Niclosamide

327.12

327.12

200-056-8

8KK8CQ2K8G

758440|178296

DTXSID7040362

C66240

PALE, YELLOW CRYSTALS|ALMOST COLORLESS CRYSTALS|A cream-colored or yellowish-white powder|Bright yellow crystalline solid

P02DA01|P - Antiparasitic products, insecticides and repellents

2924299090

95.2

10 @ pH 9.6

Solid

1.6±0.1 g/cm3

225-230 °C

424.5±45.0 °C at 760 mmHg

210.5±28.7 °C

1.709

acetone: methanol: soluble 50mg/mL (methanol:acetone (1:1))

0-6°C

<9.87X10-9 mm Hg at 20 deg C

Oral-Rat LD50: 2500 mg/kg; Oral-Mouse LD50: 1000 mg/kg

Combustion produces toxic chloride and nitrogen oxide gases

Tasteless

Hydrolysed in aqueous solution with a decomposition half-life at 20 °C of 7 days (pH 6.9), 18.8 days (pH 13.3). Stable to heat. Decomposes under UV irradiation. Hydrolysed by concentrated acid or alkali.|Decomposes at 208 °C|Its biological effectiveness in water is stable at pH 5-9 and is also largely independent of the concentration of calcium and magnesium ions.

UN 3077 9/PG 3

2

50

29

VN8400000

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

It is stable to heat and is hydrolysed by concentrated acid or alkali.

P273

H400

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.|Niclosamide is reported to be highly stable to heat but it is hydrolized by strong alkali or acids. Recommendable methods: Incineration & landfill. Peer review: Incinerate niclosamide in a unit with effluent gas scrubbing. (Peer-review conclusions of an IRPTC expert consultation (May 1985))

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).|Niclosamide tablets. Oral dosage form new animal drugs. Specifications and conditions of use provided for dogs.|Niclosamide. New animal drugs for use in animal feeds. Conditions of use provided for laboratory mice.

|Warning|H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P273, P280, P305+P351+P338, P337+P313, P391, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.|H400 (97.18%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|P273, P391, and P501|Aggregated GHS information provided by 71 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Concentrations of niclosamide were 9.91-74.8 ug/g and 0.028 ug/g in rice straw and unpolished rice, respectively(1).

moderately

Infrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort.

IT WAS CONCLUDED THAT CARBARYL POTENTIATED TOXICITY OF BAYER 73 TO RAINBOW TROUT BY INCREASING ITS UPTAKE FROM WATER, POSSIBLY BY EFFECTS ON GILL BLOOD FLOW OR PERMEABILITY.|Niclosamide can be admin in conjunction with several other drugs ... The effectiveness of niclosamide for tapeworms of mice is enhanced when it is given in conjunction with cucurbitine or procaine.|... To study the in utero developmental toxicity of these cmpd, pregnant female Wistar Albino rats received 1/50 LD50 of ametryne and niclosamide either individually or in combination on gestational days 5-15 before they were /sacrificed/ on day 20. The results showed neither mortality nor clinical no ... adverse effects in the treated dams throughout the study period. Also, no overt preimplantation losses were noted. ... Corrected maternal wt gain was significantly reduced under the influence of ametryne treatment. Gravid uterine weight and litter size were statistically reduced in dams treated with ametryne or a combination of ametryne and niclosamide. The percentage of postimplantation deaths was significantly raised under the influence of ametryne treatment (21.15%) or the combined treatment (25.45%) compared with 6.48% in untreated rats and 15.6% in niclosamide treated dams. ... Fetal morphological abnormality examination showed a pronounced incr in incidence of malformed fetuses (litters) up to 5.8% (29.4%), 6.48% (33.3%), and 7.9% (33.3%) in ametryne, niclosamide and combination treated groups, respectively, compared with 1.6% (11.1%) in the control group. The most common deformities were skeletal abnormalities in all groups studied, while the ametryne group showed external deformities as well. The results suggest the possibility of embryo/fetotoxicity of ametryne and fetotoxicity of niclosamide, at least at higher doses.

LD50 Rat intraperitoneal 250 mg salt/kg /2-hydroxyethylammonium salt/

Niclosamide's production and use as a medication (an anthelmintic)(1) may result in its release to the environment through various waste streams(SRC). Its use as a molluscicide(1) will result in its direct release to the environment(SRC).

AQUATIC FATE: IT...PERSISTS /IN WATER/ FOR SEVERAL MONTHS. /ETHANOLAMINE SALT/|TERRESTRIAL FATE: Based on a recommended classification scheme(1), measured Koc values from 946-1580(2) to 3111(3) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will have low to slight mobility in soil(SRC). Results reported for water and sediment samples indicate that both aerobic and anaerobic biodegradation may be major fate processes for this compound in soil(3,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(3). Niclosamide's values for vapor pressure(4) and Henry's Law constant(4,5,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC). Niclosamide will be susceptible to direct photolysis on soil surfaces; degradation was rapid when this compound was exposed to UV light on silica gel TLC plates and on glass slides. Less than 50% niclosamide remained after 24 hours and after 168 hours less than 5% of the parent compound remained(6).|AQUATIC FATE: Intense sunlight, high pH (> 9.0), and the presence of sediment have been shown to reduce the efficacy of niclosamide treatments in water(1). Measured Koc values from 946-1580(2) to 3111(1) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will adsorb strongly to suspended solids and sediment in the water column(1,2). Both aerobic and anaerobic biodegradation will be major fate processes for this compound in water(1,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(1). Rapid disappearance of niclosamide from water above the sediment was also observed with half-lives of 3.1 and 0.83 days in water above pond and river sediment, respectively(1). 11.3, 7.2, 3.5, and 6.2% of the added 14C-niclosamide was present as CO2 after 32 days for cultures incubated under river sediment/aerobic, river sediment/anaerobic, pond sediment/aerobic, and pond sediment/anaerobic conditions, respectively(1). Aminoniclosamide is the major degradation product under both aerobic and anaerobic conditions(1).|AQUATIC FATE: Niclosamide will not volatilize from water surfaces based on an estimated Henry's Law constant of 6.5X10-10 atm-cu m/mole(SRC), calculated from experimental values for vapor pressure(1) and water solubility(2). An estimated BCF value of 215(3,SRC), from a measured water solubility(2), suggests that niclosamide will bioconcentrate in aquatic organisms(SRC), according to a recommended classification scheme(4). Depuration of 14C-labeled niclosamide in rainbow trout occurred within 72 hours following exposure. Biliary concentration was high, reaching a 10,000:1 bile to water ratio within 24 hours(5). 14C-labeled niclosamide had a half-life of about 150 hours in water when it was exposed to ultraviolet light (>290 nm)(6).|ATMOSPHERIC FATE: According to a suggested classification scheme(1), a measured vapor pressure of 9.9X10-9 mm Hg at 25 °C(2) indicates that niclosamide will exist mainly in the particulate phase in the ambient atmosphere. Particulate-phase niclosamide may be physically removed from the air by dry deposition(SRC). Direct photolysis of niclosamide is indicated by experiments where this compound was spotted onto silica gel plates and exposed to UV light; less than 50% of the parent compound remained after 24 hours(3).

Intense sunlight, high pH (> 9.0), and the presence of sediment have been shown to reduce the efficacy of niclosamide treatments(1). Degradation was rapid when exposed to UV on silica gel TLC plates and on glass slides. Less than 50% niclosamide remained after 24 hours and after 168 hours there was less than 5% of the parent compound remaining(2). 14C-labeled niclosamide had a half-life of about 150 hours in water exposed to ultraviolet light (>290 nm); 5-chlorosalicylic acid is a minor photoproduct (3.8% of radioactivity) of niclosamide exposed to UV light on thin-layer plates(1). There was negligible hydrolysis of the compound after 56 days in buffered aqueous solution (pH 5, 6.9, 8.7) or in pond water(2).

An estimated BCF value of 215 was calculated for niclosamide(SRC), using a water solubility of 6.5 mg/l(1) and a recommended regression-derived equation(2). According to a classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms may be low(SRC). Depuration occurred within 72 hours for rainbow trout exposed to 14C-labeled niclosamide. Biliary concentration was high, reaching a 10,000:1 bile to water ratio in 24 hours. The metabolite formed was the glucuronide(4,5).

2.24e+03 L/kg|The Koc of niclosamide is estimated as approximately 1600(SRC), using a measured water solubility of 6.5 mg/L(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that niclosamide has low mobility in soil(SRC). Adsorption of niclosamide by sediment reached equilibrium after 4-7.5 hours of shaking; an average Koc value of 3111 +/- 1552 was measured using five different sediments (pH range = 6.8-7.8; organic carbon = 1.9-9.2%)(4). Bottom sediment samples from 3 rivers in the Upper Peninsula of Michigan gave Koc values at 20 °C of 3510, 946, 766, and 77.9 at pH 6.5, 7, 8, and 9 for the Cedar River, 1210, 1570, 828, and 234 at the same pH values for the Ford River, and 1920, 1580, 532, and 131 at the same pH values for the Tahquamenon River(5).

The Henry's Law constant for niclosamide is estimated as 6.5X10-10 atm-cu m/mole(SRC) from its experimental values for vapor pressure, 9.9X10-9 mm Hg(1), and water solubility, 6.5 mg/L(2). This value indicates that niclosamide will be essentially nonvolatile from water surfaces(3,SRC). Niclosamide's values for vapor pressure(1) and Henry's Law constant(1,2,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC).

Occupational exposure to niclosamide from respiratory or dermal routes may occur during this compound's use as a molluscide. The general population may be exposed to niclosamide through the ingestion of this compound in either food or mdeicine. (SRC)

For the treatment of tapeworm and intestinal fluke infections: Taenia saginata (Beef Tapeworm), Taenia solium (Pork Tapeworm), Diphyllobothrium latum (Fish Tapeworm), Fasciolopsis buski (large intestinal fluke). Niclosamide is also used as a molluscicide in the control of schistosomiasis.

Anticestodal Agents; Antinematodal Agents; Molluscacides|THERE ARE NO CONTRAINDICATIONS TO THE USE OF NICLOSAMIDE AS A TENIACIDE.|MEDICATION (VET): Niclosamide can also be used to treat tapeworm infections of lab animals /eg mice, rabbits, monkeys, or reptiles/. ... Niclosamide is admin orally in tablet form to dogs and cats ... It is usually admin to ruminants /eg cattle, sheep and goats/ ... as a drench ...|Therapeutic Use Niclosamide in the free-base form only is used primarily as a cestocide and to a lesser extent as a trematocide. The drug is formulated as a chewable tablet containing 500 mg of niclosamide. It is very effective against tapeworrn infections caused by Taenia saginata, Taenia solium, and Diphyllobothrium latum; tapeworms such as Hymenolepis diminuta, Hymenolepis nana, and Dipylidium caninum are somewhat more recalcitrant. For infections of Taenia saginata, Taenia solium, and Diphyllobothrium latum, single oral dosages of 2 gm (adult), 1.5 gm (child > 34 kg), and 1.0 gm (child 11-34 kg) are recommended. 0ther tapeworms may require repeated treatment for example, 2 gm/day in single daily doses for 7 days (adults), 1.5 gm given in a single dose on the first day followed by 1 gm/day for the next 6 days (child > 34 kg), and 1 gm given in a single dose on the first day followed by 500 mg/day for next 6 days (child 11-34 kg). Safety for use in children under 2 years of age has not been established. Since niclosamide is active only against intestinal cestodes, it is not effective for treatment of cysticercosis. As a trematocide, niclosamide is active mainly against flukes such as Fasciolopsis buski in the intestines.|For more Therapeutic Uses (Complete) data for NICLOSAMIDE (10 total), please visit the HSDB record page.

SINCE TAPEWORM INFECTIONS GENERALLY ARE NOT LIFE THREATENING, IT IS RECOMMENDED THAT TREATMENT OF PREGNANT WOMEN BE POSTPONED UNTIL AFTER DELIVERY.|VET: DO NOT TREAT LACTATING ANIMALS.|... It is important to note that the lethal action of the drug against the adult worn does not extend to the ova. Thus, use of niclosamide in Taenia solium infections may expose the patient to the risk of cysticercosis, since, following digestion of the dead segments, viable ova will be liberated into the lumen of the gut. It is desirable to give an adequate purge within 3 to 4 hours after the drug has been given, to clear the bowel of all dead segments before they can be digested.|The drug causes segments to disintegrate, releasing viable eggs; hence, if used against pork tapeworm, a purge should be given 1 or 2 hr after treatment. Untoward effects occur only occasionally; nausea and abdominal pain have been reported.|For more Drug Warnings (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.

Niclosamide is an antihelminth used against tapeworm infections. It may act by the uncoupling of the electron transport chain to ATP synthase. The disturbance of this crucial metabolic pathway prevents creation of adenosine tri-phosphate (ATP), an essential molecule that supplies energy for metabolism.

Agents used to treat tapeworm infestations in man or animals. (See all compounds classified as Anticestodal Agents.)|Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice. (See all compounds classified as Antinematodal Agents.)|Agents destructive to snails and other mollusks. (See all compounds classified as Molluscacides.)

Niclosamide appears to be minimally absorbed from the gastrointestinal tract—neither the drug nor its metabolites have been recovered from the blood or urine.|VERY LITTLE IS ABSORBED FROM THE GI TRACT ... .|EXPOSING RAINBOW TROUT TO (14)C-BAYER 73 CAUSED BILE TO WATER (14)C RATIO OF 10,000:1. AFTER 24 HR OF EXPOSURE, THIN LAYER CHROMATOGRAPHY OF UNFRACTIONATED BILE FROM FISH SHOWED 1 MAJOR RADIOACTIVE PEAK. UNCHANGED BAYER 73 WAS FOUND IN BILE.|Niclosamide is excreted in feces.|When male and female volunteers each were treated orally with 2000 mg of radiocarbon-labeled niclosamide, between 2 and 25% of the dose was eliminated in the urine over a 4-day period; the remainder was found in the feces. Elimination of niclosamide equivalents was essentially complete after 1-2 days. Maximal niclosamide equivalents in serum ranged from 0.25 to 6.0 ppm; the variation associated with this parameter was attrributed to differential rates of absorption among the individual.|For more Absorption, Distribution and Excretion (Complete) data for NICLOSAMIDE (6 total), please visit the HSDB record page.

ANTHELMINTIC NICLOSAMIDE...REDUCED TO CORRESPONDING AMINO DERIVATIVE BY BOTH MOUSE- & SHEEP-LIVER ENZYME PREPARATIONS & BY ENZYMES FROM CESTODES & NEMATODES. ...NICLOSAMIDE WAS NOT HYDROLYZED EITHER BY MAMMALIAN & HELMINTH ENZYME PREPN OR BY WHOLE HELMINTHS.|In warm-blooded organisms, the nitro group is reduced to an amino group (5,2'-dichloro-4-aminosalicylanilide).|Pregnant rats were treated orally with niclosamide at 1000 mg/kg on day 13, 19, or 20 of gestation, and rats were sacrificed at 4, 8, 16, or 24 hr posttreatment. Highest concentrations of niclosamide and 2,5'-dichloro-4'-aminosalicylanilide were detected in liver and kidney 8 hr after treatment. Niclosamide, but not its amino metabolite, was present in fetuses from rats treated on day 13, whereas both compounds were found in fetuses from rats treated on day 19 or 20. It was suggested that 19- and 20-day-old fetuses, but not 13-day-old fetuses, were able to metabolize niclosamide.|Niclosamide ... is absorbed from the gastrointestinal tract, and mutagenic metabolites are excreted in the free form and as conjugated glucuronides. as in the case of other secondary amides, phase I metabolism of niclosamide may result in hydrolytic cleavage of the amide bond, giving rise to 5-chlorosalicylic acid and 2-chloro-4-nitroaniline. ...

Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA.|Niclosamide has prominent activity against most of the cestodes that infect man; Enterobius (Oxyuris) vermicularis is also susceptible. At low concn, niclosamide stimulates oxygen uptake by Hymenolepis diminuta, but at higher concn respiration is inhibited and glucose uptake is blocked. The principal action of the drug may be to inhibit anaerobic phosphorylation of adenosine diphosphate (ADP) by the mitochondria of the parasite, an energy producing process that is dependent on CO2 fixation ... .|Cestocidal activity is due to inhibition of absorption of glucose by the tapeworm and uncoupling of the oxidative phosphorylation process in the mitochondria of cestodes. Resultant blocking of the Krebs cycle leads to accumulation of lactic acid, which kills the tapeworm. ... overstimulation of adenosine triphosphatase (ATPase) activity of the mitochondria may be related to cestodal action of niclosamide.

Niclosamide is quite free of undesirable effects other than very occasional gastrointestinal upset.|UP TO 10% OF PATIENTS MAY EXPERIENCE...MILD ABDOMINAL PAIN & NAUSEA ON DAY DRUG IS ADMIN.|YOMESAN GIVEN ORALLY TO HUMANS AT 30 MG/KG DID NOT CAUSE FORMATION OF METHEMOGLOBIN.|A transient erythema was the only reaction in 4 of 7 persons when niclosamide was applied to their forearms for 24 hr. 2 of 6 reacted similarly to the ethanolamine salt.|For more Human Toxicity Excerpts (Complete) data for NICLOSAMIDE (10 total), please visit the HSDB record page.

Bayer 2353

TABLETS: 500 MG. THE TABLETS ALTHOUGH NOT MARKETED IN THE US, MAY BE OBTAINED BY LICENSED PHYSICIANS FROM THE PARASITIC DISEASE DRUG SERVICE, CENTER FOR DISEASE CONTROL, ATLANTA, GA, 30333.|CLONITRALID (FOR 2-HYDROXYETHYLAMMONIUM SALT) FOR PUBLIC HEALTH USE (FED REP GERM). /2-HYDROXYETHYLAMMONIUM SALT/|... EC (250 G AI/L); WP (700 G/KG).|BAYLUSCIDE /ETHANOLAMINE SALT OF NICLOSAMIDE/...WETTABLE POWDER; EMULSIFIABLE CONCENTRATE /ETHANOLAMINE SALT/|For more Formulations/Preparations (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.

... US PATENT ... 3,113,067 ... NICLOSAMIDE IS A POWERFUL MOLLUSCICIDE GIVING A TOTAL KILL OF AUSTRALORBIS GLAB @ 0.3 MG/L; IT IS NON-PHYTOTOXIC @ FIELD CONCN.|BASIC PRODUCER: BAYER AG (FEDERAL REPUBLIC OF GERMANY) (BAYLUSCID) /2-HYDROXYETHYLAMMONIUM SALT/|IT IS EFFECTIVE AGAINST MOST AQUATIC SNAILS @ 0.3-1.0 PPM ... IT HAS THE ADVANTAGE OF CONSIDERABLE SELECTIVITY ... /ETHANOLAMINE SALT/|It is marketed in the USA for use only in dogs and cats among domestic animals ...|For more General Manufacturing Information (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page.

Analysis of products: As in residue analysis ... or reduction with stannous chloride, reaction with p-dimethylaminobenzaldehyde, and determination of the intensity of the yellow dye at 460 nm (R Strufe, Pflanzenschutz-Nachr Bayer 1965, 18, 130-9); or reduction of the nitro group with titanium(III) chloride and back-titration of the excess titanium chloride with ferric chloride (WHO Specifications for Pesticides, 3rd ed, Geneva 1967, 224, 235). Analysis of residues: Determination in water samples according to R Strufe (Pflanzenschutz-Nachr Bayer 1965, 18, 130-9). Reduction of the nitro group with zinc dust/hydrochloric acid to give the amino group, diazotization, coupling with naphthylethylenediamine and spectrophotometric determination of the coloration at 560 nm.|DETERMINATION OF NICLOSAMIDE IN WATER AND SEDIMENT SAMPLES BY GAS CHROMATOGRAPHY WITH ELECTRON-CAPTURE OR ALKALI-FLAME DETECTION, OR DIRECTLY BY HIGH PRESSURE LIQUID CHROMATOGRAPHY WITH A UV ABSORBANCE DETECTOR.|Product analysis by redox titration (WHO Specifications Pestic. Used in Public Health, p. 309). Residues in water measured by colorimetry (R. Strufe, Pflanzenschutz-Nachr. Engl. Ed., 1962, 15, 42) or by titrations (details from Bayer AG).

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