Nitrogen mustard hydrochloride

HCID 5935CAS 55-86-7

Grundinformationen

Standard-SMILES
CN(CCCl)CCCl.Cl
InChIKey
QZIQJVCYUQZDIR-UHFFFAOYSA-N
Summenformel
C5H11Cl2N.ClH
Durchschnittliche Molmasse
192,5 g/mol
Monoisotopische Masse
191,00353242

Überblick

Nitrogen Mustard Hydrochloride (Mechlorethamine Hydrochloride) 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.

Namen und Bezeichner

Bevorzugter Name
Nitrogen mustard hydrochloride
IUPAC
2-chloro-N-(2-chloroethyl)-N-methylethanamine;hydrochloride

Namen und Synonyme

55-86-7Mechlorethamine hydrochlorideChlormethine hydrochloride2-CHLORO-N-(2-CHLOROETHYL)-N-METHYLETHANAMINE HYDROCHLORIDEMechlorethamine HClNitrogen mustard hydrochlorideChlorethamineChlormethinumStickstofflostChloraminMustine hydrochlorideHN2 hydrochloride
Weitere Namen anzeigen
AzotoyperiteDichlorenDimitanEmbikhineMitoxineErasolNitolBis(2-chloroethyl)methylamine hydrochloride

Datenbank-Bezeichner

CAS
55-86-7
PubChem CID
5935
DTXSID
DTXSID8025757
ChEMBL
CHEMBL1201001
ChEBI
CHEBI:55368
UNII
L0MR697HHI
EC Number
200-246-0

Eigenschaften

Berechnete Struktureigenschaften

Polarare Oberfläche (TPSA)
3,2 Ų
H-Brücken-Donoren
1
H-Brücken-Akzeptoren
1
Frei drehbare Bindungen
4
Schwere Atome
9

Experimentelle und physikochemische Eigenschaften

Chemical ClassesCarcinogens
pHInitial pH of 2% aqueous solution: 3.0-4.0
LogPlog Kow = -1.24 /Estimated/
Density1.118 @25 °C
Color/Form · 3 Einträge

Hygroscopic leaflets from acetone or chloroform

White hygroscopic crystals

White, crystalline, hygroscopic powder

Solubility · 3 Einträge

greater than or equal to 100 mg/mL at 66 °F (NTP, 1992)

Soluble in ethanol

Soluble in water at 1 g/100 ml

Sicherheit und Regulatorisches

GHS-Klassifizierung

GHS Classification · 4 Einträge

Danger

H300+H310 (97.5%): Fatal if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]

P203, P260, P262, P264, P270, P280, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P318, P321, P330, P361+P364, P363, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Regulatory Information · 2 Einträge

Hazard Traits - Carcinogenicity; Developmental Toxicity

The 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.)

DOT LabelPoison
Fire HazardsFlash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
Health Hazards · 1 Eintrag

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the mucous membranes, vesication, burning sensation, destruction of tissues of the skin, eyes, mucous membranes and upper respiratory tract, shortness of breath and headache. Other symptoms may include nausea, vomiting and anorexia. It can cause irritation, severe damage and burns of the eyes, and necrotizing uveitis. Exposure can lead to depression of the formed elements in the blood, weakness, diarrhea, and rarely, jaundice, alopecia, vertigo, tinnitus, diminished hearing, hemolytic anemia, various chromosomal abnormalities, agranulocytosis, thrombocytopenia (which may lead to bleeding from the gums and gastrointestinal tract, petechiae and small subcutaneous hemorrhages), immunosuppression, erythema multiforme, delayed catamenia, severe and even uncontrollable depression of the hematopoietic system, persistent pancytopenia, oligomenorrhea, temporary or permanent amenorrhea, and in males, impaired spermatogenesis, azoospermia and total germinal aplasia. Other symptoms may include leukopenia, granulocytopenia, hypoplasia of all elements of bone marrow, lymphopenia and precipitation of uric acid in kidney tubules. It can cause myelosuppression and gastrointestinal symptoms. It can also cause hemorrhagic complications, maculopapular skin eruptions, herpes zoster, and on injection, thrombophlebitis. It can also cause thrombosis on injection. Exposure can also lead to latent viral infection and menstrual irregularities in women. Necrosis has occurred following extravascular injections.

FDA Requirements · 1 Eintrag

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

Reactive GroupAmines, Phosphines, and Pyridines

Sicherheit und Schutzausrüstung

Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)
First Aid · 1 Eintrag

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.

Cleanup Methods · 2 Einträge

/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/

/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/

Nonfire Spill Response · 1 Eintrag

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Disposal Methods · 5 Einträge

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

/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 MECHLORETHAMINE HYDROCHLORIDE (8 total), please visit the HSDB record page.

Preventive Measures · 5 Einträge

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Contact with skin: Wash immediately with large amounts of water. Can be neutralized with sodium thiosulphate or sodium bicarbonate.

/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/

For more Preventive Measures (Complete) data for MECHLORETHAMINE HYDROCHLORIDE (21 total), please visit the HSDB record page.

Toxikologische Informationen

Interactions · 5 Einträge

Morphine and pethidine hydrochloride significantly potentiated mechlorethamine hydrochloride toxicity. The potentiation seems dose related. Morphine converted sublethal doses of mechlorethamine to maximal LD's.

In HT29 human colon carcinoma cells, amphotericin b (approx 120 ug/ml) increased uptake of mechlorethamine hydrochloride due to increases in vmax without change in km.

Mechlorethamine may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse mechlorethamine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents.

Leukopenic and/or thrombocytopenic effects of mechlorethamine may be increased with concurrent or recent therapy /with blood dyscrasia-causing medications/ if these medications cause the same effects; dosage adjustment of mechlorethamine, if necessary, should be based on blood counts.

For more Interactions (Complete) data for MECHLORETHAMINE HYDROCHLORIDE (8 total), please visit the HSDB record page.

Exposure RoutesPartially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable.
Toxicity Summary · 1 Eintrag

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations. Mechlorethamine is cell cycle phase-nonspecific.

Medical Surveillance · 1 Eintrag

/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/

Human Toxicity Excerpts · 3 Einträge

/SIGNS AND SYMPTOMS/ Adverse CNS effects which have occurred following IV administration of mechlorethamine include weakness, headache, drowsiness, vertigo, lightheadedness, convulsions, progressive muscle paralysis, paresthesia, cerebral degeneration, coma, and death. Serious neurotoxicity appears to be a problem only when high doses or intra-arterial and regional perfusion administration techniques are used. Immediate and delayed neurotoxicity, sometimes severe, has been reported in patients receiving higher than recommended doses of the drug in preparation for bone marrow transplantation; neurotoxicity appeared to increase with age and dose administered and occurred more frequently in patients who also received procarbazine or cyclophosphamide.

/CASE REPORTS/ ... Four women with Hodgkin's disease ... treated with mechlorethamine during first and third (1 case) or second & third (3 cases) trimesters of pregnancy. No abnormalities were recorded in offspring at 2 months, 8.5, 7.5 and 9.5 yr.

/CASE REPORTS/ 52 yr old woman with lymphocytic lymphoma received chemotherapy including mechlorethamine; iv, 9 mg on day 1 and 4.5 mg on day 8. Within 1 hr of administration she developed facial angioneurotic edema after each course of therapy.

Carcinogen ClassificationChlormethine is probably carcinogenic to humans (Group 2A). Chlormethine is part of MOPP, a combination chemotherapy regimen that is carcinogenic to humans (Group 1). (L135)

Regulatorische Informationen

FDA Requirements · 1 Eintrag

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

DHS Chemicals of Interest (COI) · 4 Einträge

Nitrogen mustard hydrochloride

30.00

2.2

Chemical Weapons/Chemical Weapons Precursors chemical material that, if stolen or diverted, can be converted into weapons using simple chemistry, equipment, or techniques.

Chemie und Industrie

Pharmakologische Informationen

Mechanism of Action · 2 Einträge

Mechlorethamine, as an alkylating agent, interferes with DNA replication and transcription of RNA and ultimately results in the disruption of nucleic acid function. Mechlorethamine also possesses weak immunosuppressive activity.

Mechlorethamine, as an alkylating agent, interferes with DNA replication and transcription of RNA, and ultimately results in the disruption of nucleic acid function.

Metabolism/Metabolites · 2 Einträge

Following its in vivo admin, mechlorethamine or its hydrochloride is probably converted into ethyleneimmonium ion which reacts with guanine residues in /either the same or/ adjacent strands of DNA as well as with SH groups.

Undergoes rapid chemical transformation and combines with water or reactive compounds of cells, so that the drug is no longer present in active form a few minutes after administration. Half Life: 15 minutes

FDA Pharmacological Classification · 2 Einträge

MECHLORETHAMINE HYDROCHLORIDE

Alkylating Activity [MoA]; Alkylating Drug [EPC]

MeSH Pharmacological Classification · 4 Einträge

Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.

Chemicals that are used to cause the disturbance, disease, or death of humans during WARFARE.

Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants.

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 · 3 Einträge

Following IV injection, the drug undergoes rapid chemical transformation and unchanged mechlorethamine is undetectable in the blood within a few minutes. Less than 0.01% of an IV dose is excreted unchanged in the urine.

Mice given 35 mg/kg body wt mechlorethamine hydrochloride iv and examined by autoradiography had significant levels of compound in brain, spinal cord, lung and submaxillary glands.

Mechlorethamine is incompletely absorbed following intracavitary administration, probably because of rapid deactivation by body fluids.

Verwendung und Herstellung

Uses · 5 Einträge

MEDICATION

Antineoplastic agent

Its use as chemosterilant and as cross-linking agent in mfr of ion exchange fibers was investigated. /mechlorethamine hydrochloride/

MEDICATION (VET)

For the palliative treatment of Hodgkin's disease (Stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma. Also for the palliative treatment of metastatic carcinoma resulting in effusion.

U.S. Production... 1.5 kg of the chemical were manufactured and sold in 1974 in the US.
Methods of Manufacturing · 2 Einträge

Nitrogen mustard hydrochloride can be prepared by treating N-methyldiethanolamine with thionyl chloride.

After purification, base may then be converted conveniently to hydrochloride by dissolving it in suitable organic solvent and passing hydrochloride into solution.

Formulations/PreparationsParenteral: For injection: 10 mg, Mustargen (with sodium chloride), Merck

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