Nitrogen Mustards

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Nitrogen mustards are vesicants (blister agents) and alkylating agents. They are colourless to pale yellow, oily liquids that evaporate slowly. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1] They are also known by their military designations of HN-1, HN-2, and HN-3. [2] HN-1 has a faint, fishy or musty odour. It is sparingly soluble in water but miscible with acetone and other organic solvents. At temperatures greater than 194ºC, it decomposes. HN-2 has a fruity odour at high concentrations and a soapy odour at low concentrations. Its solubility is similar to HN-1. HN-3 is odourless when pure but has been reported to have a butter almond odour. It is the most stable of the nitrogen mustards but decomposes at temperatures greater than 256ºC. It has a much lower vapour pressure than HN-1 or HN-2 and is insoluble in water. [1]

 

Uses [2]

 

  • HN-1 originally was 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 cancer treatment. Other treatment agents now have replaced it.
  • HN-3 was designed solely as a military agent.

 

Sources and Routes of Exposure

 

Sources of Exposure [2]

 

  • If nitrogen mustards are released into the air as a vapour, you could be exposed through skin contact, eye contact, or breathing.
  • If nitrogen mustards are released into water, you could exposed by drinking the contaminated water or getting it on your skin.
  • You could be exposed by coming in direct contact with liquid nitrogen mustards.
  • Because it is heavier than air, nitrogen mustard vapour will settle in low-lying areas.

 

Routes of Exposure [1]

 

  • Inhalation: Inhalation is an important route of exposure. Nitrogen mustard vapours are heavier than air. The LCt50 (the product of concentration times time that is lethal to 50% of the exposed population by inhalation) is approximately 1,500 mg-min/m³ for HN-1 and HN-3, and 3,000 mg-min/m³ for HN-2.
  • Skin/Eye Contact: Exposure to nitrogen mustard vapour can cause injury to the eyes, skin, and mucous membranes at low concentrations. Direct contact with the liquid can cause skin and eye burns. The median incapacitating dose for the eyes is 100 mg-min/m³ for HN-2 and 200 mg-min/m³ for HN-1 and HN-3. Absorption may occur after skin or eye exposure to liquid or vapour nitrogen mustard and may cause systemic toxicity.
  • Ingestion: Ingestion is an uncommon route for exposure but can lead to local effects such as oesophageal or gastrointestinal burns and systemic absorption.

 

Health Effects [4]

 

Acute Exposure

 

Nitrogen mustards are vesicants and alkylating agents; however, the mechanisms of action are not clearly understood. They 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.

  • CNS: High doses of nitrogen mustards have caused tremors, seizures, incoordination, ataxia, and coma in laboratory animals.
  • Respiratory: Damage to the mucosa of the airways begins within hours and may progress over several days. Nasal and sinus pain or discomfort, pharyngitis, laryngitis, cough, and dyspnea may occur. Pulmonary oedema is uncommon.
  • Gastrointestinal: Ingestion may cause chemical burns of the GI tract and haemorrhagic diarrhoea. Nausea and vomiting may occur following ingestion, dermal, or inhalation exposure.
  • Ocular: Exposure to nitrogen mustard vapour or liquid may cause intense conjunctival and scleral inflammation, pain, swelling, lacrimation, photophobia, and corneal damage. High concentrations can cause burns and blindness.
  • Dermal: Direct skin exposure to nitrogen mustards causes erythema and blistering. Generally, a rash will develop within several hours, followed by blistering within 6 to 12 hours. Prolonged contact, or short contact with large amounts, may result in second- and third-degree chemical burns.
  • Hematopoietic: Systemic absorption of nitrogen mustard may induce bone marrow suppression and an increased risk for fatal complicating infections, haemorrhage, and anaemia.
  • Delayed Effects: Chemotherapeutic doses of HN-2 have been associated with menstrual irregularities, alopecia, hearing loss, tinnitus, jaundice, impaired spermatogenesis, generalised swelling, and hyperpigmentation.
  • Potential Sequelae: Chronic respiratory and eye conditions may persist following exposure to large amounts of nitrogen mustards. Narrowing of the oesophagus and severe corrosive damage to the stomach lining can result from ingesting formalin.

 

Chronic Exposure

 

In laboratory animal studies, prolonged or repeated exposures to nitrogen mustards have caused cancer, developmental and reproductive effects, and hepatic toxicity. Repeated exposures result in cumulative effects because mustards are not naturally detoxified by the body.

 

Carcinogenicity

 

The International Agency for Research on Cancer (IARC) has classified nitrogen mustard as probably carcinogenic to humans (Group 2A). There is some evidence that it causes leukaemia in humans, and it has been shown to cause leukaemia and cancers of the lung, liver, uterus, and large intestine in animals.

 

Reproductive and Developmental Effects

 

Nitrogen mustards may decrease fertility. A few case reports have linked treatment with HN-2 to foetal abnormalities in humans. Nitrogen mustards have produced developmental effects in animals.

 

Safety

 

First Aid Measures [5]

 

  • EYES: First check the victim for contact lenses and remove if present. Flush victim’s eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control centre. Do not put any ointments, oils, or medication in the victim’s eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.
  • SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control centre even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas.
  • INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.
  • INGESTION: DO NOT INDUCE VOMITING. Corrosive chemicals will destroy the membranes of the mouth, throat, and oesophagus and, in addition, have a high risk of being aspirated into the victim’s lungs during vomiting which increases the medical problems. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control centre. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim’s airway is open and lay the victim on his/her side with the head lower than the body. Transport the victim IMMEDIATELY to a hospital.
  • OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

 

Pre-Hospital Management [4]

 

  • Victims whose skin or clothing is contaminated with liquid nitrogen mustard can contaminate rescuers by direct contact or through off-gassing vapour.
  • There is no antidote for nitrogen mustard toxicity.
  • Decontamination of all potentially exposed areas within minutes after exposure is the only effective means of decreasing tissue damage.

 

Hot Zone

 

Rescuers should be trained and appropriately attired before entering the Hot Zone. If the proper equipment is not available, or if the rescuers have not been trained in its use, call for assistance from the U.S. Soldier and Biological Chemical Command-Edgewood Research Development and Engineering Centre.

 

  • Rescuer Protection: Nitrogen mustard vapour and liquid are readily absorbed by inhalation and ocular and dermal contact.
  • Respiratory Protection: Pressure-demand, self-contained breathing apparatus (SCBA) is recommended in response situations that involve exposure to any amount of nitrogen mustard.
  • Skin/Ocular Protection: Personal protective equipment (PPE) and butyl rubber chemical protective gloves are recommended at all times when these chemicals are suspected to be involved.
  • Multi-Casualty Triage: Chemical casualty triage is based on walking feasibility, respiratory status, age, and additional conventional injuries. The triage officer must know the natural course of a given injury, the medical resources immediately available, the current and likely casualty flow, and the medical evacuation capabilities. General principles of triage for chemical exposures are presented in the box on the following page. There are four triage categories: immediate (priority 1), delayed (priority 2), minimal (priority 3), and expectant (priority 4). Before transport, all casualties must be decontaminated. If needed, consult with the base station physician or the regional poison control centre for advise concerning management of multiple casualties. Because most signs and symptoms of nitrogen mustard exposure do not occur for several hours postexposure, patients should be observed for at least 6 hours or sent home with instructions to return immediately if symptoms develop. Patients who develop significant dermal, ocular, or airway injury and patients who have ingested nitrogen mustard should be transported to a medical facility for evaluation. Symptoms may not develop for 24 hours. Patients with mild symptoms who are seen long enough after exposure to minimise the likelihood that the lesions will worsen may be sent home after their names, addresses, and telephone numbers have been recorded. They should be advised to rest and to seek medical care promptly if additional symptoms develop (see Follow-up Instructions included with the Nitrogen Mustard Patient Information Sheet). Consult with the base station physician or closest Metropolitan Medical Response System, or the regional poison control centre for advice regarding triage of multiple victims.

 

Chemical Dangers [4]

 

  • HN-1 is corrosive to iron alloys beginning at 149°F (65°C).
  • Toxic intermediate products are produced during hydrolysis of HN-1.
  • Contact with metals may evolve flammable hydrogen gas.

 

Explosion Hazards

 

  • No immediate danger of fire or explosion.
  • When heated, vapours may form explosive mixtures with air, presenting an explosion hazard indoors, outdoors, and in sewers.
  • Containers may explode when heated.

 

Fire Fighting Information

 

  • HN-1 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).

 

Regulation

 

United States [7]

 

No occupational exposure limits have been established for nitrogen mustard. However the United States Military has established a TLV (threshold limit value) of 0.003mg/m3.

 

References

 

  1. http://www.dhd2.org/files/Nitrogen.pdf
  2. http://emergency.cdc.gov/agent/nitrogenmustard/basics/facts.asp
  3. http://www.atsdr.cdc.gov/toxfaqs/tf.asp?id=921&tid=189
  4. http://www.atsdr.cdc.gov/MMG/MMG.asp?id=920&tid=189
  5. http://cameochemicals.noaa.gov/chemical/20776
  6. http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750010.html
  7. http://nj.gov/health/eoh/rtkweb/documents/fs/1377.pdf

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