化工社化工社 化学情報印刷レポート · 研究参考用
シントマイシン
rel-2,2-ジクロロ-N-[(αS*,βS*)-β-ヒドロキシ-α-ヒドロキシメチル-4-ニトロフェネチル]アセトアミド · (±)-クロラムフェニコール · DL-クロラムフェニコール · シントマイシン · DL-threo-2,2-ジクロロ-N-(β-ヒドロキシ-α-ヒドロキシメチル-4-ニトロフェネチル)アセトアミド · Synthomycin · CHLORONITRIN · CHLORAMPHENICOLUM
識別子と物理属性
| CAS No. | 2787-09-9 |
|---|---|
| 分子式 | C11.H12.Cl2.N2.O5 |
| 平均分子量 | 323.13 g/mol |
| 単同位体質量 | 322.01232684 g/mol |
| SMILES | O=C(N[C@H](CO)[C@H](O)c1ccc([N+](=O)[O-])cc1)C(Cl)Cl |
| InChIKey | WIIZWVCIJKGZOK-RKDXNWHRSA-N |
| PubChem CID | 5959 |
| ChEMBL | CHEMBL130 |
| ChEBI | CHEBI:17698 |
| EC No. | 200-287-4 |
| DTXSID | DTXSID7020265 |
| 現地名 | シントマイシン |
化学・物理的性質
| XLogP | 1.1 |
|---|---|
| 極性表面積 | 115 |
| 水素結合供与体数 | 3 |
| 水素結合受容体数 | 5 |
| 回転可能結合数 | 5 |
| 重原子数 | 20 |
| 形式電荷 | 0 |
| 複雑度 | 342 |
| 物質分類 | Other Uses -> Pharmaceuticals |
| 医薬品 | Pharmaceuticals -> AntibioticsPharmaceuticals -> Antibiotics (Amphenicols)Pharmaceuticals -> Listed in ZINC15 |
| pH | Neutral to litmus |
| LogP（分配係数） | log Kow = 1.140.7 |
| 味 | Bitter to taste |
| Color/Form | Needles or elongated plates from water or ethylene dichlorideWhite to greyish-white or yellowish-white fine crystalline powder or fine crystals, needles or elongated plates. Of the four possible stereoisomers, only the alphaR,betaR (or D-threo) form is active ... .Pale yellow plates or needles from water |
| 溶解度 | In water, 2.5 mg/mL at 25 °CSolubility in propylene glycol: 150.8 mg/mol. Very sol in methanol, ethanol, butanol, ethyl acetate, acetone. Fairly soluble in ether. Insoluble in benzene, petroleum ether, vegetable oils. Solubility in 50% acetamide solution about 5%.Very soluble in acetone, chloroform, ethanol4.61e-01 g/L |
| Human Drugs | Breast FeedingLactationAnti-Infective AgentsAntibacterial AgentsFDA approved drugs -> Active ingredientAccess group antibiotics |
| Animal Drugs | Active Ingredients (Chloramphenicol) -> FDA GreenbookPharmaceuticals -> Animal Drugs -> Approved in Taiwan |
| 沸点 | Sublimes in high vacuum644.9±55.0 °C(Predicted) |
| Decomposition | When heated to decomposition it emits very toxic fumes of /nitrogen oxides and chloride/. |
| 融点 | 150.5-151.5 °CMP: 149-153 °C150.5 °C151 °C148-150 °C(lit.) |
| 密度 | 1.547±0.06 g/cm3(Predicted) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 11.03±0.46(Predicted) |
| 色 | 白い |
| InChI | InChI=1/C11H12Cl2N2O5/c12-10(13)11(18)14-8(5-16)9(17)6-1-3-7(4-2-6)15(19)20/h1-4,8-10,16-17H,5H2,(H,14,18)/t8-,9-/s3 |
| InChIKey | WIIZWVCIJKGZOK-JQEWEITDNA-N |
| SMILES | C(N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1)(=O)C(Cl)Cl |&1:2,5,r| |
| CAS データベース | 2787-09-9(CAS DataBase Reference) |
安全性と法規制
| GHS 分類 | This chemical does not meet GHS hazard criteria for 2% (6 of 294) of reports.DangerH317 (18%): May cause an allergic skin reaction [Warning Sensitization, Skin]P203, P261, P264+P265, P272, P280, P302+P352, P305+P354+P338, P317, P318, P321, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 294 reports by companies from 32 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | Hazard Traits - CarcinogenicityStatus: Active Update: 30-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/26156Chloramphenicol: Does not have an individual approval but may be used under an appropriate group standard |
| その他の安全情報 | IMAP assessments - Acetamide, 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]-, [R-(R*,R*)]-: Environment tier I assessment |
| 有害性の概要 | Allergic contact dermatitis reported in pharmaceutical workers[Marks, p. 189-90] Chloramphenicol is an antibiotic, and many side effects have been reported after ingestion of therapeutic doses including, rarely, bone marrow suppression. [HSDB] The lowest dose to cause reversible bone marrow depression was 2000 mg/day for 21 days. While the reversible bone marrow depression is dose related, the rare aplastic anemia is not dose related and is thought to be an idiosyncratic reaction in susceptible individuals. IARC has noted cases of leukemia developing in patients suffering from chloramphenicol-induced aplastic anemia. Occupational allergic dermatitis reported in ophthalmologists and farmers using topical chloramphenicol solutionsNo evidence of significant skin absorptionToxic to embryos and fetuses in animal studies at 1000 mg/kg-day[AIHA] |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including chloramphenicol sodium succinate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Chloramphenicol sodium succinate/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Chloramphenicol is included on this list.Drug products withdrawn or removed from the market for reasons of safety or effectiveness. The following drug products were withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) or section 503B(a) of the Federal Food, Drug, and Cosmetic Act. Included on list: Chloramphenicol: All oral drug products containing chloramphenicol.Implantation or injectable dosage form new animal drugs. Chloramphenicol. ... Indications for use /in dogs/: Treatment of infections of the respiratory tract, the urinary tract, and enteritis and tonsillitis caused by organisms susceptible to chloramphenicol. ... Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits the extralabel use of this drug in food-producing animals.Extralabel drug use in animals. Drugs prohibited for extralabel use in animals. The following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in food-producing animals. Chloramphenicol is included on this list. |
| Special Reports | Lietman PSChloramphenicol and the Neonate- 1979 ViewClin Perinatol 6 (1): 151 (1979). Review of chloramphenicol use in newborn infant.DHHS/National Toxicology ProgramReport on Carcinogens, Fourteenth Edition: Chloramphenico (November 2016). 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. Chloramphenico (56-75-7) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of April 10, 2017: http://ntp.niehs.nih.gov/pubhealth/roc/index-1.html] |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas.Poisonous gases are produced in fire, including chlorine and nitrogen oxides. |
| Hazard Classes and Categories | Skin Sens. 1 (18%)Acute toxicity (Oral) - Category 5Germ cell mutagenicity - Category 2 |
| 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/ |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Acids, acid chlorides, acid anhydrides, oxidizing agents.Chloramphenicol has been reported to be physically incompatible with many drugs, but the compatibility depends on several factors (e.g., the concentration of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information. |
| 消火手順 | 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 dry chemical, carbon dioxide, water spray, or foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode. |
| 保管条件 | Keep container tightly closed in a dry and well-ventilated place.Store at 20 deg to 25 °C (68 deg to 77 °F). /Chloramphenicol sodium succinate/Store at or below 25 °C (77 °F) in a dry place.Chloramphenicol sodium succinate sterile powder for injection should be stored at 15-25 °C. /Chloramphenicol sodium succinate/For more Storage Conditions (Complete) data for Chloramphenicol (6 total), please visit the HSDB record page. |
| 清掃方法 | 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.Evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.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/ |
| 処分方法 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.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 permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. 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 be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.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 companyContaminated packaging: Dispose of as unused product.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/For more Disposal Methods (Complete) data for Chloramphenicol (8 total), please visit the HSDB record page. |
| Preventive Measures | 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: Avoid formation of dust and aerosols. 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. 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 Chloramphenicol (16 total), please visit the HSDB record page. |
| Protective Action Criteria (PAC) | 1.5 [mg/m3]42 [mg/m3]250 [mg/m3] |
| Personal Protective Equipment (PPE) | Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.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).For more Personal Protective Equipment (PPE) (Complete) data for Chloramphenicol (6 total), please visit the HSDB record page. |
| Other Standards Regulations and Guidelines | Workplace Environmental Exposure Level (WEEL): 8-hr Time-weighted Average (TWA) 0.5 mg/cu m. Last Revised: 2008. |
| Treatment | Drug therapy is discontinued immediatelyexchange transfusion may be required to remove the drug. Sometimes, phenobarbital (UGT induction) is used. |
| 相互作用 | Chloramphenicol-treated patient may respond poorly to cyanocobalamin therapy since chloramphenicol interferes with erythrocyte maturation.Concurrent therapy with other drugs that may cause bone marrow depression should be avoided.Chloramphenicol antagonizes the action of such antibiotics as penicillin and streptomycin, which act only on growing cells, but is synergistic to tetracycline, which also acts by inhibiting protein synthesis. It is possible the chloramphenicol would produce similar synergism with other antibiotics which act by inhibiting protein synthesis.Clinical observations in man and corresponding investigations in laboratory animals experimentally infected with various pathogenic bacteria have shown that a combination of chloramphenicol with gamma-globulin or specific antisera has a greater therapeutic effect than would be expected from a mere addition of the individual effects.For more Interactions (Complete) data for Chloramphenicol (26 total), please visit the HSDB record page. |
| 健康影響 | The most serious adverse effect associated with chloramphenicol treatment is bone marrow toxicity, which may occur in two distinct forms: 1) bone marrow suppression, which is a direct toxic effect of the drug and is usually reversible, and 2) aplastic anemia, which is idiosyncratic (rare, unpredictable) and generally fatal. Other less serious reactions from chloramphenicol use include fever, rashes, headache, and confusion. Use of intravenous chloramphenicol has also been associated with gray baby syndrome, a phenomenon resulting from newborn infants' inability to metabolize chloramphenicol in the liver via UDP-glucuronyl transferase. Gray baby syndrome is characterized by vomiting, ashen gray color of the skin, limp body tone, hypotension and cyanosis. |
| Hepatotoxicity | A proportion of patients with blood dyscrasias due to chloramphenicol also developed clinically apparent liver injury with jaundice, usually occurring before the appearance of aplastic anemia or severe thrombocytopenia. Jaundice arises in 10% to 25% of cases of aplastic anemia, usually within 1 to 2 months of starting chloramphenicol and often shortly after it is stopped. Aplastic anemia and the accompanying liver injury occur most frequently in patients who receive multiple courses of chloramphenicol or prolonged therapy. The serum enzyme pattern is usually hepatocellular and the clinical presentation is an acute hepatitis-like syndrome with onset of fatigue, nausea, anorexia and abdominal discomfort followed by dark urine and jaundice. Rare instances have a cholestatic pattern of presentation with jaundice and itching and prominent elevations in alkaline phosphatase. Some cases occur in the absence of bone marrow involvement. Immunoallergic and autoimmune features are rarely present. The course is self-limited in most instances, but examples of acute liver failure have been reported, particularly in patients without aplastic anemia. In most cases, however, the liver injury associated with chloramphenicol use is eclipsed by the severe bone marrow aplasia. |
| 生態毒性値 | EC50Species: Desmodesmus subspicatus (Green Algae) 86.71 SAG, 10+4 algae/mLConditions: freshwater, static, 23 °CConcentration: 780 ug/L for 72 hr (95% confidence interval: 210-2930 ug/L)Effect: decreased population growth rate /formulation/Concentration: 200 ug/L for 72 hr (95% confidence interval: 150-240 ug/L)Effect: decreased population biomass /formulation/Concentration: 130 ug/L for 72 hr (95% confidence interval: 6-240 ug/L)Effect: decreased population, general /formulation/LC50Species: Artemia franciscana (San Francisco Brine Shrimp) age ~48 hr naupliiConditions: saltwater, static, 25 °CConcentration: 0.00197 M for 48 hr /formulation/For more Ecotoxicity Values (Complete) data for Chloramphenicol (6 total), please visit the HSDB record page. |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 1150(2), indicates that chloramphenicol is expected to have low mobility in soil(SRC). Volatilization of chloramphenicol from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 2.3X10-18 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Chloramphenicol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Half-lives in marine and freshwater sediment of 2.4 to 18.4 days and <12 days, respectively, indicate that biodegradation may occur in terrestrial environments(4).AQUATIC FATE: Based on a classification scheme(1), a Koc value of 1150(2), indicates that chloramphenicol is 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 2.3X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Chloramphenicol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(5), an estimated BCF of 1(SRC), from its log Kow of 1.14(6) and a regression-derived equation(4), suggests the potential for bioconcentration in aquatic organisms is low. Aerobic and anaerobic half-lives in marine sediment are reported as 2.4-18.4 and 0.4-2.4 days, in freshwater sediment respective half-lives of <12 and < 4 days were reported, these half-lives indicate that biodegradation may occur in aquatic environments(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), chloramphenicol, which has an estimated vapor pressure of 1.7X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase chloramphenicol may be removed from the air by wet and dry deposition(SRC). Chloramphenicol contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| 食品調査値 | Chloramphenicol was not detected in 203 Canadian egg samples screened for veterinary antibiotics99% of the samples in this study were free of all drug residues(1). Chloramphenicol was not detected in 10 unifloral (orange, eucalyptus, lavender, rosemary, thyme) and 2 multifloral honey samples collected in Spain(2). Chloramphenicol was not detected (detection limit 0.3 ug/L) in raw, full-fat, half-skimmed or skimmed milk samples collected from a local farm and local supermarkets of China(3). Chloramphenicol was not detected in eight types of milk (whole, semi-skim, skim and raw cow's milkwhole and semi-skim goat's milkhuman milkpowdered milk) from Spain and Morocco(4).The percentage of violations of veterinary drug content in seafood inspections for chloramphenicol was reported as follows(1):[Table#4354] |
| 有害作用 | Aplastic anemia - The presence of increased methemoglobin in the bloodthe compound is classified as primary toxic effect.Chloramphenicol is associated with severe hematological side effects when administered systemically. Since 1982, chloramphenicol has reportedly caused fatal aplastic anemia, with possible increased risk when taken together with cimetidine. This adverse side effect can occur even with the topical administration of the drug, which is most likely due to the systemic absorption of the drug after topical application. |
| 暴露経路 | Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%). Well absorbed following intramuscular administration (bioavailability 70%). Intraocular and some systemic absorption also occurs after topical application to the eye. |
| Milk Concentrations | Chloramphenicol was not detected (detection limit 0.3 ug/L) in raw, full-fat, half-skimmed or skimmed milk samples collected from a local farm and local supermarkets of China(1). Chloramphenicol was not detected in eight types of milk (whole, semi-skim, skim and raw cow's milkwhole and semi-skim goat's milkhuman milkpowdered milk) from Spain and Morocco(2).Chloramphenicol is excreted in breast milk in concentrations up to 25 ug per mL. |
| 毒性の概要 | IDENTIFICATION AND USE: Chloramphenicol is an antibiotic for human and veterinary use, originally isolated from the soil bacterium Streptomyces venzeuelae. HUMAN STUDIES: Chloramphenicol is known to produce major adverse effects in humans. One of these is generally irreversible aplastic anemia and reversible bone marrow suppression. A link between chloramphenicol and liver disease has been noted. Acute myeloid leukemia is also associated with chloramphenicol exposure. Neonates, especially if premature, may develop a serious illness termed "gray baby syndrome" if exposed to excessive doses of chloramphenicol. This syndrome usually begins 2-9 days (average of 4 days) after treatment is started. Within the first 24 hours, vomiting, refusal to suck, irregular and rapid respiration, abdominal distention, periods of cyanosis, and passage of loose green stools occur. The children are severely ill by the end of the first day, and in the next 24 hours turn an ashen-gray color and become flaccid and hypothermic. A similar "gray syndrome" has been reported in adults who were accidentally overdosed with the drug. Allergic contact dermatitis has been noted from a patient using a topical cream containing chloramphenicol. Optic neuritis and scotoma with failing vision has also been reported. Chloramphenicol has been implicated in cleft lip. Chromosomal anomalies were noted in human lymphocytes treated with chloramphenicol in vitro. ANIMAL STUDIES: After three groups of ten 3-month old mice were given daily intraperitoneal injections of chloramphenicol at 20, 40 or 100 mg/kg bw for 3 months, splenomegaly, hepatomegaly, lymph adenopathy and hypertrophy of the thymus occurred in a dose-dependent fashion. An increased incidence in lymphomas in two strains of mice were noted after exposure to chloramphenicol in drinking water. Chloramphenicol has been shown to cause DNA strand breaks in bacterial cells and to inhibit DNA synthesis in lymphocytes and in the phage of Escherichia coli. Chromosomal anomalies were noted in mouse bone marrow cells given chloramphenicol ip or im in F1 generation mouse liver. When groups of 3-9 female Sprague-Dawley rats were given chloramphenicol in drinking water with or without exposure to short duration high intensity noise, ototoxicity was noted. Oral doses of this antibiotic suppressed paradoxical sleep in cats. Chloramphenicol administered to pregnant monkeys had no effect on fetal development. High oral doses of chloramphenicol of 500-2000 mg/kg to rats and mice and of 500 and 1000 mg/kg to rabbits produced high incidences of embryonic and fetal deaths and fetal growth retardation in all three species. Teratogenic effects, predominantly umbilical hernia, were observed only in rats. The pregnant animals showed no toxic sign, except that those given the highest dose gained significantly less weight than controls. Progeny of chloramphenicol-treated mice had reduced learning ability, higher brain seizure threshold and poorer performance in the open-field test. ECOTOXICITY STUDIES: Chloramphenicol was added to cultures of one freshwater green alga, Chlorella pyrenoidosa, and two marine algae, Isochrysis galbana and Tetraselmis chui. It was more toxic to the freshwater algae. Chloramphenicol exposure could significantly inhibit the growth of Scenedesmus obliquus, while Chlorella pyrenoidosa exhibited less sensitivity. Abnormal behavioral changes were observed in fish Clarias gariepinus exposed to chloramphenicol. Hematological parameters were also affected. In Egyptian toads (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks, it induced numerous, severe ultrastructural changes in almost all types of leukocytes.Chloramphenicol can be fatal in an overdosethis usually occurs with intravenous administration of the drug and is more likely to affect infants. Symptoms of poisoning include nausea and vomiting, abdominal distension, metabolic acidosis, hypotension, hypothermia, cardiovascular collapse, and coma.Chloramphenicol targets the large 39S subunit of the mitochondrial ribosome thereby deactivation mitochondrial protein synthesis. As a result chloramphenicol is cytotoxic to the most metabolically active cells or tissues including the heart, liver, thymus and bone-marrow. (A7823). The likely target of chloramphenicol is the 16S rRNA molecule in the mitochondrial ribosome, which is analogous to the 23S rRNA in bacterial ribosomes. |
| 生態毒性抜粋 | /AQUATIC SPECIES/ This study investigated the growth inhibition effects of three phenicol antibiotics on microalgae used in aquaculture. Different dose levels of chloramphenicol (CAP), florfenicol (FF), and thiamphenicol (TAP) were added to cultures of one freshwater green alga, Chlorella pyrenoidosa, and two marine algae, Isochrysis galbana and Tetraselmis chui. For the two marine algae, FF showed higher toxicity levels (EC50, 1.3-8 mg/L) than CAP (4-41 mg/L) and TAP (38-158 mg/L). CAP was more toxic to the freshwater algae (EC50, 14 mg/L) than FF (215 mg/L) and TAP (1283 mg/L). TAP was the least toxic to the three algae, but maintained the highest stability during the test period. Among the tested algae, T. chui was the species most sensitive to the three antibiotics. This study demonstrates that all three phenicol antibiotics can inhibit growth of the three microalgae and should be carefully used in aquaculture./AQUATIC SPECIES/ ... The present work aimed to assess the persistence of chloramphenicol (a banned but illegally used antibiotic) in seawater, together with its effects on the growth of the green macroalgae Ulva lactuca. Moreover, the potential use of this species as a bioindicator was assessed. Results showed CAP presented an exponential degradation pattern in seawater with concentrations decreasing faster than expected. As for the effects on U. lactuca it acted as a growth promoter also contradicting the initial assumptions. Regarding the role of this species in biomonitoring it successfully took up CAP in solution while reflecting the concentrations present conferring it good characteristics as a bioindicator. On the other hand, this ability points to a possibility of CAP being accumulated and transferred along the trophic web through the consumption of U. lactuca by organisms in higher levels./AQUATIC SPECIES/ ... The indoor experiments were ... to observe and analyze the chloramphenicol (CAP) induced changes /on Scenedesmus obliquus and Chlorella pyrenoidosa/. Results of the observations ... showed that CAP exposure could significantly inhibit the growth of Scenedesmus obliquus in almost all the treated groups, while Chlorella pyrenoidosa exhibited less sensitivity. Chlorophyll-a syntheses of Scenedesmus obliquus were all inhibited by CAP exposure, while Chlorella pyrenoidosa displayed obvious stimulation effect. Catalase (CAT) and Superoxide dismutase (SOD) activities of both algae were promoted in all the treatments. The experimental results indicated that the growth and Chlorophyll-a syntheses of Scenedesmus obliquus were more sensitive in response to CAP exposure than that of Chlorella pyrenoidosa. While for CAT and SOD activities, Chlorella pyrenoidosa showed more susceptible. .../AQUATIC SPECIES/ The present study was aimed at evaluating the effects of different concentrations of the most commonly used fish antimicrobial drug, chloramphenicol (CAP), on the behavior and hematological parameters of Clarias gariepinus. Fish specimens were exposed to three (2.5, 5.0 and 10.0 mg/L) sublethal concentrations of CAP and a control. Abnormal behavioral changes were observed in fish exposed to higher concentration of CAP. Blood erythrocytes were sampled on days 1, 5, 10 and 15 postexposure to evaluate hematological parameters. Results showed concentration- and time-dependent significant increase in packed cell volume after day 5 of exposure (p<0.05). Hemoglobin values also significantly decreased from day 5, whereas values of mean cellular volume significantly decreased throughout the experimental period (p<0.05). A mixed trend was observed in the mean values of red blood cells, white blood cells, mean cellular hemoglobin and mean cellular hemoglobin concentration as well as neutrophils. Activities of lymphocytes were significantly increased in all CAP-treated fish during the exposure period, whereas no significant differences were observed in values of monocytes, eosinophils and basophils among the treatment groups and control. Consequently, precautions must be taken, especially when high concentrations of CAP are used in long-term treatments of C. gariepinus in aquaculture.For more Ecotoxicity Excerpts (Complete) data for Chloramphenicol (6 total), please visit the HSDB record page. |
| F | 3-10 |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | AB6825000 |
| 危険文句（R） | 45 |
| 危険表示 | T |
| 安全措置（S） | 53-45 |
用途
使用
DL-Chloramphenicol is an antibiotic drug.