eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Ammonia

Author: Steven Issley, MD, FRCPC, Assistant Professor of Emergency Medicine, Assistant Director of Medical Stimulation Center, Consulting Staff, Department of Emergency Medicine, SUNY-Downstate Medical Center, Kings County Hospital Center
Coauthor(s): Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital
Contributor Information and Disclosures

Updated: Mar 14, 2007

Introduction

Background

At room temperature, ammonia (NH₃) is a highly water-soluble, colorless, irritant gas with a unique pungent odor. Ammonia has a boiling point of -33°C and an ignition temperature of 650°C.

In 1993, anhydrous ammonia was the third most produced chemical by volume in the US. The farming industry uses approximately one third of the ammonia produced in the US as a component of fertilizer and animal feed. Industrial injury most often results from ammonia leaks in fertilizer tanks and hoses and toxic ammonia levels in animal buildings. Swine confinement buildings are particularly notorious for containing toxic levels of ammonia that often exceed threshold limit values. Because ammonia is liberated during combustion of nylon, silk, wood, and melamine, firefighters also are at risk for exposure to this irritant gas.

Before the 1970s, liquid ammonia stored under high pressure was widely used for refrigeration. Although Freon largely has replaced ammonia as a refrigerant, ammonia refrigeration is still used and numerous case reports exist of severe toxicity following accidental exposure.

Ammonia also is used in the production of explosives, pharmaceuticals, pesticides, textiles, leather, flame-retardants, plastics, pulp and paper, rubber, petroleum products, and cyanide. Furthermore, ammonia is a major component of many common household cleaning and bleaching products (eg, glass cleaners, toilet bowel cleaners, metal polishes, floor strippers, wax removers, smelling salts).

Permissible levels of exposure to toxic gases are defined by time-weighted average (TWA), short-term exposure limit (STEL), and concentration at which toxic gasses are immediately dangerous to life or health (IDLH). The TWA is defined as the concentration for an 8-hour workday of a 40-hour workweek that nearly all workers can be exposed to without adverse effects. Similarly, the STEL is the concentration to which an exposure of longer than 15 minutes is potentially dangerous and may produce immediate or chronic compromise to health. Anhydrous ammonia has a TWA of 25 ppm, an STEL of 35 ppm, and an IDLH of 500 ppm.

Although injury from ammonia most commonly is caused by inhalation, it also may follow ingestion or direct contact with eyes or skin. The clinical presentations of these injuries and their investigation and treatment are discussed in this article; chloramine gas inhalation injury also is discussed.

Pathophysiology

The most common mechanism by which ammonia gas causes damage occurs when anhydrous ammonia (liquid or gas) reacts with tissue water to form the strongly alkaline solution, ammonium hydroxide.

NH₃ + H₂ O ® NH₄ OH

This reaction is exothermic and capable of causing significant thermal injury.

Ammonium hydroxide also causes severe alkaline chemical burns to skin, eyes, and especially the respiratory system. Mild exposures primarily affect the upper respiratory tract, while more severe exposures tend to affect the entire respiratory system (see Clinical). The gastrointestinal tract also may be affected if ammonia is ingested.

Tissue damage from alkali is caused by liquefaction necrosis and typically penetrates far deeper than that caused by an equipotent acid. In the case of ammonium hydroxide, the tissue breakdown liberates water, thus perpetuating the conversion of ammonia to ammonium hydroxide. In the respiratory tract, this results in the destruction of cilia and the mucosal barrier to infection. Furthermore, secretions, sloughed epithelium, cellular debris, edema, and reactive smooth muscle contraction cause significant airway obstruction.

Airway epithelium can regain barrier integrity within 6 hours following exposure if the basal cell layer remains intact. However, damaged epithelium often is replaced by granular tissue, which may be one of the etiologies leading to chronic lung disease following ammonia inhalation injury.

Liquid anhydrous ammonia (-33°C) freezes tissue on contact. To put this in perspective, critical skin damage begins at -4°C and becomes irreversible at -20°C. The degree of tissue injury, however, is proportional to the duration and concentration of exposure.

Similarly, damage to the respiratory system is proportional to depth of inhalation, duration of exposure, concentration, and pH of the gas or liquid.

Ammonia is a product of protein catabolism and is metabolized by the liver. Normal blood ammonia levels range from 80-110 mcg/dL. This increases 10% with exposure to 25 ppm but is not considered harmful. Theoretically, patients with liver dysfunction are at increased risk for ammonia toxicity; however, currently no sufficient clinical evidence can confirm this.

Frequency

United States

Similar to previous years, in 2002, US poison control centers reported nearly 6000 cases of toxic ammonia exposure. Of exposures, 93% were unintentional, and 11% resulted in moderate to severe outcomes. Of note, in cases of household exposure, only 5% were moderate to severe.

Age

Of the 6000 toxic ammonia exposures reported in the American Association of Poison Control Centers' 2002 Annual Report, 70% occurred in adults and 20% occurred in children younger than 6 years.

• Ingestion of household solutions usually is accidental and occurs in young children; adult ingestions, however, most often are suicide attempts.
• Inhalation injury is almost always accidental. Because inhalation exposure generally occurs in an industrial setting, it usually is associated with working adults.

Clinical

History

• Gaseous ammonia effects at various concentrations are as follows:
  • 25 ppm or less - TWA
  • 25-50 ppm - Detectable odor; unlikely to experience adverse effects
  • 50-100 ppm - Mild eye, nose, and throat irritation; may develop tolerance in 1-2 weeks with no adverse effects thereafter
  • 140 ppm - Moderate eye irritation; no long-term sequelae in exposures of less than 2 hours
  • 400 ppm - Moderate throat irritation
  • 500 ppm - IDLH
  • 700 ppm - Immediate eye injury
  • 1000 ppm - Directly caustic to airway
  • 1700 ppm - Laryngospasm
  • 2500 ppm - Fatality (after half-hour exposure)
  • 2500-6500 ppm - Sloughing and necrosis of airway mucosa, chest pain, pulmonary edema, and bronchospasm
  • 5000 ppm - Rapidly fatal exposure
• Inhalation injury
• • Because of its high water solubility, ammonia has a tendency to be absorbed by the water-rich mucosa of the upper respiratory tract. However, unlike most highly water-soluble irritant gases that tend to affect exclusively the upper respiratory tract, ammonia can damage proximally and distally.
  • In 1941, Caplin was the first to classify victims of accidental ammonia exposure; he described them as mild, moderate, and severe. Patients in the mild group presented with conjunctival and upper respiratory inflammation and pain but showed no signs of respiratory distress. The moderate group presented similarly but with more exaggerated symptoms. The severe group presented in frank respiratory distress with productive cough, pulmonary edema, and dysphagia.
  • Following a brief ammonia exposure, damage generally is limited to the upper airway mucosa. Brief exposures at very high concentrations, however, can be overwhelming and affect the entire respiratory system. People who are capable of escaping their environment usually are not subject to severe exposures, because they can flee upon detection of ammonia's pungent odor; furthermore, absence of symptoms following inhalational exposure to ammonia essentially rules out significant injury.
  • Pain (oropharyngeal, retrosternal)
  • Dyspnea, hemoptysis - As expected, individuals with reactive airway disease, such as asthmatics, are particularly sensitive to ammonia inhalation.
  • Hoarseness
  • Dysphagia
  • Loss of consciousness
• Farming industry
  • In enclosed animal confinement buildings, ammonia is adsorbed by dust particles that transport it more directly to small airways. Because of this synergistic effect, symptoms have reportedly developed within minutes of entering animal confinement buildings.
  • Symptoms include rhinorrhea, scratchy throat, chest tightness, cough, dyspnea, and eye irritation and usually subside within 24-48 hours.
• Contact - Burns and cold injury
• • Gaseous ammonia combines with water of the skin, eyes, and airways to form ammonium hydroxide. This exothermic reaction results in both heat and chemical burns. Liquid ammonia freezes tissue on contact and may cause full-thickness tissue damage that penetrates deeper than the more conspicuous superficial chemical burns.
  • Concentrations greater than 10,000 ppm are required to cause skin damage. The eyes begin to feel irritated at concentrations of 50-100 ppm; at 700 ppm, immediate eye damage occurs.
• Ingestion
• • Typical household ammonia products (3-10% ammonium hydroxide) have a pH less than 12.5, although the pH of industrial solutions (up to 30% ammonium hydroxide) is often greater than 13. Because caustic alkali burns generally are thought to occur when pH is greater than 12.5, ammonia ingestions in the home usually do not lead to significant damage. However, Klein et al reported 3 cases of oropharyngeal and esophageal injury following intentional ingestion of household solutions with a pH less than 12.
  • Patients present with oropharyngeal, epigastric, and retrosternal pain.
  • Abdominal pain and other gastroenterologic symptoms may occur if ingestion causes viscus perforation (perforation may occur up to 24-72 hours postingestion).
  • Respiratory symptoms may be present if aspiration pneumonia or pneumonitis complicates ingestion.
  • Smelling salts are a less common source of household ammonia ingestion. Often in capsule form, smelling salts, which contain approximately 20% ammonia, release a pungent odor when broken. Smelling salts are found in many first-aid kits as a treatment for syncope; unfortunately, children sometimes bite into them, resulting in minor esophageal burns and mild respiratory symptoms.

Physical

• Inhalation injury
• • Head, ears, eyes, nose, throat (HEENT) - Facial and oral burns and ulceration
  • Respiration - Tachypnea, oxygen desaturation, stridor, drooling, cough, wheezing, rhonchi, and decreased air entry
  • Central nervous system (CNS) - Loss of consciousness (if exposure is massive)
• Contact - Burns and cold injury
• • Skin - Alkali burns to the skin are yellow, soapy, and soft in texture. When burns are severe, skin turns black and leathery.
  • HEENT - Burns to the eye penetrate particularly deeply and rapidly, leading to destruction of the inner structures within 2-3 minutes; this may progress to globe perforation. Ammonia typically causes more corneal epithelium and lens damage than other alkalis. Intraocular pressure and pH of the anterior chamber rise, resulting in a syndrome similar to acute narrow-angle glaucoma. Other symptoms include iritis, corneal edema, semi-dilated fixed pupil, and eventual cataract formation.
• Ingestion
• • Cardiovascular - With intentional ingestion, hypovolemic shock may occur because of vomiting and third-spacing of intravascular fluid.
  • HEENT - Symptoms include edema of the lips, oropharynx, and upper airway.
  • GI - Patient may experience epigastric tenderness; mediastinitis and peritoneal signs may be present with viscus perforation, which can occur as late as 24-72 hours postingestion.
  • Respiratory - Aspiration pneumonia and pulmonary edema may occur.

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