テトラエチルチウラムジスルフィド

3.88

log Kow= 3.88

1.9

3.9

Slight odor.

Odorless

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

1.30

1.3 g/cm³

1.3

1.3 @25 °C

1.30

WHITE TO OFF-WHITE CRYSTALLINE POWDER

Light-gray powder

White, yellowish, or light-gray powder.

less than 0.1 mg/mL at 70 °F (NTP, 1992)

4.09

Sol in alc (3.82 g/100 ml), ether (7.14 g/100 ml), acetone, benzene, chloroform, carbon disulfide

Soluble in aromatic

In water, 4.09 mg/L at 25 °C

1.26e-02 g/L

243 °F at 17 mmHg (NTP, 1992)

117

117 °C at 17 mm Hg

at 2.3kPa: 117 °C

243 °F

117 °C @760 [mm Hg]

158 °F (NTP, 1992)

71.5

71.5 °C

71.5 °C

71 °C

158 °F

0 mmHg at 68 °F approximately (NTP, 1992)

0.00087 [mmHg]

0 mmHg

Tetraethylthiuram disulfide appears as odorless or almost odorless white or almost white to tan powder. Unpleasant taste with metallic or garlic aftertaste. pH of a solution obtained by shaking 1 g with 30 mL of water is 6 to 8. (NTP, 1992)

Dry Powder; Gas Vapor; Dry Powder; Other Solid; Large Crystals; Dry Powder

White, yellowish, or light-gray powder with a slight odor.(fungicide); [NIOSH]

Solid

WHITE-TO-GREY POWDER WITH CHARACTERISTIC ODOUR.

White, yellowish, or light-gray powder with a slight odor.

Positive

3.52

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]；H317: May cause an allergic skin reaction [Warning Sensitization, Skin]；H373 **: May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P260, P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P319, P321, P330, P333+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Warning

Chemical: Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), tetraethyl-

Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl- 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: 23-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/11549

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

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

Combustible. Finely dispersed particles form explosive mixtures in air.

Excerpt from NIOSH Pocket Guide for Disulfiram:；Exposure Routes: Inhalation, ingestion, skin and/or eye contact；Symptoms: Irritation eyes, skin, respiratory system; sensitization dermatitis; lassitude (weakness, exhaustion), tremor, restlessness, headache, dizziness; metallic taste; peripheral neuropathy; liver damage；Target Organs: Eyes, skin, respiratory system, central nervous system, peripheral nervous system, liver (NIOSH, 2024)

Disulfiram is tested in the standard allergen tray as one of the components of the thiuram mix (tetraethylthiuram disulfide); Thiuram-sensitive patients who take Antabuse may develop a generalized contact dermatitis or localized hand and foot dermatitis. [Marks, p. 132] A nurse dispensing disulfiram developed contact dermatitis; [Kanerva, p. 1837] Drug-induced hepatitis has been rarely reported in patients taking therapeutic doses of Antabuse. [HSDB] Poisoning by ingestion (with alcohol): headache, flushing, hypotension, sweating, dizziness, nausea, vomiting, and diarrhea; Poisoning by ingestion (acute overdose): delirium, agitation, CNS depression; Poisoning by ingestion (chronic overdose): encephalopathy and neuropathy; [Ford, p. 591-4]

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl disulfiram, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Tetraethylthiuram disulfide is an indirect food additive for use only as a component of adhesives.

Eneanya DI et al; The actions and metabolic fate of disulfiram; Annu Rev Pharmacol Toxicol 21: 575-96 (1981). A review with 170 references on the metabolism and toxicity of disulfiram.

Wise JD; Disulfiram toxicity- a review of the literature; J Arkansas Med Soc 78 (2): 87-92 (1981). A review with 41 references of disulfiram toxicity.

Brien JF, Loomis CW; Chemical assays for disulfiram and carbimide (cyanamide) in biological fluids; Alcohol: Clin Exp Res 7 (3): 256-63 (1983). A review on the determination of disulfiram and carbimide in biological fluids; 33 references.

McNichol RW et al; Disulfiram: A Guide to Clinical Use in Alcoholism Treatment; Am Fam Physician 44 (2): 481-4 (1991).

For more Special Reports (Complete) data for DISULFIRAM (7 total), please visit the HSDB record page.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Disulfiram is included on this list.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use water spray, powder, foam, carbon dioxide.

Rinse skin with plenty of water or shower.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Give a slurry of activated charcoal in water to drink. Refer for medical attention .

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.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

(General first aid procedures)；Eye: Irrigate immediately - If this chemical contacts the eyes, immediately wash (irrigate) the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately.；Skin: Soap wash immediately - If this chemical contacts the skin, immediately wash the contaminated skin with soap and water. If this chemical penetrates the clothing, immediately remove the clothing, wash the skin with soap and water, and get medical attention promptly.；Breathing: Respiratory support；Swallow: Medical attention immediately - If this chemical has been swallowed, get medical attention immediately.

Commercially available disulfiram tablets should be protected from light and stored in tight, light-resistant containers at a temperature less than 40 °C preferably between 15-30 °C. Oral suspensions of disulfiram have been prepared extemporaneously from commercially available tablets of the drug. A suspension of 1% disulfiram, 1/4% methylcellulose, and 10% Tang /breakfast drink/ in distilled water has been reported to be stable for up to 6 months if refrigerated at 2-8 °C and protected from light.

Separated from strong oxidants.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing 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.；STORAGE PRECAUTIONS: You should protect this material from exposure to light. Keep it away from oxidizing materials and store it under ambient temperatures. (NTP, 1992)

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting.

Simultaneously feeding of the animals with disulfiram caused a potentiation of the hepatotoxicity of 1,2-dichloroethane, possibly due to an inhibition of microsomal mixed-function oxidase-mediated metabolism of 1,2-dichloroethane and to a compensatory increase in metabolism to reactive metabolites generated by glutathione-S-transferase-mediated conjugation of 1,2-dichloroethane with reduced glutathione.

Use of alcohol or alcohol containing products within 14 days of disulfiram therapy will result in disulfiram-alcohol reaction.

Chronic preoperative administration or perioperative use of hepatic enzyme inhibitors, such as disulfiram, may decrease the plasma clearance and prolong the duration of action of alfentanil.

Metabolism of bacampicillin produces low plasma concentrations of alcohol and acetaldehyde; although the risk of disulfiram-alcohol interaction appears minimal, caution is recommended if concurrent use is unavoidable. A similar reaction is thought to occur with amoxicillin and clavulanate combination.

For more Interactions (Complete) data for DISULFIRAM (35 total), please visit the HSDB record page.

Chronic therapy with disulfiram is associated with mild serum aminotransferase elevations in up to 25% of patients, but elevations above 3 times the upper limit of normal (ULN) occur in 4% of patients or less. Importantly, disulfiram is a well established cause of clinically apparent liver injury, which can be severe and even fatal. The estimated incidence of acute liver injury is 1 per 10,000 to 30,000 patient-years of disulfiram treatment. The injury usually arises within 2 to 12 weeks of starting disulfiram, but the latency can be shorter in cases of reexposure and may arise only after 3 to 6 months, particularly with intermittent therapy. The clinical presentation resembles acute viral hepatitis and the pattern of injury is typically hepatocellular (Cases 1 and 2). Rash, fever and eosinophilia are not uncommon, but are rarely severe. The injury can be severe (Case 3) and the fatality rate is at least 10% in cases with jaundice. Rechallenge or reexposure is usually associated with rapid recurrence of liver injury and should be avoided. The clinical presentation and histology differ greatly from alcoholic hepatitis, in that disulfiram liver injury is marked by viral hepatitis-like changes of focal hepatocellular necrosis, lobular disarray and chronic inflammatory cell infiltrates with eosinophils, but without significant fat, neutrophils or Mallory bodies. In the 1980s and 1990s, disulfiram was often listed among the most common causes of acute liver injury and liver failure due to medications. More recently, disulfiram use has decreased and cases of clinically apparent liver injury from disulfiram are now rare. The majority of cases of disulfiram hepatotoxicity have been reported from Scandinavian countries.；Chronic therapy with disulfiram can cause widespread homogenous eosinophilic inclusions in hepatocytes, similar to the “ground glass” changes that can occur in chronic HBsAg carriers.；Likelihood score: A (well known cause of clinically apparent liver injury).

LC50 Poecilia reticulata (Guppy) 0.32 mg/L/96 hr /Conditions of bioassay not specified in source examined/

LC50 Daphnia magna 0.12 mg/L/48 hr /Conditions of bioassay not specified in source examined/

LC50 Oncorhynchus mykiss (Rainbow trout, donaldson trout; early life stage (fertilized egg to fry)) 9.0 ug/L/60 days (95% confidence interval: 8.0-10.0 ug/L); renewal /formulated product/

LC50 Brachydanio rerio (Zebrafish) early life stage 2.2 mg/L/7 days (95% confidence interval: 1.0-4.7 mg/L); renewal /formulated product/

EC50 Brachydanio rerio (Zebrafish) early life stage; (embryolethality and malformations) 0.13 mg/L/7 days (95% confidence interval: 0.10 -0.18 mg/L); renewal /formulated product/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,100(SRC), determined from a log Kow of 3.88(2) and a regression-derived equation(3), indicates that disulfiram is expected to have slight mobility in soil(SRC). Volatilization of disulfiram from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.3X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Disulfiram is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.7X10-4 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,100(SRC), determined from a log Kow of 3.88(2) and a regression-derived equation(3), indicates that disulfiram is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 8.3X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 14 hours and 12 days, respectively(SRC). Volatilization is expected to be attenuated by adsorption; the half-life for a model pond is 120 days when adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 280(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound is expected undergo very slow hydrolysis at environmental conditions(SRC). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), disulfiram, which has an estimated vapor pressure of 8.7X10-4 mm Hg at 25 °C (SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase disulfiram 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 0.04 days(SRC), calculated from its rate constant of 3.9X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Disulfiram has a low absorption of light >290 nm(4), therefore, disulfiram is not expected to be susceptible to direct photolysis(SRC).

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；Skin Sensitizer - An agent that can induce an allergic reaction in the skin.；ACGIH Carcinogen - Not Classifiable.

Disulfiram has an acceptable risk profile. However, it is associated with many adverse events and drug-drug interactions, including death. The most common and less serious adverse effects include headache, sleepiness, tiredness, and halitosis (or metallic taste). Dermatological, neurological, psychiatric, and cardiac events have been reported. Serious adverse effects include hepatitis, hepatotoxicity, psychosis, seizures, peripheral neuropathy, and optic neuritis. Dermatological adverse effects are rare and include exfoliative dermatitis, rash, and pruritis. Hepatic failure may develop after many months of therapy. There have been cases of fatal fulminant hepatic failure that have been reported despite discontinuation of medication (1 in 30,000 patients treated per year).；Psychiatric adverse effects are rare. Psychosis, confusional states, mutism, headbanging, memory impairment, and rarely stupor have been reported, and effects are dose-dependent. Symptoms usually resolve after discontinuation of disulfiram and a short course of antipsychotic medication. Psychosis may occur as a result of an interaction between disulfiram and cannabis. Neurological adverse effects may occur as early as 10 days after initiation. Axonal polyneuropathy is a rare adverse effect. Some cases of severe sensory-motor polyneuropathy with the involvement of cranial nerves have been reported within weeks of initiation of disulfiram 500 mg. Neuropathy occurs in 1 per 1000 patients treated with disulfiram per year.；Drug-Drug Interactions；Drug interactions occur with compounds utilizing the cytochrome P450 enzyme system for oxidative metabolism. This interaction can occur with the following medications: amitriptyline, imipramine, phenytoin, chlordiazepoxide, diazepam, omeprazole, and acetaminophen. Drug-drug interactions may occur with other medications not listed. Slow elimination of disulfiram may give rise to the disulfiram-alcohol reaction up to 14 days after the discontinuation. Disulfiram-alcohol reactions have been reported in patients exposed to environmental chemical compounds containing alcohol. Prolonged administration of disulfiram has demonstrated the inhibition of the metabolism of theophylline, phenytoin, and warfarin.

The substance can be absorbed into the body by inhalation of dust and by ingestion.

inhalation, ingestion, skin and/or eye contact

Inhalation (MSDS, A308); ingestion (MSDS, A308); dermal (MSDS, A308) ; eye contact (MSDS, A308) Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).

Signs and Symptoms of Overdose；One case report features a 4-year-old girl who accidentally ingested 4–5 tablets of disulfiram, resulting in hypoglycemia and encephalopathy. After management in the intensive care unit, the child exhibited normalization of blood sugars after 8 hours and displayed characteristic MRI brain findings, including bilateral globus pallidus hyperintensity in T2-weighted and diffusion-weighted images. The conclusion underscores the potential severity of acute disulfiram poisoning in children and emphasizes the importance of considering it in the diagnosis of idiopathic encephalopathy with extrapyramidal symptoms.；Management of Overdose；Contact the local poison control center in case of an overdose. No information is available on the treatment of disulfiram overdose, and there is no antidote available. Supportive care via supplemental oxygen, cardiac monitoring, and intravenous fluids may be necessary. Consult a physician if symptoms are severe. Cases of ingestion of 5 g or greater resulted in parkinsonism, choreoathetosis, and thalamic syndrome. Doses should not exceed 500 mg/d for treatment of alcohol dependence, and doses for malignancy remain as yet undetermined.

Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.

Confusion. Headache. Nausea. Vomiting.

irritation eyes, skin, respiratory system; sensitization dermatitis; lassitude (weakness, exhaustion), tremor, restlessness, headache, dizziness; metallic taste; peripheral neuropathy; liver damage

Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.

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=97-77-8]

Chemical: Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), tetraethyl-

Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl- 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: 23-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/11549

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

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl disulfiram, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Tetraethylthiuram disulfide is an indirect food additive for use only as a component of adhesives.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Disulfiram is included on this list.

N07BB01

N - Nervous system；N07 - Other nervous system drugs；N07B - Drugs used in addictive disorders；N07BB - Drugs used in alcohol dependence；N07BB01 - Disulfiram

P - Antiparasitic products, insecticides and repellents；P03 - Ectoparasiticides, incl. scabicides, insecticides and repellents；P03A - Ectoparasiticides, incl. scabicides；P03AA - Sulfur containing products；P03AA04 - Disulfiram

QN - Nervous system；QN07 - Other nervous system drugs；QN07B - Drugs used in addictive disorders；QN07BB - Drugs used in alcohol dependence；QN07BB01 - Disulfiram

Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol.

Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.

Acetaldehyde, produced as a result of oxidation of ethanol by alcohol dehydrogenase, ordinarily does not accumulate in the body, because it is further oxidized almost as soon as it is formed, primarily by aldehyde dehydrogenase. Following the administration of disulfiram, both cytosolic and mitochondrial forms of this enzyme are irreversibly inactivated to varying degrees, and the concentration of acetaldehyde rises. It is unlikely that disulfiram itself is responsible for the enzyme inactivation in vivo; several active metabolites of the drug, especially diethylthiomethylcarbamate, behave as suicide-substrate inhibitors of aldehyde dehydrogenase in vitro. These metabolites reach significant concentrations in plasma following the administration of disulfiram.

Disulfiram (700 mg/kg, orally) increase brain levels of serotonin (i) and 5-hydroxyindoleacetic acid (5-hiaa) in rats. Ethanol (1 g/kg and 2x1.5 g/kg, ip) did not affect the serotonin level, but at the higher dose it increase the 5-hiaa level. When disulfiram was given in combination with ethanol, the brain level of serotonin was higher and the 5-hiaa level was lower, compared to the results with disulfiram alone. Thus, the biogenic aldehyde derived from serotonin may influence serotonin metab and the elimination of 5-hiaa from the brain.

When disulfiram was given orally to rats at 40-400 mg/kg, the serum and, to a lesser extent, the liver cholesterol concentrations were increased and the liver microsome cholesterol 7alpha-hydroxylase activity decreased. The 7alpha-hydroxylase inhibition was completely reversed by dithiothreitol, indicating that disulfiram acted through its disulfide on 7alpha-hydroxylase. Increased serum cholesterol of alcoholics treated with disulfiram may be related to the inhibition of 7alpha-hydroxylase.

Human aldehyde dehydrogenase consists of two main isozymes with low and high Km for acetaldehyde. Studies regarding the inhibitory reaction of disulfiram and its metabolites were performed. Among the metabolites, diethylamine inhibited the low Km enzyme strongly. Vasomotor symptoms and high acetaldehyde concn in blood after ethanol intake in patients who are treated with disulfiram might be mainly due to a decrease in activity of the low Km enzyme caused by diethylamine which is produced in vivo as one of the metabolites from disulfiram, rather than to an inhibitory reaction of disulfiram only. Thus, alcohol sensitivity in Mongoloids and the disulfiram-ethanol reaction may have a common mechanism.

For more Mechanism of Action (Complete) data for DISULFIRAM (19 total), please visit the HSDB record page.

The elimination half-life of disulfiram in plasma is 7.3 hr. /From table/

Following a 250 mg dose, the half-lives of disulfiram, diethyldithiocarbamate and carbon disulfide are 7.3 +/-1.5 hours, 15.5 +/-4.5 hours, and 8.9 +/-1.4 hours, respectively.

Hepatic.

Disulfiram is slowly metabolized in the liver to diethyldithiocarbamate, diethylamine, and carbon disulfide. Six hr after oral administration of the drug, one third of plasma disulfiram is in the form of diethyldithiocarbamate.

In rats the following metabolites of disulfiram were found: diethyldithiocarbamate; diethyldithiocarbamate s-glucuronide; inorganic sulfate; diethylamine and carbon disulfide. A small amount of S was bound to proteins as mixed disulfides. ... Metabolism of disulfiram in man is similar to that in animals.

Recently, n,n-diethylthiocarbamoyl-1-thio-beta-glucopyranosiduronic acid was isolated from combined urine of 4 men given oral doses of tetraethylthiuram disulfide.

Diethylthiocarbamic acid methyl ester, in contrast to other disulfiram metabolites, is a potent inhibitor of liver aldehyde dehydrogenase in vitro. Like disulfiram, diethylthiocarbamic acid methyl ester had a pronounced hypothermic effect in rats. This hypothermic effect and the augmented blood pressure response to ethanol challenge in rats developed rapidly with diethylthiocarbamic acid methyl ester but were somewhat delayed with disulfiram. The blood pressure response outlasted the presence of diethylthiocarbamic acid methyl ester in plasma (less than 24 hr); a significant effect was found 48 hr after pretreatment but not 72 hr after a single dose. No effect was observed when ethanol was given 15 min before diethylthiocarbamic acid methyl ester or disulfiram. These latter two observations are consistent with a function of diethylthiocarbamic acid methyl ester as a suicide inhibitor of aldehyde dehydrogenase. Since diethylthiocarbamic acid methyl ester has been reported to inhibit aldehyde dehydrogenase in vitro, even under anaerobic conditions, diethylthiocarbamic acid methyl ester may be the active metabolite of disulfiram.

For more Metabolism/Metabolites (Complete) data for DISULFIRAM (7 total), please visit the HSDB record page.

TR3MLJ1UAI

DISULFIRAM

Mechanisms of Action [MoA] - Acetyl Aldehyde Dehydrogenase Inhibitors

Established Pharmacologic Class [EPC] - Aldehyde Dehydrogenase Inhibitor

Disulfiram is an Aldehyde Dehydrogenase Inhibitor. The mechanism of action of disulfiram is as an Acetyl Aldehyde Dehydrogenase Inhibitor.

DISULFIRAM

Substances interfering with the metabolism of ethyl alcohol, causing unpleasant side effects thought to discourage the drinking of alcoholic beverages. Alcohol deterrents are used in the treatment of alcoholism.

Compounds that bind to and inhibit the enzymatic activity of acetaldehyde dehydrogenases.

Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).

Absorption /of disulfiram is/ slow. Eighty to ninety percent of an oral dose is absorbed. /Its/ biotransformation /is predominately/ hepatic /and/ a single dose will begin to affect ethanol metabolism within 1 to 2 hours.

Disulfiram is ... completely absorbed from the human GI tract. However, a period of 12 hr is required for its full action, perhaps because, being highly sol in lipid, it is initially localized in fat. Elimination is relatively slow, and about 1/5 still remains in body at end of a week. The greater part of the absorbed drug is ... excreted in the urine as the sulfate, partly free and partly esterified.

After a single oral dose of 50, 100, 200, or 400 mg/kg, disulfiram was found in dose-dependent quantities in blood, liver, kidney, spleen, brain, muscle, and peri-epididymal adipose tissue of rats. After a 2-mo treatment, accumulation was not dose-dependent, suggesting a saturation point for various organs.

The human plasma protein binding characteristics of disulfiram and its therapeutically active metabolite, diethylthiocarbamic acid methyl ester were investigated. Both compounds were bound principally to albumin over the ranges 200-800 and 345-2756 nM, respectively. The average number of binding sites was approximately one for both substances, whereas the average association constants were 7.1X10+4 and 6.1X10+3/M, respectively.

For more Absorption, Distribution and Excretion (Complete) data for DISULFIRAM (7 total), please visit the HSDB record page.

Used as a fungicide, a rubber accelerator, and a drug to treat alcoholism; [ACGIH]

Rubber accelerator; vulcanizer; seed disinfectant; fungicide

A vulcanization accelerator in the production of natural rubber and synthetic elastomers isobutylene-isoprene, butadiene, styrene-butadiene, isoprene, and nitrile-butadiene rubber. An activator of thiazole accelerators, plasticizer in neoprene. Bis(diethylthiocarbamoyl) disulfide is used to obtain colored vulcanizates.

Major use of disulfiram is as accelerator in compounding natural, styrene-butadiene, Isobutylene-isoprene & neoprene W rubbers. It is fast-curing, non-discoloring & non-staining & can be used with or without sulfur. It can be used as primary or secondary accelerator with aldehyde amines & guanidines and is also used as cure retarder in chloroprene & neoprene g rubbers. ... Although disulfiram may have been used as pesticide it has not been approved for that use in US by EPA.

MEDICATION: Alcohol deterrent

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

2023: 850,000 - <1,000,000 lb；2022: 1,000,000 - <2,500,000 lb；2021: 1,000,000 - <2,500,000 lb；2020: 850,000 - <1,000,000 lb

Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), tetraethyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).[EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program. Thioperoxydicarbonic diamide (

Disulfiram is available in US for rubber processing with following specifications: ... Ash, 0.5% max; moisture, 1.0% max; available sulfur, 10.8%. It is also avail in dispersion containing 25-30% binder and in 50:50 mixt with thiram (methyl tuads).

Disulfiram, USP (antabuse), is available in form of oral tablets that contain 250 or 500 mg of drug.

All Other Basic Organic Chemical Manufacturing；Synthetic Rubber Manufacturing；Rubber Product Manufacturing

Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl-: ACTIVE