HuagongsheHuagongshe Chemistry Print Report · For research reference only
Metronidazole
Metronidazol · Metronidazole Base · 2-METHYL-5-NITROIMIDAZOLE-1-ETHANOL · MNZ · etronidazole · METRONIDAZOLE BP · 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol · Cont
Identifiers & Physical Properties
| CAS No. | 443-48-1 |
|---|---|
| Molecular formula | C6H9N3O3 |
| Average molar mass | 171.15 g/mol |
| Monoisotopic mass | 171.06439115 g/mol |
| SMILES | Cc1ncc([N+](=O)[O-])n1CCO |
| InChIKey | VAOCPAMSLUNLGC-UHFFFAOYSA-N |
| PubChem CID | 4173 |
| ChEMBL | CHEMBL137 |
| ChEBI | CHEBI:6909 |
| EC No. | 207-136-1 |
| DTXSID | DTXSID2020892 |
Chemical & Physical Properties
| XLogP | 0 |
|---|---|
| Topological polar surface area | 83.9 |
| Hydrogen bond donors | 1 |
| Hydrogen bond acceptors | 4 |
| Rotatable bonds | 2 |
| Heavy atoms | 12 |
| Formal charge | 0 |
| Complexity | 170 |
| Drugs | PharmaceuticalsPharmaceuticals -> Antibiotics (Nitroimidazole)Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Antibiotics |
| pH | pH of saturated aq soln is 5.8 |
| LogP (partition coefficient) | log Kow = -0.02-0.1 |
| Odor | ODORLESS |
| Color/Form | Cream-colored crystalsWHITE TO PALE YELLOW CRYSTALS OR CRYSTALLINE POWDER |
| Solubility | less than 1 mg/mL at 68 °F (NTP, 1992)g/100 ml at 20 °C: 1.0 in water, 0.5 in ethanol, less than 0.05 in ether, chloroformsol in dilute acidssparingly sol in dimethylformamideIn water, 11,000 mg/L at 25 °C5.92e+00 g/L>25.7 [ug/mL] (The mean of the results at pH 7.4)acetic acid: 0.1 M, clear, faintly yellow<0.1 g/100 mL at 20 ºC |
| Human Drugs | Breast FeedingLactationMilk, HumanAnti-Infective AgentsAntibacterial AgentsAntiprotozoal AgentsNitroimidazolesFDA approved drugs -> Active ingredientAccess group antibiotics |
| Animal Drugs | Active Ingredients (Metronidazole) -> FDA GreenbookPharmaceuticals -> Animal Drugs -> Approved in TaiwanPharmaceuticals -> UK Veterinary Medicines Directorate List |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Melting point | 316 to 320 °F (NTP, 1992)158-160 °C159-161 °C (lit.) |
| Physical Description | Metronidazole is a white to pale-yellow crystalline powder with a slight odor. Bitter and saline taste. pH (saturated aqueous solution) about 6.5. (NTP, 1992)Solid |
| Stability/Shelf Life | Stable in air but darkens on exposure to light.Metronidazole conventional tablets should be stored in well-closed, light-resistant containers at less than 25 °C. Metronidazole capsules should be stored in tight containers at 15-25 °C. Metronidazole extended-release tablets should be stored in well-closed containers at approximately 25 °Ctemporary exposure to temperatures of 15-30 °C is acceptable.Metronidazole hydrochloride powder for injection should be protected from light and stored at less than 30 °C. Metronidazole injection should be protected from light and freezing and stored at 15-30 °C. The manufacturer (Baxter) of commercially available metronidazole injection ... states that this injection has an expiration date of 24 months following the date of manufacture. |
| Boiling point | 301.12°C (rough estimate) |
| Density | 1.3994 (rough estimate) |
| Refractive index | 1.5800 (estimate) |
| Flash point | 9℃ |
| Storage conditions | 2-8°C |
| Physical state | crystalline |
| pKa (acidity coefficient) | pKa 2.62(H2O,t =25±0.2,Iundefined) (Uncertain) |
| Color | white to light yellow |
| Merck | 14,6157 |
| BRN | 611683 |
| Henry's law constant | 5.8×105 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 1,3 |
| Stability | Stable. Incompatible with strong oxidizing agents. |
| Major applications | clinical testing |
| InChI | 1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3 |
| InChIKey | VAOCPAMSLUNLGC-UHFFFAOYSA-N |
| SMILES | CC1=NC=C([N+]([O-])=O)N1CCO |
| LogP (partition coefficient) | -0.02 |
| EWG's Food Scores | 1-2 |
| NCI Dictionary of Cancer Terms | Flagylmetronidazole |
| FDA UNII | 140QMO216E |
| NCI Drug Dictionary | Flagyl |
| ATC code | A01AB17,D06BX01,G01AF01,J01XD01,P01AB01,P01AB51 |
| Proposition 65 List | Metronidazole |
| IARC | 2B (Vol. 13, Sup 7) 1987 |
| NIST Chemistry Reference | Metronidazole(443-48-1) |
| EPA Substance Registry System | Metronidazole (443-48-1) |
| UNSPSC Code | 51282808 |
| NACRES | NA.76 |
| Protein binding | 10-20% |
| Excreted unchanged in urine | 20% |
| Volume of distribution | 0.7-1.5(L/kg) |
| Biological half-life | 5.6-11.4 / 7-21 |
| GHS pictogram | GHS08 |
| Signal word | Danger |
| GHS hazard statements | H340-H350-H373 |
| GHS precautionary statements | P202-P260-P280-P308+P313-P405-P501 |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Gloves |
| Hazard symbols | Xn |
| Risk statements (R) | 40-46-45-39/23/24/25-23/24/25-11 |
| Safety statements (S) | 36/37-45-53-16-7 |
| Water hazard class (WGK) | 3 |
| RTECS number | NI5600000 |
| F | 8 |
| Customs code | 29332990 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Hazard class | Carc. 1BMuta. 1BSTOT RE 2 |
| Hazardous substances data | 443-48-1(Hazardous Substances Data) |
| REACH registrations | Active |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 1.1% (2 of 177) of reports.DangerH302 (15.3%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P317, P318, P319, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 177 reports by companies from 31 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatory information | Hazard Traits - CarcinogenicityStatus: Active Update: 12-03-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/22643Metronidazole: Does not have an individual approval but may be used under an appropriate group standard |
| Other safety information | IMAP assessments - 1H-Imidazole-1-ethanol, 2-methyl-5-nitro-: Human health tier I assessment |
| Fire hazards | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
| Health hazards | SYMPTOMS: Symptoms of exposure to this chemical may include nerve or sheath structural changes, eye changes, tremors, fever, jaundice and other liver changes. It may cause convulsive seizures, numbness, nausea, vomiting, abdominal discomfort, diarrhea, sharp, unpleasant metallic taste, erythematous rash, pruritus, dizziness, syncope, ataxia, thrombophlebitis after intravenous infusion, darkened urine, anorexia, epigastric distress, constipation, glossitis, stomatitis, reversible thrombocytopenia and vertigo. Flattening of the T-wave may be seen in electrocardiographic tracings. It may also cause incoordination, irritability, depression, weakness, insomnia, nasal congestion dysuria, cystitus, polyuria, incontinence, a sense of pelvic pressure, dyspareunia, decrease of libido, proctitis and fleeting joint pains sometimes resembling serum sickness. It may cause skin rash and drowsiness. Other symptoms of exposure include malaise, transient rashes, gastrointestinal disturbances and peripheral neuropathy. It may cause coated tongue, dry mouth, urethral discomfort, temporary leukopenia, increase in chromosome aberrations, candidal vaginitis, lethargy and sore furred tongue. In conjunction with alcohol it may provoke a disulfuram-like reaction. Pregnant women expose to this compound have given birth to premature, stillborn infants. One infant has died of white asphyxia. It may cause epigastric distress, abdominal cramping, numbness or paresthesia of an extremity, urticaria, flushing, dryness of vagina or vulva, abdominal distress, headache (if ingested with alcohol), confusional and psychotic states, blood dyscrasias, temporary neutropenia which reverses after therapy, and low concentrations of lipids in plasma. |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl metronidazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Reactive group | Alcohols and Polyols |
| Special Reports | National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Metronidazole (443-48-1) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf] |
| FIFRA requirements | As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Metronidazole is found on List C. Case No: 3096Pesticide type: antimicrobialCase Status: No products containing the pesticide are actively registered ... The case /is characterized/ as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.Active ingredient (AI): metronidazoleData Call-in (DCI) Date(s): 09/23/93AI Status: The active ingredient is no longer contained in any registered pesticide products ... "cancelled." |
| Reactivity Profile | METRONIDAZOLE darkens on exposure to light. This chemical is incompatible with strong oxidizing agents. (NTP, 1992). |
| Air and Water Reactions | Insoluble in water. |
| Hazard Classes and Categories | Acute Tox. 4 (15.3%) |
| Shipment Methods and Regulations | PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/ |
| Fire fighting | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| First aid | 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. |
| Storage conditions | PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/ |
| Cleanup methods | PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/ |
| Nonfire spill response | SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then dampen the solid spill material with toluene, then transfer the dampened material to a suitable container. Use absorbent paper dampened with toluene to pick up any remaining material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash all contaminated surfaces with toluene followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. |
| Disposal methods | 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.PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/For more Disposal Methods (Complete) data for METRONIDAZOLE (6 total), please visit the HSDB record page. |
| Preventive Measures | PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/For more Preventive Measures (Complete) data for METRONIDAZOLE (9 total), please visit the HSDB record page. |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/ |
| Interactions | It is recommended that metronidazole not be used concurrently with, or for at least 1 day following, ingestion of alcoholaccumulation of acetaldehyde by interference with the oxidation of alcohol may occur, resulting in disulfiram-like effects such as abdominal cramps, nausea, vomiting, headache, or flushingin addition, modifications in the taste of alcoholic beverages have been reported during concurrent use.Effects may be potentiated when /coumarin- or indandione-derivative anticoagulants/ are used concurrently with metronidazole, because of inhibition of enzymatic metabolism of anticoagulantsperiodic prothrombin time determinations may be required during therapy to determine if dosage adjustments of anticoagulants are necessary.Hepatic metabolism of metronidazole may be decreased when metronidazole and cimetidine are used concurrently, possibly resulting in delayed elimination and increased serum metronidazole concentrationsmonitoring of serum concentrations as a guide to dosage is recommended since dosage adjustments of metronidazole may be necessary during and after cimetidine therapy.It is recommended that metronidazole not be used concurrently with, or for 2 weeks following, disulfiram in alcoholic patientssuch use may result in confusion and psychotic reactions because of combined toxicity.For more Interactions (Complete) data for METRONIDAZOLE (12 total), please visit the HSDB record page. |
| Hepatotoxicity | Despite the wide use of metronidazole, only rare cases of hepatotoxicity have been reported, and metronidazole is not listed among causes of drug induced liver injury and acute liver failure in large case series. High doses of metronidazole given parenterally or in an overdose can cause elevations in serum aminotransferase levels, but these are usually self-limited and minimally symptomatic (Case 1). Acute, clinically apparent liver injury from metronidazole is rare. Ornidazole, another synthetic nitroimidazole that was available in Europe, was implicated in several cases of drug induced liver injury, with a latency of a few days or weeks and a hepatocellular pattern of injury. Metronidazole has been associated with a similar acute hepatitis-like syndrome with a short incubation period, but much more rarely. Fever, rash and eosinophilia are uncommon as are autoimmune features. A fatal recurrence of acute liver injury after reexposure to metronidazole has been published (Case 2). Strikingly, multiple instances of metronidazole hepatoxicity have been reported in the rare genetic disease, Cockayne syndrome in which there is an absence or deficiency in an important DNA repair enzyme responsible for nucleotide excision repair. The cases were marked by a short latency (1 to 7 days) to onset of jaundice, a hepatocellular pattern of enzyme elevations and severe course with a high mortality rate. Whether patients with Cockayne syndrome have a similar high risk for severe hepatitis with other nitroimidazoles (such as tinidazole) is not known. |
| Ecotoxicity values | LD50 Anas platyrhynchos (Mallard duck, 19 weeks old) oral >5000 mg/kgLC50 Anas platyrhynchos (Mallard duck, 17 days old) diet >5000 ppm/8 daysLC50 Colinus virginianus (Bobwhite quail, 12 days old) diet >5000 ppm/8 daysLC50 Americamysis bahia (Opossum shrimp, age 2 days) 182 ppm/96 hr (95% confidence limit: 140-230 ppm)static /98% AI formulated product/For more Ecotoxicity Values (Complete) data for METRONIDAZOLE (10 total), please visit the HSDB record page. |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a log Kow of -0.02(2) and a regression-derived equation(3), indicates that metronidazole is expected to have very high mobility in soil(SRC). Volatilization of metronidazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.7X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Metronidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3X10-7 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation half-lives in sandy soil-manure slurry of 9.7 to 14.7 days and in clay soil-manure slurry of 13.1 to 26.9 days(5), suggesting biodegradation may be an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 23(SRC), determined from a log Kow of -0.02(2) and a regression-derived equation(3), indicates that metronidazole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.7X10- 11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). No biodegradation was observed using closed bottle tests(7), suggesting that biodegradation is a slow environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), metronidazole, which has an estimated vapor pressure of 3.1X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase metronidazole 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 41 hrs(SRC), calculated from its rate constant of 9.3X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase metronidazole may be removed from the air by wet or dry deposition(SRC). Metronidazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Adverse effects | The primary adverse effects of metronidazole include confusion, peripheral neuropathy, metallic taste, nausea, vomiting, and diarrhea. Adverse events seen in greater than 10% of the population include headache (18%), vaginitis (15%), and nausea (10% to 12%). Adverse events affecting less than 10% of the population are metallic taste (9%), dizziness (4%), genital pruritus (5%), abdominal pain (4%), diarrhea (4%), xerostomia (2%), dysmenorrhea (3%), urine abnormality (3%), urinary tract infection (2%), bacterial infection (7%), candidiasis (3%), flu-like symptoms (6%), upper respiratory tract infection (4%), pharyngitis (3%), and sinusitis (3%). Rarely, there are reports of transient leukopenia and neutropenia as well. |
| Exposure routes | Well absorbed (at least 80%) with peak plasma concentrations achieved in 1-3 hours following oral administration of therapeutic doses of immediate release formulation. |
| Toxicity summary | There have been reports of disulfiram-like reactions in patients drinking alcohol while administered systemic or vaginal metronidazole. A typical disulfiram reaction causes flushing, tachycardia, palpitations, nausea, and vomiting. Alcohol should be avoided during treatment and from up to forty-eight hours to fourteen days after treatment completion, depending on the sourcethe manufacturer's product information recommends avoiding alcohol ingestion during metronidazole therapy and for at least 48 hours afterward. Ethanol-containing medications such as elixirs and tipranavir, capsules, intravenous (IV) anidulafungin, IV trimethoprim-sulfamethoxazole, and many cough/cold syrups can also lead to a disulfiram-like reaction when ingested with metronidazole.Metronidazole is a prodrug. Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death. |
| Signs and Symptoms | Adverse effects include reversible peripheral neuropathy with prolonged therapy, CNS toxicity, disulfiram effect with alcohol, dark red-brown urine, metallic taste, nausea, epigastric distress, dizziness, vertigo and paresthesias associated with high doses, and neutropenia (reversible and mild). |
| Effluent Concentrations | Metronidazole may be released to treatment systems as a result of excretion and disposal of unused or expired medications(1). An estimated 20 to 40% of outdated and unused medications are disposed down household drains in Germany(2). A theoretical mean effluent concentration of metronidazole was calculated to be 6.2 ug/L from 1992 to 1994 in one hospital(3). |
| Medical Surveillance | PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/ |
| Soil Adsorption/Mobility | The Koc of metronidazole is estimated as 23(SRC), using a log Kow of -0.02(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that metronidazole is expected to have very high mobility in soil. |
| Natural Pollution Sources | Although metronidazole is closely related to natural antitrichomonal agent, azomycin, it is not known to occur in nature(1). |
| F | 8 |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Gloves |
| Water hazard class (WGK) | 3 |
| RTECS number | NI5600000 |
| Customs code | 29332990 |
| Risk statements (R) | 40-46-45-39/23/24/25-23/24/25-11 |
| Signal word | Danger |
| GHS pictogram | GHS08 |
| Hazard symbols | Xn |
| Safety statements (S) | 36/37-45-53-16-7 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| GHS hazard statements | H340-H350-H373 |
| REACH registrations | Active |
| Hazard class | Carc. 1BMuta. 1BSTOT RE 2 |
| GHS precautionary statements | P202-P260-P280-P308+P313-P405-P501 |
| Hazardous substances data | 443-48-1(Hazardous Substances Data) |
Applications & Uses
Description
Metronidazole is a nitroimidazole antibiotic first isolated in the 1950s. Many nitroimidazoles were being studied at the time, as the class was found to have trichomonacidal properties. Metronidazole was of particular interest due to its high activity against Trichomonas vaginalis and Entamoeba histolytica both in vitro and in vivo as well as clinical activity against many anaerobic pathogens including Gram-positive and Gramnegative bacteria and Giardia lamblia. Metronidazole is often used clinically for intra-abdominal infections and is the firstline treatment for Clostridium difficile–associated diarrhea.
Uses
Metronidazole is the drug of choice for amebiases, vaginal trichomonasis and trichlomonadic urethritis in men, lambliosis, amebic dysentery, and anaerobic infections caused by microorganisms that are sensitive to the drug. Synonyms of this drug are flagyl, protostat, trichopol, and vagimid.
Uses
Metronidazole is available as oral, intravaginal, topical, and parenteral preparations. It is manufactured by several companies, but is only available by prescription. Unintentional environmental exposure is unlikely, and if it occurs, it is very unlikely to cause toxicity.
Uses
Metronidazole, is an antibiotic and antiprotozoal agent. It is mainly used to treat or prevent systemic or local infections caused by anaerobic bacteria, such as anaerobic bacterial infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints, etc. Inflammation, meningeal infections, and colitis caused by antibiotic use are also effective. Tetanus is often treated with tetanus antitoxin (TAT). It can also be used for oral anaerobic infection. On October 27, 2017, the list of carcinogens published by the World Health Organization's International Agency for Research on Cancer was preliminarily sorted for reference, and metronidazole was included in the list of class 2B carcinogens. In January 2020, metronidazole was selected into the second batch of national centralized drug procurement list.
Uses
Used as an antibacterial in the treatment of rosacea. Antiprotozoal (trichomonas). A potential human carcinogen.
General Description
White to pale-yellow crystalline powder with a slight odor. Bitter and saline taste. pH (saturated aqueous solution) about 6.5.