Chlormethin

2-Chloro-N-(2-chloroethyl)-N-methylethanamine · C07115 · Mustine · Mustagen · chlormethine · Dichloramine · Chlorethazine · MECHLOROETHAMINE

https://huagongshe.com/de/chemical/4033

Identifikatoren & physikalische Daten

CAS No.	51-75-2
Summenformel	C5H11Cl2N
Durchschnittliche Molmasse	156,05 g/mol
Monoisotopische Masse	155,02685471 g/mol
SMILES	CN(CCCl)CCCl
InChIKey	HAWPXGHAZFHHAD-UHFFFAOYSA-N
PubChem CID	4033
ChEMBL	CHEMBL427
ChEBI	CHEBI:28925
EC No.	200-120-5
DTXSID	DTXSID2020975
Lokaler Name	Chlormethin

Chemische & physikalische Eigenschaften

XLogP	0,9
Polarare Oberfläche (TPSA)	3,2
H-Brücken-Donoren	0
H-Brücken-Akzeptoren	1
Frei drehbare Bindungen	4
Schwere Atome	8
Formalladung	0
Komplexität	43,7
Stoffklassen	Toxic Gases & Vapors -> Chemical WeaponsCarcinogens-> NIOSH Emergency Response Categories
Arzneimittel	Pharmaceuticals -> Listed in ZINC15
SpringerMaterials Properties	Boiling point
LogP (Verteilungskoeffizient)	log Kow = 0.911.6
Geruch	Faint odor of herring
Dichte	1.118 at 77 °F (EPA, 1998) - Denser than waterwill sink1.118 @ 25 °C/4 °C1.118 @25 °Cd425 1.118
Color/Form	Mobile liquidDark liquidLiquid, colorless/pale yellow when fresh
Löslichkeit	Very solubleVery slightly soluble in watermiscible with dimethyl formamide, carbon disulfide, carbon tetrachloride, many organic solvents and oils3.34e+01 g/L
Human Drugs	Breast FeedingLactationMilk, HumanAntineoplastic AgentsAlkylating AgentsIrritantsEMA approved medicines: Human medicine (Orphan designations)
Siedepunkt	189 °F at 18 mmHg (EPA, 1998)87°C at 1.80E+01 mm Hg87 °C @ 18 mm Hgbp18 87°bp10 75°bp5 64°bp2 59°
Schmelzpunkt	-76 °F (EPA, 1998)-60 °C108 - 111 °C-60°
Dampfdichte	5.9 (Air=1)0.17 mm at 25°C
Brechungsindex	1.5500 (estimate)
pKa (Säurekonstante)	6.40±0.30(Predicted)
Aggregatzustand	HN-2 has a soapy odor at low concentrations and a fruity odor at higher concentrations.
Farbe	Dark liquid
Henry-Konstante	3.4×100 mol/(m3Pa) at 25℃, Duchowicz et al. (2020)
NIST chemische Informationen	Bis(2-chloroethyl)methylamine(51-75-2)
EPA chemische Informationen	Nitrogen mustard (HN-2) (51-75-2)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH300: Fatal if swallowed [Danger Acute toxicity, oral]P203, P260, P262, P264, P264+P265, P270, P271, P280, P284, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P308+P316, P316, P317, P318, P320, P321, P330, P361+P364, P363, P403+P233, P405, and P501 (click each P-code to see the statement)
Regulatorische Informationen	Hazard Traits - CarcinogenicityDevelopmental ToxicityThe 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.)
Weitere Sicherheitsinformationen	- Indoor Air: HN-2 can be released into indoor air as a liquid spray (aerosol) or as a vapor.
Brandgefahren	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)
Gesundheitsgefahren	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)
Gefahrenübersicht	Nitrogen mustards are vesicants causing skin, eye, and respiratory tract injury. Although these agents cause cellular changes within several minutes of contact, the onset of pain and other clinical effects is delayed for hours. Nitrogen mustards are alkylating agents that may cause bone marrow suppression and neurologic toxicity. . . . Nitrogen mustards may decrease fertility. [ATSDR MMG] Danger of skin sensitizationGerm cell mutagens that have shown to increase the mutant frequency in the progeny of exposed mammals. [MAK]
Reaktive Gruppe	Amines, Phosphines, and Pyridines
Explosion Hazards	- No immediate danger of fire or explosion.
Special Reports	DHHS/ATSDRMedical Management Guidelines for Blister Agents: Nitrogen Mustard (HN-1), Nitrogen Mustard (HN-2), Nitrogen Mustard (HN-3) (updated: 8/22/2003) Available from: http://www.atsdr.cdc.gov/MHMI/mmg164.html as of November 26, 2003.
Reactivity Profile	MECHLORETHAMINE is a chlorinated amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Chemical Dangers	- HN-2 is not stable except as dry crystals.
Physical Dangers	- Vapors are heavier than air. They will spread along the ground and collect and stay in poorly-ventilated, low-lying, or confined areas (e.g., sewers, basements, tanks).
DOT Emergency Guidelines	If ... THERE IS NO FIRE, go directly to the Table of Initial Isolation and Protective Action Distances /(see table below)/ ... to obtain initial isolation and protective action distances. IF THERE IS A FIRE, or IF A FIRE IS INVOLVED, go directly to the appropriate guide /(see guide(s) below)/ and use the evacuation information shown under PUBLIC SAFETY. /HN-2 (when used as a weapon)//GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXICinhalation, ingestion, or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution./GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors, and sewers explosion hazards. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form./GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas.For more DOT Emergency Guidelines (Complete) data for MECHLORETHAMINE (9 total), please visit the HSDB record page.
Brandbekämpfung	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)- HN-2 is combustible.
Erste Hilfe	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)
Expositionsschutz und Persönliche Schutzausrüstung	TIH (Toxic Inhalation Hazard) - Term used to describe gases and volatile liquids that are toxic when inhaled. Some are TIH materials themselves, e.g., chlorine, and some release TIH gases when spilled in water, e.g., chlorosilanes. [ERG 2016].
Lagerbedingungen	PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable 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/
Reinigungsverfahren	PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens//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/
Freisetung ohne Brand	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)
Entsorgungsverfahren	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 qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations.PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/For more Disposal Methods (Complete) data for MECHLORETHAMINE (6 total), please visit the HSDB record page.
Preventive Measures	PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/For more Preventive Measures (Complete) data for MECHLORETHAMINE (10 total), please visit the HSDB record page.
Isolation and Evacuation	For initial isolation and protective action distances for chemical warfare blister agents see the Chemical Warfare Agents table in the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)
Effects of Short Term Exposure	HN-2 is a suspected carcinogen, developmental toxin, and reproductive toxin. Chronic or repeated exposure to HN-2 may cause bone marrow suppression, lymph node damage, weakening of the immune system, kidney damage, and reproductive system damage. Chronic or repeated exposure to HN-2 may cause genotoxicity.
Protective Action Criteria (PAC)	0.002 [mg/m3]0.022 [mg/m3]0.37 [mg/m3]
Personal Protective Equipment (PPE)	For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/GENERAL INFORMATION
Wechselwirkungen	The aim of this study was to test the efficacy of several candidate molecules against sulfur mustard (SM) and nitrogen mustard (HN2) using a human bronchial-epithelial cell line (16HBE14o-). Candidate molecules were chosen on the basis of the known cytotoxicity mechanisms of mustards or their efficacy previously observed on other cellular models. It included the sulfhydryl-containing molecules N-acetyl-cysteine (NAC) and WR-1065, the nucleophile hexamethylenetetramine (HMT), the energy-level stabilizer niacinamide (NC), the antioxidant dimethylthiourea (DMTU), L-arginine analogues such as L-thiocitrulline (L-TC) and L-nitroarginine methyl ester (L-NAME), and the anti-gelatinase doxycycline (DOX). Their efficacy was determined using 2-(4-[3-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2Htetrazolium (WST-1) reduction by viable cells 24 h after initial exposure to 100 microM HN2 or SM. On individual immediate cotreatment, some molecules exhibited selective protection against only one mustard, such as DMTU and WR-1065 against HN2 and DOX against SM, whereas NAC and L-TC were effective against both SM and HN2 cytotoxicity. However, as the level of protection against SM was always weak compared to HN2, several combinations were investigated against SM to improve the protection. The effective combinations (L-TC + DOX, NAC + DOX, NAC + DMTU, NAC + HMT, NC + DOX) combined agents, reducing the bioavailability of the mustard with compounds possibly acting on the consequences of alkylation. One of these combinations, NAC + DOX, appeared to be the most interesting, as these agents are already used in human therapy. It exhibited good efficacy in delayed cotreatment (up to 90 min) against SM.The present study was undertaken to find potent molecules against the toxicity of nitrogen mustard mechlorethamine (HN2) on respiratory epithelial cells, using a human bronchial epithelial cell line (16HBE14o-) as an in vitro model. The compounds examined included inhibitors of poly(ADP-ribose) polymerase (PARP), sulfhydryl-group donors as nucleophiles, and iron chelators and inhibitors of lipid peroxidation as antioxidants. Their effectiveness was determined upon observance of metabolic dysfunction induced by HN2 following a 4-hr exposure, using (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and ATP-level assays as indicators. Moreover, the fluorescent probe, monobromobimane (mBBr), and 2',7'-dichlorofluorescin-diacetate (H2DCF-DA) were used to assess intracellular sulfhydryl and peroxide level modifications by flow cytometry, respectively, following a 3-h exposure. Cell death was assessed by flow cytometry using the propidium iodide (PI)-dye-exclusion assay following 24-hr exposure. PARP inhibitors (niacinamide, 3-aminobenzamide, 6(5H)-phenanthridinone), and two sulfhydryl-group donors (N-acetylcysteine, WR-1065) were found to be effective in preventing HN2-induced metabolic dysfunction when added in immediate or delayed treatment with HN2. Only N-acetylcysteine, however, was found to prevent cell death induced by HN2, though it must be present at the time of the HN2 challenge.Cycloheximide is reported to protect rat intestinal crypt cells from mitotic inhibition by mechlorethamine as it is an inhibitor of protein synthesis.Caffeine potentiates the cytotoxic action of mechlorethamine against cultured P388 mouse lymphoma cells. Caffeine did not potentiate the cytotoxic action of the /mechlorethamine/ against W256 rat mammary carcinosarcoma cells, which were 5 to 7 times more sensitive than P388 cells to the cytotoxic action of /mechlorethamine/. Potentiation was observed ... When caffeine was present during ... 12 to 100 hr after a 1 hr exposure of P388 cells to /mechlorethamine/ caffeine ... At concentrations <0.1 m/m increased the mean population doubling times of the two types of cells.For more Interactions (Complete) data for MECHLORETHAMINE (12 total), please visit the HSDB record page.
Hepatotoxicity	Mild and transient elevations in serum aminotransferase levels were not uncommon during cycles of cancer chemotherapy regimens that included mechlorethamine, but its role in causing these abnormalities was never entirely clear. The enzyme elevations were usually mild, transient and without symptoms, so that dose modifications of mechlorethamine were rarely needed. Mechlorethamine has not been associated specifically with clinically apparent liver injury. Sinusoidal obstruction syndrome has been reported after MOPP therapy, but largely in patients with other risk factors for this complication, such as total body irradiation or previous courses of antineoplastic therapy. Topical mechlorethamine has not been associated with liver injury, although the possibility of systemic absorption continues to make hepatic adverse events mentioned as a concern. Careful analysis for bone marrow toxicity and plasma concentrations of the drug, however, have failed to demonstrate any evidence for significant absorption with proper use of the cutaneous gel.
Umweltverhalten	TERRESTRIAL FATE: The hydrolysis of mechlorethamine is generally described as rapid(1,2). A hydrolysis half-life of 11 hours was reported for mechlorethamine in a 66.7% acetone-water solution at 25 °C(3), and would be expected to be more rapid in a solution with just water as the solvent (SRC). The predominate environmental fate of mechlorethamine is expected to be hydrolysis, and it will not be expected to leach in soil(SRC). Mechlorethamine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.17 mm Hg at 25 °C(1).AQUATIC FATE: The hydrolysis of mechlorethamine is generally described as rapid(1,2). A hydrolysis half-life of 11 hours was reported for mechlorethamine in a 66.7% acetone-water solution at 25 °C(3), and would be expected to be more rapid in a solution with just water as the solvent(SRC). The predominate environmental fate of mechlorethamine is expected to be hydrolysis and therefore bioconcentration is not expected to be an important environmental fate process(SRC). The hydrolysis of mechlorethamine may be limited by its rate of dissolution(SRC) as is seen for a related compound, bis(2-chloroethyl)sulfide (mustard gas)(4).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), mechlorethamine, which has a vapor pressure of 0.17 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase mechlorethamine 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 2 days(SRC), calculated from its rate constant of 8.4X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Mechlorethamine does not contain any functional groups that would be expected to absorb light with wavelengths >290 nm, and it would not be expected to be susceptible to direct photolysis by sunlight(SRC).
Unerwünschte Wirkungen	Neurotoxin - Other CNS neurotoxin
Expositionspfade	HN-2 can be absorbed into the body by inhalation, ingestion, eye contact, and skin contact. Inhalation is an important route of exposure. Ingestion is an uncommon route of exposure. Tender skin, the moist lining of body passages and cavities (mucous membranes) and perspiration-covered skin are more sensitive to the effects of this agent.Partially absorbed following intracavitary administration, most likely due to rapid deactivation by body fluids. When it is topically administered, systemic exposure was undetectable.
Toxizitätsübersicht	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.
Signs and Symptoms	- Mild (onset within 4 to 12 hours): Tear production (lacrimation), irritation, itching, burning, spasmodic blinking (blepharospasm), dryness or gritty feeling, and possible pinpoint pupils (miosis).- Nausea, vomiting (emesis), pain, hemorrhagic diarrhea, and chemical burns of the gastrointestinal (GI) tract.- Mild (onset within 2 to 24 hours): Runny nose (rhinorrhea), sneezing, nosebleed (epistaxis), hoarseness progressing to “toneless” voice, barking cough, loss of taste and smell, wheezing and difficulty breathing or shortness of breath (dyspnea) in smokers and asthmatics, and nasal and sinus pain (occurring later).- Tender skin, the moist lining of body passages and cavities (mucous membranes), and perspiration-covered skin are more sensitive to the effects of nitrogen mustard.
Medical Surveillance	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	A hydrolysis half-life of 11 hours was reported for mechlorethamine in a 66.7% acetone-water solution at 25 °C(1) and would be expected to be more rapid in a solution with just water as the solvent (SRC). The predominant environmental fate of mechlorethamine is expected to be hydrolysis, and it will not be expected to leach in soil(SRC).
Natural Pollution Sources	Mechlorethamine is not know to occur in nature(1).
Human Toxicity Excerpts	/HUMAN EXPOSURE STUDIES/ During the Iraq-Iran war (1980-1988), a group of patients exposed to mustard gas (one of the chemical warfare agents used by Iraq) were referred to our dermatology department. ... A group of patients, including 14 children and teenagers, exposed to mustard gas were studied. Laboratory tests including blood cell counts, hemoglobin, hematocrit, urine analysis, etc., were determined. Among the most frequent disorders were facial involvement (78%), which dominated the clinical picture, followed by genital (42%), truncal, and axillary lesions (both 14%). Eosinophilia was the most prominent laboratory disorder seen in 12% of the patients. Skin lesions started 4-18 hours after exposure. Erythema developed within 20-30 hours after exposure, followed by blisters. The time of onset of manifestations had been shorter and severity of the lesions higher in children and teenagers compared with adults. Both phenomena could be attributed to the more delicate skin of the young patients. Genital manifestations were less frequent in this subgroup while ophthalmic, pulmonary, and gastrointestinal lesions were more frequently encountered in children than in adults. /Unspecified mustard gas//SIGNS AND SYMPTOMS/ Nitrogen mustard exposure following absorption from the skin or respiratory or gastrointestinal tracts may exert profound effects on the hematopoietic and lymphoid tissue. Degenerative bone marrow changes may be detected within 12 hours and may progress to severe aplasia. There may be a transient leukocytosis for a few hours, followed by severe lymphopenia, granulocytopenia, thrombocytopenia, and a moderate anemia. /Nitrogen mustard//CASE REPORTS/ A 55-year-old man with chronic, active diffuse psoriasis was accidentally given 30 mg of mechlorethmine deep into the buttock muscles. About 5 hours after the intramuscular (IM) mechlorethamine injection, 1/6 M sodium thiosulfate was infused around the intramuscular site. Although systemic responses to the mechlorethamine developed, the expected muscular and adjacent skin destruction did not occur. Instead, IM mechlorethamine induced only minimal local tenderness./SPECIAL STUDIES/ The temporal regulation, of cyclin A- and B1-dependent kinases /were investigated/ in human lymphoma cells treated with nitrogen mustard and pentoxifylline, to determine whether the activity of these complexes correlated with cell cycle arrest induced by DNA damage. Cells were synchronized in Gl/S, treated with nitrogen mustard, and then postincubated with pentoxifylline. Nitrogen mustard-induced a protracted delay in G2 phase. This delay correlated with suppression of cyclin Bl- and cdc2-kinase activities, and stabilization of hyperphosphorylated-cdc2 in the presence of similar cyclin Bl levels to those found in mitosis. Nitrogen mustard had no discernible effect on the S phase activity of cyclin A- or cdk2-immune complexes. Entry of control cells into mitosis correlated with destruction of cyclin A, disappearance of cyclin A-bound cdk2 and decreased cdk2 kinase activity. G2 delay induced by nitrogen mustard was associated with stabilization of cyclin A, increased abundance of cyclin A-bound cdk2, and increased cdk2 activity. Cyclin A was also associated with cdc2, which, contrary to complexes containing cdk2, were only activated upon entry into mitosis. Pentoxifylline abrogated cell cycle arrest induced by aphidicolin and nitrogen mustard in human lymphoma cells. Pentoxifylline also reverted the activity of cyclin A- and Bl-kinases in nitrogen mustard-treated cells to approximately that observed in controls. Delayed entry into mitosis following DNA damage correlates with suppression of cyclin B1/cdc2 and cyclin A/cdc2 complexes, while maintaining cyclin A/cdc2 complexes in an active state. Furthermore, pentoxifylline disrupts the signal transduction pathway that regulates these complexes when damaged DNA is present, resulting ln abrogation of cell cycle arrest.For more Human Toxicity Excerpts (Complete) data for MECHLORETHAMINE (6 total), please visit the HSDB record page.
Artificial Pollution Sources	Mechlorethamine as its hydrochloride salt is used as an antineoplastic agent(1,2). Mechlorethamine hydrochloride's production and use may result in the release of mechloroethamine to the environment through various waste streams(SRC). Mechlorethamine was produced as a vesicant in chemical warfare(2). While mechlorethamine was not used for military purposes, stockpiles may have existed in the US as recently as 1974(2). Mechlorethamine production and storage may result in its release to the environment through various waste streams(SRC), although it is not manufactured in commercial quantities in the US(2).
CERCLA-Meldepflichtmengen	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. Mechlorethamine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 10 lbs.
DHS Chemicals of Interest (COI)	HN2 (nitrogen mustard-2)CUM 100gChemical Weapons/Chemical Weapons Precursors chemical material that, if stolen or diverted, can be converted into weapons using simple chemistry, equipment, or techniques.
TSCA-Inventar-Status	TSCA listed
UN-Transportnummer	2810
Toxizität	LD50 oral in rabbit: 5mg/kg
Gefahrenklasse	6.1(a)
Verpackungsgruppe	II
Gefahrstoffdaten	51-75-2(Hazardous Substances Data)

Anwendungen & Verwendung

Beschreibung

Nitrogen mustards are very potential chemical substances of yesteryears and produced during the 1920s and 1930s as chemical warfare weapons. They are vesicants (or blister agents) similar to the sulphur mustards. They smell fishy, musty, soapy, or fruity and are either in the form of an oily textured liquid or a vapour (the gaseous form of a liquid) or a solid. It is in liquid form at normal room temperature (70 F) with a clear, pale amber, or yellow colour. HN-1, HN-2, and HN-3 are the military designations of nitrogen mustard (for more data, refer to Muatars gas). Nitrogen mustards (HN-1, HN-2, HN-3) are colourless to yellow, oily liquids that evaporate very slowly. HN-1 has a faint fishy or musty odour. HN-2 has a soapy odour at low concentrations and a fruity odour at higher concentrations. HN-3 may smell like butter almond. Use of nitrogen mustards is very much restricted other than for chemical warfare. In fact, presently, its use has no records. HN-1 has been used to remove warts in the past, and HN-2 has been used sparingly in chemotherapy.

Verwenden

Antineoplastic.