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

Medical Aspects of Chemical Warfareronmental application of PS as a fumigant have beenreported. Most recently, 165 persons reported symptomsconsistent with PS exposure following applicationof 100% PS at a concentration of 36 kg per acre to 34acres in Kern, California. 112,113 Although PS dissipatesreadily in the environment, trace amounts are foundin drinking water disinfected by chlorination. 60,114,115Despite its historical and current uses, PS-inducedtoxicity resulting from inhalation, ingestion, or directskin or eye contact remains poorly documented.Physical Characteristics and DeploymentThe molecular weight of PS is 164.4, and its molecularformula is CCl 3NO 2(Figure 13-8). PS is anoily, volatile, colorless to faint-yellow liquid with anintensely irritating odor. Weaponized PS is primarilydisseminated through wind dispersion, the simplesttechnique of delivering an agent to its target. It consistsof placing the agent directly on or adjacent to thetarget immediately before dissemination (eg, antitheftdevices placed on safes). Analogous dispersion methodswere used in the early 20th century for delivery ofchlorine, phosgene, and mustard gases. It was learnedfrom the 2003 Kern, California, incident that whenPS was injected 17 to 18 inches into the soil, peopleresiding one quarter of a mile downwind experiencedirritating effects. 112 See Table 13-3 for a summary of thecharacteristics of DM and other agents.Physiological EffectsCl- O ON +ClClFig. 13-8. Chemical structure of PS.The immediate physiological effect of PS is sensoryirritation via stimulation of the trigeminal nerveendings located in the nasal mucosa, which leads tothe clinical signs of exposure: a burning sensationof the nasal passages, inhibition of respiration, andlacrimation. 111,116 As an irritant, PS causes cellular lesionsat the site of exposure (ie, lung lesions followinginhalation, dermal lesions following contact with skin,and forestomach lesions following ingestion). Althoughthese clinical and pathological effects have beencharacterized, the mechanisms of toxicity, particularlythe biotransformation of the parent compound and thetoxicity of the metabolites, are poorly understood. 117 Ithas been known for some time that PS can react directlywith hemoglobin to form methemoglobin and that thetoxicity of PS in mice is linked to the oxidative state ofhemoglobin. 117,118 However, the contribution of theselaboratory observations to the tissue damage observedin the clinic has yet to be resolved.Other studies conducted in the 1940s suggestedthat the lacrimatory effect may be due, in part, to aselective reaction of PS with certain tissue dehydrogenases(eg, pyruvate dehydrogenase and succinatedehydrogenase). 119 Likewise, a causal relationshipbetween these metabolic effects and toxicity has notbeen established. Rapid reductive dechlorination ofPS to CHCl 2NO 2by glutathione and other tissue thiolsin vitro suggests that metabolites may be mediatorsof toxicity, but major differences in urinary metabolitesof the compounds only partially support thishypothesis. 117 More recent evidence suggests a novelmetabolic pathway for PS that involves conversion toraphanusamic acid; this study suggested that toxicitywas mediated by the parent compound rather thanmetabolites. 117Clinical EffectsThe major organs affected following acute exposureto PS are the eyes, skin, and respiratory tract. 69With increasing doses or prolonged exposure times,systemic toxicity and lethality are observed. The doseof PS required to induce acute symptoms appears tobe intermediate between the corresponding doses ofchlorine and phosgene. Unlike with phosgene, thereis no latent period between PS exposure and clinicalsymptoms. 60 “Chloropicrin syndrome” is characterizedby unusual taste; eye tearing; nose and throatirritation; neurological symptoms (headache, nausea,and vomiting); shortness of breath; and anxiety. 111 TheIDLH for PS is 2 ppm (1 ppm=6.72 mg/m 3 ) and theestimated LCt 50is 2,000 mg•min/m 3 . 96 The inhalationLD 50in cats and pigs appears to be 800 mg/m 3 for a20-minute exposure. 120 Acute pulmonary edema anddyspnea were observed in both species, and emphysemawas reported in the pig. In mice, the LD 50isreported at 66 mg/m 3 for a 4-hour exposure. 120 Themurine intraperitoneal LD 50for PS is 15 mg/kg, andthe rat oral LD 50is 250 mg/kg. 117,121Respiratory effects. Inhalation of a sensory irritantcauses inhibition of respiration and Kratschmer reflex.In the laboratory, inhibition of respiration is often measuredby the dose required to cause a 50% decrease in456