Imidazol

log Kow = -0.08

-0.08

-0.02

-0.08

Density: 1.0303 g/cu m at 101 °C

Relative density (water = 1): 1.03

1.0303 @ 101°C

Monoclinic prisms from benzene

Colorless crystals

Colorless-yellow solid

Very soluble in water

In water, 241 g/100 g at 20 °C

In water, 2060 g/kg H2O at 19 °C

In water, 663 g/L at 20 °C

Very soluble in ethanol; soluble in diethyl ether, acetone, pyridine; slightly soluble in benzene

Solubility in water, g/100ml at 20 °C: 63.3 (good)

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P270, P280, P301+P317, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P318, P321, P330, P363, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.2% (2 of 945) of reports.

Danger

H302 (97.9%): Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: 1H-Imidazole

Hazard Traits - Reproductive Toxicity

1H-Imidazole is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1H-Imidazole are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 21-08-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/2052

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

Corrosive to skin and irritating to eyes in rabbits--may cause permanent eye injury; A 90-day oral study of rats showed histopathological changes of the liver and kidney at 180 mg/kg/day; No evidence of neurotoxicity; No effects on sperm parameters or toxicity to male or female reproductive organs observed in the 90-day study; Teratogenicity and developmental toxicity observed at doses maternally toxic in rats; [OECD SIDS] No increase in abnormalities of offspring in rats dosed 240 mg/kg by gavage during embryogenesis (non-standard study, no information on maternal toxicity); [REPROTOX] Causes burns; Inhalation may cause corrosive injuries to upper respiratory tract and lungs; Harmful by ingestion; May be toxic to human reproduction and cause harm to the unborn child; [Sigma-Aldrich MSDS]

Acute Tox. 4 (97.9%)

Acute toxicity (ingestion) - category 4

Acute toxicity (Oral) - Category 4

Reproductive toxicity - Category 1B

Repr. 1B

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer immediately for medical attention.

Rinse with plenty of water (remove contact lenses if easily possible). Refer immediately for medical attention.

Rinse mouth. Rest. Do NOT induce vomiting. Give one or two glasses of water to drink. Refer immediately for medical attention.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use water spray, foam, powder, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): 6.1D: Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects.

Separated from strong acids and food and feedstuffs.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Personal protection: complete protective clothing including self-contained breathing apparatus. Sweep spilled substance into covered containers. Then wash away with plenty of water.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for Imidazole (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 19(SRC), determined from a log Kow of -0.08(2) and a regression-derived equation(3), indicates that imidazole is expected to have very high mobility in soil(SRC). The pKa of imidazole is 7.0(4), indicating that this compound will exist partially in cation form and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of the neutral species of imidazole from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 3.8X10-6 atm-cu m/mole(6)(SRC), using a fragment constant estimation method(6). Imidazole's neutral species is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.44X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Volatilization is not expected for the cationic form because cations do not volatilize(SRC). A 90% of theoretical BOD using activated sludge in the Japanese MITI test(7) suggests that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 19(SRC), determined from a log Kow of -0.08(2) and a regression-derived equation(3), indicates that imidazole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces may be expected(4) based upon an estimated Henry's Law constant of 3.8X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 8 days and 62 days, respectively(SRC). A pKa of 7.0(6) indicates imidazole will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the ion from water surfaces is not expected to be an important fate process because cations do not volatilize(SRC). According to a classification scheme(7), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 90% of theoretical BOD using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), imidazole, which has an estimated vapor pressure of 4.44X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase imidazole 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 11 days(SRC), calculated from its rate constant of 3.6X10-11 cu cm/molecule-sec at 25 °C(3). Imidazole does not absorb at light wavelengths >240 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight, since sunlight consists of wavelengths above 290 nm(SRC).

IDENTIFICATION AND USE: Imidazole, an organic alkaloid, is an important pharmacophore in drug discovery. Imidazole is used as a Karl Fischer reagent in analytical chemistry and a reagent in synthetic organic chemistry. It is also used in the biological control of pests, especially fabric-feeding insects, often in combination with dl-p-fluorophenylalanine. HUMAN STUDIES: Autophagic events are induced by imidazole in HEC-1B cells. Accumulation of autophagic vacuoles in imidazole-treated cells was verified by conversion of LC3 protein, as well as confocal and transmission electron microscopy. Furthermore, imidazole blocked autophagic degradation by impairing maturation of autophagosomes into autolysosomes. Concurrently, imidazole treatment induced apoptosis in HEC-1B cells, accompanied by activation of caspase 9 and 3. The proapoptotic effect was mediated by increased Bim expression. Moreover, imidazole upregulated the protein level of FoxO3a and induced its increased nuclear localization. In addition, siRNA-mediated silencing of FoxO3a effectively attenuated imidazole-induced Bim upregulation and cell death, indicating direct involvement of this pathway in the imidazole-induced apoptosis. ANIMAL STUDIES: When 80% Imidazole was applied to the intact rabbit skin as an aqueous paste for 1 or 4 hours under occlusive dressing skin reactions were noted as early as one hour after removal of the dressing. Focal necrosis developed overnight in all animals and was described as leather-like at the end of the observation period. The application of 0.1 g of unchanged imidazole to the rabbit's eye (Draize test) affected conjunctiva, cornea, and the nictating membrane of the animals. In rats, the symptoms of acute oral exposure were described as convulsions and disequilibria with lateral posture. Deaths occurred within one day. Apathy and accelerated respiration was noted in survivors. Imidazole was given daily by gavage to rats at 20, 60, and 180 mg/kg bodyweight per day. Liver and the male kidney were identified as target organs in the animal groups receiving 180 mg/kg bw per day as substantiated by significantly increased relative liver weights in males and females which correlated with minimal to slight centrilobular liver cell hypertrophy in males and females, and by a significant increase of absolute and relative kidney weight in high-dose males that was accompanied by an accumulation of alpha2u-microglobulin in the epithelia and lumina of the proximal tubules of the male rat renal cortex. No changes of the male and female reproductive organs including sperm quality were noted in a rat 3-month study. In a developmental study in rats, the incidence of external malformations (anasarca and/or cleft palate) was significantly increased. About 10% of the high dose fetuses (180 mg/kg) were affected while no such changes were observed in the control. Skeletal malformations were also statistically significantly increased: 7.8% affected fetuses per litter were noted in the high dose group compared to 1.1% in the control. The incidences of shortened scapula, bent radius, bent ulna, malpositioned and bipartite sternebrae were statistically significantly increased. Soft tissue variations (dilated renal pelvis and ureter) were significantly increased in fetuses from high dose dams compared to controls (27% vs. 6.4%). The incidences of skeletal variations, mainly delays of the ossification process, were statistically significantly increased from 91% in the control group to 98.4% in the high dose group. Imidazole was not mutagenic when tested with Salmonella typhimurium TA 1535, TA 100, TA 1537, and TA 98 both in the presence and absence of metabolic activation.

Cough. Sore throat. Burning sensation.

Redness. Pain. Serious skin burns.

Redness. Pain. Blurred vision. Temporary loss of vision.

Sore throat. Burning sensation in the throat and chest.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

The Koc of imidazole is estimated as 19(SRC), using a log Kow of -0.08(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that imidazole is expected to have very high mobility in soil. The first pKa of imidazole is 7.0(4), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/ALTERNATIVE and IN VITRO TESTS/ Imidazole, an organic alkaloid, is an important pharmacophore in drug discovery. Anti-neoplastic potential of imidazole derivatives has been documented in several studies; however, mechanisms by which tumor cells respond to these stimuli remain to be elucidated. Autophagy and apoptosis have key roles in tumorigenesis and tumor treatment. In this study, we systematically examined autophagic events induced by imidazole in HEC-1B cells. Accumulation of autophagic vacuoles in imidazole-treated cells was verified by conversion of LC3 protein, as well as confocal and transmission electron microscopy. Furthermore, imidazole blocked autophagic degradation by impairing maturation of autophagosomes into autolysosomes. Concurrently, imidazole treatment induced apoptosis in HEC-1B cells, accompanied by activation of caspase 9 and 3. The proapoptotic effect was mediated by increased Bim expression. Moreover, imidazole upregulated the protein level of FoxO3a and induced its increased nuclear localization. In addition, siRNA-mediated silencing of FoxO3a effectively attenuated imidazole-induced Bim upregulation and cell death, indicating direct involvement of this pathway in the imidazole-induced apoptosis. Taken together, our data provided a molecular link between imidazoles and anticancer therapies; understanding of these properties of imidazole is essential for development of effective cancer therapeutics using imidazoles.

Imidazole's production and use as a chemical intermediate in the production of pharmaceuticals, pesticides, dye intermediates, auxiliaries for textile dyeing and finishing, photographic chemicals and corrosion inhibitors(1), and its use as a buffering agent in cosmetics(2) may result in its release to the environment through various waste streams(SRC). Imidazole has been identified as a constituent of tobacco, tobacco smoke, and tobacco smoke substitute(3).

AEROBIC: Imidazole, present at 100 mg/L, reached 90% of its theoretical BOD(NH3) in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). Other screening studies give similar results, imidazole reached 98% degradation after 18 days meeting the 10-day window criteria in the OECD 301A DOC Die-Away test(2), and is confirmed to be readily biodegradable.

An estimated BCF of 3 was calculated in fish for imidazole(SRC), using a log Kow of -0.08(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for the neutral species of imidazole is estimated as 3.8X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that the neutral species of imidazole may volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 8 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 62 days(SRC). Imidazole's Henry's Law constant indicates that volatilization of the neutral species from moist soil surfaces may occur(SRC). A pKa of 7.0(3) indicates imidazole will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the ion from water surfaces is not expected to be an important fate process because cations do not volatilize(SRC).

Response of enzymes involved in liver drug metabolism to imidazole treatment was determined in several studies. No increase in total microsomal P450 content was observed after a 4 day i.p. administration of 200 mg/kg bw per day in female Sprague-Dawley rats. Statistically significantly increased activities of 7-ethoxycoumarin-O-deethylase (1.7-fold) and Aminopyrine-N-demethylase (1.26-fold) were noted whereas aniline and p-nitrophenol hydroxylases were insignificantly reduced. New Zealand White rabbits treated with imidazole (200 mg/kg bw, 4 days) showed increased total p450-content in liver (1.24-fold) compared with controls and a 4.47-fold increase of the isozyme 3a. No significant changes were noted in pretreated Syrian Hamsters of both sexes (200 mg/kg bw, 4 days) with respect to relative liver weight, total microsomal p450-content, microsomal and cytosolic enzyme activities involved in phase I (demethylation of p-nitroanisole and ethylmorphine, NADPH-Cytochrome C-reductase) and phase II drug metabolism (sulfotransferase, glutathione transferase).

Imidazole reached peak plasma levels within 15 to 30 minutes in rats dosed with approximately 17 mg/kg bw and disappeared within 4 hours. Similar results were obtained for imidazole with ITF 182, a novel drug called Selezen that consists of the salt of protonated imidazole and 2-hydroxybenzoate in 1:1 molar quantities, with doses containing up to 66 mg imidazole/kg bw. The pharmacokinetic parameters were determined in human studies with ITF 182 in single (248 mg of imidazole) and multiple dose (3 single doses per day) studies. The pharmacokinetic parameters were comparable between different experiments, i.e. single or multiple dosing, oral or rectal applications, or oral tablet or oral drops did not exert marked influences. The main pharmacokinetic parameters in humans after oral intake may be summarized as follows: maximum plasma levels were reached after approximately 3 hours, elimination half-life was approximately 1.8 to 3 hours. Bioavailability was complete. Protein binding was determined to range between 5 to 15 %. In contrast, no effects were noted in a pilot study after dermal application.

Used as an intermediate (pharmaceuticals, pesticides, dye intermediates, auxiliaries for textile dyeing and finishing, photographic chemicals, and corrosion inhibitors) and hardener for epoxy resins; Also used in process regulators, anti-freeze agents, photographic applications, laboratory applications, glues/adhesives, cement fillers or sealing compounds, paints, varnishes, lacquers, consumer cleaning and washing agents, swimming pool applications, and in publishing, printing, and reproduction of recorded media; [OECD SIDS]

Textiles (Fiber & Fabric Manufacturing) [Category: Industry]

Karl Fischer reagent in analytical chemistry. Reagent in synthetic organic chemistry.

... the bulk of imidazole produced is used in the preparation of biologically active compounds.

Biological control of pests, especially fabric-feeding insects, often in combination with dl-p-fluorophenylalanine, an amino-acid inhibitor; also as a contact insecticide in an oil spray.

In the chemical industry as an intermediate in the production of pharmaceuticals, pesticides, dye intermediates, auxiliaries for textile dyeing and finishing, photographic chemicals and corrosion inhibitors.

2023: 50,000 - <250,000 lb

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Imidazole:

In the generally applicable Radziszewski reaction, a 1,2-dicarbonyl compound is condensed with an aldehyde and ammonia ... in a molar ratio of 1:1: 2, respectively. Replacement of a molar equivalent of ammonia with a primary amine ... leads to the corresponding 1-substituted imidazoles. ... The reaction is usually carried out in water or a water-alcohol mixture at 50-100 °C. Work-up may involve the usual processes (e.g., distillation, extraction, and crystallization). Distillation leads to imidazole with a purity > 99%. The yield is generally 60-85%.

Prepared by the action of ammonia on glyoxal; ... from glyoxal, ammonia, and formaldehyde; ... vapor phase synthesis from formamide and ethylenediamine in the presence of a dehydrogenation catalyst.

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

Cosmetics -> Buffering

All Other Basic Organic Chemical Manufacturing

1H-Imidazole: ACTIVE