CBRNE - Lung-Damaging Agents, Toxic Smokes - NOx, HC, RP, FS, FM, SGF2, Teflon 

Smokes and obscurants long have been used by the military as a means of hiding troops, equipment, and certain areas from view of the opposing forces and from engagement by weapons with electro-optical control systems. In the past, smoke also has been a form of communication and identification. Smokes are not unique to the military but also are produced in industry by explosion, by mechanical generation, or as a by-product of a chemical interaction. Smoke is made of solid particles of varying sizes that are suspended in air. Although smokes typically are not used as direct chemical agents, they may produce toxic injury to skin, eyes, and all parts of the respiratory tract.

Although most smokes used for obscuring purposes are not concentrated enough to be hazardous, any smoke can be hazardous to health if the concentration is sufficient or if the exposure is long enough. The smoke itself can be directly toxic, or it may carry, adsorbed to the particulate surface, any of a variety of toxic gaseous substances that interact with mucosa, skin, or any surfaces of the airway. Smokes consist of particles of various sizes, sedimentation rate, and impact rate. Therefore, smoke inhalation has a complex distribution pattern at various levels in the airway.

This article reviews the pathophysiology and toxic effects of lung and airway injury caused by different smokes: the oxides of nitrogen (NOx), zinc oxide (HC), red phosphorus (RP), sulfur trioxide (FS), titanium tetrachloride (FM), standard gas fuel-2 (ie, fog oil [SGF2]), and pyrolysis of Teflon.

Oxides of nitrogen

NOx are components of photochemical smog, usually approximately 0.053 ppm. Nitrogen dioxide exists as a mixture of nitrogen dioxide, a reddish brown gas, and nitrogen tetroxide, a colorless gas. Other forms of nitrogen oxide include nitrous oxide, which is a common anesthetic or (when given without oxygen) asphyxiant, and nitric oxide, which quickly decomposes to nitrogen dioxide in the presence of moisture.

Zinc oxide

HC smoke, also termed "white smoke," is a mixture of equal amounts of hexachloroethane, zinc oxide, and approximately 7% grained aluminum or aluminum powder. Upon combustion, the pyrotechnic mixture of zinc chloride and hexachloroethane rapidly absorbs moisture from the air to form a grayish white smoke. More humid air results in thicker smoke. Other chemicals also are released in the combustion process, such as chlorinated hydrocarbons (eg, phosgene and carbon tetrachloride), chlorine gas, carbon monoxide, and several other compounds.

HC smoke resulted from the French and US Chemical Warfare Service, which, after World War I, sought an obscurant that was not fraught with as many difficulties as white phosphorus. HC has a sweetish acrid odor, even at moderate concentrations. Although HC can irritate the upper airway mucous membranes, it probably is studied most for its role in fume fever.

Red phosphorus

After World War II, RP smoke was developed as an attempt to avoid the toxicity associated with the manufacturing of white phosphorus. RP is 95% phosphorus in a 5% butyl rubber base and provides an adequate tank screen on the battlefield. When RP is oxidized, it forms a mixture of phosphorus acids. When these acids are exposed to water vapor, they in turn form polyphosphoric acids, which may be responsible for the toxic injuries to the upper airways. Most of these injuries are mild irritations. No human deaths have been reported from exposure to either white phosphorus or RP smokes.

Sulfur trioxide

FS, also known as sulfuric oxide, chlorosulfonic acid, or sulfuric anhydride, is typically a colorless liquid, which can exist as ice, fiberlike crystals, or gas. When it is exposed to air, it rapidly takes up water and forms white fumes. The smoke consists of 50% sulfur trioxide and 50% chlorosulfonic acid. It usually is dispersed by spray atomization. The sulfur trioxide evaporates from spray particles, reacts with surrounding moisture, and forms sulfur acid. The sulfur acid condenses into droplets that produce a dense white cloud. FS is extremely corrosive, which led to its disuse in the army.

Titanium tetrachloride

FM is a colorless – to – pale yellow liquid that has fumes with a strong odor. Once it comes in contact with water, it rapidly forms hydrochloric acid and titanium compounds. It is used to make titanium metal, white pigment in paints, and other products. It breaks down rapidly in the environment.

FM readily hydrolyzes in the presence of water or moist air via an exothermic reaction that occurs in 2 stages. First, FM reacts to form a highly dispersed particulate smoke. This smoke reacts with more moisture in the air to form hydrolytic products of FM such as hydrochloric acid, titanium oxychlorides, and titanium dioxide. Generation of the smoke has been used as screens in military operations. The formation of hydrochloric acid makes it irritating and corrosive.

When FM liquid is exposed to the air, it produces white fumes. These white fumes can come into contact with skin, where a mild epithelial irritation results and usually subsides within 24 hours. When it is mixed with water, it generates a vigorous exothermic reaction that produces both heat and hydrochloric acid, which can work synergistically to produce deep thermal burns.

Oil fog

SGF2 is one type of chemical smoke obscurant used in the military. SGF2 is generated by injecting a light petroleum-based lubricating oil onto a heated engine exhaust manifold, causing the oil to vaporize and eventually recondense in the atmosphere. Any industry that generates an oil mist also may produce similar exposures. Petroleum oil smokes are the least toxic smokes. They seldom produce ill effects even after prolonged or multiple exposures.

Teflon particles

Teflon (polytetrafluoroethylene [PTFE]) is used widely in a variety of industrial and commercial settings such as lubricants and fabric treatments. Its lubricity, high dielectric constant, and chemical inertness make it a desirable component in military vehicles such as tanks and aircraft. Closed-space fires in such settings have prompted studies of the toxicity of exposure to the by-products created from incinerated organofluorines. Pyrolysis of PTFE produces a particulate smoke, which, if inhaled, produces a constellation of symptoms termed polymer fume fever (PFF).

Oxides of nitrogen

Inhalation of nitric oxide causes the formation of methemoglobin. Inhalation of nitrogen dioxide results in the formation of nitrite, which leads to a fall in blood pressure, production of methemoglobin, and cellular hypoxia. Inhalation of high concentrations causes rapid death without the formation of pulmonary edema. Milder yet still severe exposures may result in death with production of yellow frothy fluid in the nasal passages, mouth, and trachea and marked pulmonary edema. The symptoms following the inhalation of NOx are mostly due to nitrogen dioxide.

Zinc oxide

HC is probably the most acutely toxic of the military smokes and obscurants. HC's toxicity mainly is attributed to the irritating effects of zinc chloride. Most likely, carbon monoxide, phosgene, hexachloroethane, and other products contribute to the observed respiratory effects. While upper respiratory tract damage can occur from zinc chloride, the mean diameter of the primary smoke particles is approximately 0.1 micrometers, allowing them to reach the alveoli.

Studies have demonstrated that HC exposure can produce a gradual decrease in total lung capacity, vital capacity, and diffusion capacity of carbon monoxide (DLCO). It also is associated with the presence of pulmonary edema, increased airway resistance, and decreased compliance. When these episodic exposures were stopped, the changes were reversible.

Lung injury comes primarily from the zinc chloride product of HC combustion. In a retrospective cohort study of 20 patients, Hsu et al correlated findings on high-resolution CT with pulmonary function tests (PFTs) performed within 3-21 days following acute exposure.^[1] CT findings were predominantly diffuse ground-glass opacities in the lung parenchyma. PFTs showed a restrictive functional impairment with significant reduction in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), total lung capacity (TLC), and diffusing capacity of lung for carbon monoxide (D_LCO) without impairment of FEV₁/FVC ratio. Follow up in 1-2 months showed significant improvement with mild-to-moderate exposures. Severe exposures led to interstitial fibrosis and continued functional limitation.

In a study by Conner et al performed with guinea pigs, exposure to ultrafine HC particles (0.05 µm) in increasing degrees was associated with a dose-response elevation in protein, neutrophils, and angiotensin-converting enzyme found in lavage fluid.^[2] A direct relationship also was observed with alkaline phosphatase, acid phosphatase, and lactate dehydrogenase in lavage fluid. Centriacinar inflammation was seen histologically, indicating evidence of pulmonary damage.

An interesting study by Marrs et al involving mice, rats, and guinea pigs demonstrated a positive association of alveologenic carcinoma in a dose-response trend to HC smoke as well as a variety of inflammatory changes.^[3] The article states that hexachloroethane and zinc, as well as carbon tetrachloride (which may be present in HC smoke), may be animal carcinogens in certain circumstances. This raises the suspicion of HC as a potential carcinogen.

Metal fume fever (MFF) is a well-documented acute disease induced by intense inhalation of metal oxides. The exact pathology is not well understood but likely involves the deposition of fine metal particulates in the alveoli that results in a self-limited syndrome of fever, myalgias, headache, and nausea 4-12 hours after exposure to metal fumes. MFF is primarily associated with the inhalation of zinc oxide fumes that are produced when zinc-oxide coated steel (galvanized) or zinc containing alloys (eg, brass) are exposed to high temperatures.

Keyes found that 1 in 5 welders has experienced MFF by age 30.^[4] A study by Kuschner et al on human volunteers showed that pulmonary cytokines such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and interleukin 8 (IL-8) may play important initial roles in mediating metal fume fever.^[5] Symptoms of MFF typically last several hours. Severe cases generally resolve in 1-2 days. Observation is usually all that is necessary.

Hepatotoxicity has also been described in humans exposed to HC/ZnO smokes in enclosed spaces during military training.^[6] The toxic effects appear to be primarily due to the chlorinated compounds produced by combustion: tetrachloromethane, tetrachloroethylene, hexachlorobenzene, and carbon tetrachloride. This last compound is well known for its hepatotoxicity. Acute exposure causes elevated liver enzyme levels by day 1 or 2, with a peak around day 18-21. Liver function test results should normalize by 6 weeks.

Red phosphorus

Most of the pathologic consequences associated with phosphorus are from elemental white phosphorus fumes or vapor. Contact with elemental phosphorus can cause burns to body surfaces. A well-described condition termed phossy jaw is associated with longer-term occupational exposures to airborne phosphorus fumes. This disease is a degenerative condition affecting the entire oral cavity including soft tissue, teeth, and bones. Massive necrosis of teeth, bone, and soft tissue can lead to life-threatening infections. Treatment typically consists of soft tissue and bone debridement, abscess drainage, and reconstructive surgery.

White phosphorus and RP smokes may cause respiratory tract irritation after 2-15 minutes of exposure. This probably is caused by the polyphosphoric acids that react with moist mucosal membranes. Respiratory tract irritation has been observed at concentrations of 187 mg phosphorus pentoxide equivalents per cubic meter for 5 minutes or longer. Intense congestion, edema, and hemorrhages were observed in lung tissue following a 1-hour exposure at varying concentrations in studies using rats, mice, and goats.

Sulfur trioxide

Since FS is an intermediate used to produce sulfuric acid upon its reaction with moisture, the resulting toxicity is that of an acidic irritation to mucosal membranes and even skin. The corrosive effect of acid on mucosa and keratinized skin causes significant irritations and chemical burns.

Titanium tetrachloride

The same pathophysiologic effects that occur with FS smoke occur with FM smoke, since both are associated with the production of corrosive and irritating acids.

Oil fog

Concentrations of oil mists in industrial settings vary over a wide range (0.8-50 mg/m³), with most at 3 mg/m³. The particle sizes also vary more than 1-5 µm in median diameter. They typically have a high molecular weight and are saturated hydrocarbons derived from distilled petroleum. Exposures to such smoke are likely to last for many hours in a single day or repeatedly over consecutive days.

Animal studies have demonstrated, after chronic exposure, that pulmonary function endpoints such as total lung capacity, vital capacity, residual volume, D _LCO , compliance, and end-expiratory volume were unaffected by oil fog. One exception exists; male rats exposed at 1.5 mg/L had decreased end-expiratory volume.

Bronchiolar lavage and histopathology showed changes consistent with a mild inflammatory edema (ie, increased protein content, total cells, polymorphonuclear leukocytes [PMNs], macrophages).

Teflon particles

Pyrolysis of Teflon occurs at approximately 450°C. The mixture of particles that is produced contains a substance called perfluoroisobutylene (PFIB), which appears to be the main cause of toxicity in polymer fume fever. The ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which suggests an oxidative injury. PMNs may regulate the inflammatory process with cytokine and antioxidant expression.

PFIB particles cause an extremely rapid toxic effect on pulmonary tissues. Evidence of microscopic perivascular edema is observed within 5 minutes. Less intense exposures are followed by a latent period during which normal physiologic compensatory measures to control developing pulmonary edema ensue. Once these mechanisms are overcome, the time frame of which depends on the degree of exposure, the clinical syndrome of fume fever follows. More intense exposures also may produce a chemical conjunctivitis. Hemorrhagic inflammation of the lungs also can occur.