Allantoin

158.12

158.12

102364

202-592-8

757792|7606

DTXSID3020043

Crystals from aqueous methanol|White to colorless powder or crystals|Monoclinic plates

29332100

113

-2.2

White Powder

1.7±0.1 g/cm3

239 °C

478ºC

230-234°C

1.616

Slightly soluble in water. Freely soluble in alkalis

Refrigerator

4.32X10-9 mm Hg at 25 deg C (est)

Odorless

Tasteless

pH = 4.5 - 6 (5% in water, 20 °C)

Henry's Law constant = 3.41X10-18 atm-cu/mol at 25 °C (est)

145.61 Ų [M+Na]+ [CCS Type: DT, Method: stepped-field]|128.39 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|142.2 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|125.5 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|126.7 Ų [M-H]-

Stable at pH 4-9. Hydrolytic decomposition with strong acids and bases|Hydroxyl radical reaction rate constant = 1.97X10-11 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

1

22-36/37/38

22-24/25-36-26

YT1600000

Xn,Xi

Stable. Incompatible with strong oxidizing agents.

P301 + P312 + P330

H302

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.

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.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 290 companies from 3 notifications to the ECHA C&L Inventory.

No studies on repeated dose toxicity and reproductive toxicity have been submitted. Moreover, studies show that the tumor incidence in allantoin treated animals did not differ largely from that found in untreated controls. As a result, further or additional toxicity, mutagenicity, or carcinogenicity tests are not required in view of the endogenous nature of allantoin and the general lack of overall toxicity. Finally, as allantoin is a normal component of the diet in humans and is a substance of endogenous origin present in the body of humans, it is generally recognized as being a safe substance for humans.

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 ...

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

Allantoin's production and use as a topical medication(1) may result in its release to the environment through various waste streams(SRC).

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).

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).

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).

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 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).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 33,966 workers (20,108 of these are female) are potentially exposed to allantoin in the US(1). Occupational exposure to allantoin may occur through dermal contact with this compound at workplaces where allantoin is produced or used(SRC). Exposure to allantoin among the general population may occur to those administered the drug allantoin, a cell poliferation and enhancement agent(SRC). Exposure to allantoin will occur through contact with natural sources containing allantoin(SRC).

Allantoin is commonly applied in a variety of topical vehicles or applications such as cosmetic creams, toothpastes, mouthwashes, shampoos, lipsticks, anti-acne products, and lotions for the purpose of moisturizing skin, enhancing the smoothness of skin, stimulating the healing of wounds, and soothing irritated skin.|FDA Label|Treatment of epidermolysis bullosa

A urea hydantoin that is found in URINE and PLANTS and is used in dermatological preparations.|Allantoin, a component in Comfrey, stimulates tissue repair and wound healing through cell proliferation. Allantoin has also had significant effect on cellular multiplication in degenerating and regenerating peripheral nerves.|In humans, the allantoin to uric acid ratio in plasma increases during oxidative stress, thus this ratio has been suggested to be an in vivo marker for oxidative stress in humans.|Diagnostic marker for oxidative stress during antituberculous (anti-TB) therapy.|For more Therapeutic Uses (Complete) data for ALLANTOIN (8 total), please visit the HSDB record page.

Skin: For external use only. Ocular: Avoid contact with eyes. Sensitization: Mederma is contraindicated in individuals who have shown hypersensitivity to any of its components /Mederma/

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.

Drugs used to treat or prevent skin disorders or for the routine care of skin. (See all compounds classified as Dermatologic Agents.)

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.

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.

When studied in cattle, sheep, and horses, the half-life of allantoin is in the range of 1 to 2.5 hours.

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.

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Allantoin

Mederma, a topical skin gel produced by Merz Pharmaceuticals, LLC, 4215 Tudor Lane Greensboro, NC 27410, contains water (purified), PEG-4, allium cepa (onion) bulb extraxt, xanthan gum, allantoin, fragrance, methylparaben and sorbic acid.

Soap, cleaning compound, and toilet preparation manufacturing|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.

Analyte: allantoin; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: allantoin; matrix: chemical identification; procedure: thin-layer chromatography with comparison to standards|Analyte: allantoin; matrix: chemical identification; procedure: reaction with sodium hydroxide and water; addition of hydrochloric acid; addition of potassium bromide solution, resorcinol solution and sulfuric acid; heating results in a dark blue color, which turns red after cooling and adding to water|Analyte: allantoin; matrix: chemical purity; procedure: dissolution in water; potentiometric titration with sodium hydroxide, using a suitable electrode system

A new enzymatic assay using allantoinase and allantoate amidohydrolase for specifically measuring allantoin concentration in serum has been developed. The procedure is simple, rapid, and accurate. The method has been used to measure serum allantoin levels after oral administration of purine nucleotides to experimental animals, including rats that have uricase catalyzing the conversion of urate to allantoin.|A micellar electrokinetic chromatographic method is described for the determination and quantitation of allantoin, an end-product of purine metabolism in mammals. This method is applicable to biofluids of different mammal species and man.|An analytical procedure was developed for determining allantoin using high pressure liquid chromatography (HPLC) separation of an ultraviolet labeled allantoin derivative. The method was applied to the quantitative measurement of allantoin in cosmetic preparations. ... The allantoin was derivatized to an ultraviolet labeled product and read by reverse phase chromatography on an octadecylsilyl silica column.|A stability indicating HPLC method for the determination of allantoin in cream and lotion formulations is presented. An extraction step in methanol-distilled water and separation from interferences by reversed phase chromatography precedes the LC.|A high performance liquid chromatography (HPLC) method was developed for determination of allantoin derivatives in cosmetic and pharmaceutical products. Solutions of allantoin or chlorohydroxy aluminium allantoinate (ALCA) or samples of toothpastes, creams, shampoos, soaps, lipsticks, and powders were extracted in hot water and injected on a resin based strong cation exchanger using water as eluent. The allantoin derivatives were determined from post column reactions.

Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Cosmetics -> Soothing