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Cosmetic ingredients (Allantoin) -> CIR (Cosmetic Ingredient Review)

Soothing

Odorless

Pleasant smelling

Crystals from aqueous methanol

White to colorless powder or crystals

Monoclinic plates

Soluble in alcohol, methanol, pyridine

Soluble in ethanol, sodium hydroxide; insoluble in ethyl ether, methanol

Water: 0.57% (25 °C); ethanol (96%): 0.04% (25 °C); eth/water (1/1): 0.35% (25 °C); propylene glycol/water (1/1): 0.40% (25 °C); glycerol/water (1/1): 0.60% (25 °C)

In water, 5.26X10+3 mg/L at 25 °C

5.26 mg/mL

239 °C /Racemic form/

MP: 230 °C (decomposes)

239 °C

Dry Powder

Colorless to white odorless solid; [Hawley] White powder; [MSDSonline]

Solid

125.5 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

145.61 Ų [M+Na]+ [CCS Type: DT; Method: stepped-field]

134.17 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

143.3 Ų [M+Na]+

This chemical does not meet GHS hazard criteria for 86.9% (319 of 367) of all reports.

Warning

H302 (13.1%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 367 reports by companies from 4 notifications to the ECHA C&L Inventory.

Chemical: Urea, (2,5-dioxo-4-imidazolidinyl)-

Urea, N-(2,5-dioxo-4-imidazolidinyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Urea, N-(2,5-dioxo-4-imidazolidinyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 30-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/13641

Allantoin: Does not have an individual approval but may be used under an appropriate group standard

Skin protectant active ingredients. The active ingredients of the products consist of any of the following, within the concentration specified for each ingredient. Allantoin, 0.5 to 2 percent.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: allantoin is included in dandruff/seborrheic dermatitis/psoriasis drug products.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: allantoin (wound healing claims only) is included in skin protectant drug products.

Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. Allantoin ... /has/ been present in oral mucosal injury drug products for use as oral wound healing agents. Oral wound healing agents have been marketed as aids in the healing of minor oral wounds by means other than cleansing and irrigating, or by serving as a protectant. Allantoin, carbamide peroxide in anhydrous glycerin, water soluble chlorophyllins, and hydrogen peroxide in aqueous solution are safe for use as oral wound healing agents, but there are inadequate data to establish general recognition of the effectiveness of these ingredients as oral wound healing agents.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Allantoin is found on List C. Case No: 3015; Pesticide type: insecticide; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects; Active ingredient (AI): allantoin; AI Status: The active ingredient is no longer contained in any registered products. Thus, we characterize it as "cancelled."

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Feed containing 0.2% allantoin ... with or without 0.2% sodium nitrite, was given ad lib. to groups of 20 or 24 male and 20 or 24 female F344 rats for 106 wk. ... Control rats were given untreated feed ... and nitrite-treated controls were given sodium nitrite at a concentration of 0.2% in feed or drinking-water. At the end of the treatment period the rats were given untreated feed ...and observed until death. There was little or no life-shortening effect in any treatment group. /Allantoin / administered alone /and in combination with sodium nitrite did not induce/ an increase in the incidence of any tumor in comparison with the untreated control groups ...

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that allantoin is expected to have very high mobility in soil(SRC). Volatilization of allantoin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.4X10-18 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Allantoin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.3X10-9 mm Hg(SRC), determined from a fragment constant method(4). Allantoin was biodegraded 6, 10, and 88% in 5, 15, and 30 days, respectively(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that allantoin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.4X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -3.14(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Allantoin was biodegraded 6, 10, and 88% in 5, 15, and 30 days, respectively(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), allantoin, which has an estimated vapor pressure of 4.3X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase allantoin may be removed from the air by wet or dry deposition(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of allantoin can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that allantoin is expected to have very high mobility in soil(SRC).

The end product of purine metabolism in mammals other than humans and other primates; it results from the oxidation of uric acid

... present in tobacco seeds, sugar beets, white sprouts

An estimated BCF of 3 was calculated in fish for allantoin(SRC), using an estimated log Kow of -3.14(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for allantoin is estimated as 3.4X10-18 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that allantoin is expected to be essentially nonvolatile from water surfaces(2). Allantoin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.3X10-9 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Feed containing 0.2% allantoin ... with or without 0.2% sodium nitrite, was given ad lib. to groups of 20 or 24 male and 20 or 24 female F344 rats for 106 wk. ... Control rats were given untreated feed ... and nitrite-treated controls were given sodium nitrite at a concentration of 0.2% in feed or drinking-water. At the end of the treatment period the rats were given untreated feed ...and observed until death. There was little or no life-shortening effect in any treatment group. /Allantoin / administered alone /and in combination with sodium nitrite did not induce/ an increase in the incidence of any tumor in comparison with the untreated control groups ...

/ALTERNATIVE and IN VITRO TESTS/ Rabbit renal cortical slices were incubated at 25 degrees C, pH 7.4, for 2 hr under 100% O2 in a phosphate-buffered medium. (14-C)allantoin was accumulated to a tissue water/medium ratio of 1.38 +/- 0.03 (mean +/- S.E., n = 22). Under 100% N2, the tissue water/medium ratio fell significantly to 0.90 +/- 0.02 (n = 14, P less than .001). Probenecid (an anion) inhibited the uptake of allantoin at doses which had no effect on the water content of the slices, i.e., did not appear to have a toxic effect on the tissue. Its effect was specific. In contrast, salicylate (another anion) and quinine (a cation) inhibited the uptake of allantoin only at concentrations which simultaneously increased the water content of the slices. These results suggest a toxic effect on cell metabolism. Salicylate (an anion) and quinine (a cation), in dosage which inhibited allantoin uptake, also inhibit the uptake of the para-aminohippuric acid (an anion) and tetraethylammonium bromide (a cation). Net secretion of allantoin was observed in urinary clearance experiments on anesthetized rabbits acutely loaded with allantoin, under mannitol diuresis. At flow rates less than 1 ml/kg/min, fractional excretion of (14-C)allantoin was 0.85 +/- 0.03 (n = 27 clearance periods) indicating significant net reabsorption. When urine flow was increased above 1 ml/kg/min, fractional excretion of (14-C)allantoin reached 1.07 +/- 0.03 (n = 18 clearance periods), i.e., net secretion.

The rate constant for the vapor-phase reaction of allantoin with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 20 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1).

Skin protectant active ingredients. The active ingredients of the products consist of any of the following, within the concentration specified for each ingredient. Allantoin, 0.5 to 2 percent.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: allantoin is included in dandruff/seborrheic dermatitis/psoriasis drug products.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: allantoin (wound healing claims only) is included in skin protectant drug products.

Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. Allantoin ... /has/ been present in oral mucosal injury drug products for use as oral wound healing agents. Oral wound healing agents have been marketed as aids in the healing of minor oral wounds by means other than cleansing and irrigating, or by serving as a protectant. Allantoin, carbamide peroxide in anhydrous glycerin, water soluble chlorophyllins, and hydrogen peroxide in aqueous solution are safe for use as oral wound healing agents, but there are inadequate data to establish general recognition of the effectiveness of these ingredients as oral wound healing agents.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Allantoin is found on List C. Case No: 3015; Pesticide type: insecticide; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects; Active ingredient (AI): allantoin; AI Status: The active ingredient is no longer contained in any registered products. Thus, we characterize it as "cancelled."

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Uricase is the enzyme that possesses the functionality to convert uric acid to allantoin. Considering humans do not possess any endogenous uricase, uric acid is the only final breakdown product in the purine degradation of unwanted waste product purine nucleotides. The presence of allantoin in human urine is subsequently the result of non-enzymatic processes on uric acid with reactive oxygen species. Such non-enzymatic processes are consequently potentially suitable biomarkers for measuring oxidative stress in chronic illnesses and aging. Furthermore, as allantoin is found endogenously and is part of basic, natural metabolic pathways, no accumulation is expected of it. Additionally, allantoin is not believed to be metabolized to a measurable extent in humans and animals.

In humans, uric acid is the final breakdown product of unwanted purine nucleotides. Uric acid is the last stage in purine degradation, because humans lack the enzyme uricase which converts uric acid into allantoin.

Allantoin in the presence of calcium ions has been implicated as a potential toxic agent in Reye's syndrome. An investigation of possible alternative sources of allantoin in humans, which lack the enzyme uricase, has been initiated. Urate is a strong reducing agent which can reduce cytochrome c nonenzymatically, with the concomitant production of CO2 and H+. The stoichiometries measured for the various reactants and products were 1 urate:2 cytochrome c:1 H+:1 CO2. The initial reaction rate depended on the concentrations of both urate and cytochrome c, with reaction kinetics that were first order with respect to urate and second order with respect to cytochrome c. The participation of molecular oxygen in this reaction could not be detected. The pH and ionic strength optima for this reaction were determined to be 9.5-10.5 and 10(-5) M, respectively. Based on the results reported here, the following balanced equation can be written: urate-2 + 2 cytochrome c+3 + 2 H2O----allantoin + 2 cytochrome c+2 + H+ + HCO3-. /The authors/ propose that allantoin can be generated from the oxidation of urate by cytochrome c+3, and that this is a potential source of allantoin in human tissues.

Uric acid is the main nitrogenous waste product in birds but it is also known to be a potent antioxidant. Hominoid primates and birds lack the enzyme urate oxidase, which oxidizes uric acid to allantoin. Consequently, the presence of allantoin in their plasma results from non-enzymatic oxidation.

In most mammals purine degradation ultimately leads to the formation of allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric acid to allantoin.

For more Metabolism/Metabolites (Complete) data for ALLANTOIN (11 total), please visit the HSDB record page.

In studies on human subjects, a recovery of 19% and 34% of allantoin in the urine was observed but only in two individuals and only after the administration of massive doses of allantoin. After intravenous administration, recovery in the urine was practically quantitative with doses of 75 to 600 mgm in the human model. After 240 mgm, excretion continued for 72 hours in human subjects and the results were similar in regards to subcutaneous injection.

Urinary clearance is the predominant excretion route.

Some studies suggest that the average renal clearance of allantoin in normal, healthy human subjects is approximately 123 cc per minute. It is generally agreed upon that exogenously administered allantoin is rapidly excreted.

Allantoin administered to dogs orally as solid or solution was excreted in the urine to an extent of between 35 and 92 per cent within 24 hours. No allantoin was recovered either in urine or feces when given to rabbits orally. In man the recovery was 19 and 34 per cent in two individuals after massive doses. After intravenous administration recovery in the urine was practically quantitative with doses of 75 to 600 mgm. in the dog and in man. After 240 mgm. in man excretion continued for 72 hours. The results were similar after subcutaneous injection. Uric acid injected intravenously into a dog was converted into allantoin within two hours.

CIR ingredient: Allantoin

Occurs naturally in tobacco seeds, sugar beets, and wheat sprouts; [Hawley] Used as a medicine for wound healing, in biochemical research, and in the preparation of estrogenic compounds; Also used as a dermatological preparation to treat dandruff, seborrheic dermatitis, psoriasis, hair loss, corns, and calluses; It is an ingredient in sunscreens; [HSDB]

For allantoin (USEPA/OPP Pesticide Code: 085701) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Subpart B: Section 310.545: Drug products containing certain active ingredients offered over-thecounter (OTC) for certain uses. Ingredients-Approved as of May 7, 1991: Allantoin (wound healing claims only).

Subpart B: Section 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of the following, within the concentration specified for each ingredient: (a) Allantoin, 0.5 to 2 percent.

Allantoin is listed on the FDA OTC Ingredient List as used for or having reviews pending for use as a wound healing agent, skin protectant and external analgesic, a dandruff/seborrheic dermatitis/psoriasis product, a grower for hair loss, a corn/callus remover, and a sunscreen ingredient.

2023: <50,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7149]

Produced by oxidation of uric acid. Also present in tobacco seeds, sugar beets, wheat sprouts.

Various heterocyclic compounds can be obtained by coupling polynucleophiles with glyoxylic acid: ... with urea and an acid catalyst, allantoin is obtained in 60% yield.

Urea, N-(2,5-dioxo-4-imidazolidinyl)-: ACTIVE

One of several compounds identified in comfrey (Symphytum officinale)

The main effect of allantoin is the powerful stimulation of cell proliferation and the enhancement of the rebuilding of intact granulation tissue. In pharmaceutical applications, allantoin is used ... in the treatment of ulcers, slow-healing wounds and burns.

Pesticide: Cancelled

The Food and Drug Administration (FDA) final monograph establishing conditions under which over-the-counter (OTC) skin protectant drug products are generally recognized as safe and effective and not misbranded includes allantoin as an active ingredient for symptoms of /skin/ dryness and as a Category III skin protectant for wound-healing based on the lack of effectiveness data (43 FR 34628 at 34644 through 34647).

Allantoin ... /has/ been present in oral mucosal injury drug products for use as oral wound healing agents. Oral wound healing agents have been marketed as aids in the healing of minor oral wounds by means other than cleansing and irrigating, or by serving as a protectant. Allantoin /is/ safe for use as oral wound healing agents, but there are inadequate data to establish general recognition of the effectiveness of these ingredients as oral wound healing agents. ...Clinical investigations designed to obtain evidence that any drug product labeled, represented, or promoted for OTC use as an oral wound healing agent is safe and effective for the purpose intended must comply with the requirements and procedures governing the use of investigational new drugs set forth in part 312 of this chapter. (d) After the effective date of the final regulation, any OTC drug product that is labeled, represented, or promoted for use as an oral wound healing agent may not be initially introduced or initially delivered for introduction into interstate commerce unless it is the subject of an approved new drug application.