Medical Aspects of Chemical Warfare (2008) - The Black Vault

Toxic Inhalational Injury and Toxic Industrial Chemicalshigh temperature arc welding, and the production andtransport of nitric acid. N 2O may also be produced inthe dipping of aluminum, brass, and copper and incombustion and pyrolysis processes. 21Polytetrafluoroethylene (Teflon [Dupont, Wilmington,Del]) can form toxic gases when heated totemperatures above 400ºC. Combustion and pyrolysisbyproducts of Teflon, which have been known for sometime, have been implicated in pulmonary injury andeven deaths following a single exposure. 22 Illnessescaused by the inhalation of combustion byproductshave been given the label “polymer fume fever.” One ofthe more common byproducts is perfluoroisobutylene(PFIB), which is reportedly 10 times more toxic thanphosgene. 23Phosgene has been used extensively for the past 60years in the production of pharmaceuticals, anilinedyes, polyfoam rubber, isocyanates, and plastic productsin the United States and worldwide. In 1998 theUnited States used 4.3 million pounds of phosgenein manufacturing processes. 24 Phosgene is used ina “phosgenation” reaction to help supply chlorinegroups to reaction products. Babad and Zeiler 25 havereviewed phosgene chemical reactions, finding thatphosgene rapidly reacts with water to form carbondioxide and hydrochloric acid, and it also reacts withmacromolecules containing sulfhydryl, amine, andhydroxyl groups in aqueous solutions. Phosgene canbe formed by the thermal decomposition of chlorinatedhydrocarbons and poses a threat for welders,refrigeration mechanics, and automobile mechanics. 26Commonly used industrial degreasers contain chlorinatedhydrocarbons, such as perchloroethylene, whichcan form phosgene when heated. Therefore, industrialworkers, fire fighters, military personnel, and othersare at risk for accidental or occupational exposure tophosgene. In Poland, for example, because of heavyindustrialization in proximity to densely populatedareas, phosgene, along with chlorine, ammonia, andsulfur dioxide, has been identified as one of the mostsignificant threats to the environment. 27Smoke is a general classification of a complexmixture of particulate/gaseous emissions. Smokesare products of the combustion process of burning orsmoldering. The major cause of death from fire-relatedevents is smoke inhalation. Smoke can include manyof the chemicals mentioned earlier. Particulate mattersuch as carbon soot particles can make up a significantproportion of toxic smoke, as can carbon monoxide,HCN, phosgene, aldehydes such as formaldehyde,ammonia, and PFIB.Sulfur dioxide is a major air pollutant and a principalsource of photochemical smog and acid rain. Acolorless, water-soluble gas 2.26 times heavier thanwater, sulfur dioxide is used in a number of industrialprocesses such as the smelting production of copper,iron, lead, and zinc ores. When it comes into contactwith moist surfaces, sulfur dioxide is hydrolyzed andoxidized to form sulfuric acid. It is extremely corrosiveto the nasopharynx region, eyes, and upper airways.Inhalation exposure may progress to acute respiratorydistress syndrome (ARDS) and has been implicated incausing RADS. 28 Prolonged exposure causes inflammationof the airways and impairs the immune systemand lung resistance. 29 Table 10-4 provides a very limitedoverview of some well-known gaseous irritants.Mechanisms of ToxicityNumerous studies have been undertaken to determinethe mechanisms of toxicity and the basis for lunginjury from exposure to toxic gases. These investigationshave historically involved animal models. Asearly as 1919 the progression and intensity of exposureto agents such as phosgene was demonstrated in dogs.In later decades, animal models included mice, rats,guinea pigs, swine, and monkeys to more accuratelypredict the temporal effects of injury progression andscope in humans. Many of these models involvedthe use of inhalation techniques, focused essentiallyon the establishment of a fundamental relationship:lethal concentration (C), in ppm, times the duration(T), in minutes, of exposure (also known as Haber’slaw). 30 The product of C × T corresponds to a standardresponse measure describing a biological endpoint ofedema formation, death, or any other consistent physiologicalparameter. Conceptually, this product simplymeant that the same biological endpoint would occurwhether the animals were exposed to 100 ppm of gasfor 10 minutes, 50 ppm for 20 minutes, or 20 ppm for50 minutes (all resulting in a C × T of 1,000 ppm•min).However, later experiments showed that for a gas suchas phosgene and other irritants, Haber’s law was applicableonly over short exposure times. 31,32 It is nowgenerally agreed that concentration rather than durationof exposure determines the gas’s effect.As implied by this discussion of Haber’s law, theuse of such a general quantitative assessment forexposure-response effects includes inherent problems.Many fundamental physiological, toxicological, histopathological,and biochemical effects are lost in suchan evaluation, especially when death is the endpoint.As shown in Table 10–4, many of these compoundshave varying solubility ranges, resulting in a rangeof effects within the pulmonary tree. For example,345