IngredientesAllantoin is a skin protectant also known as 5-ureidohydantoin or glyoxyldiureide, with the chemical formula C4H6N4O3 and the chemical name 2,5-Dioxo-4-imidazolidinyl urea. It is also called glyoxyldiureide and is a diureide of glyoxylic acid. Its CAS number is 97-59-6, with EINECS/ELINCS number 202-592-8 and COSING REF No. 31411. The INCI (International Nomenclature of Cosmetic Ingredients) name is simply Allantoin.
Allantoin is a white crystalline powder with a molecular weight of 158.1164 g/mol and a melting point of 239°C. It has a solubility in water of 0.5% at 25°C.
Allantoin is a major metabolic intermediate in most organisms including animals, plants, and bacteria, though not humans. It is produced from uric acid, which itself is a degradation product of nucleic acids, by the action of urate oxidase (uricase). Named after the allantois (an amniote embryonic excretory organ in which it concentrates during development in most mammals except humans and other hominids), it is a product of oxidation of uric acid by purine catabolism. After birth, it is the predominant means by which nitrogenous waste is excreted in the urine of these animals. In humans and other higher apes, the metabolic pathway for conversion of uric acid to allantoin is not present, so uric acid is excreted instead.
Allantoin is found in plants such as chamomile, wheat sprouts, sugar beet, and comfrey — a herb with purple flowers. Its main botanical extract comes from comfrey (Symphytum officinale), although it is also found in tobacco seed, chamomile, and wheat sprouts. It can be extracted from the leaves and roots of comfrey, and the allantoin content in the root varies between 0.7% and 2.5%. Allantoin can also be found in mammalian amniotic fluid and urine, and in the mucus of snails.
Allantoin was first isolated in 1800 by the Italian physician Michele Francesco Buniva (1761–1834) and the French chemist Louis Nicolas Vauquelin, who mistakenly believed it to be present in amniotic fluid. In 1821, the French chemist Jean Louis Lassaigne found it in the fluid of the allantois, calling it "l'acide allantoique." In 1837, the German chemists Friedrich Wöhler and Justus Liebig synthesized it from uric acid and renamed it "allantoïn."
While allantoin may be obtained from natural sources, it is normally prepared synthetically for cosmetic use, either by oxidation of uric acid, reaction of dichloroacetic acid and urea, or condensation reaction between glyoxylic acid and urea. Chemically synthesized bulk allantoin is chemically equivalent to natural allantoin and is safe, non-toxic, and compatible with cosmetic raw materials, meeting CTFA and JSCI requirements.
The comfrey plant has been used for medicinal purposes for over 2,000 years, with the earliest recorded use of comfrey as a traditional herbal remedy traceable to the ancient Greeks in approximately 400 BCE. Comfrey (Symphytum officinale) is a shrub found in Europe and some parts of Asia and has been used since Roman times for its medicinal properties.
Historically, comfrey developed the nickname "knitbone" because herbalists associated the plant with supporting the healing of bones, ligaments, and connective tissue. For centuries, herbal traditions used comfrey for sprains and other connective tissue injuries, applied externally in ointments, oils, poultices, and salve preparations to support recovery from sprains, strains, and muscle injuries.
Both the comfrey leaf and the root have historically been used in herbal medicine. Traditional herbalists prepared infused oils, comfrey salve, and comfrey ointment using these plant parts. In traditional medicine, people may take comfrey by mouth or apply it topically using balms, ointments, and other preparations.
In 1912, scientists submitted samples of comfrey root for chemical analysis and thereby isolated the compound allantoin as the primary active. Historically, allantoin was used to promote wound healing and treat skin ulcers. Early 20th-century researchers, including British physician Dr. C.J. MacAlister, conducted clinical observations on comfrey and its constituent allantoin, publishing work as early as 1936 that characterized its cell-proliferating and wound-healing properties.
MacAlister proposed that allantoin induces cell proliferation in a physiological way, rendering it useful not only as a vulnerary but also as a promoter of leucocytosis to help establish immunities in some infective conditions.
Allantoin (5-ureide-hydantoin) has been widely cited in the literature as possessing numerous pharmacological activities, including wound healing, anti-irritating, hydrating, and removal of necrotic tissue, as well as stimulating cell mitosis, promoting epithelial stimulation, and analgesic and keratolytic activity.
Allantoin is a moderate keratolytic agent that aids in the natural desquamation of the stratum corneum and improves skin smoothness by dissolving the intercellular cement that keeps cornified cells together. It facilitates the desquamation of the stratum corneum, and one of its key benefits relative to other desquamation agents is that it is non-irritating to the skin. By softening keratin, allantoin allows the skin to hold onto water better, making it moister, softer, and better hydrated.
Allantoin has been shown to facilitate proliferation of healthy tissue by promoting cell proliferation and extracellular matrix synthesis. Allantoin may also have a role in tissue formation and differentiation, specifically in stimulating the development of granulation tissue and epithelialization.
Studies indicate that allantoin stimulates cell proliferation, particularly of keratinocytes and fibroblasts. This has been demonstrated in in vitro models, where allantoin-treated fibroblasts showed increased DNA synthesis and mitotic activity. This regenerative capability is attributed to allantoin's ability to stimulate fibroblast activity, which is essential for collagen synthesis and repair of damaged tissue.
Several beneficial effects of allantoin include a moisturizing and keratolytic effect, increasing the water content of the extracellular matrix and enhancing the desquamation of upper layers of dead skin cells, increasing the smoothness of the skin; promoting cell proliferation and wound healing; and a soothing, anti-irritant, and skin protectant effect by forming complexes with irritant and sensitizing agents.
Allantoin modulates inflammatory pathways by downregulating pro-inflammatory cytokines such as TNF-α and IL-6. It is believed to inhibit NF-κB signaling in immune cells, thereby reducing oxidative stress and inflammation in the dermis. Allantoin has been shown to have multiple properties expected to facilitate transition of a wound from an inflammatory to a proliferative state, including antioxidant and anti-inflammatory properties, direct antimicrobial effects, and keratolytic activity.
Allantoin may also reduce scar formation by preventing epidural fibrosis, as tested in a rat hemilaminectomy model.
The mechanism of action of allantoin is complex, including demonstrated healing properties, antibacterial effects, keratolytic activity in humans, and anti-inflammatory/soothing properties. It is important to note that while different allantoin-containing preparations have been used clinically to study its therapeutic effects in wound healing, its specific mechanisms of action are not known with certainty.
Preclinical evidence (animal and in vitro): A systematic literature search identified approximately 100 preclinical studies (in vitro and animal models) and approximately 30 clinical studies focused on the mechanism of action of allantoin that impacts multiple steps of the wound healing process.
One key preclinical study evaluated the wound healing process profile induced by allantoin incorporated in a soft lotion oil/water emulsion using planimetric and histological methods. The results suggest that the wound healing mechanism induced by allantoin occurs via the regulation of inflammatory response and stimulus to fibroblastic proliferation and extracellular matrix synthesis. Female Wistar rats (n=60) were randomly assigned to control, emulsion excipient, and 5% allantoin emulsion groups. The emulsions were topically administered for 14 days, and the wound area was evaluated by planimetry and histological analysis.
A further experimental study described a liquid allantoin-enriched pectin hydrogel applied topically to surgically induced skin wounds in a rat model. Results indicated that the hydrogel improved wound contraction, reducing around 71.43% of the total healing time and reaching total wound closure in 15 days, compared to a calculated 24 days in the control group.
Evidence strength: The majority of wound healing evidence for allantoin as an isolated compound originates from animal models and in vitro studies. While mechanistically suggestive, these do not constitute high-quality human clinical evidence on their own. The interpretability of compiled results is complicated by the use of different formulations of allantoin and the lack of information on the stability or dermal penetration of allantoin in tested preparations. Additional research is warranted to further characterize clinically relevant mechanisms of action in human skin.
Notably, one rat study examining oral wound healing found that allantoin did not positively or negatively affect wound healing, and none of the tested agents had a negative effect on the rate of wound healing when applied on an excisional wound with epithelial and connective tissue defect. This mixed result underscores that outcomes may depend heavily on wound type, formulation, and route of application.
SD-101 6% is a topical cream containing 6% allantoin developed for treating skin lesions in patients with epidermolysis bullosa (EB). A phase 3, multicenter, randomized, double-blind, vehicle-controlled study assessed the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB. Eligible patients were ≥1 month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional), and a target wound 10–50 cm² that had been present for ≥21 days. Patients were randomly assigned to receive SD-101 6% cream or vehicle, applied topically once daily to the entire body for 3 months.
In total, 169 patients were enrolled and randomly assigned to SD-101 6% (n=82) or vehicle (n=87). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio 1.004; 95% CI 0.651, 1.549; P=0.985) or proportion of patients with complete target wound closure within 3 months (odds ratio [95% CI] 0.733 [0.365, 1.474]; nominal P=0.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to <12 years and those with total body wound burden ≥5% at baseline. SD-101 6% cream was well tolerated.
Evidence strength: This was a well-designed Phase 3 RCT published in Orphanet Journal of Rare Diseases (2020). The trial failed its primary endpoints, demonstrating that 6% allantoin cream was not superior to vehicle for wound closure in EB patients. This is a significant negative result that tempers enthusiasm for high-dose allantoin as a standalone intervention for serious skin lesions.
There is evidence that allantoin diminishes hyperkeratotic changes, erythema, infiltration, and the subjective symptoms of itching and burning in patients with psoriasis. Though most studies investigating these mechanisms were performed in animal models, these clinical observations exist for psoriasis. The overall body of clinical evidence specific to psoriasis remains limited, and findings have not been confirmed in large randomized controlled trials.
Based on wide use and clinical acceptance of allantoin, as well as on published reports in the literature, a U.S. FDA OTC review panel approved statements for products containing allantoin for: "temporarily relieves, protects, soothes, gives comfort to minor skin irritations, such as chapping, peeling, scaling, minor burns, sunburn, windburn, scrapes, abrasions or cracked lips." The FDA OTC Topical Analgesic Review Panel classified allantoin in Category I (Safe and Effective) as an active skin "protectant."
Allantoin is considered safe and effective at concentrations of 0.5% to 2.0% as a "skin protectant" under the OTC monograph, which only allows claims relating to minor cuts, scrapes, burns, or chapped skin.
Allantoin is a moderate keratolytic agent that aids in the natural desquamation of the stratum corneum by dissolving the intercellular cement that keeps cornified cells together. Its capacity to increase the amount of water attached to keratin and the intercellular matrix results in a moisturizing effect. Allantoin enhances skin hydration by increasing the water content of the extracellular matrix. These moisturizing effects are well-established in the cosmetic science literature, though much of the evidence is mechanistic rather than derived from large-scale clinical trials.
Allantoin is used in a wide range of topical dosage forms. It is typically used at concentrations of 0.0001% – 2.0% (w/w) in cosmetic formulations. Concentrations of 0.5% to 2.0% are recognized as safe and effective under the FDA OTC skin protectant monograph.
Specific concentrations reported in studies and formulations include:
There is currently no established oral dosage for allantoin as a dietary supplement. All formalized dosage guidance pertains to topical application.
The safety test data in the CIR safety assessment and in previous safety assessments were considered sufficient to support the safety of allantoin and its allantoin complexes in product categories and at the concentrations reviewed. The Cosmetic Ingredient Review (CIR) Expert Panel rated allantoin as "Safe" in its final report (International Journal of Toxicology, Vol. 29, Suppl. 2, pp. 84–97, 2010).
Allantoin has a high level of skin and cosmetic raw material compatibility, is risk-free, and is not irritating. Allantoin has a long history of use in topical medications and cosmetics without any reports of toxicity or negative side effects.
An important safety distinction must be made between purified allantoin as an isolated ingredient and whole comfrey preparations. Isolated allantoin does not contain pyrrolizidine alkaloids (PAs). The safety concerns relating to PAs are specific to comfrey plant extracts, not to the purified allantoin molecule.
Due to hepatotoxic pyrrolizidine alkaloids (PAs), the EMA restricts the use of comfrey root to external use only and for short periods of time. In the United States, the FDA in 2001 ordered the withdrawal of all dietary supplements containing comfrey.
Following a German drug-safety protocol of 1992, the application of cutaneous preparations with a German Commission E monograph (as is the case with comfrey) would not be restricted when the exposure to PAs does not exceed 10 μg per day. The European Medicines Agency's Public Statement on herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids deemed short-term use of up to 14 days acceptable for orally applied medicinal products, provided that the daily oral intake of unsaturated toxic PAs does not exceed 0.35 μg/day.
PAs such as intermedine, lycopsamine, and their N-oxides have been shown in vitro to be hepatotoxic; however, their permeability through the skin after direct topical application may be very low. It was shown that the penetration of lycopsamine through human epidermis into receptor fluid was in the range of 0.04–0.22% in one study, and 0.6% in another.
Oral use of comfrey products is currently not recommended due to their high content of hepatotoxic pyrrolizidine alkaloids.
In the ESSENCE Phase 3 trial, SD-101 6% allantoin cream was well tolerated. No specific safety signals beyond those expected in the EB patient population were identified in that trial.
The FDA has issued a final monograph establishing conditions under which OTC skin protectant drug products are generally recognized as safe and effective. The final monograph includes OTC skin protectant drug products for minor cuts, scrapes, burns, chapped skin and lips, poison ivy, poison oak, poison sumac, and insect bites. Allantoin was classified as a Category III skin protectant for wound-healing specifically, based on lack of effectiveness data for that specific claim (43 FR 34628). This means that while allantoin is generally recognized as safe, the OTC monograph does not extend to explicit wound-healing efficacy claims.
No clinically documented drug–drug interactions for topically applied isolated allantoin have been identified in the peer-reviewed literature reviewed here. Allantoin has been identified as an enhancer for other active ingredients in skincare formulations — it can improve the absorption and efficacy of various compounds, making it a versatile addition to complex cosmetic products. This property theoretically means that co-formulated actives may have altered bioavailability, though this has not been characterized as a safety risk in the reviewed evidence base.
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Allantoin has been used in acne-relevant formulations for its soothing, anti-irritant, and keratolytic properties. A double-blind trial found that an allantoin and panthenol combination led to significant lesion count reduction and skin texture improvement after 4 weeks in subjects with mild acneiform lesions. The aluminum salt of allantoin has also been specifically noted as an effective acne treatment component.
Allantoin is a wound-healing compound found in comfrey root with documented scientific support for blister management. It has been specifically tested in epidermolysis bullosa (a genetic blistering skin disorder) where SD-101 (6% allantoin cream) reduced blister outbreaks. The FDA classifies allantoin as an OTC skin protectant, and it promotes cell proliferation, tissue regeneration, and reduces inflammation.
Allantoin has documented clinical and preclinical use in burn wound management, particularly in combination formulations. Silver-zinc-allantoinate cream was studied in a clinical series of 264 patients with chronic cutaneous ulcers including burn-related wounds, achieving healing in 339 of 400 lesions. Tissue engineering research has also incorporated allantoin into wound scaffolds specifically designed for severe burns.
Allantoin exhibits documented anti-inflammatory activity through inhibition of COX-2, modulation of NF-κB, and downregulation of pro-inflammatory cytokines such as IL-4, IL-5, TNF-α, and IL-8. In murine allergic models, allantoin reduced IgE levels and Th2 cytokine production. A 2022 in vitro and in vivo study demonstrated dose-dependent inhibition of mast cell degranulation and histamine release.
Allantoin-containing creams have been evaluated in diaper dermatitis in a randomized controlled trial, showing significant reduction of erythema and lesion scores comparable to low-potency steroids. In radiation-induced dermatitis, allantoin-containing emulsions improved skin healing and reduced discomfort. Its keratolytic, anti-inflammatory, and barrier-restoring properties are mechanistically relevant to multiple dermatitis subtypes.
Allantoin (0.5–2%) is recognized by the FDA as a Category I safe and effective OTC skin protectant for diaper rash per the Skin Protectant Drug Products monograph. It promotes keratinocyte proliferation and re-epithelialization, accelerating healing of irritated skin. Multiple DailyMed-listed diaper rash products contain allantoin as an active ingredient alongside zinc oxide.
Allantoin is incorporated in the betaine–allantoin (Xeros Dentaid) saliva substitute mouthwash clinically validated for xerostomia. A randomized controlled trial (n=51) found this formulation was comparable to 1% malic acid spray in significantly improving dry mouth sensation and oral health-related quality of life in drug-induced and idiopathic xerostomia.
Allantoin acts as a humectant and keratolytic agent, increasing water content in the stratum corneum and reducing transepidermal water loss (TEWL). The FDA recognizes allantoin as an OTC skin protectant at 0.5–2%, and clinical formulations containing allantoin have demonstrated measurable improvements in skin hydration. It is widely incorporated into moisturizer products for dry skin conditions.
Moisturizers containing allantoin have been shown to reduce symptoms of mild-to-moderate atopic dermatitis, and a study of chronic hand eczema found allantoin cream combined with tazarotene/betamethasone significantly improved lesion and pruritus scores. Allantoin's keratolytic, humectant, and mild anti-inflammatory properties address key eczema features including barrier disruption, scaling, and inflammation.
A placebo-controlled, double-blind trial in 80 patients with first- and second-degree hemorrhoids evaluated a topical combination preparation containing allantoin (with standardized leech extract and polidocanol). Both subjective and objective symptoms improved significantly faster under the active preparation versus placebo over one week, with histologically confirmed reduced inflammation.
Allantoin is a naturally occurring compound found in plantain (Plantago major), comfrey, and other herbs, used topically for wound healing and skin inflammation. It promotes keratinocyte proliferation, accelerates skin repair, and has anti-inflammatory effects relevant to poison ivy rash recovery. It is present in numerous OTC skin preparations for dermatitis and irritated skin.
Clinical evidence shows allantoin diminishes hyperkeratotic changes, erythema, infiltration, and subjective symptoms of itching and burning in psoriasis patients. Keratolytic activity on psoriatic scales has been demonstrated in vitro at concentrations as low as 0.2%. A clinical pilot study using allantoin at 3% demonstrated clearing of psoriatic plaques, while formulations at 1.5% showed limited efficacy.
A 2022 study published in Molecules (PMC9182162) demonstrated that allantoin dose-dependently inhibited mast cell degranulation, histamine release, and pro-inflammatory cytokine levels in vitro and in vivo, directly relevant to hive formation. Allantoin is also recognized by the FDA as an OTC skin protectant for minor skin irritations, and its anti-irritant properties have been demonstrated in human volunteer studies.
Allantoin is identified in peer-reviewed dermatology literature as one of the most effective OTC ingredients for rosacea redness reduction, often combined with bisabolol. A 2025 RCT (PMID 40177799, n=82) evaluated topical heparin sodium allantoin gel with quercetin in papulopustular rosacea, showing improvements in erythema scores and skin barrier function over 12 weeks.
Allantoin is a keratolytic and moisturizing compound used extensively in commercial scar formulations, including the well-studied onion extract/allantoin combination (e.g., Contractubex). Clinical studies show it improves scar texture, reduces pruritus, and supports re-epithelialization. Its moisturizing and immune-modulatory properties complement anti-scarring actions.
Allantoin promotes cell proliferation, stimulates fibroblast activity, and has been shown to promote collagen production, all of which are relevant to skin aging. It reduces TEWL and improves stratum corneum hydration, addressing dry, aged skin. These properties collectively support its use in anti-aging formulations, though dedicated anti-aging RCTs with allantoin as the sole active are limited.
Allantoin stimulates fibroblast proliferation and extracellular matrix synthesis, including collagen production, as demonstrated in multiple preclinical studies. Animal studies documented early collagen deposition in allantoin-treated wounds. Allantoin has been described as accelerating the growth of connective tissue and promoting skin elasticity.
Silver-zinc-allantoinate cream (AZAC 1%) was studied in a clinical series of 264 patients with 400 chronic cutaneous ulcers (venous, diabetic, and other etiologies); 339 of 400 lesions healed, including cases that had failed prior treatments. AZAC also exhibited broad antimicrobial activity, debrided necrotic tissue, and stimulated healthy granulation tissue.
Allantoin is a natural compound found in comfrey (Symphytum officinale) and other plants, widely used in topical wound-care formulations. It stimulates cell proliferation, accelerates re-epithelialization, and exerts anti-inflammatory effects. It is an approved active ingredient in many over-the-counter skin healing products.
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