Bis(2-chloroethyl)ethylamine

Toxic Gases & Vapors -> Chemical Weapons

-> NIOSH Emergency Response Categories

1.0861 at 73.4 °F (EPA, 1998) - Denser than water; will sink

1.09 g/cc @ 25 °C

Relative density (water = 1): 1.09

1.09 @25 °C

In water, 160 mg/l @ 25 °C

Miscible with many organic solvents

Solubility in water at 25 °C: very poor

185 °F at 12 mmHg (EPA, 1998)

194 °C with decomposition

When heated to decomposition it emits very toxic fumes of /Hydrogen Chloride and Nitrogen Oxide/.

At temperatures >194 °C, it decomposes.

194 °C

-29 °F (EPA, 1998)

-34 °C

Crystals, from acetone; MP: 141 °C /Hydrochloride/

-34 °C

-34 °C

5.9 (EPA, 1998) - Heavier than air; will sink (Relative to Air)

5.9 (Air = 1)

Relative vapor density (air = 1): 5.9

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

Combustible. Heating will cause rise in pressure with risk of bursting. Gives off irritating or toxic fumes (or gases) in a fire.

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] Causes lachrymation; [ICSC]

When dissolved in water, ETHYLBIS(2-CHLOROETHYL)AMINE is a strong base; reacts violently with strong oxidants and acids ; attacks copper and copper compounds. [Handling Chemicals Safely 1980. p. 123]; reacts with hypochlorites to give N-chloroamines, some of which, are explosives when isolated [Bretherick 1979 p. 108].

The substance polymerizes under the influence of heat and light. Attacks many metals. This produces flammable gas (hydrogen - see ICSC 0001).

- HN-1 is corrosive to iron alloys beginning at 149°F (65°C).

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

Use water spray, alcohol-resistant foam, carbon dioxide, powder. In case of fire: keep drums, etc., cool by spraying with water.

- HN-1 is combustible.

Half-upright position. Artificial respiration may be needed. No mouth-to-mouth artificial respiration. Refer immediately for medical attention.

Wear protective gloves when administering first aid. Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer immediately for medical attention.

Rinse with plenty of water (remove contact lenses if easily possible). Refer immediately for medical attention.

Rinse mouth. Give one or two glasses of water to drink. Do NOT induce vomiting. Refer immediately for medical attention.

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].

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.

Evacuate danger area! Consult an expert! Personal protection: gas-tight chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Collect leaking liquid in sealable air tight containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations. NEVER direct water jet on liquid.

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

Only mature, experienced and responsible /SRP: workers/ should be employed in work with chloroethylamines. High standards of maintenance, good housekeeping and cleanliness should be observed in the work premises. Personal hygiene should be emphasized ... Even if not expressly mentioned in actual official carcinogen lists, analogous safety and health measures and regulations can be recommended for chloroethylamines as for the carcinogens listed. /Chloroethylamines/

Based on the recent pathognomic accomplishment in the mechanisms of toxic actions, the favorable degree of protection was achieved by several drugs in acute poisoning of rats with sulfur and nitrogen mustards. It has been established that dexamethasone, promethazine, vitamin E, heparin, and sodium thiosulfate (a) prolonged the survival time in animals poisoned by 3 LD50s of toxic agents, (b) diminished the lethalty (with the protective indices ranging from 1.5 to 2.7), (c) antagonized the decrease of body weight, and (d) lessened the degree of pathological organ changes. The simultaneous administration of two or three of the drugs mentioned, of which sodium thiosulfate as chemical inactivator of the toxic agents was basic and consonant component, led to the further increase in effectiveness. /Nitrogen mustards/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 360(SRC), determined from a structure estimation method(2), indicates that ethylbis(2-chloroethyl)amine is expected to have moderate mobility in soil(SRC). The hydrolysis half-life of ethylbis(2-chloroethyl)amine is 12.5 days at 5 °C(3), therefore, hydrolysis in moist soil surfaces is expected to be an important fate process(SRC). Ethylbis(2-chloroethyl)amine has a pKa of 6.57(4) and is expected to exist in both the protonated form and neutral species in the ambient environment. At neutral to basic conditions, the neutral species will be the dominant form of ethylbis(2-chloroethyl)amine, while acidic conditions will favor the protonated form. The protonated form of ethylbis(2-chloroethyl)amine may adsorb to soil surfaces more strongly than the neutral species(SRC). Volatilization of the neutral species of ethylbis(2-chloroethyl)amine from moist soil surfaces is expected to be an important fate process(SRC) based on an estimated Henry's Law constant of 3.4X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 0.25 mm Hg(3), and water solubility, 160 mg/l(3). The protonated form of ethylbis(2-chloroethyl)amine will not volatilize from moist soil surfaces since cations do not volatilize(SRC). Ethylbis(2-chloroethyl)amine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3).

AQUATIC FATE: The hydrolysis half-life of ethylbis(2-chloroethyl)amine is 12.5 days at 5 °C (pH not specified)(1) and the product of this hydrolysis is the nontoxic bis-beta-hydroxyethyl ethylamine(2). This suggests that hydrolysis is a major environmental fate process for ethylbis(2-chloroethyl)amine in most waters(SRC). Based on a classification scheme(3), an estimated Koc value of 360(SRC), determined from a structure estimation method(4), indicates that non-hydrolyzed ethylbis(2-chloroethyl)amine is expected to adsorb to suspended solids and sediment(SRC). Ethylbis(2-chloroethyl)amine has a pKa of 6.57(5) and is expected to exist in both the protonated form and neutral species in aquatic systems. At neutral to alkaline conditions, the neutral species will be the dominant form of ethylbis(2-chloroethyl)amine while acidic conditions will favor the protonated form. Volatilization of the neutral species from water surfaces is expected(6) based upon an estimated Henry's Law constant of 3.4X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 0.25 mm Hg(1), and water solubility, 160 mg/l(1). Using this Henry's Law constant and an estimation method(6), volatilization half-lives for a model river and model lake are 3.6 hrs and 6.2 days, respectively(SRC). The protonated form of ethylbis(2-chloroethyl)amine will not volatilize from water surfaces since cations do not volatilize(SRC). According to a classification scheme(7), an estimated BCF of 7(SRC), from an estimated log Kow of 2.0(8) and a regression-derived equation(9) suggests the potential for bioconcentration in aquatic organisms is low and hydrolysis should preclude bioconcentration from being a major fate process(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethylbis(2-chloroethyl)amine, which has a vapor pressure of 0.25 mm Hg at 25 °C(2), is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase ethylbis(2-chloroethyl)amine 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 1 day(SRC), calculated from its rate constant of 1.6X10-11 cu cm/molecule-sec at 25 °C(SRC), determined using a structure estimation method(3).

The substance can be absorbed into the body by inhalation of its vapour, by inhalation of its aerosol, through the skin and by ingestion. Serious local effects and systemic effects by all routes of exposure.

HN-1 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. Warm, moist areas with thin skin, the moist lining of body passages and cavities (mucous membranes) and perspiration-covered skin are more sensitive to the effects of this agent.

Sore throat. Burning sensation. Cough. Tremor. Incoordination. Convulsions. Laboured breathing. Shortness of breath. Wheezing. Symptoms may be delayed.

MAY BE ABSORBED! Redness. Pain. Blisters. Symptoms may be delayed. Further see Inhalation.

VAPOUR WILL BE ABSORBED! Watering of the eyes. Redness. Pain. Spasms, photophobia and dilated pupils. Blurred vision. Severe deep burns. Loss of vision.

Sore throat. Abdominal pain. Burning sensation in the throat and chest. Nausea. Vomiting. Diarrhoea. Further see Inhalation.

- Mild (onset within 4 to 12 hours): Tear production (lacrimation), irritation, itching, burning, spasmodic blinking (blepharospasm), dryness or gritty feeling, possible pinpoint pupils (miosis).

- Nausea, vomiting (emesis), pain, hemorrhagic diarrhea, and chemical burns of the gastrointestinal (GI) tract.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for ethylbis(2-chloroethyl)amine can be estimated to be 360(SRC). According to a classification scheme(2), this estimated Koc value suggests that ethylbis(2-chloroethyl)amine is expected to have moderate mobility in soil. Ethylbis(2-chloroethyl)amine has a pKa of 6.57(3) and is expected to exist in both the protonated form and neutral species in the ambient environment. At neutral to basic conditions, the neutral species will be the dominant form of ethylbis(2-chloroethyl)amine, while acidic conditions will favor the protonated form. Protonated ethylbis(2-chloroethyl)amine will generally adsorb to organic carbon and clay more strongly than its neutral counterpart.

/HUMAN EXPOSURE STUDIES/ It has been observed that workers briefly exposed to nitrogen mustard in concn estimated to be between 10 and 100 ppm became severely ill with nausea, vomiting and dilated pupils. In normal human volunteers single oral doses of some mg resulted in nausea, vomiting and diarrhea. Large doses produce neurotoxic effects such as prolonged tremor, uncoordinated movements, ataxia, derangement of positional reflexes, and convulsions. /Chloroethylamines/

/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/ In contact with the skin and eye, the nitrogen mustards are severely vesicant and damaging, their action being similar to that of the sulfur variety of mustard gas but with more immediate effect and deeper injury. Accidental burns of human skin leading to deep and slow-to-heal ulcers, and accidental corneal damage, including the injury of iris and lens, have been reported. Industrially, irritation of the eyes, nose, skin and respiratory system occurs following exposure to vapor. Delayed pulmonary edema following accidental vapor exposure has been observed. /Chloroethylamines/

/SIGNS AND SYMPTOMS/ Ingestion is an uncommon route for exposure but can lead to local effects such as esophageal or gastrointestinal burns and systemic absorption. /Nitrogen mustards/

For more Human Toxicity Excerpts (Complete) data for ETHYLBIS(2-CHLOROETHYL)AMINE (6 total), please visit the HSDB record page.

The nitrogen mustards (including ethylbis(2-chloroethyl)amine) are not manufactured in significant commercial quantities in the United States and they were never stockpiled as part of the U.S. chemical warfare inventory (1). Although several of the nitrogen mustards have medicinal uses as antineoplastic agents, ethylbis(2-chloroethyl)amine does not appear to be used in the United States(2). Because these agents are not a significant part of the U.S. chemical warfare agent inventory, they are not anticipated to be released into the environment in any appreciable amount(1).

An estimated BCF of 7 was calculated for ethylbis(2-chloroethyl)amine(SRC), using an estimated log Kow of 2.0(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low, provided the compound is not altered physically or chemically once released into the environment(SRP).

The hydrolysis half-life of ethylbis(2-chloroethyl)amine is 12.5 days at 5 °C (pH not specified)(1). This suggests that hydrolysis will be an important fate process and will compete with volatilization in moist soils and water(SRC). The Henry's Law constant for ethylbis(2-chloroethyl)amine is estimated as 3.36X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 0.25 mm Hg(1), and water solubility, 160 mg/l(1). This Henry's Law constant indicates that the ethylbis(2-chloroethyl)amine neutral species is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life of the neutral species from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 3.6 hrs(SRC). The volatilization half-life of the neutral species from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 6.2 days(SRC). Ethylbis(2-chloroethyl)amine's estimated Henry's Law constant(1) indicates that volatilization of the neutral species from moist soil surfaces may occur(SRC). Ethylbis(2-chloroethyl)amine has a pKa of 6.57(3) and is expected to exist in both the protonated form and neutral species in the ambient environment. At neutral to basic conditions, the neutral species will be the dominant form of ethylbis(2-chloroethyl)amine, while acidic conditions will favor the protonated form. The protonated form of ethylbis(2-chloroethyl)amine is not expected to volatilize from water or moist soil surfaces(SRC). Ethylbis(2-chloroethyl)amine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Acute Exposure/ An acute head-only inhalation study was conducted in rats exposed for 1 hr to product solution (wastestream) resultant from the chemical neutralization of Chemical Agent Identification Sets (CAIS) containing agent (sulfur mustard (HD), nitrogen mustard (HN-1) or lewisite (L)) in chloroform. Groups of Sprague-Dawley rats were exposed to varying concentrations (24000, 18000, 12000 or 6000 ppm) of CAIS wastestream. An additional group was exposed to the vehicle (chloroform/t-butanol) only, at a concentration equivalent to the concentration of vehicle at the highest exposure level. Animals were evaluated for toxic effects, including assessment of toxicant-induced alterations to the ocular and respiratory systems. Mortality on exposure to 24000 ppm of test article or to vehicle alone was high. Mortality in the other exposure groups was roughly proportional to the concentration of test article (wastestream). Toxic signs were consistent with exposure to solvent system components (chloroform/t-butanol) and to agent decomposition products/by-products. Incidence and severity of ocular effects were similar in vehicle control and treatment groups.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Bone marrow depression may be observed ... with leukopenia and bleeding as an early sign. Alopecia may occur. They can cause impairment of menses and spermatogenesis; mutagenic activity has been proved. They can exert cytotoxic effects on the embryo ... Lymph node damage, involution of lymphatic tissues and the thymus, and immunosuppression may occur; intercurrent infections may come out. The development of tumors following exposure to some of these substances could be due to a direct chemical action or to impairment of the immune system or to both. Most of the very dangerous effects have been proved in animals only. /Chloroethylamines/

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In laboratory animal studies, prolonged or repeated exposures to nitrogen mustards have caused cancer, developmental and reproductive effects, and heptic toxicity. Repeated exposures result in cumulative effects because mustards are not naturally detoxified by the body. /Nitrogen mustards/

/LABORATORY ANIMALS: Neurotoxicity/ High doses of nitrogen mustards have caused tremors, seizures, incoordination, ataxia, and coma in laboratory animals. /Nitrogen mustards/

The rate constant for the vapor-phase reaction of ethyl(2-chloroethyl)amine with photochemically-produced hydroxyl radicals has been estimated as 1.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of approximately 1 day at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The hydrolysis half-life of ethylbis(2-chloroethyl)amine is 12.5 days at 5 °C (pH not specified)(2). The product of this hydrolysis is the nontoxic bis-beta-hydroxyethyl ethylamine(3). Nitrogen mustards are unstable in the presence of light and heat and form dimers at temperatures above 50 °C(3).

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. Ethylbis(2-chloroethyl)amine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 lbs.

HN1 (nitrogen mustard-1)

CUM 100g

CUM 100g

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

...The chloroethylamines (or metabolites) react readily with important groups of proteins and nucleic acids. They transfer alkyl groups to essential cell constituents by combining with amino, sulfhydryl, carboxyl, and phosphate groups. ...The alkylation of DNA and, more specifically, guanine, results in the formation of single strand breaks or interstrand crosslinks and, ultimately, in an inhibition of DNA synthesis. A marked decrease of the RNA chain length in both nucleoplasm and nucleolus of some cells... under the influence of nitrogen mustard has been proved. Lesions can be produced which affect base pairing during DNA replication and cause permanent genetic alterations or tumor initiation. /Chloroethylamines/

Nitrogen mustards are absorbed through the skin, respiratory and GI tract ... /Chloroethylamines/

Absorption may occur after skin or eye exposure to liquid or vapor nitrogen mustard and may cause systemic toxicity. .../Nitrogen mustards/ ...are highly reactive and combine rapidly with proteins, DNA, or other molecules. Therefore, within minutes following exposure intact mustard or its reactive metabolites are not found in tissue or biological fluids. /Nitrogen mustards/

Nitrogen mustards were first developed in the late 1920s and early 1930s. HN-1 was originally designed to remove warts but was later identified as a potential chemical warfare agent; None of the nitrogen mustards have been used on the battlefield, and none are included in U.S. stockpiles. [ATSDR MMG]

Warfare /blister/ agent

...Originally designed to remove warts... .

HN-1 is one of three nitrogen mustard blister agents (vesicants). Nitrogen mustards have not previously been used in warfare. The properties of nitrogen mustards are only slightly different from those of sulfur mustards, another major class of blister agents. However, exposure to nitrogen mustards may be more immediately toxic than exposure to sulfur mustard. Nitrogen mustards are alkylating agents that affect DNA and other molecules in the body. Exposure to nitrogen mustard damages the eyes, skin, and respiratory tract and suppresses the immune system. Although the nitrogen mustards cause cellular changes within minutes of contact, the onset of pain and other symptoms is delayed. Exposure to large amounts can be fatal. HN-1 has a faint fishy or musty odor. It evaporates slowly.

Ethanamine, 2-chloro-N-(2-chloroethyl)-N-ethyl-: ACTIVE

Bis(2-chloroethyl)ethylamine is listed as a Schedule 1 chemical.

Nitrogen mustards were first developed in the late 1920s and early 1930s. HN-1 was originally designed to remove warts but was later identified as a potential chemical warfare agent; HN-2 was designed as a military agent but was later used in chemotherapy; HN-3 was developed as a military agent. None of the nitrogen mustards have been used on the battlefield, and none are included in U.S. stockpiles.