Bithionol

356.05

356.05

202-565-0

AMT77LS62O

47129|9872

2811

DTXSID9021342

White or grayish-white, crystalline powder

D - Dermatologicals|P - Antiparasitic products, insecticides and repellents

2930909090

65.8

5.8

white to beige

1.73 g/cm³ @ Temp: 25 °C

188 °C

444.7°C at 760 mmHg

222.8±28.7 °C

1.741

H2O: <0.1 g/100 mL at 23 ºC;DMSO: soluble 20mg/mL, clear

0-6°C

1.1X10-9 mm Hg at 37 deg C

LD50 oral in rat: 7mg/kg

Odorless or with slight aromatic or phenolic odor

4.82None

Henry's Law constant = 1.0X10-13 atm-cu m/mol at 25 °C (est)

4.82|pK1= 4.82; pK2= 10.50

Hydroxyl radical reaction rate constant = 8.8X10-12 cu cm/molec-sec at 25 °C (est)|log Kow= 4.13 /Bithionol sulfoxide/

Insoluble in water.

Sulfides, Organic

2,2'-THIOBIS(4,6-DICHLOROPHENOL) is incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials may generate heat and toxic or flammable gases.

II

6.1(a)

UN 2811 6.1/PG 2

3

28-20/21/22

28-36/37-45-36

SN0525000

T+,Xn

Stable. Incompatible with strong oxidizing agents.

P301 + P312 + P330

H302

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.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Bithionol is included in external analgesic drug products/poison ivy, poison oak, and poison sumac drug products.|Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Bithionol is included in skin protectant drug products/poison ivy, poison oak, and poison sumac drug products.|Cosmetics containing bithionol. (a) Bithionol has been used to some extent as an antibacterial agent in cosmetic preparations such as detergent bars, shampoos, creams, lotions, and bases used to hide blemishes. New evidence of clinical experience and photopatch tests indicate that bithionol is capable of causing photosensitivity in man when used topically and that in some instances the photosensitization may persist for prolonged periods as severe reactions without further contact with sensitizing articles. Also, there is evidence to indicate that bithionol may produce cross-sensitization with other commonly used chemicals such as certain halogenated salicylanilides and hexachlorophene. It is, therefore, the view of the Food and Drug Administration that bithionol is a deleterious substance which may render any cosmetic product that contains it injurious to users. Accordingly, any cosmetic containing bithionol is deemed to be adulterated under section 601(a) of the Federal Food, Drug, and Cosmetic Act. (b) Regulatory proceedings may be initiated with respect to any cosmetic preparation containing bithionol shipped within the jurisdiction of the act after March 15, 1968.

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

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 195 companies from 2 notifications to the ECHA C&L Inventory.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an 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, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck 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, 2016)

SMALL SPILLS AND LEAKAGE: 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 your contaminated clothing and the adsorbent paper 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 store this material in a refrigerator. (NTP, 1992)

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)

Toxicity is moderately to markedly enhanced when bithionol is admin in combination with carbon tetrachloride, sodium antimonyl tartrate, emetine hydrochloride, hexachloroethane, or hexachloroparaxylene.

LD50 Rat oral 1430 mg/kg|LD50 Mouse oral 2100 mg/kg|LD50 Mouse iv 18 mg/kg

Bithionol's production and use as an anthelmintic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2,000(SRC), determined from a water solubility of 4 mg/L(2) and a regression-derived equation(3), indicates that bithionol is expected to have slight mobility in soil(SRC). The pKas of bithionol are 4.82 and 10.50(2), indicating it will exist primarily as an anion under environmental conditions and anions tend to have greater mobility in soils than neutral species(4). Volatilization from moist soil surfaces is not an important environmental fate process since anions do not volatilize(SRC). Bithionol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.1X10-9 mm Hg measured at 37 °C(2). Biodegradation data were not available(SRC, 2006).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2,000(SRC), determined from a water solubility of 4 mg/L(2) and a regression-derived equation(3), indicates that bithionol is expected to adsorb to suspended solids and sediment(SRC). The pKas of bithionol are 4.82 and 10.50(2), indicating it will exist primarily as an anion under environmental conditions and anions may not adsorb as strongly to sediment as neutral species(4). Volatilization from water surfaces is not an important environmental fate process since anions do not volatilize(SRC). According to a classification scheme(5), an estimated BCF of 284(SRC), from its water solubility(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Bithionol is not expected to undergo hydrolysis due to the lack of functional groups that hydrolyze under environmental conditions, but may be susceptible to direct photolysis in sunlit surface water since it absorbs light greater than 290 nm(7). Biodegradation data were not available(SRC, 2006).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bithionol, which has a vapor pressure of 1.1X10-9 mm Hg at 37 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase bithionol may be removed from the air by wet and dry deposition(SRC).

Bithionol is not expected to undergo hydrolysis due to the lack of functional groups that hydrolyze under environmental conditions(1). Bithionol has a UV absorption band at 307 nm(2), suggesting it may be susceptible to direct photolysis in the environment; however, no rate for this potential reaction was measured.

An estimated BCF of 284 was calculated for bithionol(SRC), using a water solubility of 4 mg/L(1)(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

The Koc for bithionol is estimated as 2,000(SRC), using a water solubility of 4 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that bithionol is expected to have slight mobility in soil(SRC). The pKas of bithionol are 4.82 and 10.50(1), indicating that this compound will exist primarily as an anion in the environment and anions generally possess higher mobility in soil than neutral species(4).

The pKas of bithionol are 4.82 and 10.50(1), indicating this compound will exist primarily as an anion in the environment. Volatilization from moist soil and water surfaces is not expected since anions do not volatilize. Bithionol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.1X10-9 mm Hg measured at 37 °C(1).

Occupational exposure to bithionol may occur through dermal contact with this compound at workplaces where bithionol is produced or used(SRC). Bithionol is used in medicine as an anthelmintic(1); therefore, human exposure may occur through its therapeutic use(SRC).

Anti-Infective Agents, Local; Antiplatyhelmintic Agents|Bithionol is used in treatment of paragonimiasis in a dosage of 30 to 50 mg/kg body wt, given by mouth on alternate days for 10 to 15 doses. In the treatment of clonorchiasis, the same dose has been given. Bithionol has also been used in a dose of up to 3 g daily on alternate days for 15 doses, in the treatment of fascioliasis. Doses of up to 60 mg/kg body wt, in 2 divided doses about 1 hr apart, have been given in tapeworm infection.|Cerebral infection occurs in 0.8% of patients with pulmonary infection. In a group of 24 patients with cerebral infections, bithionol was effective in all in eliminating ova from the sputum & terminating the prodn of rusty sputum. However, in only 9 patients was it effective in control of cerebral symptoms, including loss of vision, frank meningitis, & one case of intradural abscess.|The drug is given ... with meals to reduce the incidence of intensity of gastrointestinal symptoms.|For more Therapeutic Uses (Complete) data for BITHIONOL (16 total), please visit the HSDB record page.

Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects. (See all compounds classified as Anti-Infective Agents, Local.)|Agents used to treat cestode, trematode, or other flatworm infestations in man or animals. (See all compounds classified as Antiplatyhelmintic Agents.)

Bithionol is ... absorbed to a limited degree from the host digestive tract and detected in blood and especially in bile in which it is excreted from the body. Peak concentrations are found in bile within 2 hr following treatment. Blood concentrations of the drug are significantly lower than those found in bile.|When (35)S-bithionol, (35)S-bithionol sulfoxide, or (35)S-bithionol sulfone were fed to rats, urinary excretion of the metabolites ... was very low. Bithionol sulfoxide was excreted mainly in the feces. More than 90% of biliary radioactivity was in the form of glucuronides of the 3 compounds with more than 70% of the glucuronides present as bithionol glucuronide.

When (35)S-bithionol sulfoxide was orally admin to rats, urine, feces & bile were collected. Eight metabolites were observed in the urine. Paper chromatography & chemical tests identified one of these as inorganic sulfate. A strong acid was identified as 3,5-dichloro-2-hydroxysulfonic acid. Two other cmpd were identified as bithionol sulfone & bithionol. In addition to these, 3 cmpd were identified as glucuronides of bithionol, bithionol sulfoxide, & bithionol sulfone. One other metabolite was not identified. Except for free bithionol sulfone, the same metabolites were found in bile as were present in urine. Quantitative differences, however, were large. The glucuronide of bithionol sulfone comprised 71% of (35)S in bile but only 16.5% in urine. /Bithionol sulfoxide/|When (35)S-bithionol, (35)S-bithionol sulfoxide, or (35)S-bithionol sulfone were fed to rats, urinary excretion of the metabolites ... was very low. ... More than 90% of biliary radioactivity was in the form of glucuronides of the 3 compounds with more than 70% of the glucuronides present as bithionol glucuronide. The sulfone was metabolized to catechol & guaiacol.|/Bithionol and bithionol sulfone are major metabolites of bithionol sulfoxide/

Bithionol interferes with the neuromuscular physiology of helminths /(the target species)/, impairs egg formation, and may cause the protective cuticle covering the worms to become defective. At the biochemical level, oxidative phosphorylation is inhibited, and the bithionol molecule can chelate iron so that it may inactivate iron-containing enzyme systems.|/In the target species,/ bithionol treatment of adult worms in vivo decreases glycolytic and oxidative metabolism. Specifically, succinate oxidation is inhibited. Although the exact mode of action of bithionol is not known, it is suggested that it may depend on phenolic OH groups acting as acceptors of hydrogen that otherwise would enter into reactions associated with succinate oxidation. Interference of these reactions perhaps deprives the fluke of the necessary quantity of energy for maintenance of life.

ACUTE/CHRONIC HAZARDS: This chemical is a skin irritant. When heated to decomposition or upon contact with acid or acid fumes, toxic fumes are evolved. (NTP, 1992)

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)

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Administer activated charcoal ... . Cover skin burns with dry sterile dressings after decontamination ... . /Sulfur and related compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasms ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Sulfur and related compounds/

/SIGNS AND SYMPTOMS/ Up to 40% of patients experience abdominal cramps, diarrhea, nausea and vomiting. Approx 16% have skin eruptions, including pruritic urticarial or papular rashes.|/HUMAN EXPOSURE STUDIES/ 18 consecutive patients with a history of photocontact dermatitis from ketoprofen were investigated. Patch and photopatch tests were performed. As expected, ... positive photopatch tests to Ketum gel and ketoprofen 2.5% in petrolatum /were observed/ in all patients (100%). However, it was remarkable to note positive photopatch tests to other unexpected and non-relevant allergens, including fentichlor (67%), tetrachlorosalicylanilide (28%), triclosan (17%), tribromsalan (11%) and bithionol (11%) ... . these agents belong to the family of halogenated salicylanilides and related compounds, which have been forbidden in Europe since the 1970s. /The/ results raise the question of hyper-photosusceptibility to non-relevant allergens induced by photosensitivity to ketoprofen. The mechanism may involve the high photoreactivity induced by the association of a benzene ring with an oxygen group.|/SIGNS AND SYMPTOMS/ Photosensitivity reactions have occurred in persons using soap containing bithionol. Adverse effects in patients taking bithionol by mouth include anorexia, nausea, vomiting, abdominal discomfort, diarrhea, salivation, dizziness, headache, & skin rashes.|/SIGNS AND SYMPTOMS/ Abdominal pain, diarrhea, anorexia, nausea, vomiting, dizziness, headache, skin rashes, urticaria. Hepatic and renal involvement are rare complications.|/CASE REPORTS/ A case of bithionol (lorothiodol) induced photodermatitis is discussed. The clinical course of the disease, including persistent photosensitivity, may be due to persistence of the fungicide on the skin for extended periods.

Bithionol

Bithionolate sodium, Vancide BN /Sodium salt/|BTS, Bitin-S, Disto-5 /Bithionol sufoxide/|Grade: National Formulary grade of chemical (NF).

Phenol, 2,2'-thiobis[4,6-dichloro-: INACTIVE|Not marketed in the United States, but /bithionol is/ available from the Parasitic Disease Drug Service Center for Disease Control, Atlanta, GA ...|Proposed as agricultural fungicide.|Like hexachlorophene, it shows a greater inhibitory effect upon Staphylococcus aureus than upon Salmonella typhosa ...|Bithionol continues to be the drug of choice /in treating fascioliasos/, although it is available in the United States only under an investigational protocol from the Centers for Disease Control and Prevention (CDC).

Bithionol is extracted from acid soln with hexane, reextracted into alkaline soln, & reacted with 4-aminoantipyrine & potassium ferric hexacyanide. Colored product is extracted into butyl alcohol & determined spectrophotometrically at 500 nm.