Pulegone

Aroma and sensory profile

Pulegone is peppermint with a shadow. Fragrance references type (R)-(+)-pulegone minty with medium strength and describe it neat as peppermint, camphor, fresh, herbal, and buchu, or minty, sulfuraceous, and sweet with metallic buchu nuances; its flavor at 20 parts per million is minty and sulfuraceous with fruity blackcurrant and raspberry and fresh green leafy nuances [1]. The Merck Index, as compiled by PubChem, calls it a pleasant odor midway between peppermint and camphor [2].

The molecule is a cyclic monoterpene ketone with one stereocenter and it is chiral. Nearly all natural pulegone is the (R)-(+) form, isolated in quantity from pennyroyal oils [2]. The enantiomers differ in the body more than in the nose: human metabolism studies found that (S)-(−)-pulegone is readily reduced at its double bond to menthone-type metabolites, while (R)-(+)-pulegone has a strongly diminished ability to be reduced and is diverted into oxidative pathways that produce the toxic metabolites [7]. No separate panel description of (S)-(−)-pulegone was found, so no claim about how the two smell apart is made here.

Effects and research

Pulegone is the best-characterized toxicant on this site, and its research is about harm. The National Toxicology Program gave it by gavage at up to 600 milligrams per kilogram in short studies and at up to 150 milligrams per kilogram for two years: in rats it damaged the liver, kidney, and nose and significantly increased urinary bladder papillomas in females at 150 milligrams per kilogram; in mice it significantly increased hepatocellular adenomas at 75 and 150 milligrams per kilogram and combined liver neoplasms in males at 75 and females at 150 [4]. The bladder mechanism was traced to cytotoxic urinary metabolites causing superficial necrosis, exfoliation, and regenerative proliferation [8].

The liver mechanism is metabolic. Rat liver microsomes convert (R)-(+)-pulegone to menthofuran and 9-hydroxypulegone, and the alpha,beta-unsaturated aldehyde metabolites are the reactive species behind its hepatotoxicity [6]; a 2025 study found that blocking CYP2E1 in mice did not prevent liver injury from 200 milligrams per kilogram, so more than one pathway is involved [10]. Pennyroyal oil poisoning is a recognized cause of liver failure.

The benefit-side literature exists and is dwarfed. Topical (R)-(+)-pulegone suppressed skin thickening, scratching, immunoglobulin E, and cytokines in a mouse atopic dermatitis model [9]. A 2019 analysis in JAMA Internal Medicine measured pulegone in leading mint- and menthol-flavored e-cigarettes and smokeless tobacco and calculated margins of exposure against the NTP reference doses, concluding that users are exposed to a carcinogen at levels FDA would not permit in food [5].

Natural sources

Pulegone is a mint-family ketone concentrated in a few harsh mints. HSDB records that it occurs in oils of the mint family as the (+) form and is readily isolated in quantity from the pennyroyal oils of Mentha pulegium, Mentha longifolia, and Hedeoma pulegioides, and that it is a component of Ziziphora clinopodioides oil from Iran, Iraq, and Turkey [2]. Fragrance databases log it at 86.7 percent in pennyroyal oil, 25 to 41 percent in Uruguayan and Cuban pennyroyal, 53.8 percent in Agathosma crenulata, the buchu, 41 percent in Calamintha nepeta, 35.3 percent in Satureja viminea, and, at the other end, 1.4 percent in Idaho peppermint oil, 0.2 to 0.3 percent in other peppermints, and 0.1 percent in cornmint [1]. Catnip and some catmints carry it. In cannabis pulegone is a trace terpenoid, occasionally reported in minty chemotypes and usually absent.

Boiling point and vaporization

PubChem compiles pulegone's boiling point as 224 °C from the Merck Index and from the Joint FAO/WHO Expert Committee on Food Additives, with reduced-pressure values of 151 to 153 °C at 100 mmHg, 103 °C at 17 mmHg, and 84 °C at 6 mmHg, and 220 to 222 °C at 760 mmHg from fragrance references [1][2]. This profile uses 224 °C (435 °F), the JECFA and Merck value, three degrees above the 221 °C the site previously listed. That places pulegone with citronellol and geranyl acetate in the heart-note band. Heating does not detoxify it: pulegone survives distillation and cooking, and the toxic transformation happens in the liver rather than in the pan. No thermal degradation study of pulegone was found.

Safety and regulation

Pulegone is the exception on this site. It was removed from the FDA synthetic flavoring list at 21 CFR 172.515 by a final rule of October 9, 2018, under the Delaney Clause, which bars any food additive found to induce cancer in animals; FDA stated in the same rule that its own analysis found these substances do not pose a risk to public health at their intended use levels, but the statute allowed no other outcome [3][11]. The Research Institute for Fragrance Materials assessed it in 2021 incorporating the carcinogenicity data [12].

Under Europe's classification inventory, 96 percent of notifications flag it as harmful if swallowed, and separate notifications carry the codes for toxic if swallowed, suspected carcinogen, and organ damage through repeated exposure [2]. The practical reading is short. Pennyroyal oil should not be ingested at all; buchu and pennyroyal products belong out of reach of children.

Industries and uses

Fragrance: pulegone supplies a harsh peppermint-camphor note with a cassis-buchu edge in mint and herbal accords, and is used sparingly and under RIFM limits; its removal from the FDA flavoring list means it has no synthetic culinary use [1][3][11][12]. Aromatherapy: pennyroyal and buchu oils are its carriers, and pennyroyal oil is the one essential oil this site advises against using at all, by any route, because of pulegone [2][4][6].