Bis(2-chloroethyl)ethylamine is the

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...

C₂H₅N(CH₂CH₂Cl)₂. Often abbreviated HN1, it is a powerful

vesicant A blister agent (or vesicant), is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affec ...

and a

nitrogen mustard Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen m ...

gas used for

chemical warfare Chemical warfare (CW) involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from nuclear warfare, biological warfare and radiological warfare, which together make up CBRN, the military acronym ...

. HN1 was developed in the 1920s and 1930s to remove warts and later as a military agent. Because of the latter use, it is a Schedule 1 chemical within the

Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...

and therefore use and production is strongly restricted. It has never been used in warfare.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009. It is an oily liquid with a colorless to pale yellow appearance and a faint fishy or musty odor. HN1 is also an

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009.

Reactions

Nitrogen mustards react via an initial cyclization to the corresponding aziridinium salt. The rate of this reaction is pH dependent because the protonated amine cannot cyclize. The aziridinium ion reacts with water in a slower reaction. At pH 8, the nitrogen mustards are essentially quantitatively converted to the aziridinium ion for subsequent slow reaction with water. In contrast, at pH 4 cyclization and hydrolysis show the classic form of reactions in series. Hydrolysis of HN1 produces toxic intermediates.
National Institute for Occupational Safety and Health. Accessed March 19, 2009. HN1 reacts with

iron alloys This is a list of named alloys grouped alphabetically by base metal. Within these headings, the alloys are also grouped alphabetically. Some of the main alloying elements are optionally listed after the alloy names. Alloys by base metal Alumini ...

, corroding them at and above 65 °C (149 °F), and reacts with metals in general, producing

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...

gas. This can potentially cause explosions.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009.

Toxicity

Because HN1 is an alkylating agent, it damages DNA, causes

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

, and causes injury to areas that come into contact with it. Exposure to HN1 can be fatal, and its effects on skin and mucous membranes are worsened when they are moist. The alkylation effects cause damage to the spleen, bone marrow, and lymph nodes, which causes

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

, low white cell counts, and

internal bleeding Internal bleeding (also called internal hemorrhage) is a loss of blood from a blood vessel that collects inside the body. Internal bleeding is usually not visible from the outside. It is a serious medical emergency but the extent of severity depen ...

. The vesicant effects cause blistering and damage to the skin.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009. The symptoms of exposure depend on the route of exposure. Eye exposure to vapor can cause

lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

(tears),

blepharospasm Blepharospasm is any abnormal contraction of the orbicularis oculi muscle. The condition should be distinguished from the more common, and milder, involuntary quivering of an eyelid, known as myokymia, or fasciculation. In most cases, blepharosp ...

(eyelid twitching), irritation, itching, burning pain, dry feeling, and sometimes miosis (pinpoint pupils). More severe vapor exposure can also cause swelling and fluid buildup (

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

) in the eyelids, increased pain, and redness. Very severe exposure to vapor or exposure to liquid can cause

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...

(aversion to light),

corneal ulceration Corneal ulcer is an inflammatory or, more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal stroma. It is a common condition in humans particularly in the tropics and the a ...

, and

blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...

.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009. Inhaling the vapor causes symptoms that begin in the upper airway and expand to the lower airway. Increased concentrations cause worse symptoms. Mild inhalation exposure causes

rhinorrhea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies ( hay fever) or certain viral infections, such as the common cold or COVID- ...

(runny nose), sneezing, barking cough (a harsh cough that sounds somewhat like a dog barking),

epistaxis A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...

(nosebleed),

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...

(shortness of breath) that affects smokers and asthmatics,

hoarseness A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the ...

that turns into toneless voice,

ageusia Ageusia (from negative prefix ''a-'' and Ancient Greek ''γεῦσις'' geûsis 'taste') is the loss of taste functions of the tongue, particularly the inability to detect sweetness, sourness, bitterness, saltiness, and umami (meaning 'pleasant ...

(loss of taste), and

anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a num ...

(loss of smell); later on, sinus and nose pain develops. With more severe inhalation exposure, the airway becomes inflamed, pneumonia develops, and the respiratory epithelium can begin to have necrosis and slough off, forming a pseudomembrane that can occlude the airway. This occlusion can be fatal, as can the pneumonia.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009. Skin contact with nitrogen mustard in low concentrations causes symptoms beginning with redness, then moving to blistering, itching, and burning pain. More severe exposure can cause

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

(cell death) in the blisters, and systemic toxicity, which causes

malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

, vomiting, exhaustion, and

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

. Skin exposure that causes symptoms over more than 25% of the body area is often fatal. Though ingestion is uncommon, nitrogen mustard can burn the GI tract and cause

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

, hemorrhagic diarrhea, and

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...

.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009. Nitrogen mustard exposure does not cause symptoms until several hours to several days afterwards, but more severe exposure causes symptoms sooner. With severe exposure, eye injury can manifest within 1-2 hours, airway damage within 2-6 hours, and skin damage within 6-12 hours (sooner in hot or humid weather). Mild exposure takes longer to manifest symptoms: eye injury within 3-12 hours, airway damage within 12-24 hours, and skin damage up to 48 hours post-exposure.
National Institute for Occupational Safety and Health. Accessed March 19, 2009.

Long-term sequelae

Effects of nitrogen mustard exposure can be long-term or permanent; it is also a known

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

, reprotoxin, and developmental toxin after chronic and acute exposure, causing

skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...

and airway cancers in particular. Blindness from an acute exposure is usually temporary, resolving in days to months depending on severity. Chronic

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...

and eye infections are also common after acute nitrogen mustard exposure. Other consequences of acute exposure include ageusia, anosmia,

pulmonary fibrosis Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...

, scarring,

bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...

, chronic respiratory disease,

mental illness A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

, and central nervous system damage. Consequences of chronic exposure beyond cancer include permanent

kidney damage Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...

and immunosuppression.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009.

Treatment

Treatment for HN1 exposure is primarily supportive, since there is no

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

. First aid involves

decontamination Decontamination (sometimes abbreviated as decon, dcon, or decontam) is the process of removing contaminants on an object or area, including chemicals, micro-organisms or radioactive substances. This may be achieved by chemical reaction, disinfecti ...

, irrigation, removing the affected person from the source of exposure, immediate medical attention,

airway management Airway management includes a set of maneuvers and medical procedures performed to prevent and relieve airway obstruction. This ensures an open pathway for gas exchange between a patient's lungs and the atmosphere. This is accomplished by either cl ...

(in cases of inhalation exposure), and medical

monitoring Monitoring may refer to: Science and technology Biology and healthcare * Monitoring (medicine), the observation of a disease, condition or one or several medical parameters over time * Baby monitoring * Biomonitoring, of toxic chemical compounds, ...

of respiratory and cardiac function. If the affected person has trouble breathing (

) or stops breathing (

apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...

), ventilatory support and oxygen therapy can be helpful. If HN1 has been ingested, emetics (agents that induce vomiting) and

gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...

are contraindicated, and nothing should be consumed by mouth because they could damage the gastrointestinal system.The Emergency Response Safety and Health Database: NITROGEN MUSTARD HN-1
National Institute for Occupational Safety and Health. Accessed March 19, 2009.

References

{{Nitrogen mustards Amines Organochlorides Nitrogen mustard vesicants Chloroethyl compounds

Reactions

Toxicity

Long-term sequelae

Treatment

See also

References