ビス(4-アミノフェニル) スルホン

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.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Keep container tightly closed in a dry and well-ventilated place. Light sensitive.

Dapsone tablets should be stored at 20-25 °C and protected from light. Dapsone may discolor following exposure to light.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust; Environmental precautions: Do not let product enter drains; Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

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.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

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.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

0.087 [mg/m3]

0.96 [mg/m3]

7.7 [mg/m3]

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

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

... When dapsone is co-administered with trimethoprim the resulting plasma concentrations for both drugs are higher than when either drug is taken alone. In a comparative trial of TMP/dapsone versus TMP-SMX, response rates of 93% and 90% were observed, respectively.

Because the drugs have similar adverse hematologic effects, concurrent use of a folic acid antagonist (e.g., pyrimethamine) and dapsone may result in an increased risk of these adverse effects. Agranulocytosis has developed during the second and third months of therapy in patients receiving concomitant treatment with weekly pyrimethamine and dapsone. If pyrimethamine is used concomitantly with dapsone, the patient should be monitored more frequently than usual for adverse hematologic effects. Because effects may be additive, dapsone should be used with caution in patients with G-6-PD deficiency receiving or exposed to other drugs or agents which are capable of inducing hemolysis in these individuals (e.g., nitrite, aniline, phenylhydrazine, naphthalene, niridazole, nitrofurantoin, primaquine).

Results of several studies indicate that concomitant clofazimine does not affect the pharmacokinetics of dapsone, although a transient increase in urinary excretion of dapsone reportedly occurred in a few patients receiving concomitant therapy with the drugs. In a study in lepromatous leprosy patients receiving dapsone (100 mg daily) and rifampin (600 mg daily), concomitant administration of clofazimine (100 mg daily) did not affect plasma dapsone concentrations or the plasma half-life or urinary elimination of dapsone. There is some evidence that dapsone may decrease or nullify some of the anti-inflammatory effects of clofazimine.

Failure of dapsone to prevent Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) was reported in about 40% of patients with human immunodeficiency virus (HIV) infection who were receiving didanosine concomitantly. This failure rate was substantially higher than that reported in other studies in which dapsone was not administered with didanosine or that were observed when didanosine was used in patients receiving co-trimoxazole or aerosolized pentamidine for prevention of PCP. Although the possibility of a pharmacokinetic interaction was not evaluated in these patients, it was suggested that the buffers present in the didanosine preparation, which provides a pH of 7-8 to facilitate GI absorption of the antiretroviral agent, may interfere with GI absorption of dapsone.

For more Interactions (Complete) data for DAPSONE (9 total), please visit the HSDB record page.

Methemoglobinemia and hemolysis are the main risks of acute intoxication. Hemolytic anemia, agranulocytosis, aplastic anemia and other blood dyscrasias may occur in chronic poisoning. Target organs are central and peripheral nervous systems, blood, liver and skin. Methemoglobinemia is the principal and constant feature of dapsone poisoning. Hemolytic anaemia and agranulocytosis may occur with the relatively low doses used for leprosy and malaria, whereas peripheral neuropathy and hepatitis are only observed with the higher doses used in the treatment of dermatitis herpetiformis. (L1040).

Dapsone, like other sulfonamides, causes a characteristic idiosyncratic liver injury that has features of drug-allergy or hypersensitivity. The typical onset is sudden development of fever and rash followed by jaundice within a few days or weeks of starting the medication. Eosinophilia or lymphocytosis are also common. The presentation can resemble acute mononucleosis and is often referred to as "sulfone syndrome" which is a variant of the "drug rash with eosinophilia and systemic symptoms" (DRESS) syndrome. Rare instances of Stevens Johnson Syndrome and Toxic epidermal necrosis can also occur with dapsone therapy, arising generally within the first 1 to 3 months of therapy. The pattern of injury is typically cholestatic or mixed and can be complicated and prolonged. Severe cholestatic forms of dapsone hepatotoxicity can result in vanishing bile duct syndrome with chronic cholestasis ultimately resulting in chronic liver failure and death. In rare instances, dapsone induced liver injury has resulted in acute hepatocellular injury and acute liver failure. However, most cases resolve rapidly, usually within 2 to 4 weeks of stopping dapsone, unless cholestasis is severe.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 260(SRC), determined from a structure estimation method(2), indicates that dapsone is expected to have moderate mobility in soil(SRC). Volatilization of dapsone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.1X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Dapsone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 260(SRC), determined from a structure estimation method(2), indicates that dapsone is 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 3.1X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 0.97(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Dapsone in aqueous media, was completely photodegraded in 6 hours following exposure to sunlight irradiation(7). Biodegradation data in water were not available(SRC, 2016).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dapsone, which has an estimated vapor pressure of 2.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase dapsone 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 0.23 days(SRC), calculated from its rate constant of 4.6X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase dapsone may be removed from the air by wet and dry deposition(SRC). Dapsone in aqueous media, was completely photodegraded in 6 hours following exposure to sunlight irradiation(4) and, therefore, may 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.

Adverse effects of oral dapsone include:

IDENTIFICATION AND USE: Dapsone is a white or creamy white crystalline powder. Dapsone is approved for use in dermatitis herpetiformis and leprosy. It is particularly useful in the treatment of linear immunoglobulin (IgA) dermatosis, bullous systemic lupus erythematosus, erythema elevatum diutinum, and subcorneal pustular dermatosis. The drug is used as an alternative for treatment of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) and prevention of P. jirovecii infections. Dapsone is designated an orphan drug by the US FDA for treatment and prevention of PCP. It is also effective in treatment of endogenous uveitis, chronic conjunctivitis, keratitis, and keratoconjunctivitis, all caused by a previously unreported pathogenic microorganism, Micromyces intracellularis, in human eye. Dapsone may also be used as an analytic reagent and a hardening agent in the curing of epoxy resins. HUMAN EXPOSURE AND TOXICITY: Methemoglobinemia is the principal and constant feature of dapsone poisoning. Clinical features may include headache, dizziness, agitation, restlessness, nausea, vomiting, abdominal pain, bluish-grey cyanosis, tachycardia, hyperventilation, stupor, convulsions, coma, jaundice, and intravascular hemolysis. Adverse hematologic effects are most severe in patients with a G-6-PD deficiency. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Dapsone may induce acute pancreatitis. ANIMAL STUDIES: Dapsone was added to rat food in a 78-week study. Mesenchymal tumors of abdominal organs or peritoneal tissues occurred in low and high dose males only. Fibroma, fibrosarcoma or sarcoma of spleen or peritoneum occurred most commonly. When dapsone was added to the food of mice at 500 or 1000 ppm for 78 weeks, it was not carcinogenic to either sex. Intragastric administration of 100 mg/kg dapsone to rats for 104 weeks produced spleen sarcomas in male, and higher morbidity from C-cell thyroid carcinomas of both sexes. Tumors appeared after lifetime treatment with maximum tolerated doses. Nervous effects developed following its oral administration to sheep. Incoordination, blindness, recumbency, bloat, opisthotonus, groaning and involuntary movements of the legs were reported in goats treated with an intramammary preparation containing dapsone, chloramphenicol and hyaluronidase. Oral administration of dapsone did not result in a significant degree of immunotoxicity in mice.

Dapsone-induced methemoglobinemia typically results from acute poisoning, either by accidental ingestion or suicidal intent. Presenting symptoms include headache, fatigue, tachycardia, dizziness, and weakness. More severe cases (levels above 60%) can result in arrhythmias, dyspnea, seizures, or coma. Methemoglobinemia is treatable with gastric decontamination, early administration of activated charcoal, or intravenous (IV) methylene blue.

Dapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of March 9, 2016: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page for dapsone, which tabulates all of the Short-Term Toxicity, Long-term Carcinogenicity, Genetic Toxicology, and Organ Systems Toxicity studies performed with this chemical.[Available from: http://ntp.niehs.nih.gov/testing/status/agents/ts-10890-x.html]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dapsone can be estimated to be 260(SRC). According to a classification scheme(2), this estimated Koc value suggests that dapsone is expected to have moderate mobility in soil. Aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that mobility may be much lower in some soils(SRC).

/HUMAN EXPOSURE STUDIES/ Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4'-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by /greater than or equal to/ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild.

/SIGNS AND SYMPTOMS/ Hemolysis develops in almost every individual treated with 200-300 mg of dapsone per day. ... Methemoglobinemia is also common. A genetic deficiency in the NADH-dependent methemoglobin reductase can result in severe methemoglobinemia after administration of dapsone. Isolated instances of headache, nervousness, insomnia, blurred vision, paresthesias, reversible peripheral neuropathy (thought to be sue to axonal degeneration), drug fever, hematuria, pruritus, and a variety of skin rashes have been reported. An infectious mononucleosis-like syndrome, which may be fatal, occurs occasionally.

/SIGNS AND SYMPTOMS/ Methemoglobinemia is the principal and constant feature of dapsone poisoning. Clinical features may include headache, dizziness, agitation, restlessness, nausea, vomiting, abdominal pain, bluish-grey cyanosis, tachycardia, hyperventilation, stupor, convulsions, coma, jaundice, and intravascular hemolysis.

/SIGNS AND SYMPTOMS/ Dapsone has been assoc clinically with prodn of agranulocytosis. The oxidant-induced suppression of human marrow colony forming unit cell proliferation in vitro can be mediated by a metab of dapsone, 4'-amino-4'-hydroxylaminodiphenyl sulfone.

For more Human Toxicity Excerpts (Complete) data for DAPSONE (26 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. Effective date: 9/30/91; Reporting date: 11/27/91.

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. 4,4'-Diaminodiphenyl sulfone is included on this list. Effective date: 9/30/91; Sunset date: 12/19/95.

Used as an antimicrobial drug in the treatment of leprosy and a curing agent for epoxy resins;[HSDB] Also used in the treatment of malaria, Pneumocystis carinii, and some rheumatologic disorders; [Olson, p. 211]

Plastic Composites Manufacturing [Category: Industry]

Anti-Infective Agents; Antimalarials; Folic Acid Antagonists; Leprostatic Agents

Used in leprosy treatment and veterinary medicine.

Hardening agent in the curing of epoxy resins.

Dapsone is approved for use in dermatitis herpetiformis and leprosy. It is particularly useful in the treatment of linear immunoglobulin (IgA) dermatosis, bullous systemic lupus erythematosus, erythema elevatum diutinum, and subcorneal pustular dermatosis.

(1977) 2.60X10+6 grams (princpl custms dists)

(1979) 2.86X10+6 grams (princpl custms dists)

2023: 550,000 - <700,000 lb

(1977) Not produced commercially in US

(1979) Not produced commercially in US

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzenamine, 4,4'-sulfonylbis-. National Production Volume: 1,000,000 - 10,000,000 lb/yr.

Reaction /of 4-chloronitrobenzene/ with sodium sulfide can be controlled to give 4-amino-4'-nitrodiphenyl sulfide, which after N-acetylation and oxidation with hydrogen peroxide forms /4-nitro-4'-acetylaminodiphenyl sulfone/: subsequent reduction and hydrolysis yields 4,4'-diaminodiphenyl sulfone (dapsone) ...

Preparation: French patent 829926 (1938 to I. G. Farbenind)

Benzene is condensed with sulfuric acid to yield phenyl sulfone which is then nitrated by standard procedures to yield the 4,4'-dinitro derivative. Reduction with tin and HCl /hydrochloric acid/ or with various other appropriate reductants yields dapsone.

Reaction of excess sodium sulfide with 1-chloro-4-nitrobenzene followed by acetylation, oxidation with hydrogen peroxide, reduction and acidic or basic hydrolysis; amination of bis(4-chlorophenyl)sulfone

Plastics Material and Resin Manufacturing

Benzenamine, 4,4'-sulfonylbis-: ACTIVE

The diffusion chamber technique can apparently be used to evaluate inhibitory effect of antileprosy drugs on growth of M. lepraemurium. It also provides relatively rapid in vitro method for directly comparing effects of drugs outside metab influence of host.