Rotundone

CAS:
18374-76-0
Family:
sesquiterpene ketone
Also:
FEMA No. 4867, Rotundone

Found heavily in (1 oils total)

Recorded sensory reference values
  • Affect valence: 0.35
  • Affect arousal: 0.55
  • Recorded odor threshold: 0.008 ppb

Reference values depend on measurement conditions and do not describe an effective dose or the perception of a custom blend.

Rotundone is a sesquiterpene ketone best known as the trace-impact aroma molecule behind black-pepper notes in Syrah-style wines and in peppercorn itself. The live evidence base is unusually strong for aroma science: public sources support its identity, extremely low odor threshold, specific anosmia in a meaningful subset of people, and a defined biosynthetic route from alpha-guaiene through oxidation. The benefit-facing literature is not therapeutic; AromaForge should present rotundone primarily as a high-impact peppery odor constituent with strong sensory and biosynthetic evidence, plus a modern fragrance safety assessment that is still more robust than any human wellness literature.

Chemical identity and composition

PubChem and NIST both identify rotundone as the stereodefined sesquiterpene ketone C15H22O with InChIKey NUWMTBMCSQWPDG-SDDRHHMPSA-N. In the local archive it appears in nagarmotha/cypriol context, while the broader literature most strongly associates it with grape skin, Syrah wine, black and white pepper, and several fruits. Biosynthesis work places alpha-guaiene as the direct precursor, with both aerial oxidation and enzyme-mediated alpha-guaiene 2-oxidation reported as plausible formation routes depending on system.

Aroma and practical use

pepperyspicywoodypeppercorn-like
  • Use the recorded peppery, spicy, woody, peppercorn-like descriptors to explore a blend's scent character; perceived strength also depends on the other ingredients.
  • Read the route, preparation and experimental context before using a study finding to choose an oil.

Reported benefits and effects

Findings retain their study context. An animal or laboratory result describes that experiment.

A 2008 sensory paper identified rotundone as a potent spicy aroma compound, found strong correlations with black-pepper aroma intensity in grapes and wine, and reported detection thresholds of 16 ng/L in red wine and 8 ng/L in water for sensitive panelists.

The abstract also notes that about 20% of panelists could not detect rotundone even at 4000 ng/L in water, making it one of the archive's clearest examples of specific anosmia affecting constituent perception.

human sensoryRoute not recorded

Apply this finding only to the studied preparation, participants, route and outcome. It does not establish the same result for a custom oil blend.

A 2017 fruit-aroma paper identified rotundone as a common woody odor-active compound in grapefruit, orange, apple, and mango and reported that even subthreshold additions changed overall model-beverage flavor toward a more natural profile.

This supports rotundone as a trace aroma modulator rather than only a directly perceivable pepper note.

aroma scienceRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

A 2017 grapefruit study quantified rotundone at 2180 and 1920 ng/kg in white and pink peel and at 29.6 and 49.8 ng/kg in the corresponding juices, with the authors concluding that rotundone is indispensable for grapefruit juice aroma.

The study also reported high flavor dilution factors and used stable isotope dilution analysis with a deuterated internal standard.

aroma scienceRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

A 2016 grapevine biosynthesis paper identified VvSTO2/CYP71BE5 as an alpha-guaiene 2-oxidase that forms (-)-rotundone, with higher expression in Syrah grape skin matching rotundone accumulation patterns.

The abstract supports enzymatic formation in grapes rather than relying only on spontaneous oxidation chemistry.

mechanisticRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

A 2020 Pennsylvania consumer study found orthonasal and retronasal detection thresholds of about 140 and 146 ng/L in red wine in a non-expert cohort and estimated that roughly 40% of participants were anosmic to rotundone.

The same abstract reports that added rotundone was generally disliked in that cohort, underscoring segmentation risk for pepper-forward sensory positioning.

human sensoryRoute not recorded

Apply this finding only to the studied preparation, participants, route and outcome. It does not establish the same result for a custom oil blend.

Use concerns and concentration limits

Sensitization concernNot flagged

Not flagged in the current model. This is not proof of absence or unrestricted safety.

Phototoxicity concernNot flagged

Not flagged in the current model. This is not proof of absence or unrestricted safety.

Oxidation concernNot flagged

Not flagged in the current model. This is not proof of absence or unrestricted safety.

Penetration enhancementNot flagged

Not flagged in the current model. This is not proof of absence or unrestricted safety.

No numeric constituent-specific use limit is available here. Missing is not an unrestricted-use clearance.

A 2024 RIFM fragrance safety assessment concluded that available target data and read-across from nootkatone do not indicate genotoxicity, skin-sensitization concern at declared use levels, or photoirritation/photoallergenicity concern for rotundone.
safety reviewRoute not recorded

The source assessment applies to its specified exposure and preparation; this entry is not an unrestricted-use clearance.

No direct public citation is attached to this entry.

The same RIFM review states that repeated-dose, reproductive-toxicity, and local-respiratory-toxicity datasets for rotundone itself are insufficient, so those endpoints were handled through Threshold of Toxicological Concern evaluation rather than robust constituent-specific toxicology.
safety reviewRoute not recorded

The source assessment applies to its specified exposure and preparation; this entry is not an unrestricted-use clearance.

No direct public citation is attached to this entry.

No human therapeutic studies specific to isolated rotundone were verified in this pass; archive copy should stay focused on aroma science, chemistry, and safety context rather than wellness claims.
evidence synthesisRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

No direct public citation is attached to this entry.

Constituents it may interact with

No constituent-pair interaction is recorded for this identity. The report does not assume either amplification or incompatibility.

How the effects were investigated

alpha-guaiene aerial oxidation

A 2014 study identified alpha-guaiene as the first known precursor to rotundone and reported that simple aerial oxidation can generate rotundone.

mechanisticRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

VvSTO2 alpha-guaiene 2-oxidase activity

A 2016 grapevine study functionally characterized VvSTO2/CYP71BE5 as an alpha-guaiene 2-oxidase that forms (-)-rotundone and is expressed in Syrah grape exocarp where rotundone accumulates.

mechanisticRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

precursor supply via VvGuaS

A parallel 2016 study identified VvGuaS, a TPS24 allele that produces alpha-guaiene, linking terpene-synthase polymorphisms to the upstream availability of the rotundone precursor.

mechanisticRoute not recorded

This reference does not establish a therapeutic result or a safe use level for a custom oil blend.

What this report cannot establish

  • A reported constituent percentage does not establish an effective human therapeutic dose or the amount absorbed into the body.
  • The presence of a constituent does not guarantee a clinical benefit, rash treatment or sleep improvement from a custom blend.
  • An unflagged concern or missing use limit does not establish safety for ingestion, inhalation, skin exposure or a particular person.
  • A candidate constituent interaction does not establish that two oils amplify one another at the selected proportions.
  • Constituent descriptors alone do not establish a precise top, heart or base lifetime in a finished blend.
Known data gaps (7)
  • No human clinical efficacy literature specific to isolated rotundone was verified.
  • Constituent-specific repeated-dose, reproductive, and inhalation toxicology remain limited in public sources; the best accessible safety synthesis relies partly on TTC and read-across.
  • Most direct rotundone literature is in aroma chemistry, analytical chemistry, or grape and pepper biosynthesis rather than broader constituent pharmacology.
  • The 2024 RIFM assessment supports sensitizing:false and phototoxic:false via read-across from nootkatone and available target data, but does not publish a specific numeric dermal-limit percentage; the previous dermal_limit_pct value of 2 had no locatable citation and was corrected to null on 2026-07-13.
  • Second-pass 2026-07-13 search targeting an IFRA Standards Library restriction level for rotundone (CAS 18374-76-0) by name and CAS found no rotundone-specific entry in the IFRA Standards documentation (checked via the 51st Amendment index and IFRA standards library pages); rotundone does not appear to be one of the individually restricted IFRA Standards materials, consistent with the existing RIFM-only (no numeric limit) sourcing already on file. No correction made; dermal_limit_pct remains null and dermal_limit_source remains the RIFM 2024 assessment already cited.
  • No constituent-specific numeric dermal reference is available here.
  • Some findings do not record an explicit exposure route; consult the linked study before applying them to a use.
All public references (13)