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로무스팅

Lomustine

HCID 3950
노트반응
기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
부분 구조 검색유사 구조 찾기

기본 정보

CAS
13010-47-4
표준 SMILES
O=NN(CCCl)C(=O)NC1CCCCC1
InChIKey
GQYIWUVLTXOXAJ-UHFFFAOYSA-N
분자식
C9H16ClN3O2
평균 분자량
233.69 g/mol
단동위원소 질량
233.0931045

개요

1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (Lomustine) can cause cancer according to an independent committee of scientific and health experts. It can cause developmental toxicity according to state or federal government labeling requirements.

이름 및 식별자

우선 이름
Lomustine
IUPAC
1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
현지명
로무스팅
영어명
Lomustine
분자식
C9H16ClN3O2
분자량
233.7

이름 및 동의어

lomustine13010-47-41-(2-Chloroethyl)-3-cyclohexyl-1-nitrosoureaBelustineCeeNUCCNUCecenuCINUChloroethylcyclohexylnitrosoureaLomustinaN-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosoureaUrea, N-(2-chloroethyl)-N'-cyclohexyl-N-nitroso-
이름 더 보기
로무스틴로무스팅로무스팅(LOMUSTINE)Lomustinrb1509sri2200nsc79037icig1109
LomustinumNSC-79037GleostineCyclohexyl chloroethyl nitrosourea1-(2-Chloroethyl)-3-cyclohexylnitrosoureaNSC 79037ICIG 1109NCI-C04740

데이터베이스 식별자

CAS
13010-47-4
PubChem CID
3950
DTXSID
DTXSID2023222
ChEMBL
CHEMBL2062293、CHEMBL514
ChEBI
CHEBI:6520
UNII
7BRF0Z81KG
EC Number
235-859-2
Nikkaji
J3.122D

물성

구조 계산 물성

XLogP
2.8
극성 표면적
61.8 Ų
수소 결합 공여자 수
1
수소 결합 수용자 수
3
회전 가능 결합 수
3
무거운 원자 수
15
형식 전하
0
복잡도
219

실험 및 물리화학적 성질

DrugsPharmaceuticals -> Listed in ZINC15
SpringerMaterials Properties15N nuclear magnetic resonance spectrum
LogP · 3건

log Kow = 2.83

3

2.8

Color/Form · 2건

Solid

Yellow powder

Solubility · 4건

Soluble in ethanol

Freely soluble in chloroform; soluble in acetone.

Solubility in water, 0.1N NaOH, 0.1N HCl, or 10% ethanol: <0.05 mg/mL; in absolute ethanol: 70 mg/mL

7.55e-01 g/L

Human Drugs · 2건

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

DecompositionHazardous decomposition products formed under fire conditions: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas.
Melting Point · 3건

88-90 °C

90 °C

88 - 90 °C

Physical DescriptionSolid

물리화학적 성질

녹는점
88 · 88-90
끓는 점
63.6 °C · 63.6°C (rough estimate)
밀도
1.384 · 1.3840 (rough estimate)
굴절률
1.579 · 1.5790 (estimate)
저장 조건
2 · 2-8°C
용해도
물에는 거의 녹지 않으며, 아세톤과 염화메틸렌에는 잘 녹고, 에탄올(96%)에는 녹습니다.
산도 계수 (pKa)
10.88 · 10.88±0.20(Predicted)
물리적 상태
Solid
색상
Light orange to Yellow to Green
Merck
14 · 14,5564
Henry's Law Constant
5.5 · 5.5×104 mol/(m3Pa) at 25℃, HSDB (2015)
InChI
InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)
InChIKey
GQYIWUVLTXOXAJ-UHFFFAOYSA-N
SMILES
N(CCCl)(N=O)C(NC1CCCCC1)=O
EPA
1 · 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4)

화학적 성질

Lomustine is a pale yellow powder.

안전 및 규제

안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.

GHS 분류

GHS Classification · 6건

Danger

H228 (34.4%): Flammable solid [Danger Flammable solids]

P203, P210, P234, P235, P240, P241, P260, P264, P270, P280, P301+P316, P308+P316, P318, P319, P321, P330, P370+P378, P403, P405, P410, P411, P420, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 64 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

유해성 정보

Regulatory InformationHazard Traits - Carcinogenicity; Developmental Toxicity
Other Safety InformationIMAP assessments - Urea, N-(2-chloroethyl)-N'-cyclohexyl-N-nitroso-: Environment tier I assessment
FDA Requirements · 1건

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl lomustine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Special Reports · 1건

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. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4) is listed as reasonably anticipated to be a human carcinogen. First listed in the Fourth Annual Report on Carcinogens (1985) as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s035ccnu.pdf]

Toxic Combustion ProductsHazardous decomposition products formed under fire conditions: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas.
Hazard Classes and Categories · 2건

Flam. Sol. 1 (34.4%)

Acute toxicity (Oral) - Category 3

Shipment Methods and Regulations · 3건

/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/

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/

Shipping Name/ Number DOT/UN/NA/IMOUN2811, Toxic solid, organic, NOS (Lomustine)[Sigma-Aldrich; Safety Data Sheet for Lomustine (Product Number: L5918) Version 3.1 (June 19, 2009). Available from, as of November 20, 2009: http://www.sigmaaldrich.com]
Skin, Eye, and Respiratory Irritations... May cause respiratory tract irritation. ... May cause skin irritation. May cause eye irritation.
Hazardous Reactivities and IncompatibilitiesMaterials to avoid: Strong oxidizing agents, strong bases.

안전 및 보호

Fire Fighting Procedures · 2건

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

Storage Conditions · 4건

Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C. Light sensitive.

Commercially available lomustine capsules should be stored in well-closed containers at a temperature less than 40 °C.

The bulk drug should be stored in a deep freeze and protected from moisture.

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 · 5건

Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Evacuate personnel to safe areas.

Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.

/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 goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and 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 pad; powder 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 immediately; a 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/

For more Cleanup Methods (Complete) data for LOMUSTINE (6 total), please visit the HSDB record page.

Disposal Methods · 5건

SRP: 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.

Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state, and local environmental regulations. Contact a licensed professional waste disposal service to dispose of this material.

/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/

For more Disposal Methods (Complete) data for LOMUSTINE (14 total), please visit the HSDB record page.

Preventive Measures · 5건

In case of skin contact: Wash off with soap and plenty of water. Consult a physician.

In case of eye contact: Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.

Hygiene measures: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

/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/

For more Preventive Measures (Complete) data for LOMUSTINE (32 total), please visit the HSDB record page.

Personal Protective Equipment (PPE) · 5건

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Hand protection: The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Handle with gloves.

Eye protection: Face shield and safety glasses.

Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.

For more Personal Protective Equipment (PPE) (Complete) data for LOMUSTINE (10 total), please visit the HSDB record page.

독성 정보

Interactions · 2건

The combined action of the antitumor antibiotic bleomycin and chloroethylnitrosourea was studied in human lymphocytes in vitro. All the experiments were carried out with 20 ug/mL bleomycin for a given treatment time. By adding 0.7 and 3.5 ug/mL chloroethylnitrosourea at late G1-S phase we have demonstrated a considerable increase in both percent of aberrant cells and production of dicentrics and rings (5-fold, p < 0.001). At late S-G2 the combined treatment led to a significant enhancement of breaks per cell (p < 0.0001) and cells with more than 12 aberrations. A possible explanation could be the known repair inhibitory potential of chloroethylnitrosourea, but its pure clastogenic action still has to be considered. The results presented here point out the need for seeking chemotherapeutic regimens with reduced concentrations of the drugs in combination.

Three patients developed the sudden onset of total blindness several months after treatment with oral CCNU and low dose whole brain radiation. The anterior visual system was included in the radiation field in all patients. Radiotherapy was given for a frontal lobe glioblastoma multiforme, for central nervous system prophylaxis in a patient with oat cell carcinoma of the lung, and for a parietal lobe glioblastoma multiforme. None of the neoplasms involved the anterior visual system. The radiation dose ranged from 3000 to 4650 rad and the oral CCNU dosage from 300 mg to 1050 mg. Patients 1 and 2 also received other chemotherapeutic agents. Patient 3 who was treated only with oral CCNU and cranial irradiation died. At autopsy the brain showed a widely infiltrating residual high grade glioma as well as patchy coagulative necrosis with swollen axons and dystrophic calcifications. The optic chiasm showed severe demyelination, axonal loss, and hyalinized vessels. Synergism between oral CCNU and radiation may account for the blindness produced.

Hepatotoxicity · 1건

Mild and transient elevations in serum aminotransferase or alkaline phosphatase levels are found in a high proportion of patients treated antineoplastic regimens that include lomustine. The abnormalities are generally transient, do not cause symptoms and do not require dose modification. Clinically apparent liver injury from lomustine has been described, but is uncommon. The pattern of serum enzyme elevations were described as cholestatic and onset was after 3 to 4 months of therapy, but otherwise its clinical characteristics have not been clearly characterized. Lomustine is often given in combination with other antineoplastic agents, many of which are also hepatotoxic, so the effect of lomustine in causing liver injury is often difficult to assess. Lomustine has not been associated specifically with sinusoidal obstruction syndrome, but it is not generally given in high doses or used for myeloablation in preparation for bone marrow transplantation, the situations in which this syndrome generally occurs.

Environmental Fate · 3건

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a structure estimation method(2), indicates that lomustine is expected to have moderate mobility in soil(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization of lomustine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.8X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Lomustine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-5 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a structure estimation method(2), indicates that lomustine is expected to adsorb to suspended solids and sediment(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.8X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 34(SRC), from its log Kow of 2.83(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Lomustine is an alkylating agent that may hydrolyze under environmental conditions(4). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), lomustine, which has an estimated vapor pressure of 2.6X10-5 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 lomustine 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 18 hours(SRC), calculated from its rate constant of 2.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase lomustine may be removed from the air by wet or dry deposition(SRC). Lomustine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Exposure RoutesWell and rapidly absorbed from the gastrointestinal tract.
Milk ConcentrationsLomustine metabolites are present in milk, but in concentrations than those in maternal plasma.
Toxicity Summary · 1건

Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.

Ongoing Test Status · 1건

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=13010-47-4]

Medical Surveillance · 2건

/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/

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 · 1건

Using a structure estimation method based on molecular connectivity indices(1), the Koc of lomustine can be estimated to be 200(SRC). According to a classification scheme(2), this estimated Koc value suggests that lomustine is expected to have moderate mobility in soil. However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC).

Human Toxicity Excerpts · 5건

/SIGNS AND SYMPTOMS/ The occurrence of acute leukemia and bone marrow dysplasias have been reported in patients following long-term nitrosourea therapy.

/SIGNS AND SYMPTOMS/ Pulmonary toxicity, sometimes fatal, has occurred rarely in patients receiving lomustine. Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has occurred at 6 months or longer following initiation of lomustine therapy in patients typically receiving cumulative doses exceeding 1100 mg/sq m; however, pulmonary fibrosis has occurred with lower total doses.

/SIGNS AND SYMPTOMS/ Delayed onset of pulmonary fibrosis occurring up to 17 years after treatment has been reported in patients receiving related nitrosoureas combined with cranial radiation therapy for intracranial tumors during childhood and adolescence (age 1-16 years). Late onset of reduction in pulmonary function was observed in all long-term survivors. Nitrosourea-induced pulmonary fibrosis may be slowly progressive and can cause death.

/SIGNS AND SYMPTOMS/ Pulmonary toxicity, sometimes fatal, has occurred rarely in patients receiving lomustine. Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has occurred at 6 months or longer following initiation of lomustine therapy in patients typically receiving cumulative doses exceeding 1100 mg/sq m; however, pulmonary fibrosis has occurred with lower total doses.

For more Human Toxicity Excerpts (Complete) data for LOMUSTINE (11 total), please visit the HSDB record page.

Artificial Pollution SourcesLomustine's production and use as an antineoplastic(1) may result in its release to the environment through various waste streams(SRC).
Carcinogen Classification · 6건

1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (Lomustine)

Group 2A: Probably carcinogenic to humans

Volume 26: (1981) Some Antineoplastic and Immunosuppressive Agents

1987

1987

NB Overall evaluation upgraded to Group 2A with supporting evidence from other relevant data

규제 정보

FDA Requirements · 1건

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl lomustine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

안전 데이터

wgk
3
rtecs
YS4900000
ridadr
3249
독성
LD50 in male mice (mg/kg): 51 orally; 56 i.p.; 61 s.c. (Thompson, Larson)
HS 번호
29299090
risk_code
45-25
hazard_code
T
safety_code
53-45
포장분류
II
위험 등급
6.1(a)
Hazard Classifications
Acute Tox. 3 OralCarc. 1B
스토리지 클래스
6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
유해 물질 데이터
13010-47-4(Hazardous Substances Data)
중점관리물질 필터링
별표2-258

화학 및 산업

약리 정보

ATC Code · 2건

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Protein Binding50%
Pharmacodynamics · 1건

Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle&ndash;phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing.

Mechanism of Action · 2건

Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.

Although lomustine is believed to act by alkylation, the mechanism of action has not been completely elucidated, and other effects as carbamoylation and modification of cellular proteins may be involved. The overall result is thought to be the inhibition of both DNA and RNA synthesis.

Biological Half-Life · 2건

Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.

The half-life of lomustine metabolites is biphasic; although the initial plasma half-life is 6 hours, the second phase plasma half-life is 1-2 days, and 15-20% of the metabolites remain in the body 5 days after administration of lomustine.

Metabolism/Metabolites · 4건

Hepatic. Rapid and complete, with active metabolites.

CCNU undergoes spontaneous decomposition under physiological conditions to release both alkylating and carbamoylating entities. It disappears from plasma within 5 minutes following its oral administration, but the antitumor effect of its metabolites may persist for up to 15 minutes. ... In addition to chemical decomposition, CCNU may be converted by microsomal metabolism to 6 isomeric hydroxylated derivatives, some of which may differ in their biological properties from CCNU.

Virtually all of a dose of lomustine is metabolized within 1 hour after oral administration. The half-life of lomustine metabolites is biphasic; although the initial plasma half-life is 6 hours, the second phase plasma half-life is 1-2 days, and 15-20% of the metabolites remain in the body 5 days after administration of lomustine. Prolongation of plasma concentrations is thought to reflect a combination of protein binding and enterohepatic circulation of metabolites.

Hepatic. Rapid and complete, with active metabolites. Route of Elimination: Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours. Half Life: Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.

FDA Pharmacological Classification · 6건

7BRF0Z81KG

LOMUSTINE

Mechanisms of Action [MoA] - Alkylating Activity

Established Pharmacologic Class [EPC] - Alkylating Drug

Lomustine is an Alkylating Drug. The mechanism of action of lomustine is as an Alkylating Activity.

LOMUSTINE

MeSH Pharmacological Classification · 1건

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)

Absorption, Distribution and Excretion · 6건

Well and rapidly absorbed from the gastrointestinal tract.

Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours.

Lomustine is excreted primarily in the urine as metabolites. Following oral administration of (14)C-labeled lomustine, about 50% of the radioactivity is excreted within 12 hr and about 75% within 4 days.

Lomustine is reported to be widely distributed. Lomustine and/or its metabolites cross the blood-brain barrier and are rapidly transported into cells due to their high lipid solubility. Although intact lomustine is not detectable in the CSF, active metabolites of the drug appear in substantial concentrations within 30 minutes after oral administration of lomustine. CSF concentrations of metabolites have been reported to be 15-50% or greater than concurrent plasma concentrations. Lomustine metabolites are present in milk, but in concentrations than those in maternal plasma.

Lomustine is rapidly absorbed from the GI tract; the drug is also absorbed following topical application. Peak plasma concentrations of metabolites occur within 1-6 hours following administration of an oral dose of lomustine.

Following its ip or iv injection or oral administration, (14)C-labelled CCNU was rapidly distributed to many tissues in mice, rats, rabbits and dogs.. About 80% of label was excreted in the urine of mice 24 hours after a single parenteral or oral dose of 50 mg/kg bw.

Cellular LocationsCytoplasm

용도 및 제조

Uses · 5건

Nitrosourea used in the treatment of certain neoplastic diseases

Medicine: Antineoplastic

Medication to treat brain tumors, Hodgkin's disease, and other kinds of cancer

MEDICATION

For the treatment of primary and metastatic brain tumors as a component of combination chemotherapy in addition to appropriate surgical and/or radiotherapeutic procedures. Also used in combination with other agents as secondary therapy for the treatment of refractory or relapsed Hodgkin's disease.

Methods of Manufacturing/Lomustine/ may be prepared by nitrosation of its substituted urea moiety, /1-(2-chloroethyl)-3-cyclohexylurea in a cold acid medium (e.g., formic acid)/.
Formulations/Preparations · 4건

Belustine

Cecenu

Ceenu

Table: Lemustine Preparations [Table#6034]

General Manufacturing Information · 2건

Made in Italy

An alkylating agent of value against both hematologic malignancies and solid tumors.

응용 분야 · 2건

용도CCNU is an oral anticancer drug that was approved by the U.S. Food and Drug Administration in 1976 for marketing, as lomustine (FDA 2009a). CCNU is used alone or in combination with other antineoplastic agents, including procarbazine and vincristine, etoposide and prednimustine, and other combinations (IARC 1981, HSDB 2009). It is used primarily in the treatment of Hodgkin’s disease and brain tumors, but it has also been used to treat other cancer, includ-ing lung cancer, non-Hodgkin’s lymphoma, malignant melanoma, breast cancer, kidney cancer, and cancer of the gastrointestinal tract (MedlinePlus 2009). It has also been applied to the skin to treat mycosis fungoides and psoriasis.

일반 설명Lomustine is available in 10-, 40-, and 100-mg capsules fororal administration in the treatment of primary and metastaticbrain cancers and Hodgkin’s lymphoma. This lipophilicagent is well absorbed, widely distributed, and crosses theblood-brain barrier. Lomustine undergoes extensive hepaticmetabolism, which is mediated by CYP3A4 to give severalhydroxylated metabolites, which arise as a result of oxidationof the cyclohexyl ring. Several of these are more activethan the parent compound. Denitrosation and dechlorinationhave also been demonstrated to occur for lomustine as well.The intact drug was not found in plasma when the agent wasadministered orally. Elimination occurs primarily in theurine with an elimination half-life of 16 to 72 hours.Myelosuppression is dose limiting and presents in a mannersimilar to that seen with carmustine. Other toxicities includenausea, vomiting, anorexia, impotence, sterility, amenorrhea,and infertility. Pulmonary and renal toxicity are rarelyseen during standard-dose therapy but increase during highdosetherapy.

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추가 설명 · 1건

정의ChEBI: An N-nitrosourea that is urea in which one of the nitrogens is substituted by a 2-chloroethyl group and by a nitroso group, while the other nitrogen is substituted by a cyclohexyl group. An alkylating antineoplastic agent, it is used in he treatment of brain tumours, lung cancer, malignant melanoma and other solid tumours.

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