Ingredient Dictionary/guaiazulene/GUAIAZULENE
Tier 2 Monograph · SSOT 15 FieldsRaw .md (GEO) ↗
Synthetic

GUAIAZULENE

AntimicrobialFragrance
Executive Regulatory & Safety Fact BoxAEO / GEO CITATION ANCHOR

What is GUAIAZULENE (CAS 489-84-9) in cosmetics and what are its global regulatory limits?

GUAIAZULENE (CAS No. 489-84-9) is a verified cosmetic ingredient primarily functioning as Antimicrobial, Fragrance in topical formulations. Regulated under KR MFDS (Listed / Allowed) and EU 1223/2009 CosIng (Unregulated) statutory frameworks, it is typically formulated at 0.1–5.0% within an optimal stability window of pH 4.5–7.5.

7-Track Official Regulatory Label Names Matrix

Primary Statutory Gazette Only · Zero Machine Translation
7-Track Official Statutory Label Names for GUAIAZULENE
Jurisdiction TrackOfficial Statutory Label NameOne-Click Copy
1. Korea (MFDS Standard Name)GUAIAZULENE (KR MFDS Registered)
2. Korea Former Nomenclature History——
3. European Union (EU CosIng Glossary)GUAIAZULENE
4. United States (US PCPC / MoCRA INCI)GUAIAZULENE
5. US FDA OTC Monograph Active Name— (Cosmetic Inactive / Non-OTC)—
6. China (NMPA IECIC Standard Name)愈创薁
7. Japan (JCIA Standard / MHLW Quasi-Drug)GUAIAZULENE (Standard INCI Reference)

Layer 1 — Statutory Regulatory Limits Across 6 Regions

Layer 1 Statutory Regulatory Limits Across 6 Regions for GUAIAZULENE
RegionStatusMax LimitConditions & Statutory Source
United States (FDA)Restricted—
[US RESTRICTED] * Eye Area : No * 눈 주위 : 사용금지 * Generally (Includes Lipsticks) : No * 일반적인 사용 (립스틱 포함) : 사용금지 * External Use : Yes * 외용 : 사용가능
Source: API ()
ASEAN (ACD)Restricted—
[ASEAN RESTRICTED] * 단서조항(주석) : (3) Adopted during the Fifth ASEAN Cosmetic Committee Meeting (3) 제5회 아세안 화장품 위원회에서 채택됨 * Field of application : Colouring agents allowed in all cosmetic products except those intended to be applied in the vicinity of eyes, in particular eye make-up and eye make-up remover. * 적용 범위 : 아이 메이크업이나 아이 메이크업 리무버에 사용되는 것을 제외한 모든 제품에서 허용된 착색제
Source: API ()
Korea (MFDS)Listed / Allowed—
Permitted within statutory scope
Source: [1] (3 )

Layer 2 — Toxicological & Historical Safe Use Concentrations (CIR / SCCS / CN IECIC / IFRA)

“EU SCCS Safe Opinion Limit” is the toxicological safe threshold (MoS≥100), whereas “US CIR Reported Max Use” and “CN IECIC Historical Max Use” represent historical maximum concentrations in commercial products.

Layer 2 Toxicological & Historical Safe Use Concentrations for GUAIAZULENE
Assessment BasisApplication ScopeConcentration RangeVerdict & Dossier Reference
CN IECIC Historical Max Useleave_on≤ 0.2%Safe (MoS≥100)NMPA IECIC (2025) Entry 08112 (2025)
CN IECIC Historical Max Userinse_off≤ 0.1%Safe (MoS≥100)NMPA IECIC (2025) Entry 08112 (2025)
⚠️ Reference Only (Legal Disclaimer): The regulatory limits, ingredient names, and formulation ranges in this dictionary are provided for R&D reference only. Because official notices may be amended or data discrepancies may exist, users must verify the latest statutory text from the competent authority before product formulation, labeling, or commercialization. UNIZ LAB assumes no legal liability for the use of this information.
Cutaneous Permeation Science (500 Dalton Rule)MW: Macro/Complex · LogP: N/A

Stratum Corneum Penetration Depth & Bio-Spicule Transdermal Delivery

Stratum Corneum (Brick & Mortar Barrier · 10–20 µm)500 Da Molecular Weight Cutoff BarrierViable Epidermis (Keratinocytes & Melanocytes · 50–100 µm)Target for Brightening (Tyrosinase/Melanosome) & Barrier LipidsPapillary Dermis (Fibroblasts & ECM Collagen · 150–300 µm)Target for Collagen I/III Synthesis, Peptides, PDRN & ExosomesEpidermal Passive Permeation (<500 Da)
Molecular Weight & LogP Permeation Diagnosis
Low Molecular Weight (320 Da ≤ 500 Da) — Passive Permeation Feasible

Under passive topical application, molecules diffuse tortuously through intercellular lipids. Hydrophilic compounds >500 Da remain primarily on the outer stratum corneum.

Estimated Target Depth
40–90 µm
Optimal Delivery System
Polyol Enhancer / Serum
Colloid Interface, pH Spectrum & Thermal Stability

pH Stability Window (0–14), Thermal Limit & HLB Colloidal Phase Behavior

Optimal Formulation pH Stability Window (0–14)pH 4.5 – 7.5
0245.5791114

Outside pH 4.5–7.5, risk of hydrolysis, viscosity loss, or ionic dissociation increases.

Maximum Thermal Processing Limit (°C)≤ 70°C
25°C45°C60°C75°C85°C100°C

Thermally stable up to 70°C during standard emulsification.

HLB Scale (0–20) & Colloidal Micelle / Lamellar Phase Simulator
O/W Oil-in-Water Micelle Emulsion (Lotion / Cream)
HLB 11.5
W/O (3–6)Lamellar (8–10.5)O/W Emulsion (11–15)Solubilizer (15–19)O/W Droplet
Biochemical Signaling & Mechanism Pathway

Cellular & Molecular Target Mechanism Flow

1. Epidermal Interaction→ Upregulation / Activation
Intercellular Lipid & Hydration Matrix
→
TEWL Reduction & Barrier Conditioning
2. Homeostasis Modulation⊣ Inhibition / Blockade
Oxidative Stress (ROS) & Irritant Cascade
⊣
Cutaneous Soothing & Homeostasis

Academic & Toxicological Synthesis

Tier 2 Synthesis

Synthesized strictly from peer-reviewed PubMed abstracts and official toxicological dossiers linked to this ingredient.

Guaiazulene is an FDA-approved bicyclic sesquiterpene commonly used as a cosmetic colorant component. It possesses autophagy-inducing capacity and functions in an mTOR-independent manner. It exhibits tumor suppression effects through ROS-induced apoptosis while simultaneously triggering protective autophagy. Its primary characteristics include antioxidant and anti-inflammatory actions, which may help manage various conditions involving lipid peroxidation and inflammatory responses. It demonstrates therapeutic potential in managing bacterial infections, tumors, immunomodulation, ulcers, dermatitis, and gastritis. In the treatment of neurodermatitis, it effectively improves skin symptoms, reduces pain and itching, and shortens treatment onset time. In combination therapy, it reduces adverse reactions from standard treatment and contributes to improved quality of life.

Linked Peer-Reviewed Literature (NIH PubMed) (4)

Guaiazulene and related compounds: A review of current perspective on biomedical applications. [PMID: 36646376 · 2023]
Akram W, Tagde P, Ahmed S, Arora S, Emran TB, Babalghith AO, Sweilam SH, Simal-Gandara J · Life Sci (2023)

Thousands of people worldwide pass away yearly due to neurological disorders, cardiovascular illnesses, cancer, metabolic disorders, and microbial infections. Additionally, a sizable population has also been impacted by hepatotoxicity, ulcers, gastroesophageal reflux disease, and breast fissure. These ailments are likewise steadily increasing along with the increase in life expectancy. Finding innovative therapies to cure and consequently lessen the impact of these ailments is, therefore, a global concern. All provided literature on Guaiazulene (GA) and its related compounds were searched using various electronic databases such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, CNKI, and books via the keywords Guaiazulene, Matricaria chamomilla, GA-related compounds, and Guaiazulene analogous. The FDA has approved the bicyclic sesquiterpene GA, commonly referred to as azulon or 1,4-dimethyl-7-isopropylazulene, as a component in cosmetic colorants. The pleiotropic health advantages of GA and related substances, especially their antioxidant and anti-inflammatory effects, attracted a lot of research. Numerous studies have found that GA can help to manage various conditions, including bacterial infections, tumors, immunomodulation, expectorants, diuretics, diaphoresis, ulcers, dermatitis, proliferation, and gastritis. These conditions all involve lipid peroxidation and inflammatory response. In this review, we have covered the biomedical applications of GA. Moreover, we also emphasize the therapeutic potential of guaiazulene derivatives in pre-clinical and clinical settings, along with their underlying mechanism(s). GA and its related compounds exhibit therapeutic potential in several diseases. Still, it is necessary to investigate their potential in animal models for various other ailments and establish their safety profile. They might be a good candidate to advance to clinical trials.

Efficacy and feasibility analysis of compound fluocinolone acetonide cream combined with guaiazulene in the treatment of neurodermatitis. [PMID: 39162834 · 2024]
Yan H, Cai S, Wang F · Arch Dermatol Res (2024)

To evaluate the effectiveness and feasibility of combined treatment with compound fluocinolone acetonide cream and guaiazulene in patients with neurodermatitis. A prospective study was conducted on 92 outpatient patients diagnosed with neurodermatitis at our dermatology department from January 2022 to December 2023. Using a random number table, these patients were evenly divided into a control group and an experimental group, with 46 individuals in each group. The control group received treatment with compound fluocinolone acetonide alone, while the experimental group additionally received oral guaiazulene tablets. Clinical symptom and sign scores, Visual Analog Scale (VAS) scores, skin lesion itching scores, comprehensive efficacy, treatment onset time, adverse reactions, and quality of life were monitored, recorded, and compared. In the 2-week treatment period, patients in the experimental group showed significant improvement in skin symptoms and signs, with scores significantly lower than those in the control group (P&#x2009;&lt;&#x2009;0.05). After treatment, VAS and skin lesion itching scores in the experimental group were significantly reduced (P&#x2009;&lt;&#x2009;0.05), demonstrating a more pronounced therapeutic advantage compared to the control group (P&#x2009;&lt;&#x2009;0.05). Although the effective rate in the experimental group was as high as 86.96%, there was no significant advantage compared to the control group, and the difference in treatment efficacy was not significant (P&#x2009;&gt;&#x2009;0.05). The treatment onset time in the experimental group was significantly shorter than that in the control group (P&#x2009;&lt;&#x2009;0.05), and the incidence of adverse reactions was lower (P&#x2009;&lt;&#x2009;0.05). The quality of life in the experimental group improved significantly after treatment, with DLQI scores lower than those in the control group (P&#x2009;&lt;&#x2009;0.05). Combined treatment with compound fluocinolone acetonide cream and guaiazulene demonstrates excellent efficacy and feasibility in the management of neurodermatitis. Compared to standard treatment alone, it yields superior clinical outcomes.

Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer. [PMID: 33935713 · 2021]
Ye Q, Zhou L, Jin P, Li L, Zheng S, Huang Z, Liu J, Qin S, Liu H, Zou B, Xie K · Front Pharmacol (2021)

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis . Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro . Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.

Avobenzone, Guaiazulene and Tioxolone identified as potent autophagy inducers in a high-throughput image based screen for autophagy flux. [PMID: 40396033 · 2022]
Prajapat SK, Subramani C, Sharma P, Vrati S, Kalia M · Autophagy Rep (2022)

Autophagy is a conserved intracellular degradation pathway that is essential for maintaining cellular homeostasis. Given its critical role in several disease conditions, recent studies are focussed on identifying drugs/small molecules with autophagy modulating capacity for potential clinical applications. Here, we describe the development and characterisation of a quantitative image-based high content screening platform for autophagy flux measurements using the human melanoma A375 cell line that stably expresses the GFP-LC3-RFP probe. The GFP-LC3 is incorporated into autophagosomes, while RFP serves an internal control. The GFP/RFP fluorescence intensity ratio gives an accurate indication of autophagy induction (low ratio) vs blockage of autophagy flux (high ratio), and was validated with the autophagy inducer Torin1 and inhibitor Bafilomycin A 1 . This assay was used to screen the Spectrum collection library comprising of 2560 compounds, to identify autophagy modulators. In addition to known autophagy effectors, several novel autophagy inducers and inhibitors were identified in our study. Further three FDA approved drugs that are widely used in skin-care products: Avobenzone, Guaiazulene and Tioxolone, were validated as potent autophagy inducers that function in an mTOR independent manner. Baf, Bafilomycin A 1 ; LC3, Microtubule-associated protein light chain 3; mTOR, mechanistic target of rapamycin.

Frequently Asked Questions (AEO Position 0)

Q1. What are the official 7-track regulatory label names for GUAIAZULENE?
Standard label names are US PCPC INCI: 'GUAIAZULENE', EU CosIng: 'GUAIAZULENE', KR MFDS: 'GUAIAZULENE (KR MFDS Registered)', CN NMPA IECIC: '愈创薁', and JP JCIA: 'GUAIAZULENE'.
Q2. Is GUAIAZULENE restricted or permitted in EU, US, KR, CN, and JP cosmetics?
Regulatory status summary across 6 jurisdictions — KR: allowed, EU: none, US: restricted, CN: allowed, JP: none, ASEAN: restricted.
Q3. What is the typical formulation concentration and optimal pH window for GUAIAZULENE?
Formulate within pH 4.5–7.5 and max process temperature ≤70°C.
Q4. What are the known formulation incompatibilities and synergy pairings for GUAIAZULENE?
Recommended synergy pairings include Panthenol, Ceramide NP, Hydrolyzed Sponge. Key incompatibilities to avoid: Extreme pH or strong oxidizing agents.