Menadion

2.2

log Kow = 2.20 @ pH 7.4

2.20

Very faint acrid odor

Nearly odorless

Bright yellow crystals

YELLOW NEEDLES FROM ALC, PETROLEUM ETHER

160

Slightly soluble in ethanol, acetic acid, and ligroin. Soluble in ethyl ether, benzene, chloroform, and sulfuric acid.

One gram dissolves in about 60 ml alcohol, in 10 ml benzene, in 50 ml vegetable oils; moderately soluble in chloroform, carbon tetrachloride.

Soluble in aromatic solvents

SOL IN FATS

For more Solubility (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

107

105-107 °C

107 °C

Bright yellow solid with a very mild acrid odor; [Merck Index]

Solid

Stable in air; decomp by sunlight. ... Destroyed by alkalies and reducing agents.

STABLE IN QUINONE FORM.

Solns may be heated to 120 °C without decomp.

1496.1

259.23

Warning

H302 (97.4%): Harmful if swallowed [Warning Acute toxicity, oral]；H315 (95.3%): Causes skin irritation [Warning Skin corrosion/irritation]；H317 (63.7%): May cause an allergic skin reaction [Warning Sensitization, Skin]；H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (98.4%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H400 (70.5%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (64.7%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P261, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 190 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 1,4-Naphthalenedione, 2-methyl-

Status: Active Update: 27-10-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/26040

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

A skin and mucous membrane irritant; [HSDB] May cause hemolytic anemia and cellular damage; [IARC] A skin and strong eye irritant; A possible sensitizer; Harmful by ingestion; Targets the kidney, liver, and blood; [Sigma-Aldrich MSDS] See 1,2-Naphthoquinone.

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.

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/

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).

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 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.

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).

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).

Chemical: 1,4-Naphthalenedione, 2-methyl-

Status: Active Update: 27-10-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/26040

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

B - Blood and blood forming organs；B02 - Antihemorrhagics；B02B - Vitamin k and other hemostatics；B02BA - Vitamin k；B02BA02 - Menadione

QB - Blood and blood forming organs；QB02 - Antihemorrhagics；QB02B - Vitamin k and other hemostatics；QB02BA - Vitamin k；QB02BA02 - Menadione

Deficiency may occur in the following persons or conditions: Patients receiving total parenteral nutrition (TPN); in malabsorption syndromes associated with pancreatic insufficiency (including cystic fibrosis), hepatic-biliary tract disease (obstructive jaundice, internal biliary fistula), diseases of the small intestine (celiac disease, tropical sprue, regional enteritis, ulcerative colitis, persistent diarrhea or dysentery, short bowel syndrome after extensive bowel resection); prolonged T-tube drainage; abetalipoproteinemia; infants receiving substitute formulas and those who are breast-fed. /Vitamin K/

The chief clinical manifestation of vitamin K deficiency is an increased tendency to bleed. Ecchymoses, epistaxis, hematuria, gastrointestinal bleeding, and postoperative hemorrhage are common; intracranial hemorrhage may occur. /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.

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.

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/

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.

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.

Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.

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/

Synthetic naphthoquinone derivative with the physiologic properties of vitamin K; Used as a supplement and veterinary antidote to bishydroxycoumarin poisoning (including sweet clover poisoning); [Merck Index] Used as an intermediate in phylloquinone production; [IARC]

Vitamin (prothrombogenic; VET: Vitamin (prothrombogenic); antidote to bishydroxycoumarin poisoning, including sweet clover poisoning. /Dimethylpyrimidinol bisulfite menadione/

MEDICINE, FUNGICIDES, ANIMAL FEED ADDITIVES

Menadione is of industrial importance as an intermediate in the synthesis of phylloquinone, and salts of its bisulfite adduct are used as stabilized forms in the animal feed industry.

For menadione (USEPA/OPP Pesticide Code: 006319) 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./

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.

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.