Mechlorethamine

H300: Fatal if swallowed [Danger Acute toxicity, oral]

H310: Fatal in contact with skin [Danger Acute toxicity, dermal]

H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]

H330: Fatal if inhaled [Danger Acute toxicity, inhalation]

H340: May cause genetic defects [Danger Germ cell mutagenicity]

H350: May cause cancer [Danger Carcinogenicity]

H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]

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)

For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

Warning: Mechlorethamine is a strong irritant. Direct contact may result in severe dermal or corneal burns. Effects may be delayed.

Signs and Symptoms of Mechlorethamine Exposure: Signs and symptoms of acute exposure to mechlorethamine may include strong irritation or burning of the eyes, skin, and respiratory tract. Blisters, local phlebitis (irritation of a vein) and erythema (redness of the skin) may be noted. It may cause nausea, vomiting, and severe esophageal or gastrointestinal tract irritation if ingested. Bronchopneumonia, suppression of bone marrow activity, and hearing loss are possible longer term symptoms.

Emergency Life-Support Procedures: Acute exposure to mechlorethamine may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination.

Inhalation Exposure:

1. Move victims to fresh air. Emergency personnel should avoid self-exposure to mechlorethamine.

2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support.

3. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures.

4. Rush to a health care facility.

Dermal/Eye Exposure:

1. Remove victims from exposure. Emergency personnel should avoid self-exposure to mechlorethamine.

3. Remove and isolate contaminated clothing as soon as possible.

4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. Speed in removing material from the eyes is of extreme importance.

5. Wash exposed skin areas thoroughly with soap and water. Speed in removing material from skin is of extreme importance.

6. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures.

7. Rush to a health care facility.

Ingestion Exposure:

1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support to all victims.

2. DO NOT induce vomiting or attempt to neutralize!

3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures.

4. Give the victims water or milk: children up to 1 year old, 125 mL (4 oz or 1/2 cup); children 1 to 12 years old, 200 mL (6 oz or 3/4 cup); adults, 250 mL (8 oz or 1 cup). Water or milk should be given only if victims are conscious and alert.

5. Rush to a health care facility. (EPA, 1998)

For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

(Non-Specific -- Poisonous Liquid, n.o.s.) Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Wear positive pressure breathing apparatus and special protective clothing. Move container from fire area if you can do so without risk. Fight fire from maximum distance. Dike fire control water for later disposal; do not scatter the material.

(Non-Specific -- Poisonous Liquid, n.o.s.) Small fires: dry chemical, carbon dioxide, water spray, or foam. Large fires: water spray, fog, or foam. (EPA, 1998)

- HN-2 is combustible.

- The agent may burn but does not ignite readily.

- Fire may produce irritating, corrosive, and/or toxic gases.

- For small fires, use dry chemical, carbon dioxide, or water spray.

- For large fires, use dry chemical, carbon dioxide, alcohol-resistant foam, or water spray. Move containers from the fire area if it is possible to do so without risk to personnel. Dike fire control water for later disposal; do not scatter the material.

- Avoid methods that will cause splashing or spreading.

- For fire involving tanks or car/trailer loads, fight the fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after the fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tanks. Always stay away from tanks engulfed in fire.

- Runoff from fire control or dilution water may be corrosive and/or toxic, and it may cause pollution.

- If the situation allows, control and properly dispose of run-off (effluent).

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)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

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.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

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 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/

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 "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.

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.

For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

(Non-Specific -- Poisonous Liquid, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Ventilate closed spaces before entering them. Remove and isolate contaminated clothing at the site. Do not touch spilled material; stop leak if you can do so without risk. Use water spray to reduce vapors.

Small spills: absorb with sand or other noncombustible absorbent material and place into containers for later disposal.

Large spills: dike far ahead of spill for later disposal. (EPA, 1998)

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/

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].

AEGL 1: Notable discomfort, irritation, or certain asymptomatic non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure (Unit: mg/m3)

AEGL 2: Irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape (Unit: mg/m3)

AEGL 3: Life-threatening health effects or death (Unit: mg/m3)

0.13 mg/m3

2.2 mg/m3

0.044 mg/m3

0.74 mg/m3

0.022 mg/m3

0.37 mg/m3

0.0056 mg/m3

0.093 mg/m3

0.0028 mg/m3

0.047 mg/m3

NOTE THAT VALUES ARE IN mg/m3, NOT ppm. NR = Not recommended due to insufficient data

AEGLs Status: Interim

0.002 [mg/m3]

0.022 [mg/m3]

0.37 [mg/m3]

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.

For information on chemical warfare blister agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

PRECAUTIONS FOR "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

First Responders should use a NIOSH-certified Chemical, Biological, Radiological, Nuclear (CBRN) Self Contained Breathing Apparatus (SCBA) with a Level A protective suit when entering an area with an unknown contaminant or when entering an area where the concentration of the contaminant is unknown. Level A protection should be used until monitoring results confirm the contaminant and the concentration of the contaminant.NOTE:Safe use of protective clothing and equipment requires specific skills developed through training and experience.

LEVEL A: (RED ZONE)

Select when the greatest level of skin, respiratory, and eye protection is required. This is the maximum protection for workers in danger of exposure to unknown chemical hazards or levels above the IDLH or greater than the AEGL-2.

- A NIOSH-certified CBRN full-face-piece SCBA operated in a pressure-demand mode or a pressure-demand supplied air hose respirator with an auxiliary escape bottle.

- A Totally-Encapsulating Chemical Protective (TECP) suit that provides protection against CBRN agents.

- Chemical-resistant gloves (outer).

- Chemical-resistant gloves (inner).

- Chemical-resistant boots with a steel toe and shank.

- Coveralls, long underwear, and a hard hat worn under the TECP suit are optional items.

LEVEL B: (RED ZONE)

Select when the highest level of respiratory protection is necessary but a lesser level of skin protection is required. This is the minimum protection for workers in danger of exposure to unknown chemical hazards or levels above the IDLH or greater than AEGL-2. It differs from Level A in that it incorporates a non-encapsulating, splash-protective, chemical-resistant splash suit that provides Level A protection against liquids but is not airtight.

- A hooded chemical-resistant suit that provides protection against CBRN agents.

- Coveralls, long underwear, a hard hat worn under the chemical-resistant suit, and chemical-resistant disposable boot-covers worn over the chemical-resistant suit are optional items.

LEVEL C: (YELLOW ZONE)

Select when the contaminant and concentration of the contaminant are known and the respiratory protection criteria factors for using Air Purifying Respirators (APR) or Powered Air Purifying Respirators (PAPR) are met. This level is appropriate when decontaminating patient/victims.

- A NIOSH-certified CBRN tight-fitting APR with a canister-type gas mask or CBRN PAPR for air levels greater than AEGL-2.

Mechlorethamine appears as a chemical warfare blister agent. Mobile liquid; faint odor of herring. Used as a drug for the treatment of cancer.

Colorless to pale yellow, oily liquid with a faint soapy odor or fruity odor at high concentrations; [ATSDR-MMG]

Pale amber to yellow oily liquid.

Mobile liquid

Dark liquid

Liquid, colorless/pale yellow when fresh

Faint odor of herring

189 °F at 18 mmHg (EPA, 1998)

87°C at 1.80E+01 mm Hg

87 °C @ 18 mm Hg

-76 °F (EPA, 1998)

108 - 111 °C

Very soluble

Very slightly soluble in water; miscible with dimethyl formamide, carbon disulfide, carbon tetrachloride, many organic solvents and oils

3.34e+01 g/L

1.118 at 77 °F (EPA, 1998) - Denser than water; will sink

1.118 @ 25 °C/4 °C

1.118 @25 °C

5.9 (Air=1)

0.42 [mmHg]

0.17 mm Hg @ 25 °C

0.17 [mm Hg] @25 °C

log Kow = 0.91

Henry's Law constant = 8.5X10-8 atm-cu m/mol @ 25 °C /Estimated/

The undiluted liquid decomposes on standing and forms polymeric quaternary ammonium salts which are insoluble in the free base.

6.43 (at 25°C)

pKa = 6.43 at 25 °C (conjugate acid)

126.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Volatility at 25 °C: 3.581 mg/l

The undiluted liquid decomposes on standing and forms polymeric quaternary ammonium salts which are insoluble as the free base.

Hydroxyl radical reaction rate constant = 8.4X10-12 cu cm/molecule-sec @ 25 °C /Estimated/

Chlorinating agents destroy nitrogen mustards. Dry chlorinated lime and chloramines with a high content of active chlorine vigorously chlorinate nitrogen mustards to the carbon chain giving low toxicity products. In the presence of water this interaction proceeds less actively

For more Other Experimental Properties (Complete) data for MECHLORETHAMINE (6 total), please visit the HSDB record page.

Boiling point

Heat of sublimation

Vapor pressure

Toxic Gases & Vapors -> Chemical Weapons

Carcinogens

Mutagens

Teratogens

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

Halogenated Organic Compounds

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.

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.

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.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

mechlorethamine

DILI Negative

Intravenous

DOI:10.1016/j.drudis.2019.09.022

Classification of carcinogenicity: 1) evidence in humans: limited; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2A: The agent is probably carcinogenic to humans. /From table/

Nitrogen mustard

Group 2A: Probably carcinogenic to humans

Volume 9: (1975) Some Aziridines, N-, S- and O-Mustards and Selenium

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

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

◉ Summary of Use during Lactation

Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as mechlorethamine. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding from mechlorethamine mothers should not breastfed during therapy with mechlorethamine therapy, including topical application.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

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.

- 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).

- Moderate (onset within 3 to 6 hours): Above plus increased redness, fluid accumulation (edema) in the eyelids, and moderate pain.

- Severe (usually from liquid agent; onset within 1 to 2 hours): Increased fluid accumulation (edema) in eyelids, painful sensitivity to light (photophobia), damage to the cornea (ulceration), blindness, and severe pain.

- 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).

- Severe (onset within 2 to 6 hours): Same as above, plus acute inflammation of the upper and lower airways; tissue death (necrosis) of the airway lining (respiratory epithelium); possible obstruction of both upper and lower airways due to formation of a false membrane or fibrous deposit (pseudomembrane); airway blockage (occlusion) from inflamed and dead (necrotic) cells; and death, due to inflammatory lung disease (pneumonia).

- Exposures to higher concentrations of vapor result in health effects that occur sooner and are more severe.

- Damage to the airways (and to tissues immediately surrounding the airways) begins with the upper airways and descends to the lower airways. The severity of damage increases as the concentration of nitrogen mustard increases.

- 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.

- Skin effects of liquid mustard occur sooner than do the effects of mustard vapor.

- Mild to moderate: Erythema (redness) begins to appear 1 to 24 hours after exposure (typically within 4 to 8 hours); blistering (vesication) begins 2 to 18 hours after onset of redness; possible intense itching (pruritus) and burning pain.

- Severe: As above, with more severe blistering (vesication) and areas of central tissue death (necrosis), plus whole-body (systemic) health effects including weakness (malaise), vomiting (emesis), fever, and complete exhaustion (prostration).

- Skin exposure to nitrogen mustard can be fatal. An area of redness (erythema), with or without blistering (vesication), which covers 25% or more of the body’s surface area, suggests a lethal exposure.

Neurotoxin - Other CNS neurotoxin

Aplastic anemia - The presence of increased methemoglobin in the blood; the compound is classified as primary toxic effect.

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

Dermatotoxin - Skin burns.

Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors.

IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.

Mechlorethamine's production and use as an antineoplastic agent as its hydrochloride salt and its former production as a gas warfare agent may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.17 mm Hg at 25 °C indicates mechlorethamine will exist solely as a vapor in the ambient atmosphere. Vapor-phase mechlorethamine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 2 days. 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. The hydrolysis of mechlorethamine is generally described as rapid and hydrolysis is expected to be the predominate environmental fate of mechlorethamine. A hydrolysis half-life of 11 hours was reported for mechlorethamine in a 66.7% acetone-water solution at 25 °C, and would be expected to be more rapid in a solution with just water as the solvent. Volatilization from dry soil surfaces is not expected based upon its vapor pressure. Bioconcentration is not likely be an important environmental fate due to mechlorethamine's rapid hydrolysis. Occupational exposure to mechlorethamine may occur through inhalation and dermal contact with this compound at workplaces where mechlorethamine is produced or used. The general population is unlikely to be exposed to mechlorethamine due to its limited use as a chemotherapeutic agent. (SRC)

Mechlorethamine is not know to occur in nature(1).

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).

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).

The rate constant for the vapor-phase reaction of mechlorethamine with photochemically-produced hydroxyl radicals has been estimated as 8.4X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 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). The hydrolysis of mechlorethamine is generally described as rapid(2,3); however, only limited quantitative data were located(SRC). In water, nitrogen mustards, including mechlorethamine, form cyclic imonium ions, releasing chloride ion; the cyclic imonium ion of mechlorethamine can then react with water(4). In 66.7% acetone-water solution at 25 °C and uncontrolled pH, the psuedo-unimolecular rate constant for the hydrolysis of mechlorethamine was reported as 0.001 min-1(4), corresponding to a half-life of 11 hours(SRC). In a solution with just water as the solvent, hydrolysis of mechlorethamine would be expected to be more rapid(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)(5).

Bioconcentration is not likely be an important environmental fate due to mechlorethamine's rapid hydrolysis(SRC). 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).

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).

A hydrolysis half-life of 11 hours was found 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 volatilize from water or moist soil surfaces(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(2).

Since the substance is used only as an antineoplastic agent, health professionals (eg, pharmacists, nurses, and physicians) involved in cancer chemotherapy are the principal personnel who potentially may be exposed. Exposure may occur during drug preparation, administration, or cleanup.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 4564 workers (2038 of these are female) are potentially exposed to mechlorethamine in the USA(1). Occupational exposure to mechlorethamine may occur through inhalation and dermal contact with this compound at workplaces where mechlorethamine is produced or used(SRC). The general population is unlikely to be exposed to mechlorethamine due to its limited use as a chemotherapeutic agent(SRC).

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 "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.

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)/

Table: Table of Initial Isolation and Protective Action Distances for HN-2 (when used as a weapon) ID: 2810 [Table#5121]

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXIC; inhalation, 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.

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/