Eugenol
Also known as Eugenol, 2-Methoxy-4-(2-propenyl)phenol, 4-Allyl-2-methoxyphenol, 4-Allylguaiacol, Eugenic acid, p-Allylguaiacol
“EU SCCS says: restricted.”
Eugenol (CAS 97-53-0; 4-allyl-2-methoxyphenol; C10H12O2) is the principal aromatic constituent (80-95%) of clove oil and a long-established fragrance allergen on the original list of 26 substances regulated under EU Cosmetics Regulation 1223/2009 Annex III (Reference 71), requiring label declaration above 0,001% in leave-on and 0,01% in rinse-off products. The SCCS opinion SCCS/1459/11 (2012) classifies Eugenol in Table 13-1 (p. 107) as an established contact allergen in humans with a +++ rating (101-1000 published positive patch test cases) and asterisks it as one of the 1999 SCCNFP-listed allergens. Critically, SCCS/1459/11 Section 13.4 / Table 13-6 (p. 118) classifies Eugenol as an established prohapten of clinical importance — bioactivated by skin enzymatic oxidation rather than by air-autoxidation. This distinguishes Eugenol mechanistically from prehapten allergens like Limonene and Linalool: Eugenol does NOT have a peroxide cap recommendation in SCCS/1459/11 (the 10 ppm peroxide guidance is specifically for hydroperoxide-forming prehaptens). Mechanistic studies (Bertrand et al. 1997, Chem Res Toxicol, PMID 9084914; Port-Lougarre et al. 2023, PMID 37922503) describe Eugenol's bioactivation pathway: enzymatic O-demethylation followed by oxidation to electrophilic ortho-quinone (potentially tautomerising to para-quinone methide) that haptenises skin proteins; a complementary radical-based pathway has also been proposed. Patch test data summarised in SCCS/1459/11 (p. 185) show 0.5-1.3% positive reactions across multiple consecutive-tested dermatology populations (IVDK 2007: 0.5%; Groningen 2009: 1.3%; Giusti 1998-2000: 1.2%; An 2005: 1.9%). Eugenol can also induce immediate-type airway reactions (occupational asthma case in a hairdresser) and was historically a sensitiser via eugenol/zinc oxide dental restorative materials. The RIFM Expert Panel update (Api et al. 2022, PMID 35439588; original 2016 PMID 26702986) integrates these data into a comprehensive industry safety assessment; the 2016 evaluation identified a reproductive toxicity NOAEL of 230 mg/kg/day and an MOE of 12,105 (22.6% dermal absorption assumed). CIR has NOT published a standalone Eugenol assessment — verified absent by alphabetical traversal of the September 2022 QRT (alphabetically: Etidronic Acid → [no Eugenol] → Eucalyptus Globulus Leaf), consistent with CIR's deferral of fragrance-only ingredients to RIFM/IFRA/SCCS.
Principal aromatic constituent (80-95%) of clove oil; also found in citronella oil, pimento leaf oil, and cinnamon bark oil — provides characteristic warm, spicy, clove fragrance note.
Comprehensive RIFM Expert Panel safety assessment (Api et al. 2016, FCT 97(Suppl 1):S25-S37; updated 2022 FCT 163(Suppl 1):113027) integrates skin sensitisation, genotoxicity, repeated-dose, developmental, reproductive, respiratory, and phototoxicity data — supports continued use at fragrance-typical concentrations within QRA-derived limits.
2016 RIFM evaluation identified reproductive toxicity NOAEL of 230 mg/kg/day with MOE of 12,105 (assuming 22.6% dermal absorption and 100% inhalation absorption) — large safety margin for systemic endpoints at typical cosmetic exposure.
Used historically in dentistry (zinc oxide eugenol restorative materials, dental analgesic, antiseptic mouthwash) and in food flavoring; FDA classified as GRAS for food use — evidences a long systemic-safety history independent of cosmetic dermal sensitisation concerns.
- · Reg (EU) 2023/1545 expanded the Annex III allergen list to >80 substances (transition through July 2028 for new products) but did not change Eugenol's Reference 71 disclosure thresholds.
Established contact allergen in humans per SCCS/1459/11 Table 13-1 (p. 107): +++ rating (101-1000 published positive patch test cases); asterisked as identified in the 1999 SCCNFP fragrance allergens opinion. One of the original ICDRG/baseline patch test allergens.
Established PROHAPTEN per SCCS/1459/11 Section 13.4 / Table 13-6 (p. 118): bioactivated by skin enzymatic oxidation (NOT air-autoxidation) — undergoes O-demethylation followed by oxidation to electrophilic ortho-quinone (and tautomeric para-quinone methide) which covalently bind skin proteins to form the antigenic hapten complex (Bertrand 1997 PMID 9084914; Port-Lougarre 2023 PMID 37922503).
Mandatory EU label disclosure (Annex III Reference 71) when concentration exceeds 0,001% leave-on or 0,01% rinse-off; ingredient cannot be hidden under generic 'Parfum/Fragrance' declaration above these thresholds.
Patch test prevalence: 0.5-1.3% positive reactions in baseline dermatology series across multiple European studies (IVDK 2007: 0.5% n=2065; Groningen 2009: 1.3% n=tested at 2%; Giusti 1998-2000: 1.2% n=1754); 1.9% in An 2005 study at 2% test concentration. Among the more common documented fragrance contact allergens.
Documented to cause immediate-type respiratory reactions including a well-characterised occupational bronchial asthma case in a hairdresser (SCCS/1459/11 p. 185); occupational sensitisation also reported from eugenol/zinc oxide dental restorative material exposure.
Cross-reactivity with related allergens: structurally related to isoeugenol (CAS 97-54-1, separate Annex III entry, also +++ rated) and methyl eugenol (CAS 93-15-2). Cross-sensitisation between eugenol and other Fragrance Mix I components has been documented.
No CIR safety assessment exists — verified absent by alphabetical traversal of the September 2022 CIR Quick Reference Table (alphabetically: Etidronic Acid → Eucalyptus Globulus Leaf, with no Eugenol row in between). CIR defers fragrance-only ingredients to RIFM/IFRA.
SCCS/1459/11 — Opinion on Fragrance Allergens in Cosmetic Products (adopted 26-27 June 2012). EUGENOL CAS 97-53-0 listed in Table 13-1 (p…
“EUGENOL* 97-53-0 +++”— sccs_o_102_0.pdf, p. 107 (Table 13-1: Established contact allergens in humans)
EU Regulation 1223/2009 Annex III (Restricted Substances) — Reference 71: 2-Methoxy-4-(2-propenyl)-phenol (INCI: Eugenol, CAS 97-53-0); f…
“The presence of the substance must be indicated in the list of ingredients referred to in Article 19(1)(g) when its concentration exceeds: 0,001 % in leave-on products 0,01 % in rinse-off products”— EU Reg 1223/2009 Annex III, Reference 71 (Eugenol), column (h)