Sarin lethal effects

Most chemical agents are essentially cumulative in their effects. The reason is that the human body detoxifies them very slowly or not at all. For example, a 1-h exposure to HD or CG followed within a few hours by another 1-h exposure has about the same effect as a single 2-h exposure. Continued exposure to low concentrations of HD may cause sensitivity to very low concentrations of HD. Other chemical agents also have cumulative effects. For example, an initial exposure to a small (less than lethal) amount of Sarin (GB) would decrease cholinesterase levels a second quantity less than the FDS0... 

The toxic effects model translates the exposure profiles into casualty probabilities for the personnel, assuming a probabilistic dose-effect relationship. The casualty levels and spectra can be obtained for various type of health effects, e.g. eye effects, inhalation, percutane, subdivided in two levels (incapacitating and lethal), and various protection levels, e.g. no protection, suit only, mask only, mask and suit, and collective protection. Table 1 gives a typical result for one scenario. In case no protection is used, 63% of the population dies due to inhalation of sarin and 25% dies due to percutaneous exposure. Clearly, when both mask and suit are worn, the casualty levels are dropping drastically. 

The specter of chemical death persists. Like atom bombs, chemical weapons have been classified as weapons of mass destruction. But were they, and are they Nerve agents such as VX and sarin can certainly kill swiftly. But so can hundreds of familiar drugs and poisons. The real question is whether anyone within the limits of current technology can, in fact, use them effectively as lethal weapons on the battlefield. 

The effectiveness of non-lethal doses of agent sarin, a strong inhibitor of both RBC (true) and plasma (pseudo) cholinesterase, was impressive (Fig. 70). In two subjects who were treated with the same dose of sarin, however, the benefit was greater in one (red) than the other (yellow). Differences in RBC cholinesterase inhibition may explain this disparity. In studies b Drs. Sidell and Aghajanian, levels of plasma cholinesterase were sometimes reduced almost to zero by sarin, without producing clinical signs of toxicity (note reversal in upper legend, which has plasma as xx and RBC as yy )-... 

No doubt the British government had some scruples about the use of gas, and certainly by 1940 was well aware that in fact high explosive was a much more effective killer than any of the gases available to them. This was not the case in Germany. Starting in 1940 two new works were built, at Dyhernfurth and Gendorf, to exclusively produce mustard gas and the new lethal nerve agents, tabun and sarin.6... 

Even though the lethal nerve agent exposure level for animals may be higher than that for humans, it is still possible that animals eould exhibit other nonlethal effects sooner and more notieeably than humans. Rabbits develop 90% miosis at a lower inhaled eoneentration of cyclohexyl sarin when compared to humans (2.71 mg.min/m versus 13.85 mg.min/m ) (NRC, 2003). 

For example. Berry et al. (28) observed that, although pretreatment of animals with a combination of pralldoxlme (2 -FAH) and atropine Increased the LD50 values of several compounds (e.g., TEPP and DFP), It had little effect on the lethality of sarin and none on the lethality of soman they concluded that this was the result of the rapid aging of the ChEs inhibited by sarin and soman. More direct evidence of In vivo aging was obtained Harris et al. (29), who Injected P-labeled sarin and soman Into rats and observed that the rate of aging of the Inhibited rat-brain AChE was the same In vivo as in parallel In vitro experiments ... 

FIGURE 10.1 Effectiveness of galantamine/atropine as an antidote against the acute toxicity and lethality of 1.5 X LD50 soman or sarin in guinea pigs. Note that there is no need for additional supportive therapy. (From Albuquerque, E.X. et al., Proc. Natl. Acad. Sci. USA, 103, 13220, 2006. With permission.)... 

Changes in blood pressure induced by OPC (sarin, tabun, DFP, thiophos, octamethyl, carbophos, mercaptophos, trichlorfon, DDVP) depend significantly upon a dose administered. High (lethal) doses induce a persistent fall in blood pressure, which is usually preceded by short-term hypertension. On the contrary, an effect of low doses can be accompanied by a rise in blood pressure [5, 6],... 

Calculations of the mass of a toxic material needed to contaminate a large volume of air to a lethal level are often ignored by those suggesting that a specific compound might be used effectively on a large scale. Consider sarin (GB). Let us assume that we wished to contaminate an area of 1 km2 to a depth of 10 m with GB at a concentration of 100 mg/m3. 

There are only a few reports in the open literature on the effect of oximes in nerve agent-exposed humans. Pralidoxime chloride was very effective in reactivating erythrocyte AChE in individuals exposed to sublethal intravenous or oral VX while this oxime was substantially less effective in humans exposed to IV sarin (Sidell and Groff, 1974). Accidental sarin exposure by inhalation resulted in an initial progressive deterioration (coma, apnea) of the patient despite atropine and 2-PAM treatmentand substantial recovery of erythrocyte AChE activity (Sidell, 1974). It took several hours until the patient s condition improved. Sidell also reported an accidental oral soman exposure. A lethal dose of diluted soman splashed into and around the mouth of an individual, resulting in coma, bronchoconstriction and respiratory depression, which was successfully treated with repeated atropine injections. 2-PAM (2 g IV) had no effect on inhibited erythrocyte AChE. 

---