(+)-Pulegone

log Kow = 3.08

3.08

0.9323 at 20 °C

0.927-0.939

Oil

Oily liquid

Practically insoluble in water

Miscible with alcohol. ether, chloroform

insoluble in water; soluble in oils; miscible to soluble in alcohol

miscible (in ethanol)

224 °C

BP: 151-153 °C at 100 mm Hg; 103 °C at 17 mm Hg; 84 °C at 6 mm Hg

220.00 to 222.00 °C. @ 760.00 mm Hg

224 °C

138.0 [mmHg]

0.123 mm Hg at 25 °C (extrapolated)

Index of refraction: 1.4894 at 20 °C/D

1.483-1.491

Liquid with a pleasant odor between peppermint and camphor; [Merck Index] Clear light brown liquid; [Sigma-Aldrich MSDS]

Solid

Colourless to yellow liquid, herbaceous-minty, resinous odour

Warning

H302 (96.1%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 279 reports by companies from 4 notifications to the ECHA C&L Inventory.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: Cyclohexanone, 5-methyl-2-(1-methylethylidene)-, (R)-

Hazard Traits - Carcinogenicity；Authoritative List - IARC Carcinogens - 2B; Prop 65；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

(R)-(+)-Pulegone: Does not have an individual approval but may be used under an appropriate group standard

All early deaths in 2-week oral studies of rats and mice at doses >300 mg/kg attributed to liver toxicity; Non-neoplastic lesions of the liver, kidney, nose, and forestomach of rats and mice observed in 2-year oral studies; Evidence for carcinogenic activity: None in male rats; some in female rats; clear evidence (liver neoplasms) in male and female mice; [NTP] Safe when used as a flavoring agent in food; [JECFA] May cause irritation; May be harmful if swallowed or inhaled; [Sigma-Aldrich MSDS]

Pulegone is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Final Report on the Safety Assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint); International Journal of Toxicology 20 (Suppl 3): 61-73 (2001).

Acute Tox. 4 (96.1%)

Acute toxicity (ingestion) - category 3；Carcinogenicity - category 2；Specific target organ toxicity (repeated exposure) - category 1

Strong oxidizing agents. /(R)-(+)-Pulegone/

/Conditions to avoid/ Heat, flames and sparks. /(R)-(+)-Pulegone/

Wear self contained breathing apparatus for fire fighting if necessary. /(R)-(+)-Pulegone/

For small (incipient) fires, use media such as "alcohol" foam, dry chemical, or carbon dioxide. For large fires, apply water from as far as possible. Use very large quantities (flooding) of water applied as a mist or spray; solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. /(R)-(+)-Pulegone/

Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations (see section 13). Keep in suitable, closed containers for disposal. /(R)-(+)-Pulegone/

Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. /(R)-(+)-Pulegene/

Intraperitoneal injection of R-(+)-pulegone (pulegone), the main constituent of pennyroyal oil, to ddY mice caused extensive liver injury as characterized by an increase in serum glutamic pyruvic transaminase (GPT) activity and centrilobular necrosis of hepatocytes. Treatments of mice with the cytochrome P-450 enzyme inhibitors, SKF-525A, metyrapone, piperonyl butoxide, and carbon disulfide (CS2), prevented or markedly alleviated the hepatotoxicity of pulegone. These results are compatible with the view that some metabolite of pulegone is responsible for the liver injury in mice.

Pennyroyal oil ingestion has been associated with severe hepatotoxicity and death. The primary constituent, R-(+)-pulegone, is metabolized via hepatic cytochrome P450 to toxic intermediates. The purpose of this study was to assess the ability of the specific cytochrome P450 inhibitors disulfiram and cimetidine to mitigate hepatotoxicity in mice exposed to toxic levels of R-(+)-pulegone. 20-g female BALB/c mice were pretreated with either 150 mg/kg of cimetidine intraperitoneal (IP), 100 mg/kg of disulfiram IP, or both. After one hour, mice were administered 300 mg/kg of pulegone IP and were killed 24 hours later. Data were analyzed using ANOVA. Post-hoc t-tests used Bonferroni correction. There was a tendency for lower serum glutamate pyruvate transaminase in the disulfiram and cimetidine groups compared with the R-(+)-pulegone group. The differences were significant for both the cimetidine and the combined disulfram and cimetidine groups compared with the R-(+)-pulegone group. Pretreatment with the combination of disulfiram and cimetidine most effectively mitigated R-(+)-pulegone-induced hepatotoxicity. Within the limitations of a pretreatment animal model, the combination of cimetidine and disulfiram significantly mitigates the effects of pennyroyal toxicity and does so more effectively than either agent alone. These data suggest that R-(+)-pulegone metabolism through CYP1A2 appears to be more important in the development of a hepatotoxic metabolite than does metabolism via CYP2E1.

Glutathione plays a role in the detoxication of pulegone. At hepatotoxic doses, pulegone depletes glutathione in the liver and the toxicity of pulegone on i.p. injection in mice is enhanced by treatment with diethyl maleate to decrease glutathione levels. No such increase in toxicity was seen with (R)-(+)-menthofuran . It was suggested that pulegone is analogous to acetaminophen in that saturation of the glutathione pathway leads to a higher proportion of the dose being metabolised to reactive metabolites (such as 8-pulegone aldehyde). However, in other studies, glutathione has been shown to react with menthofuran epoxide, the precursor to 8-pulegone aldehyde. Glutathione conjugation may play a major role in the detoxication of the reactive metabolite produced by cytochrome P450 ((R)-(+)-menthofuran or the gamma-ketoenal) as indicated by the isolation of glutathione conjugates, including a mixed glutathionyl glucuronide, from the bile of rats treated i.p. with pulegone. The evidencesuggests that the metabolic activation of pulegone occurring in animals also occurs in humans, resulting in the formation of (R)-(+)-menthofuran. At high concentrations, (R)-(+)-menthofuran is a proximate hepatoxic product but if the concentration of metabolites of pulegone is not sufficient to deplete hepatocellular concentrations of glutathione, hepatotoxicity may not be observed.

The role of cytochrome P450s in metabolic activation of (R)-(+)-pulegone has been demonstrated by the observations that a variety of P450-inhibitors decreased the toxicity while pretreatment with phenobarbital enhanced the toxicity of (R)-(+)-pulegone and (R)-(+)- menthofuran. Thus, oxidation appears to enhance the toxicity of (R)-(+)-pulegone and (R)-(+)-menthofuran, which is consistent with the fact that (R)-(+)-pulegone is converted to (R)-(+)-menthofuran via 9-hydroxypulegenone, and the reactive 8-pulegone aldehyde is an ultimate toxicant. Evidence that pulegone is oxidized to 9-hydroxypulegone via a free radical mechanism is provided from the observation that treatment with the free radical scavenger C-phyocyanin decreased the hepatotoxicity of pulegone in rats.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 670(SRC), determined from a log Kow of 3.08(2) and a regression-derived equation(3), indicates that pulegone is expected to have moderate mobility in soil(SRC). Volatilization of pulegone from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.9X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Pulegone is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.12 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2013).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 670(SRC), determined from a log Kow of 3.08(2) and a regression-derived equation(3), indicates that pulegone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 5.9X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 22 hours and 10 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 50(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2013).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pulegone, which has an estimated vapor pressure of 0.12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase pulegone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.1 days(SRC), calculated from its rate constant of 1.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Pulegone contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Pulegone concentrations in plants(1).；Table: 3-10153 [Table#8108]

Pulegone, detected, not quantified in plants(1).[Table#8109]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of November 21, 2013: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=89-82-7]

Pulegone is found in oils derived from plants of the Labiarae (mint) family as (+)-form(1). It is readily isolated in quantity from the pennyroyal oils from Mentha pulegium, M. Longifolia, and Hedeoma pulegioides(1,2). Pugelone is one of the components of the essential oil derived from Ziziphora clinopodioides, Blue Mint Bush or kakuti-e kuhi, (Labiarae (Lamiaceae)), which grows in Iran, Iraq, and parts of Turkey(3,4).

/SIGNS AND SYMPTOMS/ A review of cases of human intoxication with pennyroyal oil (Mentha pulegium: pulegone content 62-97%) indicate that ingestion of 10 mL resulted in moderate to severe toxicity and ingestion of greater than 15 mL (ca. 250 mg/kg bw for a 60 kg woman) resulted in death. The clinical pathology is characterised by massive centrilobular necrosis, pulmonary edema and internal hemorrhage.

/CASE REPORTS/ A review of published reports of pennyroyal poisoning (1869 to 1996) identified 18 cases in which there was moderate to severe toxicity from ingestion of at least 10 mL (about 2 tsp.) of pennyroyal oil. The toxic symptoms included coma, seizures, and hepatic and renal effects. Ingestion of less than 10 mL was generally associated with gastritis and mild central nervous system toxicity. However, the severity of the toxic effects was not always related strictly to dose and depended on the use of emetics or other treatments. In two cases reported before 1905, coma and seizures were associated with ingestion of 5 mL pennyroyal oil; two other cases reportedly survived after ingestion of 30 mL. Variability in the toxic effects of pennyroyal oil may be due to differing concentrations of pulegone contained in preparations from European and American pennyroyal.

/CASE REPORTS/ The cases of 2 infants, an 8-wk-old boy and a 6-month-old boy, who developed hepatic and neurologic injury after ingestion of mint tea that contained the toxic agent pennyroyal oil are reported. Fulminant liver failure with cerebral edema and necrosis developed in the first infant, who died. This infant was positive only for menthofuran (10 ng/mL), a metabolite of a toxic constituent (pulegone) of pennyroyal oil. In the other infant, who was positive for both pulegone (25 ng/mL) and menthofuran (41 ng/mL), hepatic dysfunction and a severe epileptic encephalopathy developed. When he was discharged 2 months after admission his hepatocellular enzyme markers remained elevated.

/CASE REPORTS/ Pennyroyal is a widely available herb that has long been used as an abortifacient despite its potentially lethal hepatotoxic effects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported. We report four cases of pennyroyal ingestion. One patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N-acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil. Pennyroyal continues to be an herbal toxin of public health importance. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine. Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted access to the herb.

For more Human Toxicity Excerpts (Complete) data for Pulegone (7 total), please visit the HSDB record page.

Pulegone

Group 2B: Possibly carcinogenic to humans

Volume 108: (2016) Some Drugs and Herbal Products

2016

2013

Pulegone

An estimated BCF of 50 was calculated in fish for pulegone(SRC), using a log Kow of 3.08(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

Chemical: Cyclohexanone, 5-methyl-2-(1-methylethylidene)-, (R)-

Hazard Traits - Carcinogenicity；Authoritative List - IARC Carcinogens - 2B; Prop 65；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

(R)-(+)-Pulegone: Does not have an individual approval but may be used under an appropriate group standard

Pulegone is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

This study addresses the adaptive dynamics of plant toxins that ward off herbivores, an aspect of chemical warfare in ecosystems. Thyme basil (Acinos suaveolens) growing in an area regularly grazed by mammals contains double the concentration of monoterpenoids (15.61 vs. 8.18 mg/g dry matter, P = 0.001) when contrasted with plants growing on inaccessible rock pillars and not exposed to mammalian herbivores. Thyme basil produces two monoterpenoids-menthone and R-(+)-pulegone-that show contrasting toxicity. The more toxic R-(+)-pulegone shows an increase in relative abundance (66.3% vs. 47.5%, P < 0.001) in plants exposed to browsing The results demonstrate how plant chemistry responds to both abiotic and biotic environmental conditions.

In rats pulegone (300 mg i.p.) caused dilation of the central veins and distension of sinusoidal spaces within 6 hours and centrilobular necrosis was observable starting at 12 hours. Electron microscopy after 24 hours showed degeneration of endoplasmic reticulum, swelling of mitochondria and nuclear changes. It has been suggested that metabolites of (R)-(+)-pulegone deactivate cytochrome P450s by modifying the prosthetic hem group or the apoprotein . In human liver microsomes in vitro, (R)-(+)-menthofuran specifically inhibits CYP2A6 and adducts with this enzyme have been isolated. CYP1A2, CYP2D6, CYP2E1 or CYP3A4 were not similarly inactivated.

(R)-(+)-Pulegone and its metabolite, (R)-(+)-menthofuran, are hepatotoxic and produce similar effects following i.p. injection in mice. These effects are similar to those reported following human intoxication with pennyroyal oil.

(R)-(+)-Pulegone, a monoterpene ketone, is a major component of pennyroyal oil. Ingestion of high doses of pennyroyal oil has caused severe toxicity and occasionally death. Studies have shown that metabolites of pulegone were responsible for the toxicity. Previous metabolism studies have used high, near lethal doses and isolation and analysis techniques that may cause degradation of some metabolites. To clarify these issues and further explore the metabolic pathways, a study of (14)C-labeled pulegone in F344 rats at doses from 0.8 to 80 mg/kg has been conducted. High-pressure liquid chromatography (HPLC) analysis of the collected urine showed the metabolism of pulegone to be extensive and complex. Fourteen metabolites were isolated by HPLC and characterized by NMR, UV, and mass spectroscopy. The results demonstrated that pulegone was metabolized by three major pathways: 1) hydroxylation to give monohydroxylated pulegones, followed by glucuronidation or further metabolism; 2) reduction of the carbon-carbon double bond to give diastereomeric menthone/isomenthone, followed by hydroxylation and glucuronidation; and 3) Michael addition of glutathione to pulegone, followed by further metabolism to give diastereomeric 8-(N-acetylcystein-S-yl)menthone/isomenthone. This 1,4-addition not only took place in vivo but also in vitro under catalysis of glutathione S-transferase or mild base. Several hydroxylated products of the two mercapturic acids were also observed. Contrary to the previous study, all but one of the major metabolites characterized in the present study are phase II metabolites, and most of the metabolites in free forms are structurally different from those previously identified phase I metabolites.

Pulegone, a monoterpene that protects source plants against predators, is a hepatotoxic constituent of the folklore abortifacient pennyroyal oil. In the rat, pulegone extensively depleted glutathione measured in both liver tissue and plasma, and its toxicity was markedly enhanced in animals treated with buthionine sulfoximine. The glutathione-depleting effect of pulegone was compromised following inhibition of cytochrome P-450 by piperonyl butoxide. In addition, /the authors/ found no evidence for conjugation of glutathione to unchanged pulegone in vitro. Administration of menthofuran, a known oxidative and hepatotoxic metabolite of pulegone, only marginally affected glutathione levels in plasma and liver, and toxicity was not augmented by buthionine sulfoximine. These results provide indirect evidence for cytochrome P-450-catalyzed bioactivation of pulegone via at least two independent pathways: 1) the formation and subsequent activation of menthofuran from pulegone; and 2) the formation of reactive intermediate(s) from pulegone, but not menthofuran, which can be detoxified through a mechanism requiring reduced glutathione.

(R)-(+)-Pulegone, a monoterpene constituent of pennyroyal oil, is a hepatotoxin that has been used in folklore medicine as an abortifacient despite its potential lethal effects. Pulegone is metabolized by human liver cytochrome P-450s to menthofuran, a proximate hepatotoxic metabolite of pulegone. Expressed human liver cytochrome (CYP) P-450s (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) were tested for their ability to catalyze the oxidations of pulegone and menthofuran. Expressed CYP2E1, CYP1A2, and CYP2C19 oxidized pulegone to menthofuran, with respective Km and Vmax values of 29 uM and 8.4 nmol/min/nmol P-450 for CYP2E1, 94 uM and 2.4 nmol/min/nmol P-450 for CYP1A2, and 31 uM and 1.5 nmol/min/nmol P-450 for CYP2C19. The human liver P-450s involved in the metabolism of menthofuran are the same as pulegone except for the addition of CYP2A6. These P-450s were found to oxidize menthofuran to a newly identified metabolite, 2-hydroxymenthofuran, which is an intermediate in the formation of the known metabolites mintlactone and isomintlactone. Based on studies with (18)O2 and H2(18)O, 2-hydroxymenthofuran arises predominantly from a dihydrodiol formed from a furan epoxide. CYP2E1, CYP1A2, and CYP2C19 oxidized menthofuran with respective Km and Vmax values of 33 uM and 0.43 nmol/min/nmol P-450 for CYP2E1, 57 uM and 0.29 nmol/min/nmol P-450 for CYP1A2, and 62 uM and 0.26 nmol/min/nmol P-450 for CYP2C19.

The major in vivo metabolites of (S)-(-)-pulegone in humans using a metabolism of ingestion-correlated amounts (MICA) experiment were newly identified as 2-(2-hydroxy-1-methylethyl)-5-methylcyclohexanone (8-hydroxymenthone, M1), 3-hydroxy-3-methyl-6-(1-methylethyl)cyclohexanone (1-hydroxymenthone, M2), 3-methyl-6-(1-methylethyl)cyclohexanol (menthol), and E-2-(2-hydroxy-1-methylethylidene)-5-methylcyclohexanone (10-hydroxypulegone, M4) on the basis of mass spectrometric analysis in combination with syntheses and NMR experiments. Minor metabolites were be identified as 3-methyl-6-(1-methylethyl)-2-cyclohexenone (piperitone, M5) and alpha,alpha,4-trimethyl-1-cyclohexene-1-methanol (3-p-menthen-8-ol, M6). Menthofuran was not a major metabolite of pulegone and is most probably an artifact formed during workup from known (M4) and/or unknown precursors. The differences in toxicity between (S)-(-)- and (R)-(+)-pulegone can be explained by the strongly diminished ability for enzymatic reduction of the double bond in (R)-(+)-pulegone. This might lead to further oxidative metabolism of 10-hydroxypulegone (M4) and the formation of further currently undetected metabolites that might account for the observed hepatotoxic and pneumotoxic activity in humans.

For more Metabolism/Metabolites (Complete) data for Pulegone (25 total), please visit the HSDB record page.

A natural oil in plants of the Labiatae family; [Merck Index] Used as flavoring agent or adjuvant; [FDA] Also used in dental products, as fragrance agents, and in herbal medicines; [NTP]

Chemical intermediate; flavoring

Several essential oils containing pulegone [e.g., mint oil (<2% pulegone), peppermint oil (<4% pulegone), pennyroyal oil (60%-90% pulegone)] are used for flavoring foods, drinks, and dental products.

Pennyroyal oil /60-90% pulegone/ has also been used as a fragrance agent and as an herbal medicine proposed to induce menstruation and abortion.

Traditional medicine

Pulegone can be produced synthetically.

Essential oils containing pulegone are derived from many plant species, including Hedeoma pulegioides (American pennyroyal), species of the genus Bystropogon (evergreen shrubs), and species of the genus Mentha [e.g., European pennyroyal (M. pulegium), cornmint, Biblical mint]. Essential (i.e., volatile) plant oils are produced in the plant tissues by the reaction of certain constituents when tissues contact water; most oils are obtained from plants by steam distillation.

Pulegone can also be produced by shoot cultures of Mentha piperita grown in fermenters.

Readily isolated in quantity from the pennyroyal oils from Mentha pulegium L., M. longifolia (L.) Huds., and Hedeoma pulegioides (L.) Pers., Labiatae.

Optically active terpene such as (R)-(+)-citronellol, (R)-(+)-pulegone or (S)-ar-turmerone is prepared in high enantiomeric excess from an intermediate, (R)-(+)-citronellic acid or (S)-(+)-3-p-tolylbutyric acid, which is easily prepared by the SN2 type of ring opening reaction of (R)-(+)-beta-methyl-beta-propiolactone with homoprenylmagnesium bromide in the presence of a copper(I) salt or di-p-tolycuprate.

Cosmetics product ingredient: Pulegone；Reason for Listing:；- Group 2B carcinogen identified by the International Agency for Research on Cancer；- Known to cause cancer and listed under Health and Safety Code section 25249.8 of the California Safe Drinking Water and Toxic Enforcement Act of 1986 (Prop 65)；Potential Health Impacts: Carcinogenicity；Product count: 253

Fragrance Ingredients

Fragrance Ingredients

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Cyclohexanone, 5-methyl-2-(1-methylethylidene)-, (5R)-: ACTIVE

(R)-(+)-pulegone, together with (R)-(+)-menthofuran, is a constituent of peppermint oil and pennyroyal oil and occurs naturally at lower levels in other foods such as oregano, beans and tea. (S)-(-)-pulegone is contained in Buchu leaf oil, a steam distillate from Agathosma betulina which is used as a source for flavorings imparting "cassis" type aromas.

Peppermint oil contains maximum 4.0 % pulegone and between 1.0 and 9.0 % menthofuran. Mint oil, partly dementholised contains maximum 2.0 % pulegone, but no limit is given for menthofuran. There is no Ph Eur monograph on pennyroyal or pennyroyal oil. It is known from the literature that pennyroyal herb contains 1-2% essential oil of which pulegone is the principal component (60-90%).

Pulegone is found in young peppermint leaves, and is metabolized to menthol as the leaves mature.

Monoterpenes, such as pulegone, may be potential environmentally safe substitutes for traditional pesticides.

Naturally occuring plant constituents are potentially useful as avian feeding deterrents. In a series of cage trials, pulegone, a compound found in various species of mint, suppressed consumption of rice seed by red-winged blackbirds (Agelaius phoeniceus) more effectively than methyl anthranilate. Furthermore, pennyroyal oil, from which pulegone is obtained, was nearly as effective as pulegone itself. Brown-headed cowbirds (Molothrus ater) were more sensitive to pulegone than were redwings, but female boat-tailed grackles (quiscalus major) were less sensitive. Because pulegone produces both sensory irritation and post-ingestive distress, it has potential for seed treatment and other bird deterrent applications. /Experimental use/