kg, positive control) blocked this effect. These doses did not affect spontaneous motor activity in methylphenidate-induced experiments, while (S)-(+)-carvone reduced spontaneous motor activity in sleep deprivation experiments, suggesting a sedative effect. Long-term (21 days) administration of (R)-(-)-carvone (100 mg/kg), (S)-(+)-carvone (100 mg/kg), and lithium also prevented methylphenidate-induced hyperactivity. These results suggest that carvone may have an anti-manic-like effect.

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Non-human toxicity values
Rats oral LD50: 1,640 mg/kg body weight / D-carvone /
Rats oral LD50: >2000 mg/kg body weight
Guinea pig oral LD50: 766 mg/kg body weight / D-carvone /
Female rat oral LD50: 2263 mg/kg body weight
For more non-human toxicity values (complete data) for carvone (11 in total), please visit the HSDB record page.

[1]. Carvone and its pharmacological activities: A systematic review. Phytochemistry. 2022 Apr:196:113080.

Carvone is a menthol monoterpene composed of a cyclohexyl-2-enone with methyl and isopropenyl substituents at positions 2 and 5, respectively. It is an allergen. Carvone belongs to the carvone class of compounds and is also a phytofungal agent. It has been reported to be found in Artemisia judaica, Citrus reticulata, and other organisms with relevant data. Carvone is a metabolite of Saccharomyces cerevisiae. See also: Elymus repens root (part); carvone (note moved here). Carvone, (-)- (note moved here).

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Therapeutic Uses Veterinary Use: Carvone oil (containing D-carvone) is used in veterinary products to promote respiration in newborn animals and to treat bloating and gastrointestinal diseases in farm animals.
...Caraway oil and caraway berries are registered as herbal products with the European Medicines Agency. They have been reported to be used as a laxative, to treat colic, freshen breath, or aid digestion in young children. Other benefits of caraway seeds include antispasmodic, carminative, emmenagogue, expectorant, galactagogue, stimulant, stomachic, and tonic effects.

C10H16O

152.23

150.104

99-49-0

(-)-Carvone;6485-40-1

7439

Colorless to light yellow liquid

0.9±0.1 g/cm3

230.5±35.0 °C at 760 mmHg

230℃

88.9±0.0 °C

0.1±0.5 mmHg at 25°C

1.481

2.27

0

1

1

11

223

0

O=C1C(C([H])([H])[H])=C([H])C([H])([H])C([H])(C(=C([H])[H])C([H])([H])[H])C1([H])[H]

ULDHMXUKGWMISQ-UHFFFAOYSA-N

InChI=1S/C10H14O/c1-7(2)9-5-4-8(3)10(11)6-9/h4,9H,1,5-6H2,2-3H3

2-methyl-5-prop-1-en-2-ylcyclohex-2-en-1-one

BRN 1861032 BRN-1861032 BRN1861032Carvone, Carveol L-Carveol NSC 68313 NSC-68313 NSC68313 AI3 27596 AI3-27596 AI327596

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)