D-Mannitol

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

Masking; Binding; Moisturising; Humectant; Skin conditioning

log Kow = -3.10

-3.10

1.489 at 68 °F (NTP, 1992) - Denser than water; will sink

1.52 @ 20 °C

Orthorhombic needles from alc

WHITE, CRYSTALLINE POWDER OR FREE FLOWING GRANULES

greater than or equal to 100 mg/mL at 68 °F (NTP, 1992)

1 g in about 5.5 ml water; more sol in hot water; insol in ether; sol in pyridine, aniline; sol in aq soln of alkalies; 1 g dissolves in 18 ml glycerol (density 1.24); 1 g dissolves in about 83 ml alc

In water, 2.16X10+5 mg/l @ 25 °C

216 mg/mL at 25 °C

This chemical does not meet GHS hazard criteria for > 99.9% (1450 of 1451) of all reports.

Not Classified

Aggregated GHS information provided per 1451 reports by companies from 2 notifications to the ECHA C&L Inventory.

This chemical does not meet GHS hazard criteria for 100% (31 of 31) of all reports.

Not Classified

Aggregated GHS information provided per 31 reports by companies from 1 notifications to the ECHA C&L Inventory.

Chemical: D-Mannitol

Chemical: Mannitol

D-Mannitol is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of D-Mannitol 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)

D-Mannitol: Does not have an individual approval but may be used under an appropriate group standard

Mannitol: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

IMAP assessments - Mannitol: Human health tier I assessment

IMAP assessments - D-Mannitol: Environment tier I assessment

SYMPTOMS: Symptoms of exposure to this compound include nausea, vomiting, headache, chills, chest pain and pulmonary edema. It may cause irritation of the skin, eyes and respiratory tract. Other symptoms may include lethargy, confusion, heart failure and death. Exposure has caused an electrolyte and fluid imbalance, hypersensitivity reactions, diarrhea, thirst, fever, tachycardia, hyponatremia, urinary retention, dehydration, blurred vision, convulsions, urticaria, hypotension and hypertension. It has also caused hyperglycemia and glycosuria. Coughing may result from inhalation. Ingestion may cause gastric irritation. Skin contact may cause discoloration of sensitive skin. Eye contact may cause redness and pain. Intravenous use has led to blood pressure elevation and bladder tubule changes.

A sugar alcohol. More closely related to carbohydrates than to other polyhydric alcohols [Noller]. Flammable and/or toxic gases are generated by the combination with alkali metals, nitrides, strong reducing agents and strong oxidizing agents.

Not Classified

Not Classified

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Hydroxyurea (HU) is a potent mammalian teratogen. Within 2-4 hours after maternal injection, HU causes 1) a rapid episode of embryonic cell death and 2) profound inhibition of embryonic DNA synthesis. A variety of antioxidants delays the onset of embryonic cell death and reduces the incidence of birth defects. Antioxidants do not block the inhibition of DNA synthesis, indicating that early embryonic cell death is not caused by inhibited DNA synthesis. We have suggested that some HU molecules may react within the embryo to produce H2O2 and subsequent free radicals, including the very reactive hydroxyl free radical. The free radicals could cause the early cell death; antioxidants are believed to terminate the aberrant free radical reactions resulting in lessened developmental toxicity. To investigate whether hydroxyl free radicals cause the early episode of cell death, pregnant New Zealand white rabbits were injected subcutaneously on gestational day 12 with a teratogenic dose of HU (650 mg/kg) in the presence or absence of 550 mg/kg of D-mannitol (Man), a specific scavenger of hydroxyl free radicals. Osmotic control rabbits received HU plus 550 mg/kg of xylose (Xyl, a nonactive aldose). At term, the teratologic effects of HU were ameliorated by Man as evidenced by decreased incidences of the expected limb malformations. Xyl exerted no demonstrable effect on HU teratogenesis. Histological examination of limb buds at 3-8 hours after maternal injection, showed that Man delayed the onset of HU-induced cell death by as much as 4 hours. Xyl had no effect. That Man acts within the embryo was shown by performing intracoelomic injections on alternate implantation sites with Man, Xyl, or saline followed by subcutaneous injection of the pregnant doe with HU. Embryos were harvested 3-8 hours later. Limb buds from saline- and Xyl-injected embryos exhibited the typical pattern of widespread HU-induced cell death at 3-4 hours, whereas Man-injected embryos did not exhibit cell death until 5-8 hours. These results are consistent with those reported for antioxidant-mediated amelioration of HU-induced developmental toxicity and with the hypothesis that hydroxyl free radicals are the proximate reactive species in HU-induced early embryonic cell death.

... Pentobarbital attenuated the blood-brain barrier disruption induced by hyperosmolar mannitol. This may be attributed, at least in part, to the blood pressure effect of pentobarbital. Implications: When the blood-brain barrier (BBB) was disrupted by a hyperosmolar solution, pentobarbital attenuated the degree of leakage of the blood-brain barrier. Systemic hypotension caused by pentobarbital played a significant role in decreasing the leakage. Our study suggests that when the blood-brain barrier is disrupted, pentobarbital may be effective in protecting the blood-brain barrier. Furthermore, systemic blood pressure plays an important role in determining the degree of disruption.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5(SRC), determined from a water solubility of 2.16X10+5 mg/l(2) and a regression-derived equation(3), indicates that D-mannitol is expected to have very high mobility in soil(SRC). Volatilization of D-mannitol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.3X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(4). D-Mannitol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.9X10-9 mm Hg(SRC), determined from a fragment constant method(5). D-Mannitol is a simple sugar alcohol and should be readily biodegraded in the environment(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5(SRC), determined from a water solubility of 2.16X10+5 mg/l(2) and a regression-derived equation(3), indicates that D-mannitol is not expected to adsorb to suspended solids and sediment in water(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.3X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1(3,SRC), from its water solubility(2) suggests the potential for bioconcentration in aquatic organisms is low(SRC). D-Mannitol is a simple sugar alcohol and should be readily biodegraded in the environment(SRC).

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

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

Signs and Symptoms of Overdose

D-mannitol is widespread in nature(SRC). It is found to a significant extent in the exudates of trees and shrubs such as the plane tree, manna ash and olive tree(1). D-Mannitol occurs in pumpkin, hedge parsley, onions, celery, strawberries, the genus Euonymus, the genus Hebe, cocoa bean, grasses, lilac, Digitalis purpurea, mistletoe and lichens(1).

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=69-65-8]

The Koc of D-mannitol is estimated as approximately 5(SRC), using a water solubility of 2.16X10+5 mg/l(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that D-mannitol is expected to have very high mobility in soil(SRC).

D-Mannitol is widespread in nature(SRC). It is found to a significant extent in the exudates of trees and shrubs such as the plane tree, manna ash and olive tree(1). D-Mannitol occurs in pumpkin, hedge parsley, onions, celery, strawberries, the genus Euonymus, the genus Hebe, cocoa bean, grasses, lilac, Digitalis purpurea, mistletoe and lichens(1).

...DEHYDRATION, & MASSIVE DIURESIS ARE COMMON UNTOWARD EFFECTS OF MANNITOL. ... OCCASIONALLY CAUSED AGITATION, DISORIENTATION, & CONVULSIONS. LARGE DOSES MAY CAUSE ACUTE INCR IN INTRAVASCULAR VOL, RESULTING IN CONGESTIVE HEART FAILURE OR INTRACRANIAL HEMORRHAGE.

HEADACHE, NAUSEA, VOMITING, CHILLS, DIZZINESS, POLYDIPSIA, LETHARGY, CONFUSION, & SENSATION OF CONSTRICTION OR PAIN IN CHEST HAVE BEEN OBSERVED FOLLOWING INFUSION OF MANNITOL. FATALITIES HAVE OCCURRED AFTER LARGE DOSES.

TOO RAPID ADMIN OF LARGE AMT WILL DRAW INTRACELLULAR WATER INTO EXTRACELLULAR SPACE, CAUSING CELLULAR DEHYDRATION & OVEREXPANSION OF INTRAVASCULAR SPACE WITH CONGESTIVE HEART FAILURE & PULMONARY EDEMA. HYPONATREMIA IS A COMMON PROBLEM. ...MAY INCR CEREBRAL BLOOD FLOW & THUS THE RISK OF POSTOPERATIVE BLEEDING IN NEUROSURGICAL PATIENTS.

A VARIETY OF SIGNS & SYMPTOMS SUGGESTIVE OF HYPERSENSITIVITY REACTIONS HAS OCCURRED IN OCCASIONAL PATIENTS.

For more Human Toxicity Excerpts (Complete) data for D-MANNITOL (7 total), please visit the HSDB record page.

D-mannitol

TR-236: Carcinogenesis Bioassay of D-Mannitol (CASRN 69-65-8) in F344/N Rats and B6C3F1 Mice (Feed Study) (1982 )

12/16/81

No Evidence

No Evidence

No Evidence

B05BC01

A - Alimentary tract and metabolism

B - Blood and blood forming organs

B - Blood and blood forming organs

R - Respiratory system

V - Various

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance.

MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER.

...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Mannitol is metabolized only slightly, if at all, to glycogen in the liver.

...POLYHYDRIC SUGAR ALC...MANNITOL (C6H14O6)...LARGELY EXCRETED UNCHANGED IN URINE.

MANNITOL OCCURS IN LARGE AMT IN SPORES OF ASPERGILLUS ORYZAE, WHERE IT IS RAPIDLY METABOLIZED IN EARLY STAGES OF GERMINATION. IT IS CONVERTED TO FRUCTOSE BY D-MANNITOL DEHYDROGENASE...

...FATE OF MANNITOL IN ANIMAL BODY (MONKEYS, RABBITS, RATS, DOGS, ETC) AFTER ABSORPTION FROM DIGESTIVE TRACT INCL LIMITED CONVERSION TO GLYCOGEN IN LIVER & ELIMINATION OF BALANCE UNCHANGED IN URINE.

3OWL53L36A

MANNITOL

Physiologic Effects [PE] - Increased Diuresis

Mechanisms of Action [MoA] - Osmotic Activity

Established Pharmacologic Class [EPC] - Osmotic Diuretic

Mannitol is an Osmotic Diuretic. The mechanism of action of mannitol is as an Osmotic Activity. The physiologic effect of mannitol is by means of Increased Diuresis.

Compounds that increase urine volume by increasing the amount of osmotically active solute in the urine. Osmotic diuretics also increase the osmolarity of plasma.

Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed)

Approximately 7% of ingested mannitol is absorbed during gastrointestinal perfusion in uremic patients. Inhalation of 635 mg of mannitol powder yields a plasma Cmax of 13.71 μg/mL in 1.5 hours (Tmax) and a mean systemic AUC of 73.15 μg\*h/mL.

Mannitol is primarily excreted unchanged in the urine. Following oral inhalation of 635 mg of mannitol in healthy volunteers, 55% of the total dose was recovered unchanged in the urine; following oral or intravenous administration of 500 mg, the corresponding values were 54 and 87%, respectively.

Mannitol administered intravenously has a volume of distribution of 34.3 L.

Intravenous administration of mannitol yields a total clearance of 5.1 L/hr and renal clearance of 4.4 L/hr.

MANNITOL IS GENERALLY REGARDED AS BEING UNABSORBED FROM GI TRACT. HOWEVER, RECENT WORK CONTRADICTS THIS BELIEF, FOR 18% OF ORAL DOSE OF D-(14)C MANNITOL WAS RECOVERED UNCHANGED IN 48-HR URINE OF HUMAN SUBJECTS & UP TO 19% AS CO2 IN EXPIRED AIR IN 12 HR. 32% PRESENT IN FECES IN 48 HR...UNABSORBED MATERIAL.

SUBSTANCES /MANNITOL/ HAVING APPARENT VOL OF DISTRIBUTION CORRESPONDING TO TOTAL EXTRACELLUR WATER, WHICH IS ABOUT 20% BODY WT...PENETRATE CAPILLARY MEMBRANES BUT DO NOT PENETRATE CELLULAR MEMBRANES.

CIR ingredient: Mannitol

Occurs in many plants; Used in electronics (with boric acid to make dry electrolytic condensers for radio applications), plastics (for making artificial resins and plasticizers), in the food industry (anticaking, free-flow agent, flavoring agent, release agent, stabilizer, thickener, and nutritive sweetener), and in medicine (diuretic and in the determination of renal function); [Merck Index] Used as flavoring agent, anticaking agent, formulation aid, lubricant or release agent, non-nutritive sweetener, and solvent for foods; [FDA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

Used in the food industry as anti-caking and free flowing agent, stabilizer, thickener, and non-nutritive sweetener.

...MANNITOL...USED IN VARIOUS WAYS: (1) AS FLAVOR CARRIER OR FLAVOR-ENCAPSULATING AGENT; (2) AS FLAVOR ENHANCER IN WIDE VARIETY OF PRODUCTS, SUCH AS COFFEE CONCENTRATES, MEAT-CURING COMPOSITION, FLAVOR ADDITIVES FOR NUTS, & PURE JUICE CONCENTRATES, & (3) IN NUMBER OF FLAVOR-ENHANCING COMPOSITIONS.

MEDICATION (VET)

MEDICATION

(1975) 1.42X10+9 GRAMS

(1975) 1.42X10+9 GRAMS

(1984) 2.13X10+9 g

2023: 1,460,000 lb

(1972) GREATER THAN 4.54X10+5 GRAMS

(1975) GREATER THAN 4.54X10+5 GRAMS

...By electrolytic reduction of glucose. Prepn from seaweed; by hydrogenation of invert sugar, monosaccharides, & sucrose.

May be extracted from manna and other natural sources with hot alcohol or other selective solvents. Commercially it is produced by catalytic or electrolytic reduction of certain monosaccharides such as mannose and glucose. Manufacture is somewhat complicated by the need for separation of stereoisomers

MANNITOL, USP (OSMITROL), IS AVAIL FOR IV ADMIN AS MANNITOL INJECTION, USP, & MANNITOL & SODIUM CHLORIDE INJECTION, USP, IN CONCN OF 5, 10, 15, 20, OR 25% MANNITOL IN VOL RANGING FROM 50 TO 1000 ML OF WATER OR 0.3 TO 0.45% SODIUM CHLORIDE SOLN.

Grades: Reagent; Commercial; NF; FCC

Resectisol (Amer. McGaw)

Information on 5 consumer products that contain Mannitol in the following categories is provided:

Information on 3 consumer products that contain Mannitol in the following categories is provided:

Fragrance Ingredients

Food Additives -> BULKING_AGENT; HUMECTANT; STABILIZER; SWEETENER; TEXTURIZER; THICKENER -> JECFA Functional Classes

Cosmetics -> Masking; Binding; Moisturising; Humectant; Skin conditioning

D-Mannitol: ACTIVE

Mannitol: ACTIVE

LEVEL OF USE RECOMMENDED: UP TO 1.0% IN CHEWING GUM, UP TO 5.0% IN CANDY.