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Suggested Citation:"Lethal Effects (LD50)." National Research Council. 1997. Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. Washington, DC: The National Academies Press. doi: 10.17226/5825.
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Page 31

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GB (SARIN) 31 ECt50 for Mild Effects CDEPAT's recommended ECt50 estimate for mild effects (miosis or rhinorrhea) after exposure to GB vapor is 0.5 mg-min/m3, assuming exposure durations of 2 to 10 min. That estimate is independent of minute volume. The existing ECt50 estimate is 2 mg-min/m3 (CDEPAT 1994). A question that needs to be addressed is the degree of miosis and rhinorrhea that should be used to estimate the ECt50 for mild effects. The data listed in the CDEPAT report do not support CDEPAT's (1994) conclusion that ''Review of other human data indicated that miosis and rhinorrhea probably occur in at least 50% of the population at GB doses of • 1.0 mg-min/m3." Further, some reports suggest that neither miosis nor rhinorrhea occurred at 0.5 mg-min/m3. The threshold symptoms appear to occur at exposures of approximately 2 mg-min/m3. Thus, the ECt50 value could be slightly higher (because of a steep dose-response curve) for the nerve agents. The subcommittee concludes that CDEPAT's estimate of 0.5 mg-min/m3 is not supported by the available data, which indicate that the value is higher; therefore, the subcommittee recommends that the proposed estimate be raised. The subcommittee also recommends that further research be conducted to establish the ECt 50 for mild effects with a greater degree of confidence. PERCUTANEOUS LIQUID EXPOSURE Lethal Effects (LD50) CDEPAT's proposed LD50 estimate for percutaneous exposure to GB liquid on bare skin is 1,700 mg for a 70-kg man. That estimate is the same as the existing estimate (CDEPAT 1994). The proposed value was calculated using a ratio of ChE50 inhibition levels in rabbits (whole blood) to ChE50 inhibition levels in humans (red blood cells) (CDEPAT 1994). In rabbits, a reduction of 88.8% ChE resulted in 53% deaths. In humans, ChE50 inhibition was based on exposure of bare skin and was estimated to be between 350 and 400 mg for a 70-kg man. One of three subjects who died was exposed to a concentration of 20 mg of GB liquid under one layer of serge plus one layer of flannel and showed a 96% inhibition of ChE. The two other subjects showed 82% and 87% ChE inhibition but had no clinical symptoms. On the basis of the limited and inconsistent data in humans, the

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No reliable acute-exposure1 standards have been established for the particular purpose of protecting soldiers from toxic exposures to chemical warfare (CW) agents. Some human-toxicity estimates are available for the most common CW agents--organophosphorus nerve agents and vesicants; however, most of those estimates were developed for offensive purposes (that is, to kill or incapacitate the enemy) and were intended to be interim values only. Because of the possibility of a chemical attack by a foreign power, the Army's Office of the Surgeon General asked the Army's Chemical Defense Equipment Process Action Team (CDEPAT) to review the toxicity data for the nerve agents GA (tabun), GB(sarin), GD (soman), GF, and VX, and the vesicant agent sulfur mustard (HD) and to establish a set of exposure limits that would be useful in protecting soldiers from toxic exposures to those agents. This report is an independent review of the CDEPAT report to determine the scientific validity of the proposed estimates.

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