5-플루오로우라실

5-플루오로우라실 · 플루오로우라실 · 51-21-8 · 5-FU · FLUOROURACIL · 5-FLUOROPYRIMIDINE-2,4(1H,3H)-DIONE · FU · 5-Flurouracil

식별자 및 물리적 특성

CAS No.	51-21-8
분자식	C4H3FN2O2
평균 분자량	130.08 g/mol
단동위원소 질량	130.01785556 g/mol
SMILES	O=c1[nH]cc(F)c(=O)[nH]1
InChIKey	GHASVSINZRGABV-UHFFFAOYSA-N
PubChem CID	3385
ChEMBL	CHEMBL185
ChEBI	CHEBI:46345
EC No.	200-085-6
DTXSID	DTXSID2020634
현지명	5-플루오로우라실

화학 및 물리적 성질

XLogP	-0.9
극성 표면적	58.2
수소 결합 공여자 수	2
수소 결합 수용자 수	3
회전 가능 결합 수	0
무거운 원자 수	9
형식 전하	0
복잡도	199
물질 분류	Teratogens
의약품	PharmaceuticalsPharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agentsPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Metabolite of Capecitabine
SpringerMaterials Properties	19F nuclear magnetic resonance spectrum
LogP(분배 계수)	log Kow = -0.89
냄새	PRACTICALLY ODORLESS
Color/Form	White to practically white crystalline powderCrystals from water or methanol-ether
용해도	less than 1 mg/mL at 66 °F (NTP, 1992)1 G IN 80 ML WATER, 170 ML ALCOHOL & 55 ML METHANOLPRACTICALLY INSOL IN CHLOROFORM, ETHER & BENZENESOLUBILITY IN AQ SOLN INCR WITH INCR PH OF SOLNSoluble in methanol-water mixturesSparingly soluble in water and slightly soluble in alcohol. 1 g is soluble in 100 ml of propylene glycol.In water, 1.11X10+4 mg/L at 22 °CH2O: 10 mg/mL, 투명
Human Drugs	Breast FeedingLactationMilk, HumanAntimetabolitesAntineoplastic AgentsAntimetabolites, AntineoplasticImmunosuppressive AgentsFDA approved drugs -> Active ingredientCytotoxic medicines
끓는 점	Decomposes at 282-283 °Csublimes (0.1 mm): 190-200 °C361 °C @760 [mm Hg]190-200°C/0.1mmHg
Decomposition	When heated to decomposition it emits very toxic fumes of /hydrogen fluoride and nitrogen oxides/.
녹는점	Decomposes at 540-541 °F (EPA, 1998)282-283282 °C (decomposes)280 - 282 °C282-286 °C (dec.) (lit.)
증기압	0.00001 [mm Hg] @25 °C
밀도	1.4593 (estimate)
저장 조건	2-8°C
물리적 상태	가루
pKa(산도 계수)	pKa 8.0±0.1 (H2O) (Uncertain)3.0±0.1(H2O) (Uncertain)
색상	하얀색
pH	4.3-5.3 (10g/l, H2O, 20℃)
용해도	12.2g/L 20℃
Merck	14,4181
BRN	127172
헨리 상수	5.8×104 mol/(m3Pa) at 25℃, HSDB (2015)
안정성	안정적인. 빛에 민감합니다. 타기 쉬운. 강한 산화제, 강한 염기와 호환되지 않습니다.
주요 응용	진단 검사 제조혈액학조직학
InChI	1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
InChIKey	GHASVSINZRGABV-UHFFFAOYSA-N
SMILES	FC1=CNC(=O)NC1=O
NIST	2,4-Pyrimidinedione, 5-fluoro-(51-21-8)
EPA	5-Fluorouracil (51-21-8)

화학적 성질

White or almost white, crystalline powder

안전 및 규제

GHS 분류	This chemical does not meet GHS hazard criteria for 32.2% (55 of 171) of reports.DangerH301 (66.7%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 171 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
규제 정보	Hazard Traits - Developmental ToxicityStatus: Active Update: 29-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/108555-Fluorouracil: Does not have an individual approval but may be used under an appropriate group standardThe New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)
기타 안전 정보	IMAP assessments - 2,4(1H,3H)-Pyrimidinedione, 5-fluoro-: Human health tier I assessment
화재 위험	Emits very toxic fumes of flourides and nitrogen oxides when heated to decomposition. Avoid decomposing heat. (EPA, 1998)
건강 유해성	Minimum toxic dose in humans is approximately 450 mg/kg (total dose) over 30 days for the ingested drug. Intravenous minimum toxic dose in humans is a total dose of 6 mg/kg over three days. Depression of white blood cells occurred after intravenous administrative of a total dose of 480 mg/kg over 32 days. Occasional neuropathy and cardiac toxicity have been reported. Do not use during pregnancy. Patients with impaired hepatic or renal function, with a history of high-dose pelvic irradiation or previous use of alkylating agents should be treated with extreme caution. Patients with nutritional deficiencies and protein depletion have a reduced tolerance to fluorouracil. (EPA, 1998)
FDA 요건	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl fluorouracil, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
반응성 그룹	Amides and Imides
Reactivity Profile	FLUOROURACIL may be sensitive to prolonged exposure to light. Solutions discolor on storage. This chemical can react with oxidizing agents and strong bases. Incompatible with methotrexate sodium. (NTP, 1992)
Air and Water Reactions	Insoluble in water.
CERCLA 보고 수량	Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Fluoroacil is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.
Hazard Classes and Categories	Acute Tox. 3 (66.7%)Acute toxicity (Oral) - Category 3Teratogens
Shipment Methods and Regulations	/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/
Hazardous Reactivities and Incompatibilities	Oxidizers, strong bases, heat.
소화	(Non-Specific -- Drugs or Medicines, n.o.s. (Solid) Poison B) Avoid breathing dusts, and fumes from burning material. Keep upwind. Avoid bodily contact with the material. Wear boots, protective gloves, and goggles. Wear self-contained breathing apparatus.
응급 처치	Signs and Symptoms of Acute Fluorouracil Exposure: Nausea, vomiting, and diarrhea are the earliest symptoms of exposure to fluorouracil. Inflammation or sores in the mouth, gastric burning, and gastrointestinal bleeding may occur in more severe cases. Other symptoms include visual disturbances, lacrimation (tearing), chest pain and tachycardia (rapid heart rate).
소화 절차	Use dry chemical, carbon dioxide, or alcohol or polymer foam extinguishers. Poisonous gases, including nitrogen oxides, hydrogen fluoride, and carbon monoxide, are produced in fire. 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. If employees are expected to fight fires, they must be trained and equipped in OSHA 1910.156.
보관 조건	Store at 25 °C (77 °F)excursions permitted to 15 °C - 30 °C (59 °F -86 °F). /Efudex Solutions/
정리 방법	/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair)low-permeability, disposable protective garments (coveralls or gown and shoe covers)safety glasses or splash gogglesrespiratorabsorbent, plastic-backed sheets or spill padsdisposable towelingat least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label)a disposable scoop for collecting glass fragmentsand a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill padpowder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediatelya spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/
비화재 누출 대응	(Non-Specific -- Drugs) Keep unnecessary people awayisolate hazard area and deny entry. Stay upwindkeep out of low areas. If water pollution occurs, notify appropriate authorities. Spill or leak: shut off ignition sourcesno flares, smoking or flames in hazard area. Keep combustibles (wood, paper, oil etc.) away from spilled material. Do not touch spilled material.
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./PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/For more Disposal Methods (Complete) data for FLUOROURACIL (8 total), please visit the HSDB record page.
Preventive Measures	/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/For more Preventive Measures (Complete) data for FLUOROURACIL (19 total), please visit the HSDB record page.
Protective Action Criteria (PAC)	0.011 [mg/m3]2.1 [mg/m3]12 [mg/m3]
Personal Protective Equipment (PPE)	For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lotstherefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/
상호 작용	To incr the complete response rate of patients with locally advanced head and neck cancer after 3 cycles of neoadjuvant chemotherapy, sequential methotrexate was added to the combination of cis-platin and continuous infusion fluorouracil. The feasibility of administering 3 additional cycles of the same regimen as adjuvant chemotherapy was examined. Thirty eight patients were treatedthe median age was 53 yr and 36 patients had stage IV disease. Chemotherapy consisted of methotrexate 120 mg/sq m followed 24 hr later by cis-platin 100 mg/sq m and a 5 day continuous infusion of fluorouracil at 1000 mg/sq m/day. Of 34 patients evaluable for response to neoadjuvant chemotherapy, 9 had a complete response, 21 a partial response, 2 a minimal response, and 1 patient each stable disease and no response. Of 31 patients who received local therapy, 15 were treated with surgery and radiotherapy and 16 with radiotherapy alone. Of 25 patients eligible to receive adjuvant chemotherapy only 10 received all 3 intended cycles, while 15 received less or no adjuvant chemotherapy because of patient refusal, cumulative toxicity, or early disease progression. With a median follow up time of 39 mo, the median survival is estimated to be 20 mo. Of 8 patients with nasopharyngeal or paranasal sinus cancer, none had disease recurrence. Patients with good initial performance status and low N-stage also had a significant survival advantage. Chemotherapy-related toxicities consisted mainly of mucositis, requiring fluorouracil dose reduction in the majority of patientssimilar toxicities were exacerbated in the adjuvant setting. The addition of methotrexate did not incr the complete response rate over what has been reported for the combination of cis-platin and fluorouracil alone.Leukopenic and/or thrombocytopenic effects fluorouracil may be increased with concurrent or recent therapy with blood dyscrasia causing medications.Concurrent use /with leucovorin/ may increase the therapeutic and toxic effects of fluorouracil.Because normal defense mechanisms may be suppressed by fluorouracil therapy the patient's antibody responses to vaccine (killed virus) may be decreased.For more Interactions (Complete) data for FLUOROURACIL (12 total), please visit the HSDB record page.
Hepatotoxicity	Several forms of hepatotoxicity have been associated with fluorouracil therapy. Serum aminotransferase elevations occur in up to 70% of patients treated with cyclic courses of fluorouracil, the rate of abnormalities being partially dose related. The aminotransferase elevations are usually transient and mild, are not commonly above 5 times the upper limit of normal and rarely associated with symptoms. The elevations may be associated with hepatic steatosis, which can be demonstrated by hepatic imaging and has been confirmed by liver biopsies that show variable degrees of macrovesicular steatosis and portal inflammation. The injury rarely leads to clinically apparent liver injury. Isolated case reports of clinically apparent acute liver injury with jaundice attributed to fluorouracil have been published, but such cases are rare and the relatedness to fluorouracil remains unclear. Intrahepatic artery infusion of fluorouracil is also associated with serum aminotransferase elevations or chemical hepatitis (in 5% to 7% of cases) and in biliary abnormalities, but it rarely causes biliary strictures or the sclerosing cholangitis-like syndrome that is common with floxuridine (FUDR) treatment. In systematic reviews of the literature, biliary strictures suggestive of sclerosing cholangitis have occurred in
생태독성 수치	EC50Species: Xenopus laevis (African clawed frog)Conditions: fresh waterstatic, temperature 24 °CConcentration: 80000 ug/L (95% confidence limit: 60000 to 100000 ug/L) for 5 days Effect: growthabnormal /formulated product//conditions of the bioassay not specified/Concentration: 0.18 ug/L for 4 days Effect: growthLC50Concentration: 1.58 ug/L for 4 days /formulated product/Concentration: 0.31 ug/L for 4 days /formulated product/For more Ecotoxicity Values (Complete) data for FLUOROURACIL (10 total), please visit the HSDB record page.
환경 거동	TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -0.89(2) and a regression-derived equation(3), indicates that fluorouracil is expected to have very high mobility in soil(SRC). Volatilization of fluorouracil from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.7X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(4)). Fluorouracil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-6 mm Hg(SRC), determined from a fragment constant method(5). 100% biodegradation in 5 days using an activated sludge inoculum and the OECD Confirmatory Test(6) suggests that biodegradation is an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a log Kow of -0.89(2) and a regression-derived equation(3), indicates that fluorouracil 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 1.7X10-10 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 an estimated log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 100% biodegradation in 5 days using an activated sludge inoculum and the OECD Confirmatory Test(7) suggests that biodegradation is an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fluorouracil, which has an estimated vapor pressure of 2.7X10-7 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 fluorouracil 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 3 days(SRC), calculated from its rate constant of 5.8X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase fluorouracil may be removed from the air by wet or dry deposition(SRC). Fluorouracil absorbs light at wavelengths 256-266 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight.
유해 작용	Fluorouracil has many adverse drug reactions when used systemically. Diarrhea was the most common adverse effect reported in patients receiving systemic fluorouracil treatment. Clinicians should withhold fluorouracil for severe diarrhea until it is resolved. Other common adverse effects include vomiting, nausea, and dehydration.
노출 경로	28-100%
독성 요약	As described above, cardiotoxicity and neurotoxicity can be severe, requiring immediate cessation of fluorouracil treatment. Patients experiencing severe adverse effects of fluorouracil treatment can be administered uridine triacetate within 4 days of fluorouracil treatment. Uridine triacetate is a pyrimidine analog composed of uridine triacetate. The mechanism of toxicity reversal is due to the high concentrations of uridine delivered by uridine triacetate that competes with fluorouracil metabolites for binding sites in the body. Uridine triacetate is administered orally, but whether it is safe or efficacious after 4 days following fluorouracil administration is unknown.The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5дус10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.
Effluent Concentrations	Fluorouracil is anticipated to be one of the compounds present in hospital effluent(1). Fluorouracil was assigned a mean theoretical sewage concentration of 2.03 ug/L in the wastewater of a large university hospital based on its use pattern(2). Neither study reported the drug as being detected(SRC).
Medical Surveillance	/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/
Soil Adsorption/Mobility	The Koc of fluorouracil is estimated as 8(SRC), using a log Kow of -0.89(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that fluorouracil is expected to have very high mobility in soil.
Human Toxicity Excerpts	/SIGNS AND SYMPTOMS/ Systemic administration of fluorouracil has also had adverse effects on the lids, lacrimal system and eyes, producing excessive tearing and discomfort from obstruction of the lacrimal system, from ectropion of the lower lids, or from blepharoconjunctivitis. Fortunately, there has been a strong tendency to recover from these side effects when fluorouracil has been discontinued./SIGNS AND SYMPTOMS/ Fluorouracil can cause both acute and delayed neurotoxicity. Acute neurotoxicity manifests as encephalopathy or as cerebellar syndromeseizures have rarely been reported. Acute neurotoxicity due to fluorouracil is dose related and generally self-limiting. Various mechanisms for such toxicity have been postulated, and treatment with thiamine has been recommended. Delayed neurotoxicity has been reported when fluorouracil was given in combination with levamisolethis form of subacute multifocal leukoencephalopathy is immune mediated and responds to treatment with corticosteroids. Clinicians should be aware of the adverse neurologic effects of fluorouracil and should include them in the differential diagnosis when patients receiving the drug present with neurologic problems./SIGNS AND SYMPTOMS/ Fluorouracil inhibits fibroblast proliferation and formation of scar tissue following trabeculectomy surgery for the treatment of glaucoma./CASE REPORTS/ A 73-year-old white man with a history of esophageal carcinoma was treated with fluorouracil 1,500 mg iv daily for four days. After completing treatment, he presented with sudden onset of confusion, cognitive disturbances, a cerebellar syndrome, and repeated seizures. A magnetic resonance image of the brain showed no structural abnormalities, and cerebrospinal fluid examination was normalnone of the other laboratory tests provided an explanation for his symptoms. The patient was treated with anticonvulsants, and the cognitive changes resolved in 72 hours. The cerebellar signs, however, did not resolve completely and persisted when the patient was examined two weeks after discharge. Fluorouracil can cause both acute and delayed neurotoxicity. Acute neurotoxicity manifests as encephalopathy or as cerebellar syndromeseizures, as seen in our patient, have rarely been reported. Acute neurotoxicity due to fluorouracil is dose related and generally self-limiting. Various mechanisms for such toxicity have been postulated, and treatment with thiamine has been recommended. Delayed neurotoxicity has been reported when fluorouracil was given in combination with levamisoleFor more Human Toxicity Excerpts (Complete) data for FLUOROURACIL (16 total), please visit the HSDB record page.
Artificial Pollution Sources	Fluorouracil's production and use as an antineoplastic(1) may result in its release to the environment through various waste streams(SRC).
수질 위해 등급(WGK)	3
TSCA 등재 상태	TSCA listed
RTECS 번호	YR0350000
운송 번호(UN)	UN 2811 6.1/PG 3
독성	LD50 orally in Rabbit: 230 mg/kg
관세 코드	29335995
위험 문구(R)	22-20/21/22-52-25
위험 표시	Xn,T,C,Xi
안전 문구(S)	36-36/37-36/37/39-22-45-26
포장분류	III
위험 등급	6.1Acute Tox. 3 OralCarc. 2
기존화학 물질	KE-17055
F 고인화성물질	10-23
위험 참고 사항	Irritant/Highly Toxic
저장 분류	6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
유해 물질 데이터	51-21-8(Hazardous Substances Data)

용도

개요

5-Fluorouracil (5-FU) is a prodrug form of the thymidylate synthase inhibitor fluorodeoxyuridylate (FdUMP). It is also converted to the active metabolites FUTP and FdUTP, which induce RNA and DNA damage, respectively. In vivo, 5-FU (15 mg/kg) when administered in combination with docetaxel reduces tumor growth in B88 and CAL 27 oral squamous cell carcinoma (OSCC) mouse xenograft models. Formulations containing 5-FU have been used in the treatment of colorectal, breast, gastric, and pancreatic cancers.

용도

5-Fluorouracil is used as an antitumor agent in the treatment of anal, breast, colorectal, oesophageal, stomach, pancreatic and skin cancers. It finds application as a suicide inhibitor due to its irreversible inhibition of thymidylate synthase. It is also used in the treatment of actinic keratoses and bowen's disease. Further, it serves as a potent antineoplastic agent in clinical use. In addition to this, it acts as a DNA synthesis inhibitor.

일반 설명

White to nearly white crystalline powder; practically odorless. Used as an anti neoplastic drug, chemosterilant for insects.