Menadione

172.18

172.18

1908453

200-372-6

723JX6CXY5

758200|4170

DTXSID4021715

Bright yellow crystals|YELLOW NEEDLES FROM ALC, PETROLEUM ETHER

B - Blood and blood forming organs

2914690090

34.1

2.2

yellow crystalline

1.225 g/cm3

105-107 °C

304.5°C at 760 mmHg

113.8ºC

H2O: INsoluble ;oil: soluble

Store at RT.

LD50 orally in mice: ~0.5 g/kg (Molitor, Robinson)

Very faint acrid odor

Alc soln is neutral to litmus

134.6 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|129.79 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

Destroyed by alkalies and reducing agents. Solutions may be heated to 120 °C without dec.

IRRITANT

NONH for all modes of transport

3

22-36/37/38-43

26-36-37/39-24

QL9100000

Xn,Xi

Stable. May be light sensitive. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H302-H315-H319-H335

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products. Menadione is included on this list.

|Warning|H302 (93.98%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P272, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 83 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Irritant to the skin and mucous membranes, especially the alcoholic solution.

URBAN/SUBURBAN: Menadione was tested for but not detected in urban air samples collected in Leeds, UK, date not specified(1).

Menadione (vitamin K3), which is not used as a nutritional supplemental form of vitamin K for humans, has been reported to cause adverse reactions, including hemolytic anemia. Large doses have also been reported to cause brain damage.

Neither normal nor excessively high doses of vitamin K have associated with adverse events, ALT elevations or clinically apparent liver injury.

Large doses of salicylates... antagonize vitamin k. ... Cmpd with ... antagonist activity is sulfaquinoxaline, a sulfonamide drug used in veterinary medicine... . /vitamin k/|Vitamin k antagonizes inhibitory effect of /acenocoumarol, phenprocoumon, anisindione, diphenadione, and phenindione/ on hepatic synthesis of vitamin k dependent clotting proteins... . /vitamin k/

LD50 Mouse oral 500 mg/kg|LD50 Mouse ip 50 mg/kg|LD50 Rat ip 75 mg/kg|LD50 Mouse sc 138 mg/kg

/PLANTS/ Vitamin K and its analogs are fungistatic against wide variety of fungi. /Vitamin K/

SRP: Persons with bleeding disorders or who are taking anticoagulants should be protected from exposure.

Menadione's production and use in medicines and animal feed additives(1) may result in its release to the environment through various waste streams(SRC). Its former production and use in fungicides(1) may have resulted in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 370(SRC), determined from a log Kow of 2.20(2) and a regression-derived equation(3), indicates that menadione is expected to have moderate mobility in soil(SRC). Volatilization of menadione from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.1X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Menadione is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-4 mm Hg(SRC), determined from a fragment constant method(5).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 370(SRC), determined from a log Kow of 2.20(2) and a regression-derived equation(3), indicates that menadione 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 3.1X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1.4(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), menadione, which has an estimated vapor pressure of 1.9X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in the vapor phase in the ambient atmosphere. Vapor-phase menadione is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 33 hrs(SRC), calculated from its rate constant of 1.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Menadione is decomposed by sunlight(4).

The rate constant for the vapor-phase reaction of menadione with photochemically-produced hydroxyl radicals has been estimated as 1.1X12-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 33 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Menadione is expected to undergo hydrolysis in the environment since this compound is destroyed by alkalies and reducing agents(2). The compound is decomposed by sunlight(3).

An estimated BCF of 1.4 was calculated for menadione(SRC), using a log Kow of 2.20(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 Koc of menadione is estimated as 370(SRC), using a log Kow of 2.20(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that menadione is expected to have moderate mobility in soil.

The Henry's Law constant for menadione is estimated as 3.1X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that menadione is expected to be essentially nonvolatile from water surfaces(2). Menadione is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-4 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 6,103 workers (2,166 of these are female) are potentially exposed to menadione in the US(1). Occupational exposure to menadione may occur through inhalation and dermal contact with this compound at workplaces where menadione is produced or used(SRC).

The primary known function of vitamin K is to assist in the normal clotting of blood, but it may also play a role in normal bone calcification.

Vitamin K is an essential fat soluble vitamin that is important in maintaining normal coagulation, serving as a cofactor in the activation of several clotting factors and anticoagulant proteins. There is no evidence that vitamin K supplementation, in physiologic or even higher doses, causes serum enzyme elevations, liver injury or jaundice.

Vitamins

The synthetic water soluble forms of vitamin K (menadione, menadiol) have long since been considered inferior to vitamin K1 (phytonadione) in the treatment of drug-induced hypoprothrombinemia.|Menadione (vitamin K3) a redox cycling quinone, is a clinically important chemotherapeutic agent. ...|Menadione, or vitamin K3 (VK3), a potent oxidative stress inducer, has been recently used as an effective and remarkably safe cytotoxic drug for treatment of several human tumors. ...

... Probably should not be given to newborn infants or women during last few wk of pregnancy.|Menadione is ineffective for the treatment of warfarin and superwarfarin toxicity. It elicits a poor response and should not be used.|Vitamin K /SRP: phytonadione preferred/ must be administered with great care to patients to whom anticoagulants have been given to combat intravascular clotting. ... The vitamin must be "titrated" against the anticoagulant, lest the patient be re-exposed to the same threat of clotting that led to anticoagulants therapy in the first place. No such problem exists in treating persons poisoned accidentally or suicidally by anticoagulant rodenticides. There is no evidence that vitamin K produces in normal persons any excessive tendency of the blood to clot. /vitamin K/|Menadione...can induce hemolysis in individuals who are genetically deficient in glucose-6-phosphate dehydrogenase.|For more Drug Warnings (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

3. 3= Moderately toxic: probable oral lethal dose (human) 0.5-5 g/kg, between 1 oz & 1 pint (or 1 lb) for 70 kg person (150 lb).

/Hereditary/ resistant individuals /to coumarin/ were found to show another characteristic, unusual sensitivity to antidotal effects of vitamin k. ... Sensitivity was...calculated to be about 20 times that observed in other patients. ...Synthesis of clotting factor ii, vii, ix and x has been modified by genetic mutation... /vitamin k/

Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times.

Agents that prevent fibrinolysis or lysis of a blood clot or thrombus. Several endogenous antiplasmins are known. The drugs are used to control massive hemorrhage and in other coagulation disorders. (See all compounds classified as Antifibrinolytic Agents.)|Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body. (See all compounds classified as Vitamins.)

Variable and ranges from 10% to 80%|Menadione and its water soluble derivatives ... are absorbed even in the absence of bile ... /and/ enter the bloodstream directly.|Eighteen hr after intracardiac admin of (3)H-menadione ... to rats fed diet deficient in vit k, 78% of (3)H had been excreted in urine, 3% in feces, and 29% remained in animals. Biliary excretion ... observed in dogs, & 5-10% of (14)c had been excreted by this route 12 hr after oral dose of (14)C-menadione.|Vit k accum in liver, spleen, and lungs. /however/ significant amounts are not stored in body for long periods.|VET: ... Menadione or vit k3 absorbed is converted to k2 for utilization, otherwise it is rapidly eliminated via urine.|The pharmacokinetics of menadione (vitamin K3)... were studied in rabbits after iv injection of 75 mg menadiol sodium diphosphate (Synkayvite). ... Plasma clearance was 0.822 L/min. Systemic clearance in RBCs was 0.407 L/min. Apparent volume of distribution was 30.833 L in plasma and 20.488 L in RBCs. Area under the concn-time curve was 32.453 ug min/ml for plasma and 67.219 ug min/ml for RBCs. /Menadiol sodium diphosphate/

Hepatic|Distribution studies with menadione tritiated in 6,7-position, ((3)H(6,7))-2-methyl-1,4-naphthaquinone, in rats showed that lipophilic metabolite of menadione, menaquinone-4, 2-methyl-3-geranylgeranyl-1,4-naphthaquinone was present in all tissues examined.|2-methyl-1,4-naphthoquinone yields in rat vit k2(20); yields vit k2(45), and vit k2(50) probably in man. /from table/|...Xenobiotics that are reduced by carbonyl reductases include... menadione... .|Menadione is excreted in part as glucuronide and competes with bilirubin for detoxification mechanism of limited capacity in newborn.|For more Metabolism/Metabolites (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

The pharmacokinetics of menadione (vitamin K3)... were studied in rabbits after iv injection of 75 mg menadiol sodium diphosphate (Synkayvite). Mean elimination half-life of menadione was 27.17 min in plasma and 35.22 min in red blood cells... . /Menadiol sodium diphosphate/

Menadione (vitamin K3) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called G1a proteins.|The vitamin K-dependent blood clotting factors, in the absence of vitamin K (or in the presence of the coumarin type of anticoagulant), are biologically inactive precursor proteins in the liver. Vitamin K functions as an essential cofactor for a microsomal enzyme system that activates these precursors by the conversion of multiple residues of glutamic acid near the amino terminus of each precursor to gamma-carboxyglutamyl residues in the completed protein. The formation of this new amino acid, gamma-carboxyglutamic acid, allows the protein to bind Ca+2 and in turn to be bound to a phospholipid surface, both of which are necessary in the cascade of events that lead to clot formation. /Vitamin K/|Vitamin k is necessary for formation of prothrombinogen and other blood clotting factors in liver. During clotting, circulating prothrombin is required for production of thrombin; in turn, thrombin converts fibrinogen to fibrin, network of which constitutes clot. /vitamin k/|The active form of vitamin K appears to be the reduced vitamin K hydroquinone, which, in the presence of oxygen, carbon dioxide, and the microsomal carboxylase enzyme, is converted to its 2,3-epoxide at the same time gamma-carboxylation takes place. The hydroquinone form of vitamin K is regenerated from the 2,3-epoxide by a coumarin sensitive epoxide reductase ... . /Vitamin K/|Menadione is a potent inhibitor of aldehyde oxidase (Ki ~0.1 uM) and can be used together with allopurinol to discriminate between aldehyde oxidase- and xanthine oxidase-catalyzed reactions.|For more Mechanism of Action (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

2-Methyl-1,4-naphthalenedione

MENADIONE, NF (VIT K3)...AVAIL IN ORAL ADMIN IN TABLETS CONTAINING 2, 5, OR 10 MG, & AS STERILE SOLN OF MENADIONE IN OIL (USUALLY 2, 10, OR 25 MG/ML) DESIGNED FOR IM ADMIN.|MENADIONE SODIUM BISULFITE, NF (HYKINONE)...WHITE CRYSTALLINE, HYGROSCOPIC POWDER. ...SOL IN WATER...MARKETED IN 5-MG TABLETS & IN AMPULS... 5-10 MG/ML. MENADIOL SODIUM DIPHOSPHATE INJECTION, NF (KAPPADIONE, SYNKAVITE)...AMPULS...5, 10, OR 37.5 MG/ML. MENADIOL SODIUM DIPHOSPHATE TABLETS, NF...5 MG...|MENADIOL SODIUM DIPHOSPHATE INJECTION, NF (KAPPADIONE, SYNKAVITE), IS MARKETED IN AMPULS CONTAINING 5, 10, OR 37.5 MG/ML. MENADIOL SODIUM DIPHOSPHATE TABLETS, NF, CONTAIN 5 MG OF SALT FOR ORAL USE.|Commercially significant forms are menadione sodium bisulfite and menadione dimethyl pyrimidinol.|For more Formulations/Preparations (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

1,4-Naphthalenedione, 2-methyl-: ACTIVE|...CORN STIGMA CONTAINS ALC SOL SUBSTANCE TERMED BY.../MIKHLIN CR/ VIT K3; HOWEVER...DIFFERENTIATION FROM VIT K1 IS NOT CLEAR. IN ANGLO-AMERICAN LITERATURE...K3 DESIGNATES MENADIONE. THIS DESIGNATION SHOULD BE DISCONTINUED...DERIV OF 1,4-NAPHTHOQUINONE WITHOUT SIDECHAIN IN 3-POSITION CANNOT EXERT ALL FUNCTIONS OF K VIT...|...MENADIONE OR VIT K3...DEPENDING ON BIOASSAY SYSTEM USED, @ LEAST AS ACTIVE ON MOLAR BASIS AS PHYLLOQUINONE. ...ACTIVE WATER-SOL DERIVATIVES OF MENADIONE...SODIUM-BISULFITE SALT OR TETRASODIUM SALT OF DIPHOSPHORIC ACID ESTER. THESE COMPD ARE CONVERTED IN BODY TO MENADIONE.|PARENT STRUCTURE OF K FAMILY OF VIT IS 2-METHYL-1,4-NAPHTHOQUINONE OR MENADIONE. THIS FAT-SOL COMPD & SEVERAL WATER-SOL DERIVATIVES SUCH AS SODIUM BISULFITE & DIPHOSPHORIC ACID ESTER ARE COMMON COMMERCIAL FORMS USED IN MEDICAL PRACTICE.|NATURAL, FAT-SOL VIT ARE MORE EFFECTIVE THAN WATER-SOL DERIVATIVES. /VIT K/|DRUGS WITH VIT K ACTIVITY MAY BE CHEMICALLY ASSAYED & DO NOT REQUIRE BIOASSAY. ...DETERMINATION OF VIT K CONTENT OF FOODS, ASSAY BASED UPON ABILITY OF PREPN TO INCR PROTHROMBIC LEVEL OF DEFICIENT CHICKS IS EMPLOYED.

Analyte: menadione; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: menadione; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: menadione; matrix: chemical purity; procedure: titration with ceric sulfate using orthophenanthroline as indicator|Analyte: menadione; matrix: pharmaceutical preparation (injection solution); procedure: absorption spectrophotometry at 635 nm with comparison to standards|For more Analytic Laboratory Methods (Complete) data for MENADIONE (7 total), please visit the HSDB record page.

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