Sulfanilamide

-0.62

log Kow = -0.62

-0.8

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

1.08 @ 25 °C

1.08 @25 °C

LEAFLETS FROM AQ ALCOHOL

CRYSTALS

0.1 to 1.0 mg/mL at 72 °F (NTP, 1992)

7500

IN WATER: 7.5 G/L AT 25 °C & 477 G/L AT 100 °C

1 G DISSOLVES IN ABOUT 37 ML OF ALC & ABOUT 5 ML ACETONE

INSOL IN CHLOROFORM, ETHER, BENZENE & PETROLEUM ETHER; SOL IN GLYCEROL, PROPYLENE GLYCOL, HYDROCHLORIC ACID, SOLN OF POTASSIUM AND SODIUM HYDROXIDE

SOL IN ETHANOL

329 to 331 °F (NTP, 1992)

165.5

165.5 °C

165.5 °C

165.5 °C

Sulfanilamide is a white powder. pH of 0.5% aqueous solution: 5.8-6.1. (NTP, 1992)

Solid; [Merck Index]

Solid

Positive

2.76

2.7

Agilent XCT

Electrospray ionization

formic acid (5.3nM)

10.6 (at 20 °C)

pKa = 10.43, pKb = 11.63

pKa = 10.58

This chemical does not meet GHS hazard criteria for 41.6% (121 of 291) of reports.

Warning

H315 (58.4%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (58.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (57%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

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

Aggregated GHS information provided per 291 reports by companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 121 of 291 reports by companies.；There are 12 notifications provided by 170 of 291 reports by companies with hazard statement code(s).；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: Benzenesulfonamide, 4-amino-

Regulation (EC) No 1107/2009 (amended)

Status: Active Update: 11-07-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/24237

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

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the skin, eyes and mucous membranes, nausea, vomiting, fever, diarrhea, jaundice, headache, crystalluria, acidosis, ataxia, convulsions, cyanosis, dizziness, dermatitis, paralysis and respiratory failure. It has been implicated in aplastic anemia.；ACUTE/CHRONIC HAZARDS: This material may cause irritation of the skin on contact. (NTP, 1992)

Photoallergic contact dermatitis reported; Sulfanilamide may induce photosensitivity in patients taking sulfanilamide systemically (photodrug reaction). [Marks, p. 201-3] In a 1946 report, occupational asthma was induced by sulfathiazole (72-14-0). [Malo] See Sulfathiazole.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

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)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with acetone, then transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should protect this container from exposure to light. Keep the container tightly closed under an inert atmosphere and store under refrigerated temperatures. (NTP, 1992)

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.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

3.0 [mg/m3]

140 [mg/m3]

830 [mg/m3]

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

The most important interactions of the sulfonamides involve those with oral anticoagulants, the sulfonylurea hypoglycemic agents, and the hydantoin anticonvulsants. In each case sulfonamides can potentiate the effects of the other drug by mechanisms that appear to involve primarily inhibition of metabolism and, possibly, displacement /from/ albumin.

PENTOBARBITAL /SRP: CNS DEPRESSION/ IN MICE WAS ENHANCED AFTER PRE-TREATMENT WITH... SULFANILAMIDE... INCR /SRP: CNS DEPRESSION/ APPEARED TO BE DUE TO RELEASE OF PENTOBARBITAL FROM SERUM-PROTEIN BINDING, RESULTING IN HIGHER CEREBRAL CONCN, RATHER THAN DUE TO INHIBITION OF METABOLISM.

INTRAGASTRIC FORMATION OF /A/ TRIAZENE OCCURRED IN SYRIAN GOLDEN HAMSTERS BY CONCURRENT ADMIN OF SULFANILAMIDE AND SODIUM NITRITE/.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 11(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that sulfanilamide should have very high mobility in soil(SRC). The adsorptivity of sulfanilamide is expected to be sensitive to pH since sulfanilamide has a pKa of 10.58(7). Also, studies have shown that covalent binding of ring-substituted anilines, such as sulfanilamide(SRC), to humates involves a reversible equilibrium which is followed by a very slow and relatively irreversible reaction(9) which may reduce sulfanilamide's mobility in soil(SRC). Volatilization of sulfanilamide should not be important from moist soil surfaces(SRC) given an estimated Henry's Law constant of 1.5X10-10 atm-cu m/mole(4,SRC), or from dry soil surfaces(SRC) based on an estimated vapor pressure of 7.3X10-6 mm Hg(5,SRC). Sulfanilamide may be susceptible to direct photolysis on soil surfaces based on its absorption of light at wavelengths >290 nm(6,SRC). Although aniline was able to degrade quickly, sulfanilamide degraded very slowly by aniline-acclimated activated sludge in a 200 hour Warburg Run(8), suggesting that biodegradation in soil will be slow(SRC).

AQUATIC FATE: An estimated Koc value of 11(SRC), determined from an experimental log Kow(1) and a recommended regression-derived equation(2), indicates that sulfanilamide should not adsorb to suspended solids and sediment(SRC) in the water(2,SRC). Sulfanilamide will be essentially non-volatile from water surfaces based on an estimated Henry's Law constant of 1.5X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). An estimated BCF value of 0.2(2,SRC), from an experimental log Kow(1), suggests that sulfanilamide will not bioconcentrate in aquatic organisms(SRC) according to a recommended classification scheme(4). Although aniline was able to degrade quickly, sulfanilamide degraded very slowly by aniline-acclimated activated sludge in a 200 hour Warburg Run(5), suggesting that biodegradation in water will be slow(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sulfanilamide, which has an estimated vapor pressure of 7.3X10-6 mm Hg at 25 °C(2,SRC) will exist as both a vapor and particulate in the ambient atmosphere. Vapor-phase sulfanilamide 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 about 17 hours(3,SRC). Particulate-phase sulfanilamide may be physically removed from the air by wet deposition(SRC).

The Koc of sulfanilamide is estimated as approximately 11(SRC), using an experimental log Kow of -0.62(1,SRC) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that sulfanilamide should have high mobility in soil(SRC). The adsorptivity of sulfanilamide is expected to be sensitive to pH since sulfanilamide has a pKa of 10.58(4). Also, studies have shown that covalent binding of ring-substituted anilines, such as sulfanilamide(SRC), to humates involves a reversible equilibrium which is followed by a very slow and relatively irreversible reaction(5) which may reduce sulfanilamide's mobility in soil(5).

Retinal and preretinal hemorrhages have in very rare instances been observed following administration of sulfanilamide ... .

Visual distrubances have in a few cases been attributed to effects of sulfonamides on the optic nerve or retina. /Sulfonamide drugs/

Sulfonamide drugs have been held responsible for several types of ocular disturbance, including acute transient myopia, conjunctivitis, and keratitis associated with skin reactions, rarely disturbances of the optic nerve and retina, and temporary impairment of depth perception. /Sulfonamide drugs/

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

sulfanilamide

DILI Positive

Vaginal

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF value of 0.2 was calculated for sulfanilamide(SRC), using an experimental log Kow of -0.62(1) and a recommended regression-derived equation(2). According to a recommended classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms will not be an important fate process(SRC).

The Henry's Law constant for sulfanilamide is estimated as 1.5X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value indicates that sulfanilamide will be essentially nonvolatile from water surfaces(2,SRC). Sulfanilamide's vapor pressure, 7.3X10-6 mm Hg(3,SRC) and Henry's Law constant(1,SRC) indicate that volatilization from dry or moist soil surfaces should not occur(SRC).

LETHAL DOSES IN ANIMALS PRODUCE ATAXIA, CLONIC CONVULSIONS, PARALYSIS AND DEATH FROM RESPIRATORY FAILURE.

COWS SHOWED...VARIABLE SUSCEPTIBILITY...IN SOME ANIMALS SINGLE DOSES OF 220 MG/KG PRODUCED DIARRHEA. LARGER DOSES 440 MG/KG BROUGHT ABOUT DROP IN MILK YIELD, INAPPETENCE, SLEEPINESS & SOME INCOORDINATION OF MOVEMENT; DIARRHEA WAS ALSO SOMETIMES SEEN.

DAILY DOSING...TO HORSES AT RATE OF 0.44 G/KG (0.2 G/LB) PRODUCED...ANOREXIA, WEAK PULSE & GENERAL DEBILITY... AT LOWER DOSE RATE OF 0.17 G/KG DAILY... GENERAL DEPRESSION, MUSCLE RIGIDITY & EDEMA /WERE OBSERVED/; IF ADMIN WAS CONTINUED ANIMALS DIED.

IN HORSE A SINGLE DOSE /ORALLY ADMIN/ AT RATE OF 440 MG/KG CAUSED SOME LISTLESSNESS & DISINCLINATION TO FEED.

For more Non-Human Toxicity Excerpts (Complete) data for SULFANILAMIDE (9 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of sulfanilamide with photochemically produced hydroxyl radicals has been estimated as 2.3X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1,SRC). This corresponds to an atmospheric half-life of about 17 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1,SRC). Sulfanilamide may be susceptible to direct photolysis on soil surfaces based on its absorption of light at wavelengths >290 nm(2,SRC). UV photolysis of an aqueous solution of sulfanilamide, with a 1 kw Xe Arc lamp equipped with an infrared filter (intensity of 1.22 kw/sq-m), yielded the following radicals: C6H4SO2NH2, C6H5SO2, SO2NH2, and SO3.-(3).

Chemical: Benzenesulfonamide, 4-amino-

Regulation (EC) No 1107/2009 (amended)

Status: Active Update: 11-07-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/24237

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

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

J - Antiinfectives for systemic use；J01 - Antibacterials for systemic use；J01E - Sulfonamides and trimethoprim；J01EB - Short-acting sulfonamides；J01EB06 - Sulfanilamide

D - Dermatologicals；D06 - Antibiotics and chemotherapeutics for dermatological use；D06B - Chemotherapeutics for topical use；D06BA - Sulfonamides；D06BA05 - Sulfanilamide

QJ - Antiinfectives for systemic use；QJ01 - Antibacterials for systemic use；QJ01E - Sulfonamides and trimethoprim；QJ01EQ - Sulfonamides (atc human differently classified, see guidelines)；QJ01EQ06 - Sulfanilamide

QD - Dermatologicals；QD06 - Antibiotics and chemotherapeutics for dermatological use；QD06B - Chemotherapeutics for topical use；QD06BA - Sulfonamides；QD06BA05 - Sulfanilamide

Sulfanilamide is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

Sulfanilamide is a competitive inhibitor of bacterial enzyme dihydropteroate synthetase. This enzyme normally uses para-aminobenzoic acid (PABA) for synthesizing the necessary folic acid. The inhibited reaction is normally necessary in these organisms for the synthesis of folic acid. Without it, bacteria cannot replicate.

Sulfonamides are structural analogs and competitive antagonist of para-aminobenzoic acid ... and thus prevent normal bacterial utilization of para-aminobenzoic acid for the synthesis of folic acid (pteroylglutamic acid). ... More specifically, sulfonamides are competitive inhibitors of dihydropteroate synthase, the bacterial enzyme responsible for the incorporation of para-aminobenzoic acid into dihydropteroic acid, the immediate precursor of folic acid. /Sulfonamides/

...DOGS...ACETYLATE SULFAMOYL GROUP & EXCRETE...N1-ACETYLSULFANILAMIDE...

When sulfanilamide, p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene or 1-aminopyrene was given orally to dogs, the corresponding N-acetyl and N-formyl derivatives were isolated from urine or feces. ... Dog intestinal flora and several bacterial strains exhibited both N-acetylating and N-formylating activities, in varying degrees, toward all of the arylamines tested. ... The results /show/ that the intestinal microflora plays an important role in the formation of N-acyl derivatives from arylamines in dogs.

Sulfonamides are absorbed through the vaginal mucosa. There are no pharmacokinetic data available describing how much of an intravaginal dose reaches the systemic circulation.

SULFANILAMIDE DIFFUSES INTO ALL TISSUES & SECRETIONS OF BODY, INCL MILK & FETAL PRODUCTS, & CEREBROSPINAL FLUID, IN CONCN APPROX THOSE FOUND IN BLOOD.

ABSORPTION /OF SULFONAMIDES/ FROM SKIN & VAGINA IS ERRATIC. ONCE INTO BLOODSTREAM, SULFONAMIDES BIND TO SERUM ALBUMIN TO VARYING DEGREES... PROTEIN-BINDING LIMITS PENETRANCE INTO TISSUES & GLOMERULAR FILTRATION &...IS DETERMINANT OF DISTRIBUTION & RATE OF EXCRETION. /SULFONAMIDES/

Sulfonamides are eliminated from the body partly as the unchanged drug and partly as metabolic products. The largest fraction is excreted in the urine, and the half life of sulfonamides in the body is thus dependent on renal function. Small amounts are eliminated in the feces and in bile, milk, and other secretions. /Sulfonamides/

Except for sulfonamides especially designed for their local effects in the bowel, this class of drugs is rapidly absorbed from the gastrointestinal tract. Approximately 70 to 100% of an oral dose is absorbed, and sulfonamide can be found in the urine within 30 minutes of ingestion. The small intestine is the major site of absorption, but some of the drug is absorbed from the stomach. Absorption from other sites, such as the vagina, respiratory tract, or abraded skin, is variable and unreliable, but a sufficient amount may enter the body to cause toxic reactions in susceptible persons or to produce sensitization. /Sulfonamides/

For more Absorption, Distribution and Excretion (Complete) data for SULFANILAMIDE (8 total), please visit the HSDB record page.

Used as human and veterinary antibacterial; [Merck Index]

MEDICATION

Antibacterial and antimicrobial.

MEDICATION (VET):

(1972) 1.28X10+8 GRAMS

(1975) 3.75X10+7 GRAMS

(1983) 6.03X10+7 g

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

Marketed in combination with aminacrine hydrochloride and allantoin

AVC Cream contains Sulfanilamide 15.0%, Aminacrine hydrochloride 0.2% and Allantoin 2.0% /per tube/

AVC/Dienestrol Cream contains /constituents of AVC cream with/ 0.01% Dienestrol in a water miscible base /each 4 oz tube/

AVC Suppositories contain sulfanilamide 1.05 g, Aminacrine hydrochloride 0.014 g and Allantoin 0.14 g /per suppository/

AVC/Dienestrol suppositories contain /constituents of AVC suppositories with/ 0.70 mg Dienestrol

Environmental transformation -> Pesticide transformation products (metabolite, successor)

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Benzenesulfonamide, 4-amino-: ACTIVE

VET: ...IN PRESURGICAL PREPN OF DEBRIS FILLED WOUNDS & ABRASIONS, & IN DEBRIDING DEEP PUNCTURES OR FISTULAS.

LAB PROCEDURES: LF FIESER, EXPT IN ORG CHEM (BOSTON, 3RD ED, 1955) P 147; HURDIS, YANG, J CHEM ED 46, 697 (1969). ... US PATENTS 2,132,178 (1938); 2,276,664 (1942)...2,237,372 (1941)

One of the first sulfonamides introduced into US medicine in 1936, now largely replaced by more effective and less toxic congeners. It is now only of historic interest and cannot be recommended for systemic therapy