Eugenol

Eugenol at a Glance

Eugenol is the clove-scented phenylpropanoid (4-allyl-2-methoxyphenol) — a guaiacol carrying an allyl side chain — that makes up roughly 70–90% of clove-bud essential oil and carries most of clove’s documented bioactivity ^{5,6Reference 5Marchese A et al. · 2017ReviewAntimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]View study →Reference 6Barboza JN et al. · 2018ReviewAn overview on the anti-inflammatory potential and antioxidant profile of eugenol — [review]View study →}. It recurs across this database as a constituent of cassia cinnamon, damiana and horopito, and is the aroma-defining volatile of cinnamon-leaf oil and eugenol-chemotype basil.

Its one genuinely human, genuinely useful role is topical local anaesthesia — the active principle of zinc-oxide-eugenol dentistry and clove-oil toothache remedies, backed by a small RCT and a well-characterised voltage-gated sodium-channel mechanism ^{1,4Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →Reference 4Teixeira-Fonseca JL et al. · 2021In vitroEugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]View study →}. Beyond that, a large antimicrobial, anti-inflammatory, gastroprotective and cardiovascular literature is almost entirely preclinical, run on isolated eugenol or essential oil at doses a culinary spice never delivers.

The safety headline is twofold. Eugenol is biphasic — antioxidant and organ-protective at low doses, toxic at high ones — and the concrete hazard is liver injury from concentrated clove oil, which has caused paracetamol-like fulminant hepatic failure in children after only a few millilitres ^{16,17Reference 16Hartnoll G et al. · 1993Case reportNear fatal ingestion of oil of cloves — [case report]View study →Reference 17Janes SEJ et al. · 2005Case reportEssential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]View study →}. It should not be confused with the genotoxic allylbenzenes methyleugenol and estragole: eugenol’s free phenol is conjugated directly, so it does not travel their carcinogenic route ^{19Reference 19Zhang X et al. · 2022ReviewA cautionary tale for using read-across for cancer hazard classification: case study of isoeugenol and methyleugenol — [review]View study →}.

Dental & Local-Anaesthetic Use

This is eugenol’s clearest real-world application and its only strong human signal. In a randomised, subject-blinded trial, a homemade eugenol/clove gel produced significantly lower pain scores than placebo and was statistically indistinguishable from benzocaine 20% before needle insertion into oral mucosa ^{1Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →}.

The mechanism is well characterised and squarely pharmacological. Eugenol blocks voltage-gated sodium channels in excitable tissue — the same target class as lidocaine and other conventional local anaesthetics ^{4Reference 4Teixeira-Fonseca JL et al. · 2021In vitroEugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]View study →} — and additionally activates the nociceptor channel TRPA1, acts as a mode-selective TRPV1 antagonist ^{3Reference 3Chung G et al. · 2014In vitroActivation of transient receptor potential ankyrin 1 (TRPA1) by eugenol — [in vitro]View study →}, and non-competitively inhibits the GABA-A current in trigeminal-ganglion neurons ^{2Reference 2Lee SH et al. · 2015In vitroEugenol inhibits the GABAA current in trigeminal ganglion neurons — [in vitro]View study →}. Together these actions quiet sensory-neuron firing at the site of contact.

This is the pharmacology behind zinc-oxide-eugenol (ZOE) dental dressings, temporary fillings and sedative cements, and behind the folk use of clove oil for toothache. The evidence is specifically topical and local: no trial defines an effective eugenol concentration, compares durability against lidocaine, or supports any systemic analgesic use ^{1Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →}.

The Biphasic Dose Response

Eugenol’s defining pharmacological signature is that the same molecule is protective at low doses and toxic at high ones — the dose, not the compound, sets the sign of the effect. Every benefit claim here has to be read with its dose-reversal attached.

The gastric-ulcer model shows it most starkly: eugenol at 1 mg/kg accelerated gastric-ulcer healing by up to ~52%, while at 100 mg/kg it enlarged the ulcerated area ^{10Reference 10Longo B et al. · 2021AnimalDual role of eugenol on chronic gastric ulcer in rats: low-dose healing efficacy and worsening gastric lesion in high doses — [animal in vivo (rat model)]View study →}; and low-dose eugenol protected the rat stomach against ethanol injury by raising mucus and prostaglandin output and lowering lipid peroxidation and TNF-α/IL-6 ^{9Reference 9Hobani YH et al. · 2022AnimalGastroprotective effect of low-dose eugenol in experimental rats against ethanol-induced toxicity — [animal in vivo (rat model)]View study →}. The same inversion runs through the liver: eugenol is antioxidant and organ-protective at low exposure but structurally and functionally hepatotoxic at high doses ^{15Reference 15Carvalho RPR et al. · 2022AnimalHigh doses of eugenol cause structural and functional damage to the rat liver — [animal in vivo (rat model)]View study →}.

The switch is metabolic. Eugenol’s free phenol is normally conjugated and cleared, but a minor CYP-mediated oxidative route generates a reactive quinone methide that depletes glutathione and binds cellular proteins ^{13,14Reference 13Thompson DC et al. · 1998In vitroComparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays — [in vitro]View study →Reference 14Mizutani T et al. · 1991AnimalHepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]View study →}. At low exposure this route is trivial and radical-scavenging dominates; once it is driven hard, or glutathione is exhausted, the pro-oxidant, thiol-depleting arm takes over ^{14Reference 14Mizutani T et al. · 1991AnimalHepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]View study →}. Because whole-herb dietary intake sits at the low end and concentrated essential oil pushes toward the high end, the “protective” low-dose findings cannot be assumed to transfer to either everyday spice use or neat clove oil.

What It's Used For

With the two load-bearing stories — topical anaesthesia and the biphasic curve — told above, the remainder of eugenol’s literature is a broad but preclinical map: antimicrobial, anti-inflammatory, gastroprotective and cardiovascular activity, mostly in cells or rodents. Two disciplines govern how to read it: nearly all systemic findings use isolated eugenol or essential oil at supra-culinary doses, and every effect sits somewhere on the biphasic dose curve.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Only the topical-analgesia row rests on human data; the rest are preclinical by design.

01Topical local anaesthesia / analgesiaPromising64%Human RCT vs benzocaine + Na⁺-channel / TRP / GABA-A mechanism ^{1,2,3,4Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →Reference 2Lee SH et al. · 2015In vitroEugenol inhibits the GABAA current in trigeminal ganglion neurons — [in vitro]View study →Reference 3Chung G et al. · 2014In vitroActivation of transient receptor potential ankyrin 1 (TRPA1) by eugenol — [in vitro]View study →Reference 4Teixeira-Fonseca JL et al. · 2021In vitroEugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]View study →}

02Antibacterial & antifungalPromising60%Broad in-vitro potency + antibiotic/antifungal synergy ^{5,8Reference 5Marchese A et al. · 2017ReviewAntimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]View study →Reference 8Biernasiuk A et al. · 2022In vitroClove essential oil and its main constituent, eugenol, as potential natural antifungals against Candida spp. alone or in combination with other antimycotics — [in vitro]View study →}

03Anti-inflammatory & antioxidantPromising57%NF-κB / cytokine suppression + radical scavenging in cells/rodents ^{6,7Reference 6Barboza JN et al. · 2018ReviewAn overview on the anti-inflammatory potential and antioxidant profile of eugenol — [review]View study →Reference 7Bachiega TF et al. · 2012In vitroClove and eugenol in noncytotoxic concentrations exert immunomodulatory/anti-inflammatory action on cytokine production by murine macrophages — [in vitro]View study →}

04Gastroprotection (biphasic)Promising48%Low-dose rat mucosal protection that reverses to ulcerogenic at high dose ^{9,10Reference 9Hobani YH et al. · 2022AnimalGastroprotective effect of low-dose eugenol in experimental rats against ethanol-induced toxicity — [animal in vivo (rat model)]View study →Reference 10Longo B et al. · 2021AnimalDual role of eugenol on chronic gastric ulcer in rats: low-dose healing efficacy and worsening gastric lesion in high doses — [animal in vivo (rat model)]View study →}

05Cardiovascular & antiplateletPromising46%Human platelets ex vivo + antiarrhythmic cardiac Na⁺-channel action ^{4,11Reference 4Teixeira-Fonseca JL et al. · 2021In vitroEugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]View study →Reference 11Huang WC et al. · 2024AnimalEugenol suppresses platelet activation and mitigates pulmonary thromboembolism in humans and murine models — [human ex vivo and mouse model]View study →}

Mechanisms

The Na⁺-channel block is the load-bearing, human-relevant mechanism; the quinone-methide/glutathione route is the load-bearing toxic one, and the two frame the whole page.

Pharmacokinetics

Eugenol is rapidly absorbed and extensively first-pass metabolised. In humans it is almost completely excreted in the urine within 24 h, with less than 0.1% of the dose appearing unchanged and roughly 95% recovered as phenolic conjugates — predominantly glucuronide and sulfate of the phenolic hydroxyl ^{12Reference 12Fischer IU et al. · 1990The metabolism of eugenol in man — [human pharmacokinetics]View study →}. That free phenol is the pharmacokinetic pivot: because it can be conjugated directly, most eugenol is efficiently detoxified and cleared. A minor oxidative route via cytochrome P450, however, generates the reactive quinone methide intermediate that is normally scavenged by glutathione; when this pathway is driven hard (high dose) or glutathione is depleted, the reactive metabolite binds cellular thiols and proteins and produces hepatotoxicity ^{13,14Reference 13Thompson DC et al. · 1998In vitroComparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays — [in vitro]View study →Reference 14Mizutani T et al. · 1991AnimalHepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]View study →}. Net: a molecule with favourable clearance at ordinary exposure whose toxicity is a saturable, dose- and glutathione-dependent phenomenon rather than a property of the parent compound.

Clinical Trials

Human clinical evidence is confined to topical/dental use — the local-anaesthesia RCT above ^{1Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →} and the long clinical record of zinc-oxide-eugenol dental materials. The systemic anti-inflammatory, antimicrobial, gastroprotective, antiplatelet and metabolic findings are preclinical; the human-subject studies that exist beyond dentistry are contact-allergy patch/ROAT trials (a safety, not an efficacy, endpoint) ^{18Reference 18Ofenloch RF et al. · 2023Clinical trialAllergic reactivity for different dilutions of eugenol in repeated open application test and patch testing — [clinical study]View study →}.

Last checked: July 2026.

Eugenol vs. Methyleugenol & Estragole

Eugenol is routinely confused with its sibling molecules methyleugenol and estragole, and the distinction is the single most important thing to get right about its long-term safety.

Methyleugenol and estragole are allylbenzenes that lack a free phenolic hydroxyl — in methyleugenol the hydroxyl is capped as a methyl ether. With no free phenol to conjugate, they are metabolised down a different road: 1’-hydroxylation followed by sulfation to DNA-reactive carbocations, which form hepatic DNA adducts. Both are therefore classed as genotoxic carcinogens ^{19Reference 19Zhang X et al. · 2022ReviewA cautionary tale for using read-across for cancer hazard classification: case study of isoeugenol and methyleugenol — [review]View study →}.

Eugenol carries that phenolic hydroxyl free. It is conjugated directly to glucuronide and sulfate and cleared ^{12Reference 12Fischer IU et al. · 1990The metabolism of eugenol in man — [human pharmacokinetics]View study →}, so it does not enter the 1’-hydroxylation/sulfation route and does not share the adduct-forming carcinogenic mechanism ^{19Reference 19Zhang X et al. · 2022ReviewA cautionary tale for using read-across for cancer hazard classification: case study of isoeugenol and methyleugenol — [review]View study →}. Eugenol’s own risk is the dose-dependent hepatotoxicity described below — a different hazard from the genotoxicity of its capped relatives. The read-across is one-directional: do not project methyleugenol’s carcinogenicity onto eugenol, and do not project eugenol’s comparatively benign phenol chemistry onto methyleugenol ^{19Reference 19Zhang X et al. · 2022ReviewA cautionary tale for using read-across for cancer hazard classification: case study of isoeugenol and methyleugenol — [review]View study →}.

Isolate vs. Plant Studies

The split here is unusually clean. The one human-efficacy result is a plant-vehicle topical — a clove/eugenol gel on oral mucosa ^{1Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →} — and it agrees with the isolated-molecule sodium-channel mechanism ^{4Reference 4Teixeira-Fonseca JL et al. · 2021In vitroEugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]View study →}. Everything else — antimicrobial, anti-inflammatory, gastroprotective, antiplatelet, hepatic — is either purified eugenol or essential oil, tested in cells or rodents at doses far above what culinary clove, cinnamon or basil delivers. Critically, the biphasic dose-reversal ^{10,15Reference 10Longo B et al. · 2021AnimalDual role of eugenol on chronic gastric ulcer in rats: low-dose healing efficacy and worsening gastric lesion in high doses — [animal in vivo (rat model)]View study →Reference 15Carvalho RPR et al. · 2022AnimalHigh doses of eugenol cause structural and functional damage to the rat liver — [animal in vivo (rat model)]View study →} means whole-herb dietary intake cannot be assumed to deliver the “protective” low-dose effects, and concentrated essential oil pushes toward the toxic high-dose end. Attribute the pharmacology to eugenol the molecule at a stated dose, never to the spice.

Its Role in Plants

In the plant, eugenol is not a passive flavour molecule but a defence and scent volatile. It is built from the amino acid phenylalanine through the general phenylpropanoid pathway — via coniferyl alcohol and coniferyl acetate — with the committed final step catalysed by the enzyme eugenol synthase.

Ecologically it works chiefly as a chemical defence: eugenol and eugenol-rich oils are broadly antibacterial and antifungal ^{5,8Reference 5Marchese A et al. · 2017ReviewAntimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]View study →Reference 8Biernasiuk A et al. · 2022In vitroClove essential oil and its main constituent, eugenol, as potential natural antifungals against Candida spp. alone or in combination with other antimycotics — [in vitro]View study →} and show insecticidal and larvicidal activity ^{20Reference 20Narayanankutty A et al. · 2021In vitroChemical composition of Cinnamomum verum leaf and flower essential oils and analysis of their antibacterial, insecticidal, and larvicidal properties — [in vitro / analytical]View study →}, deterring microbes, insects and herbivores, while the strong clove aroma contributes to floral and foliar scent. As always, a compound’s job in the plant does not predict its behaviour as a medicine — the ecological role sits off the human-pharmacology axis.

Prevalence in Nature

Eugenol is a phenylpropanoid volatile made across several unrelated plant families. Its flagship source is clove (Syzygium aromaticum, Myrtaceae), whose bud essential oil is 70–90% eugenol ^{5,6Reference 5Marchese A et al. · 2017ReviewAntimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]View study →Reference 6Barboza JN et al. · 2018ReviewAn overview on the anti-inflammatory potential and antioxidant profile of eugenol — [review]View study →}. It is the aroma-defining component of cinnamon-leaf oil (Cinnamomum verum, Lauraceae) — where content is strongly chemotype- and tissue-dependent (a measured 18.7% in one C. verum leaf-oil sample ^{20Reference 20Narayanankutty A et al. · 2021In vitroChemical composition of Cinnamomum verum leaf and flower essential oils and analysis of their antibacterial, insecticidal, and larvicidal properties — [in vitro / analytical]View study →}, but commonly reported at 70–90% in high-eugenol leaf chemotypes, in contrast to the cinnamaldehyde-dominated bark oil). It also occurs in tulsi/basil (Ocimum, as a chemotype-defining volatile), bay and allspice (Pimenta), nutmeg, and as a minor constituent of the herbs here including cassia cinnamon, damiana and horopito. Absolute concentrations are quantified for the major oils in the table below; for most minor sources only presence, not a measured percentage, is documented.

Major Natural Sources

Source	Plant part	Reported eugenol content
Clove (Syzygium aromaticum)	bud essential oil	~70–90%
Cinnamon leaf (Cinnamomum verum)	leaf essential oil	~18.7% up to ~70–90% (chemotype-dependent)
Basil (Ocimum spp., eugenol chemotype)	leaf essential oil	chemotype-defining fraction
Allspice, bay, nutmeg	fruit/leaf/seed oil	present, not routinely quantified

These figures are the percentage of the essential oil, not of the whole plant, and shift with species, chemotype, plant part and extraction method ^{5,6,20Reference 5Marchese A et al. · 2017ReviewAntimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]View study →Reference 6Barboza JN et al. · 2018ReviewAn overview on the anti-inflammatory potential and antioxidant profile of eugenol — [review]View study →Reference 20Narayanankutty A et al. · 2021In vitroChemical composition of Cinnamomum verum leaf and flower essential oils and analysis of their antibacterial, insecticidal, and larvicidal properties — [in vitro / analytical]View study →}.

Discovery & Synthesis

Clove oil was studied by the French chemist Jacques Bonastre in 1827, who noted its acidic, salt-forming character; the phenolic principle itself was first isolated from clove oil in 1834 by the German chemist Carl Jacob Ettling. It was purified and named “eugenol” around 1858 by August Cahours, after Eugenia caryophyllata — the former Linnaean name for clove. Today eugenol is obtained chiefly by fractional distillation/extraction of clove and cinnamon-leaf essential oils, which are cheap and eugenol-rich enough that natural sourcing dominates; it can also be synthesised by allylation of guaiacol with an allyl halide. Historically the molecule’s commercial importance was as a vanillin precursor — an 1891 patent isomerised eugenol to isoeugenol en route to synthetic vanillin, and Claisen-rearrangement chemistry later provided allyl-ether routes to the ring system.

Patents: not yet researched.

Toxicity & Safety

Eugenol carries a moderate flag — a reclassification from the older “low” rating, justified by dose-dependent hepatotoxicity and documented paediatric clove-oil poisonings, not by any hazard of ordinary dietary or dental use. The subsections below run from the load-bearing hazard down.

Hepatotoxicity & Clove-Oil Overdose

This is the single most important safety point on the page. At high doses (10–40 mg/kg) eugenol causes structural and functional liver damage in healthy rats ^{15Reference 15Carvalho RPR et al. · 2022AnimalHigh doses of eugenol cause structural and functional damage to the rat liver — [animal in vivo (rat model)]View study →}, and the mechanism mirrors paracetamol: CYP-mediated bioactivation to a reactive quinone methide, depletion of protective glutathione, and covalent binding to cellular thiols/proteins ^{13,14Reference 13Thompson DC et al. · 1998In vitroComparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays — [in vitro]View study →Reference 14Mizutani T et al. · 1991AnimalHepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]View study →}. In mice, eugenol is non-hepatotoxic up to 600 mg/kg but becomes hepatotoxic once glutathione is depleted ^{14Reference 14Mizutani T et al. · 1991AnimalHepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]View study →} — confirming the injury is a glutathione-dependent, saturable event.

Clinically this plays out as concentrated-clove-oil poisoning, most dangerously in children. A 15-month-old developed fulminant hepatic failure after ingesting about 10 mL of clove oil ^{17Reference 17Janes SEJ et al. · 2005Case reportEssential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]View study →}, and paediatric ingestions present with coma, seizures, coagulopathy/DIC and acute liver failure resembling severe paracetamol overdose — treated, as for paracetamol, with N-acetylcysteine ^{16,17Reference 16Hartnoll G et al. · 1993Case reportNear fatal ingestion of oil of cloves — [case report]View study →Reference 17Janes SEJ et al. · 2005Case reportEssential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]View study →}. Concentrated clove oil is not a culinary ingredient and must never be swallowed.

Bleeding Risk

Eugenol inhibits human platelet aggregation ex vivo ^{11Reference 11Huang WC et al. · 2024AnimalEugenol suppresses platelet activation and mitigates pulmonary thromboembolism in humans and murine models — [human ex vivo and mouse model]View study →}, giving a plausible pharmacodynamic interaction with anticoagulant and antiplatelet drugs and grounds to discontinue clove oil before surgery. This is the safety flip-side of the antiplatelet signal noted in the cardiovascular research above.

Contact Allergy & Irritation

Eugenol is a well-recognised fragrance contact allergen (a component of fragrance mix I) and a prohapten requiring enzymatic activation; repeated-open-application and patch testing show reactivity even at low dilutions ^{18Reference 18Ofenloch RF et al. · 2023Clinical trialAllergic reactivity for different dilutions of eugenol in repeated open application test and patch testing — [clinical study]View study →}. Undiluted oil irritates and can burn skin, oral mucosa and dental pulp — the same reactivity that underlies its antimicrobial potency.

Scope & Reproductive Note

No systematic CYP450 drug-interaction study was located, so interactions beyond the pharmacodynamic bleeding risk are unstudied rather than excluded; treat silence as unassessed, not as safety. Human reproductive data for isolated eugenol are limited and no isolate-specific verdict is issued here — pregnancy and lactation decisions belong to the herb or product page where intake is decided, not to this molecule page.

Safety at a Glance

⚠️ Moderate toxicityLiver riskBleeding riskAllergy risk

• Long dietary and dental history. A GRAS food-flavouring and the active principle of zinc-oxide-eugenol dentistry; ordinary culinary and topical use is well tolerated.
• Dose-dependent hepatotoxicity — concentrated clove oil is dangerous swallowed. Ingestion of as little as ~5–10 mL has caused paracetamol-like fulminant hepatic failure, coma, seizures and coagulopathy in young children ^{16,17Reference 16Hartnoll G et al. · 1993Case reportNear fatal ingestion of oil of cloves — [case report]View study →Reference 17Janes SEJ et al. · 2005Case reportEssential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]View study →}.
• Bleeding interaction. Eugenol inhibits platelet aggregation — plausible additive risk with anticoagulant/antiplatelet drugs, and a reason to stop clove oil before surgery ^{11Reference 11Huang WC et al. · 2024AnimalEugenol suppresses platelet activation and mitigates pulmonary thromboembolism in humans and murine models — [human ex vivo and mouse model]View study →}.
• Contact allergen. A component of fragrance mix I and a prohapten; can sensitise skin and oral mucosa, and undiluted oil irritates/burns tissue ^{18Reference 18Ofenloch RF et al. · 2023Clinical trialAllergic reactivity for different dilutions of eugenol in repeated open application test and patch testing — [clinical study]View study →}.
• Not the same risk as methyleugenol or estragole. Its free phenol is conjugated directly, so it does not follow their genotoxic 1’-hydroxylation route ^{19Reference 19Zhang X et al. · 2022ReviewA cautionary tale for using read-across for cancer hazard classification: case study of isoeugenol and methyleugenol — [review]View study →}.

Dosage

There is no established or recommended human oral dose for eugenol. The only human application with dosing detail is topical — an eugenol/clove gel applied to oral mucosa for local numbing ^{1Reference 1Alqareer A et al. · 2006RCTThe effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]View study →} — plus its use in zinc-oxide-eugenol dental materials. Systemic figures in the literature are preclinical rodent doses and are biphasic: in the gastric-ulcer model 1 mg/kg protected while 100 mg/kg harmed ^{10Reference 10Longo B et al. · 2021AnimalDual role of eugenol on chronic gastric ulcer in rats: low-dose healing efficacy and worsening gastric lesion in high doses — [animal in vivo (rat model)]View study →}, and hepatic damage appears at 10–40 mg/kg ^{15Reference 15Carvalho RPR et al. · 2022AnimalHigh doses of eugenol cause structural and functional damage to the rat liver — [animal in vivo (rat model)]View study →}. Concentrated clove oil should never be self-dosed by mouth — the margin between protective and toxic is narrow, and as little as ~5–10 mL has caused serious poisoning in children ^{16,17Reference 16Hartnoll G et al. · 1993Case reportNear fatal ingestion of oil of cloves — [case report]View study →Reference 17Janes SEJ et al. · 2005Case reportEssential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]View study →}. These are doses studied in research and are not a personal recommendation.

References

1. Alqareer A, Alyahya A, & Andersson L (2006). The effect of clove and benzocaine versus placebo as topical anesthetics — [randomised controlled trial]. Journal of Dentistry. https://pubmed.ncbi.nlm.nih.gov/16530911/
2. Lee SH, et al. (2015). Eugenol inhibits the GABAA current in trigeminal ganglion neurons — [in vitro]. PLoS One. https://pubmed.ncbi.nlm.nih.gov/25635877/
3. Chung G, et al. (2014). Activation of transient receptor potential ankyrin 1 (TRPA1) by eugenol — [in vitro]. Neuroscience. https://pubmed.ncbi.nlm.nih.gov/24384226/
4. Teixeira-Fonseca JL, et al. (2021). Eugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias — [animal in vivo / in vitro]. Life Sciences. https://pubmed.ncbi.nlm.nih.gov/34217764/
5. Marchese A, et al. (2017). Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint — [review]. Critical Reviews in Microbiology. https://pubmed.ncbi.nlm.nih.gov/28346030/
6. Barboza JN, et al. (2018). An overview on the anti-inflammatory potential and antioxidant profile of eugenol — [review]. Oxidative Medicine and Cellular Longevity. https://pubmed.ncbi.nlm.nih.gov/30425782/
7. Bachiega TF, et al. (2012). Clove and eugenol in noncytotoxic concentrations exert immunomodulatory/anti-inflammatory action on cytokine production by murine macrophages — [in vitro]. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/22420667/
8. Biernasiuk A, Baj T, & Malm A (2022). Clove essential oil and its main constituent, eugenol, as potential natural antifungals against Candida spp. alone or in combination with other antimycotics — [in vitro]. Molecules. https://pubmed.ncbi.nlm.nih.gov/36615409/
9. Hobani YH, et al. (2022). Gastroprotective effect of low-dose eugenol in experimental rats against ethanol-induced toxicity — [animal in vivo (rat model)]. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/35101571/
10. Longo B, et al. (2021). Dual role of eugenol on chronic gastric ulcer in rats: low-dose healing efficacy and worsening gastric lesion in high doses — [animal in vivo (rat model)]. Chemico-Biological Interactions. https://pubmed.ncbi.nlm.nih.gov/33245926/
11. Huang WC, et al. (2024). Eugenol suppresses platelet activation and mitigates pulmonary thromboembolism in humans and murine models — [human ex vivo and mouse model]. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/38396774/
12. Fischer IU, von Unruh GE, & Dengler HJ (1990). The metabolism of eugenol in man — [human pharmacokinetics]. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/2333717/
13. Thompson DC, et al. (1998). Comparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays — [in vitro]. Toxicology and Applied Pharmacology. https://pubmed.ncbi.nlm.nih.gov/9512727/
14. Mizutani T, et al. (1991). Hepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine — [animal in vivo (mouse model)]. Research Communications in Chemical Pathology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/2047567/
15. Carvalho RPR, et al. (2022). High doses of eugenol cause structural and functional damage to the rat liver — [animal in vivo (rat model)]. Life Sciences. https://pubmed.ncbi.nlm.nih.gov/35679916/
16. Hartnoll G, Moore D, & Douek D (1993). Near fatal ingestion of oil of cloves — [case report]. Archives of Disease in Childhood. https://pubmed.ncbi.nlm.nih.gov/8215554/
17. Janes SEJ, et al. (2005). Essential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database — [case report / database analysis]. European Journal of Pediatrics. https://pubmed.ncbi.nlm.nih.gov/15895251/
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