Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
5-Bromo-2'-deoxyuridine
BDU · bromodeoxyuridine · 5-BRDU · 5-Bromo-2'-deoxyuridine · BUDR · 5-Bromo-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione · BRUDR · BR-DU
식별자 및 물리적 특성
| CAS No. | 59-14-3 |
|---|---|
| 분자식 | C9H11BrN2O5 |
| 평균 분자량 | 307.1 g/mol |
| 단동위원소 질량 | 305.98513355 g/mol |
| SMILES | O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1Br |
| InChIKey | WOVKYSAHUYNSMH-RRKCRQDMSA-N |
| PubChem CID | 6035 |
| ChEMBL | CHEMBL222280 |
| ChEBI | CHEBI:472552 |
| EC No. | 200-415-9 |
| DTXSID | DTXSID7033105 |
화학 및 물리적 성질
| XLogP | -0.3 |
|---|---|
| 극성 표면적 | 99.1 |
| 수소 결합 공여자 수 | 3 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 2 |
| 무거운 원자 수 | 17 |
| 형식 전하 | 0 |
| 복잡도 | 386 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15 |
| SpringerMaterials Properties | Crystal structure |
| LogP(분배 계수) | log Kow = -0.29 |
| Color/Form | Crystals from absolute ethanol |
| 용해도 | 10 to 50 mg/mL at 72 °F (NTP, 1992)Water 10 - 20 (mg/mL)Dimethylacetamide ~ 200 (mg/mL)1 N NaOH > 400 (mg/mL)Dimethylsulfoxide ~ 160 (mg/mL)Acetone ~ 4 (mg/mL)NH4OH: 0.1 M at 20 °C, 투명, 무색 |
| Decomposition | When heated to decomposition it emits very toxic fumes of /hydrogen bromide and nitrogen oxides/. |
| 녹는점 | 365 to 369 °F (NTP, 1992)187-189 °C191-194 °C (dec.)(lit.) |
| Optical Rotation | (c = 1, 0.1 N NaOH) [a]20 D = +31 ± 1° |
| Physical Description | 5-bromo-2'-deoxyuridine is a white crystalline powder. (NTP, 1992) |
| Stability/Shelf Life | Solid BrdU is stable in the dark to heat and humidity for 3 months at temperatures below 60 °C. On exposure to sunlight there is discoloration to grayish-brown. Ultraviolet irritations of frozen aqueous solutions of BrdU results in liberation of bromide ion and formation of a debrominated dimer, while radiolysis of aqueous solutions in the presence of oxygen yields mainly bromide, isodialuric acid deoxyriboside, and smaller amounts of various oxygenated derivatives.Bulk: The bulk drug should be stored in tightly closed containers at controlled room temperature. Solution: BUdR solutions (0.5 and 25 mg/mL) are stable for at least seven days at room temperature. |
| 밀도 | 1.8573 (rough estimate) |
| 굴절률 | 22 ° (C=1, H2O) |
| 저장 조건 | -20°C |
| pKa(산도 계수) | 7.73±0.10(Predicted) |
| 물리적 상태 | 결정 또는 결정성 분말 |
| 색상 | 흰색에서 노란색으로 |
| 생물학적 소스 | synthetic (organic) |
| 용해도 | 22&C에서 1~5g/100mL |
| Merck | 14,1452 |
| BRN | 30395 |
| 안정성 | 안정적이지만 빛에 민감할 수 있습니다. 강한 산화제와 호환되지 않습니다. |
| InChI | 1S/C9H11BrN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1 |
| InChIKey | XMJRLEURHMTTRX-UHFFFAOYSA-N |
| SMILES | OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(Br)C(=O)NC2=O |
| LogP(분배 계수) | -0.290 |
| EPA | Uridine, 5-bromo-2'-deoxy- (59-14-3) |
화학적 성질
White crystalline powder
안전 및 규제
| GHS 분류 | DangerH340 (83.3%): May cause genetic defects [Danger Germ cell mutagenicity]P203, P280, P318, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 54 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 화재 위험 | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
| 건강 유해성 | ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits very toxic fumes of bromide ion and NOx. (NTP, 1992) |
| 반응성 그룹 | Alcohols and Polyols |
| Reactivity Profile | 5-BROMO-2'-DEOXYURIDINE may be heat and light sensitive. (NTP, 1992). |
| Air and Water Reactions | Water soluble. |
| Hazard Classes and Categories | Muta. 1B (83.3%) |
| Hazardous Reactivities and Incompatibilities | Chemical reactivity: BrdU is hydrolyzed at the N-glycosyl bond, yielding bromouracil and 2-deoxyribose. The pH dependency of this reaction varies with the experimental conditions. The rate of hydrolysis increases sharply at alkaline pH. |
| 소화 | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| 응급 처치 | 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. |
| 소화 절차 | Fire, Explosion and Reactivity Hazard Data 1. BrdU does not require special fire-fighting procedures or equipment and does not present unusual fire and explosion hazards. 2. The presence of strong alkali, acid, and/or oxidant probably contributes to instability of BrdU. 3. No incompatibilities are known. 4. BrdU does not require non-spark equipment. |
| 보관 조건 | Store solid BrdU and its solutions in dark-colored, tightly closed containers, preferably under refrigeration. Avoid exposure to light and moisture. Store working quantities of BrdU and its solutions in an explosion-safe refrigerator in the work area. |
| 정리 방법 | Decontamination: Turn off equipment that could be affected by BrdU or the materials used for cleanup. ... Wipe off surfaces with water, then wash with copious quantities of water. Glassware should be rinsed in a hood with soap and water. Animal cages should be washed with water. |
| 비화재 누출 대응 | SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces 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. |
| 처리 방법 | 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.Disposal: No waste streams containing BrdU /should/ be disposed of in sinks or general refuse. Surplus BrdU or chemical waste streams contaminated with BrdU /should/ be handled as hazardous chemical waste ... . Nonchemical waste (e.g., animal carcasses and bedding) containing BrdU /should/ be handled and packaged for incineration ... . Potentially infectious waste (e.g., tissue cultures) containing BrdU /should/ be disinfected by heat using a standard autoclave treatment and packaged for incineration, as above. Burnable waste (e.g., absorbent bench top liners) minimally contaminated with BrdU /should/ be handled as potentially infectious waste and packaged for incineration, as above. Absorbent materials (e.g., associated with spill cleanup) grossly contaminated /should/ be handled in accordance with the chemical waste disposal system.The limited available research has not concluded how extensively BrDu is metabolized making it imperative that all potentially contaminated carcasses, bedding, and other nonsharps materials be disposed of as regulated medical waste through incineration. All contaminated sharps waste materials must be placed in proper sharps container and disposed of as regulated medical waste. |
| Preventive Measures | Principal investigators /should/ develop and implement standard operating procedures (SOPs) by which laboratory staff will prepare/administer BrDu with minimal potential for exposure. All tasks having potential for occupational BrDu exposure (mixing of doses, dose preparation, administering of injections, etc.) /should/ only be conducted by competent staff whom have received appropriate training (OSHA: "Worker Right to Know") regarding the specific BrDu-related health and safety risks, SOPs, and procedures to be followed in event of an exposure incident.Avoid formation and breathing of aerosols. Laboratory operations should be conducted in a fume hood, glove box, or ventilated cabinet.Avoid skin contact. If exposed, wash with soap and cold water. Avoid washing with solvents and exposure to UV light. Avoid rubbing of skin or increasing its temperature. For eye exposure, irrigate immediately with large amounts of water. ...In case of laboratory spill, wear protective clothing during cleanup. Avoid skin contact or breathing of aerosols. Use water to dissolve compound. Use absorbent paper to mop up spill. Wash down area with soap and water. |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)Staff involved with any tasks where potential for BrDu exposure exists must don the following PPE: (a) examination gloves, (b) safety glasses or safety goggles (ANSI Z-87 approved, (c) lab coat, (d) appropriate laboratory attire, (e) if aerosol exposure threat exists suitable respiratory protection must be provided. Whenever feasible, procedures with the potential for producing BrDu aerosols should be conducted with a certified biosafety cabinet. |
| Treatment | EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration. |
| 상호 작용 | 5-Bromo-2'-deoxyuridine (BrdUrd) was found to increase the cytotoxicity induced by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin in human glioma cells. At a fixed concentration of BrdUrd and BCNU, the greatest cell loss was observed in exponentially growing cells. As cells approached plateau growth, cytotoxicity was reduced as indicated by greater cell viability. Under varying growth conditions the percentage of thymine replacement by bromouracil in DNA, as determined by gas chromatography/mass spectrometry analysis, declined as cultures approached maximum density. These data indicate BrdUrd must be incorporated into DNA for the enhanced effect to be observed. In exponentially growing cells, sensitization was dependent upon both the concentration of BrdUrd and alkylating agent. Using regression analysis (at 95% CL), a relationship between the level of bromouracil in DNA and the extent of enhanced cytotoxicity was observed at two concentrations of BCNU (r2 = 0.99, 0.96). Although it is known that bifunctional alkylating agents exert cytotoxicity by forming cross-links between cDNA strands, increased cross-link formation was not observed in BrdUrd substituted DNA as determined by alkaline elution. The data suggest that DNA damage induced by halogenated pyrimidines may not involve interstrand cross-links and that these agents may be useful in the treatment of glioma in combination with alkylating agents. |
| 건강 영향 | 5-bromodeoxyuridine is a mutagen (causes mutations), a cytotoxin, a teratogen and a weak carcinogen. The primary harmful effects are genetic mutation, anemia, reproductive disorders (fetal death or abnormality), cataracts, and skin irritation. It can cause respiratory tract irritation if inhaled, skin irritation if it contacts the skin and eye irritation if it contacts the eyes. As a reproductive toxin BrDU would be considered a “particularly hazardous substance” under the OSHA lab standard. |
| 노출 경로 | Oral (L626)inhalation (L626)dermal (L626) |
| 독성 요약 | 5-bromodeoxyuridine acts on DNA. It induces a random DNA point mutation via base substitution. The base pair will change from an A-T to a G-C or from a G-C to an A-T after a number of replication cycles. As a thymine analog, 5-bromodeoxyuridine normally pairs with adenine. |
| Signs and Symptoms | 5-bromodeoxyuridine can cause hypermotility, diarrhea, weight loss and possibly death if large amounts are repeatedly ingested. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ /The authors/ report here the results of a Phase I study conducted to determine the toxicity and serum levels that could be tolerated by patients receiving i.v. bromodeoxyuridine concomitantly with radiation therapy. Because of severe thrombocytopenia and leukopenia that was produced in three patients treated by a 96 hour infusion of bromodeoxyuridine at a dose of 1.5 g/sq m/24 hours, the dose was reduced to 0.8 g/sq m/24 hours in these patients and the remaining 9 patients in the study group. Even at this dosage, myelotoxicity was observed./SIGNS AND SYMPTOMS/ Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/sq m/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients./ALTERNATIVE and IN VITRO TESTS/ /The authors/ identified genes that immediately respond to 5-bromodeoxyuridine (BrdU) in SUSM-1, an immortal fibroblastic line, with DNA microarray and Northern blot analysis. At least 29 genes were found to alter gene expression greater than twice more or less than controls within 36 h after addition of BrdU. They took several different expression patterns upon addition of BrdU, and the majority showed a significant alteration within 12 hr. When compared among SUSM-1, HeLa, and TIG-7 normal human fibroblasts, 19 genes behaved similarly upon addition of BrdU. In addition, 14 genes, 9 of which are novel as regards senescence, behaved similarly in senescent TIG-7 cells. The genes do not seem to have a role in proliferation or cell cycle progression. These results suggest that the early BrdU-responsive genes represent early signs of cellular senescence and can be its new biomarkers./GENOTOXICITY/ The existence of a high frequency of spontaneous sister-chromatid exchanges (SCEs) in Bloom syndrome (BS) has thus far been supported by data on a small number of BS cell lines. To examine the cause of baseline SCEs more broadly, the frequencies of SCEs, as well as chromosomal aberrations (CAs) in 4 additional BS fibroblast strains were compared, under different assay and cell culture conditions, with those of normal cells in the range of approximately 0.9-90% 5-bromodeoxyuridine (BrdUrd) substitution into template DNA. SCEs at low levels of BrdUrd substitution were detected by an extremely sensitive immunofluorescent technique. From approximately 0.9% to 4.5% BrdUrd substitution, the SCE frequency in BS cells remained constant, at a level (40/cell) 8 times higher than that of normal cells. As BrdUrd substitution increased further, the SCE frequency in BS cells increased almost linearly, reaching 70-100 per cell at approximately 90% substitution, while the SCE increment in control fibroblasts was less than 5 per cell. Analysis of SCEs in 3 successive replication cycles similarly revealed that the SCE increment in BS cells depended on BrdUrd only at a high BrdUrd substitution level. In contrast to data on SCEs, CA induction by incorporated BrdUrd in BS cells was only slightly higher than that in normal cells. Thus, BS cells are extremely sensitive to BrdUrd for SCE induction, but much less so for CA induction.For more Human Toxicity Excerpts (Complete) data for BROMODEOXYURIDINE (9 total), please visit the HSDB record page. |
| Carcinogen Classification | Not listed by IARC. May cause heritable genetic damage. |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ The acute toxicity of BrdU appears to be quite low in rodentsvarious authors list acute LD50a by various parenteral routes in mice and rats to be in the range of 1.5-4 g/kg, and by the oral route 8.4 g/kg./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ No clinical or hematological signs of acute toxicity were noticed in rats receiving up to 500 mg/kg/day for 28 days in their drinking water./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Subacute effects in rodents include inflammatory skin lesions, decreased weight and hair growth, and hematological effects (anemia, leukocytopenia, thrombocytopenia)./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ This study was designed to examine the pathogenesis of bromodeoxyuridine-induced (BrdU) clefts of the secondary palate in mice. Intraperitoneal injections of BrdU (500 mg/kg body weight) were given on days 11 and 12 to some pregnant mice and on days 12 and 13, and days 11, 12 and 13 to others. Evaluation of craniofacial relations and palate development in BrdU-treated mice revealed inhibition of vertical development of the palatal shelves, mandibular hypoplasia which led to failure of downward displacement of the tongue and the creation of an obstacle to reorientation of the palatal shelves. The results of this study demonstrate a strong correlation between induction of cleft palate and the presence of structural alterations in the mandible, and the mechanism of BrdU-induced cleft palate resembles the defect in the Pierre Robin anomaly.For more Non-Human Toxicity Excerpts (Complete) data for BROMODEOXYURIDINE (15 total), please visit the HSDB record page. |
| Antidote and Emergency Treatment | 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/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/ |
| Toxicity Data | Rat(po): LD50: 8400 mg/kgRat(ip): LD50: 1500 mg/kgRat(sc): LD50: 3900 mg/kgRat(iv): LD50: 2320 mg/kgMouse(po): LD50: 9100 mg/kgMouse(ip): LD50: 3050 mg/kg |
| Non-Human Toxicity Values | LD50 Mouse iv 2500 mg/kgLD50 Mouse sc 3500 mg/kgLD50 Mouse ip 3050 mg/kgLD50 Mouse oral 9100 mg/kgFor more Non-Human Toxicity Values (Complete) data for BROMODEOXYURIDINE (8 total), please visit the HSDB record page. |
| 수질 위해 등급(WGK) | 2 |
| TSCA 등재 상태 | TSCA listed |
| RTECS 번호 | YU7350000 |
| 관세 코드 | 29349990 |
| 위험 문구(R) | 68-36/37/38-63-46-24-61 |
| 위험 표시 | Xn,T |
| 안전 문구(S) | 36/37/39-26-53-45-36 |
| F 고인화성물질 | 10-23 |
| 위험 등급 | Muta. 1BRepr. 2 |
| 저장 분류 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| 유해 물질 데이터 | 59-14-3(Hazardous Substances Data) |
용도
용도
A Thymidine analogue used as a mutagen in genetic research. Selectively incorporated into cellular DNA during S-phase
일반 설명
White crystalline powder.