Chemical Properties
Light yellow powder
Uses
A drug used in the treatment of helminthiases
Uses
anticoagulant, rodenticide
Definition
ChEBI: A member of the class of benzimidazoles carrying a 1,3-thiazol-4-yl substituent at position 2. A mainly post-harvest fungicide used to control a wide range of diseases including Aspergillus, Botrytis, Cladosporium and Fusarium.
General Description
White or cream-colored odorless, tasteless powder. Sublimes above 590°F. Fluoresces in acidic solution. Formulated as a dust, flowable powder or wettable powder for use as a systemic fungicide and anthelmintic.
Reactivity Profile
THIABENDAZOLE(148-79-8) is incompatible with a number of pesticides, including copper-containing fungicides, and with highly alkaline materials. THIABENDAZOLE(148-79-8) is a chelating agent, binding many metals including iron, but not calcium
Air & Water Reactions
Insoluble in water.
Fire Hazard
Flash point data for this chemical are not available; however, THIABENDAZOLE is probably combustible.
Originator
Mintezol,MSD,US,1967
Manufacturing Process
6.5 grams of thiazole-4-carboxylic acid is stirred with 5.9 grams of thionyl
chloride in 20 ml xylene for 10 hours at room temperature to form 4-thiazolyl
acid chloride. 1.3 grams of 4-thiazolyl acid chloride and 1.3 grams of onitroaniline
are then stirred together in 3.5 ml of pyridine at room
temperature for about 12 hours. At the end of this time, the mixture is
quenched in ice water and the solid nitroanilide recovered by filtration and
washed with dilute sodium carbonate solution. The solid is suspended in 15 ml
of glacial acetic acid, and 8 ml of 6 N hydrochloric acid added to the
suspension. 6 grams of zinc dust is added in small portions to the acetic
mixture. After the zinc addition is complete, and the reaction is essentially
finished (by visual observation), the reaction mixture is filtered and the filtrate
neutralized with concentrated ammonium hydroxide to precipitate 2-(4'-
thiazolyl)-benzimidazole. The product is purified by recrystallization from ethyl
acetate, according to US Patent 3,274,207.
Therapeutic Function
Anthelmintic
Agricultural Uses
Fungicide: Thiabendazole is a fungicide used to control blight,
mold, stain and rot that are found on fruit and vegetables;
Dutch elm disease; and diseases found in food storage
and other diseases. It is also used to treat roundworms and
similar conditions in livestock and humans. Registered
for use in EU countries. A U.S. EPA restricted use
Pesticide (RUP).
U.S. Maximum Allowable Residue Levels for Thiabendazole
and its metabolite benzimidazole (free and conjugated) in
or on the following food commodities:[40CFR 180.242(a)
(1)]: apple, wet pomace 12.0 ppm; Avocado (There are no
U.S. registrations on the indicated commodity) 10.0 ppm;
banana, post harvest 3.0 ppm; bean, dry, seed 0.1 ppm;
beet, sugar, dried pulp 3.5 ppm; beet, sugar, roots 0.25 ppm;
beet, sugar, tops 10.0 ppm; cantaloupe (There are no U.S.
registrations on the indicated commodity) 15.0 ppm; carrot,
roots, postharvest 10.0 ppm; citrus, oil 15.0 ppm; fruit,
citrus, group 10, postharvest 10.0 ppm; fruit, pome, group
11, postharvest 5.0 ppm; mango 10.0 ppm; mushroom
40.0 ppm; papaya, postharvest 5.0 ppm; potato, postharvest
10.0 ppm; soybean 0.1 ppm; strawberry (There are no U.S.
registrations on the indicated commodity) 5.0 ppm; sweet
potato (postharvest to sweet potato intended only for use as
seed) 0.05 ppm; wheat, grain 1.0 ppm; wheat, straw 1.0 ppm.
[40CFR 180.242(a)(2)]: cattle, meat 0.1 ppm; cattle, meat
byproducts 0.4 ppm; goat, meat byproducts 0.4 ppm; Hog,
meat byproducts 0.3 ppm; horse, meat byproducts 0.4 ppm;
milk 0.1 ppm; sheep, meat byproducts 0.4 ppm. [40CFR
180.2010]: Use/Limits: As a seed treatment for dry pea
(including field pea, pigeon pea, chickpea or lentil), using
a maximum application rate of 0.075 pounds of active ingredient
per 100 pounds of seed. Vines or hay grown from
treated seed may not be fed to livestock.
Pharmaceutical Applications
Thiabendazole; a thiazolyl benzimidazole available for oral
administration. It is active against most common intestinal
nematodes. As a result of its larvicidal and ovicidal activity,
it is effective in strongyloidiasis, trichinosis, visceral larva
migrans and cutaneous larva migrans.
It is well absorbed from the small intestine. Peak plasma
levels are reached about 1–2 h after a single oral dose of the
suspension. It is extensively metabolized in the liver to the
5-hydroxy derivative, which is inactive. Most of the drug is
excreted within 24 h. About 90% is excreted in the urine,
chiefly as glucuronide or sulfate conjugates; the remainder is
passed in the feces.
A wide range of unpleasant side effects occur, including
nausea and other gastrointestinal upsets, fever and neurological
effects. It has been largely replaced by the less toxic
benzimidazole carbamates. Although active against Ascaris
lumbricoides, E. vermicularis and hookworms, it should not be
used as primary therapy for these infections.
Trade name
AGROSOL? AGROSOL?T, (with thiram);
APL-LUSTER? ARBOTECT? BOVIZOLE?
BRODEX? CHEM-TEK? CITRUS LUSTR? DECCO
SALT NO.19? E-Z-EX? EPROFIL? EQUIVET
TZ? EQUIZOLE? FRESHGARD? FUNGICIDE
4 T? GRANOX? IRGAGUARD? LOMBRISTOP?
MERTEC? MERTECT 160? METASOL TK-100?
MINTEZOL? MINZOLUM? MK-360? MYCOZOL?
NEMAPAN? NSC 525040? OMNIZOLE?
POLIVAL? RIVAL? (captan + PCNB + thiabendazole);
RPH? RTU-VITAVAX-EXTRA? STA-FRESH? TBZ
6? TECTO? TECTO RPH? TECTO 10P? TECTO
40 F? TESTO? THIABEN? THIABENDAZOLUM?
THIABENZAZOLE? THIABENZOLE?
THIBENZOL? THIBENZOLE? THIBENZOLE 200?
THIBENZOLE ATT? TIABENDAZOLE? TOBAZ?
TOP FORM WORMER? VITAVAX?Thiabendazole
Chemical class: Benzimidazole
Mechanism of action
Thiabendazole is an antihelmintic drug with a broad spectrum of action. Although the
details of its mechanism of action are not conclusively known, it seems likely that its
action is mediated by the inhibition of a specific enzyme of helminthes—fumarate reductase. Thiabendazole is active with respect to most nematode infections, including
Angyostrongylus cantonesis, Strongyloides stercoralis, Trichinella spiralis, Toxocara
canis, Toxocara cati, Ancylostoma caninum, A. braziliense, A. duodenale, Dracunculus
medinesis, Capillaria philippinesis, as well as for treating Acaris cantonesis and
Shistosoma stercoralis. Synonyms of this drug are mintezol, minzolum, and others.
Clinical Use
2-(4-Thiazolyl)benzimidazole (Mintezol) occurs as a whitecrystalline substance that is only slightly soluble in waterbut is soluble in strong mineral acids. Thiabendazole is abasic compound with a pKa of 4.7 that forms complexeswith metal ions.
Thiabendazole inhibits the helminth-specific enzymefumarate reductase. It is not known whether metal ionsare involved or if the inhibition of the enzyme is related tothiabendazole’s anthelmintic effect. Benzimidazole anthelminticdrugs such as thiabendazole and mebendazolealso arrest nematode cell division in metaphase by interferingwith microtubule assembly. They exhibit a highaffinity for tubulin, the precursor protein for microtubulesynthesis.
Thiabendazole has broad-spectrum anthelmintic activity.It is used to treat enterobiasis, strongyloidiasis (threadworminfection), ascariasis, uncinariasis (hookworm infection), andtrichuriasis (whipworm infection). It has also been used torelieve symptoms associated with cutaneous larva migrans(creeping eruption) and the invasive phase of trichinosis. Inaddition to its use in human medicine, thiabendazole iswidely used in veterinary practice to control intestinalhelminths in livestock.
Synthesis
Thiabendazole, 2-(4-thiazolyl)benzimidazole (38.1.9), is also made in
the same manner?aheterocyclization which occurs upon reacting o-phenylendiamine with
1,3-thiazol-4-carboxylic acid.
Veterinary Drugs and Treatments
Thiabendazole has been used for the removal of the following parasites
in dogs: ascarids (Toxocara canis, T. leonina), Strongyloides stercoralis,
and Filaroides. It has been used systemically as an anti-fungal
agent in the treatment of nasal aspergillosis and penicillinosis.
Topical and otic use of thiabendazole for the treatment of various
fungi is also commonly employed.
Thiabendazole is indicated (labeled) for the removal of the
following parasites in cattle: Haemonchus spp., Ostertagia spp.,
Trichostrongylus spp., Nematodirus spp., Cooperia spp. and
Oesophagostomum radiatum.
Thiabendazole is indicated (labeled) for the removal of the following
parasites in sheep and goats: Haemonchus spp., Ostertagia
spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp.,
Chabertia spp., Bunostomum spp. and Oesophagostomum spp.
Thiabendazole is indicated (labeled) for the removal of the
following parasites in horses: Strongylus spp., craterstomum spp.,
Oesphagodontus spp., Posteriostomum spp., Cyathostomum spp.,
Cylicocylus spp., Cylicostephanus spp., Oxyuris spp., and Parasacaris
spp.
Thiabendazole is indicated (labeled) for the removal or prevention
of the following parasites in swine: large roundworms (Ascaris
suum) (prevention), and in baby pigs infested with Strongyloides
ransomi.
Although not approved, thiabendazole has been used in pet
birds and llamas. See the Dosage section for more information.
In many geographic areas, significant thiabendazole resistance
problems have developed and, for many parasites, other anthelmintics
would be a better choice for treatment.
When used topically, thiabendazole has antidermatophytic
properties.
Environmental Fate
Thiabendazole does not hydrolyze readily, nor it is metabolized
in soil under aerobic or anaerobic conditions. While it photodecomposes
in minutes in aqueous solutions, photodecomposition
of thiabendazole in soil did not cause more than 40%
reduction. Thiabendazole is also only slightly water soluble, and
does not migrate in soil. Thus, it is unlikely to contaminate
groundwater. If released into the atmosphere, it exists primarily
in the particulate phase. In the vapor phase, it will degrade in
the atmosphere by reacting with photochemically produced
hydroxyl radicals with an estimated half-life of 6 h.
Metabolic pathway
The primary photolytic degradation of thiabendazole involves the
cleavage of the thiazole-benzimidazole ring linkage. In animals, thiabendazole
is extensively oxidised in bluegill sunfish, hens, goats, sheep,
cattle, mice, rats and humans, followed by conjugation. When foliarly
applied to plants, degradation to benzimidazole and its conjugates
occurred. Benzimidazole formed in plants is mainly due to photolytic
action. The primary degradation/metabolic pathways of thiabendazole in
water, soil, plants and animals are depicted in Scheme 1.
Degradation
Thiabendazole (1) is quite stable in aqueous suspension and in acidic
media, and it is stable to heat (PM).
Opening and/or the cleavage of the thiazole-benzimidazole ring linkage
appeared to be the primary photolytic degradation pathway. Thiabendazole
was photolysed to (benzimidazol-2-yl)carboxamide (2) and
benzimidazole (3) under natural sunlight exposure on sugar beet leaf surfaces
or on glass plates (Jacob et al., 1975). Thiabendazole was also photolysed
in aqueous solution when exposed to a Pyrex glass filtered high
pressure mercury lamp (≥290 nm). In addition to 2 and 3, photoproducts
included degradates 4-8 (Murthy et al., 1996). Compound 2 was proposed
to result from hydrolysis of (benzimidazol-2-yl)nitrile (7). The rate constant
for photolysis was not affected sigruficantly by the presence of either
fulvic or humic acids, indicating that indirect photolysis does not play a
large role in the degradation of thiabendazole.
