4-Methylimidazole

82.1

82.10

1453

212-497-3

Q64GF9FV4I

40744

DTXSID9025617

Crystals

29339900

28.7

0.2

Reddish-brown to green to brown Powder

0.9380 g/cm³ @ Temp: 153.0 °C

56 °C

263 °C

>230 °F

1.5037 (14ºC)

soluble in water.H2O: soluble , clear, colorless to yellow (50 mg/mL)

Keep container tightly closed in a dry and well-ventilated place. Keep in a dry place.

0.007 mm Hg at 25 deg C (est)

Explosive limits 1.8-10.7 Vol. %

Henry's Law constant = 4.14X10-6 atm-cu m/mol at 25 °C (est)

pKa = 7.51 (est)

Hydroxyl radical reaction rate constant = 9.41X10-11 cu cm/molec-sec at 25 °C (est)

555 °C

III

8

UN 3263 8/PG 3

2

21/22-34-22

26-36/37/39-45-25

NI7350000

C

P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H301

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.|Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state, and local environmental regulations. Contact a licensed professional waste disposal service to dispose of this material.

Materials to avoid: Strong oxidizing agents, acids, acid chlorides, acid anhydrides.

Department of Health & Human Services/National Institute of Environmental Health Sciences, National Toxicology Program; Toxicology and Carcinogenesis Studies of 4-Methylimidazole (CAS No. 822-36-6) in F344/N Rats and B6C3F1 Mice (Feed Studies), NTP TR-535 (January 2007).|European Chemicals Bureau; IUCLID Dataset, 4-Methylimidazole (822-36-6) (2000 CD-ROM edition) contains information on use, toxicology, and environmental effects of this chemical as supplied to the European Union by industry.[Available from, as of July 15, 2009: http://esis.jrc.ec.europa.eu/]

|Danger|H302 (88.89%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P310, P311, P312, P321, P322, P330, P332+P313, P333+P313, P337+P313, P361, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 295 companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P280, P281, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P310, P321, P330, P363, P405, and P501|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Hand protection: Handle with gloves.|Eye protection: Safety glasses.|Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.|Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Not flammable

Explosive limits 1.8-10.7 Vol. %

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a POTW is acceptable only after review by the governing authority. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must meet Hazardous Material Criteria for disposal.|Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Evacuate personnel to safe areas.|Environmental precautions: Do not let product enter drains.|Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|Handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols.|In case of skin contact: Take off contaminated clothing and shoes immediately. Wash off with soap and plenty of water. Consult a physician.|In case of eye contact: Continue rinsing eyes during transport to hospital. Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.|Hygiene measures: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Irritating /to skin and eyes/.

LD50 Rat oral 751 mg/kg|LD50 Mouse oral 370 mg/kg|LD50 Mouse ip 165 mg/kg|LD50 Hen oral 590 mg/kg|For more Non-Human Toxicity Values (Complete) data for 4-Methylimidazole (6 total), please visit the HSDB record page.

Groups of 50 male and 50 female mice were fed diets containing 0, 312, 625, or 1,250 ppm 4-methylimidazole (equivalent to average daily doses of approximately 40, 80, and 170 mg 4-methylimidazole/kg body weight to males and females) for 106 weeks. Survival of all exposed groups of male and female mice was similar to that of the control groups. Mean body weights of males and females in the 1,250 ppm groups were less than those of the control groups after weeks 17 and 12, respectively. Mean body weights of 312 and 625 ppm females were less after weeks 85 and 65, respectively. Feed consumption by exposed groups of male and female mice was generally similar to that by the controls. The incidences of alveolar/bronchiolar adenoma in all exposed groups of females, alveolar/bronchiolar carcinoma in 1,250 ppm males, and alveolar/bronchiolar adenoma or carcinoma (combined) in 1,250 ppm males and 625 and 1,250 ppm females were significantly greater than those in the control groups. The incidence of alveolar epithelium hyperplasia was significantly increased in 1,250 ppm females.|4-Methylimidazole was not mutagenic in the S. typhimurium mutation assay when tested in strains TA97, TA98, TA100, and TA1535, with and without hamster or rat liver metabolic activation enzymes. No consistent or significant increases in the frequencies of micronucleated erythrocytes were seen in the bone marrow of male rats or mice treated with 4-methylimidazole by intraperitoneal injection, or in peripheral blood samples from male and female mice administered the compound in dosed feed for 14 weeks.|Groups of 50 male and 50 female rats were fed diets containing 0, 625, 1,250, or 2,500 ppm 4-methylimidazole (males) or 0, 1,250, 2,500, or 5,000 ppm 4-methylimidazole (females) (equivalent to average daily doses of approximately 30, 55, or 115 mg 4-methylimidazole/kg body weight to males and 60, 120, or 260 mg/kg to females) for 106 weeks. Survival of all exposed groups of male and female rats was similar to that of the control groups. Mean body weights of males in the 1,250 and 2,500 ppm groups and females in the 2,500 and 5,000 ppm groups were less than those of the control groups throughout the study; mean body weights of 1,250 ppm females were less after week 41. Feed consumption by 5,000 ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500 and 5,000 ppm females. The incidence of mononuclear cell leukemia in 5,000 ppm females was significantly greater than that in the controls, and the incidence exceeded the historical range in feed study controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were generally significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell focus were significantly increased in 2,500 ppm males and 5,000 ppm females.|... Groups of five male and five female rats and mice were fed diets containing 0, 300, 800, or 2,500 ppm 4-methylimidazole (equivalent to average daily doses of approximately 30, 80, or 220 mg/kg for rats and 65, 170, or 500 mg/kg for mice) for 15 days ... In the 4-methylimidazole studies, all animals survived to the end of the studies, and there were no significant differences in mean body weights, clinical findings, organ weights, or gross or microscopic lesions between exposed and control groups ...|... Groups of 10 male and 10 female rats and mice were fed diets containing 0, 625, 1,250, 2,500, 5,000, or 10,000 ppm 4-methylimidazole (equivalent to average daily doses of approximately 40, 80, 160, 300, or 560 mg/kg 4-methylimidazole to rats; and ... 100, 240, 440, 915, or 1,840 mg/kg 4-methylimidazole to male mice; and ... 110, 240, 540, 1,130, or 3,180 mg/kg 4-methylimidazole to females) for 14 weeks ... In the 14-week 4-methylimidazole studies, one 10,000 ppm male mouse was found dead during week 4, and seven 10,000 ppm female mice were found dead during weeks 1 and 2. Mean body weights were significantly less than those of the controls for male rats exposed to 2,500 ppm or greater, 5,000 and 10,000 ppm female rats, male mice exposed to 1,250 ppm or greater, and all exposed groups of female mice. Reduced feed consumption was observed in 5,000 and 10,000 ppm male and female rats. Clinical findings included nasal/eye discharge, ruffled fur, thinness, ataxia, and abnormal breathing in rats, and ruffled fur and dull coats in female mice. On days 29 and 82, functional observations in 5,000 and 10,000 ppm rats included labored or increased respiration, mild tremors, walking on tiptoes, hunched posture, piloerection, crouching over, impaired coordination of movement, ataxia, and pupillary constriction. 4-Methylimidazole induced a transient erythrocytosis and a minimal, exposure concentration-related, microcytic, normochromic, nonresponsive anemia in male and female rats. Clinical chemistry evaluations generally showed a cholestatic effect in exposed male and female rats. At week 14, there was a significant decrease in total protein and albumin concentrations of female rats exposed to 5,000 or 10,000 ppm. In mice, 4-methylimidazole induced a macrocytic, hyperchromic, responsive anemia and, particularly in males, increases in triiododthyronine concentrations and transient decreases in thyroxine concentrations. In the 4-methylimidazole studies, the liver weights of male rats exposed to 2,500 ppm or greater were significantly increased; spleen weights of female rats exposed to 2,500 ppm or greater were decreased. The absolute liver weight was decreased in 10,000 ppm male mice, and relative weights were significantly increased in all exposed groups of mice. In female mice, there was a significant decrease in the absolute weights and increase in the relative weights of the heart, right kidney, and liver in groups exposed to 2,500 ppm or greater. The epididymal spermatozoal concentration was significantly increased in 5,000 ppm male rats. Gross pathology observations included pale livers in male rats exposed to 2,500 ppm or greater and small testes and uteri in 10,000 ppm male and female rats. Microscopic analysis identified significantly increased incidences of cytoplasmic hepatocyte vacuolization of the liver of male rats exposed to 2,500 ppm or greater and 10,000 ppm female rats, hypospermia of the epididymis in 10,000 ppm male rats, atrophy and inflammation of the prostate gland in 10,000 ppm male rats, and degeneration of the testes in 5,000 and 10,000 ppm male rats.

4-Methylimidazole's production and use as a major pharmaceutical intermediate and as a photo development solution(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 33(SRC), determined from a log Kow of 0.23(2) and a structure estimation method(3), indicates that 4-methylimidazole is expected to have very high mobility in soil(SRC). The estimated pKa of 4-methylimidazole is 7.51(4), indicating that this compound will partially exist in cation form in the environment, and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of 4-methylimidazole from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 4.1X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(6). However, volatilization from moist soil may be attenuated because the base compound exists as a cation and cations do not volatilize. 4-Methylimidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.007 mm Hg at 25 °C(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 32(SRC), determined from a log Kow of 0.23(2) and a structure estimation method(3), indicates that 4-methylimidazole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may be expected(4) based upon an estimated Henry's Law constant of 4.1X10-6 atm-cu m/mole(SRC). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 195 hours and 62 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-methylimidazole, which has an estimated vapor pressure of 0.007 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 4-methylimidazole 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 4.1 hours(SRC), calculated from its rate constant of 9.4X10-11 cu cm/molecule-sec at 25 °C(3), determined using a structure estimation method(3). 4-Methylimidazole does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 4-methylimidazole with photochemically-produced hydroxyl radicals has been estimated as 9.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.1 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 4-Methylimidazole is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 4-Methylimidazole does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated in fish for 4-methylimidazole(SRC), using a log Kow of 0.23(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 Koc of 4-methylimidazole is estimated as 33(SRC), using a log Kow of 0.23(1) and a structure estimation method(2). According to a classification scheme(3), this estimated Koc value suggests that 4-methylimidazole is expected to have very high mobility in soil. The estimated pKa of 4-methylimidazole is 7.51(4), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

The Henry's Law constant for 4-methylimidazole is estimated as 4.1X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-methylimidazole may be expected to 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 195 hours(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). 4-Methylimidazole's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 4-Methylimidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.007 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to 4-methylimidazole may occur through inhalation and dermal contact with this compound at workplaces where 4-methylimidazole is produced or used. Use data indicate that limited exposure to the general population may occur via ingestion and dermal contact with products containing this compound. (SRC)

4-methylimidazole (4-MI) was given orally to a cow in increased dosages to determine if it could be detected in her milk and be present at a concn high enough to affect her nursing calf. 4-MI was found in the milk, but the calf remained clinically normal throughout the experiment. The cow died after the fourth dose of 20 g 4-MI. Four groups of 10 mice each were given oral doses of water, normal milk, cow's milk after low doses of 4-MI, or cow's milk after high doses of 4-MI. All mice remained healthy after a 2-wk feeding trial. Six 3-day-old calves were given 4-MI directly in their bottles of milk up to 2 times the highest level found in toxic feed with only mild depression noted in one calf. Two pregnant cows were given 4-MI pre-partum to determine if it would get into the colostrum at higher levels. Both cows received 4-MI 3 days before they calved and for 2 wk afterward. Cow A exhibited trembling, excessive salivation and incoordination after the initial dose. Cow B and the newborn calves were never affected throughout the experiment. Each time the dose of 4-MI reached 1.5 g or more, Cow A would exhibit the previously described signs. 4-MI was detected in the colostrum but not in higher concentrations than in the other milk samples.|The toxicokinetics and metabolism of 4-methylimidazole (4-MZ) have been studied in the male F344 rat using 14C radiolabelled compound. Radioactivity in plasma and urine was profiled by HPLC. After gavage administration of 50 mg/kg, about 85% of the administered radioactivity was recovered in urine within 48 hr. The majority of the radioactivity in urine or plasma was associated with the parent compound and only one minor hydrophilic metabolite was present in urine and in plasma. Elimination of radioactivity via fecal, biliary or respiration was negligible. Elimination of 4-MZ after an iv dose of 5 mg/kg can be described by a two-compartment process with an estimated half-life of 1.8 hr and an estimated apparent volume of distribution of 2.3 L/kg. After gavage at doses of 5, 50 and 150 mg/kg, 4-MZ was readily absorbed with a estimated bioavailability of 60-70%. Urinary excretion data indicated that renal clearance of 4-MZ accounted for about 80% of total body plasma clearance. Based on the estimated AUC of metabolite and the estimated renal clearance of 4-MZ, the formation of metabolite and the renal clearance of 4-MZ appeared to be a saturable process.

The toxicokinetics and metabolism of 4-methylimidazole (4-MZ) have been studied in the male F344 rat using 14C radiolabelled compound ... Elimination of 4-MZ after an iv dose of 5 mg/kg can be described by a two-compartment process with an estimated half-life of 1.8 hr ...

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ 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 needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ 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 bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Irritating /to skin and eyes/.|/SIGNS AND SYMPTOMS/ May be harmful if inhaled. Material is extremely destructive to the tissue of the mucous membranes and upper respiratory tract. ...May be harmful if absorbed through skin. Causes skin burns. ...Causes eye burns. ...Harmful if swallowed. Causes burns.

4(5)-methylimidazole

1H-Imidazole, 5-methyl-: ACTIVE

Purity is usually determined by reverse-phase HPLC; volatile derivatives may be analyzed by capillary column gas chromatography. /Imidazole and derivatives/