ビチオノール

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.

Store in airtight containers. Protect from light.

15-30 °C

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.

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.

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)

LC50 Oryzias latipes (medaka) 0.24 mg/L/96 hr; semistatic

EC50 Daphnia magna (water flea, immobilization) 0.3 mg/L/48 hr /Conditions of bioassay not specified in source examined/

EC50 Brachionus calyciflorus (rotifers) 0.063 mg/L/24 hr, toxic effect: death /Conditions of bioassay not specified in source examined/

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).

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).

/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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

bithionol

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

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 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).

/GENOTOXICITY/ The mutagenic effects of bithionol sulfoxide and its two major metabolites, bithionol and bithionol sulfone, on 4 Salmonella typhimurium strains (TA 97, TA 98, TA 100 and TA 102) were investigated. Bithionol sulfoxide was found to be mutagenic to TA 98 and TA 100. However, mutagenicity was abolished in the presence of rat-liver S9 fractions. /Bithionol sulfoxide/

/OTHER TOXICITY INFORMATION/ Bithionol is well tolerated by dogs, cats, sheep, cattle, goats, chickens, & geese. Occasional emesis in dogs & infrequent transient diarrhea in all species may result from admin therapeutic doses of the drug.

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.

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. Phenol, 2,2'-thiobis(4,6-dichloro)- is included on this list.

Bithionol is one of the biocides commonly used in metalworking fluids. [Occupational Exposure to Metalworking Fluids. DHHS (NIOSH) Publication No. 98-102, 1998, Table 4-1] As an antimicrobial agent, it is active against bacteria and fungi. [Merck Index, #1306] It is used in agricultural fungicides and industrial cleansers. [Marks, p. 228]

Use in cosmetics, soaps, and other personal products banned by the FDA. [Marks, p. 227]

Metal Machining [Category: Heat or Machine]

Surfactant-formulated antimicrobial against bacteria, molds and yeast

Bacteriostat for cosmetics, fungicide.

Vancide BL is a germicide used in cosmetics /former use/, polishes, and for algae control

Prepn from 2,4-halo substituted phenol with sulfur halides: ... German patent 583055 (1933 to I.G. Farbenind); ... US patent 2,849,494 (1958 to Monsanto).

/From bithionol/ sulfoxide ... obtained by the reaction of 2,4-dichlorophenol with ... /thionyl/ chloride in presence of aluminium chloride: zinc-dust

Sodium salt ... Harvey et al.,US patent 3024163 (1962 to Vanderbilt Co). /Sodium salt/

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).