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Suggested Citation:"Lethal Effects (LCt50)." 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 53

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR VX 53 INHALATION VAPOR EXPOSURE Lethal Effects (LCt50) CDEPAT's proposed LCt50 estimate for inhalation exposure to VX vapor is 15 mg-min/m3, assuming exposure durations of 2 to 10 min, minute volumes of 15 liters, and moderate temperatures. The existing LCt 50 estimate is 30 mg-min/m3 (CDEPAT 1994). There are a few reports on VX that provide definitive data about human inhalation toxicity. Most studies are in animals and often do not specify the duration of exposure. CDEPAT's proposed human-toxicity estimates considered effects produced from inhalation exposures as well as from percutaneous vapor exposures. Bramwell et al. (1963) reported that the ECt50 for ChE inhibition following percutaneous vapor exposure to VX was 27 mg-min/m3; one subject experienced systemic effects from vapor exposure at 25.6 mg-min/m3. Bramwell et al. (1963) also reported a mean ChE inhibition of 26% in humans exposed to VX vapors by inhalation at 2.6 to 3.6 mg-min/m3 for 1.5 min. Studies performed in the rat reported LCt50 values for 1 min, 5 min, and 10 min at exposures of 17 mg-min/m3, 8 mg-min/m3, and 9 mg-min/m 3, respectively (Krackow 1956). The vapor toxicity of VX was also investigated in mice for whole-body or head-only exposures (Koon et al. 1960). For a 10-min exposure, the LCt50 for whole-body exposure in mice was 4 mg-min/m3. The LCt 50 value for head only exposure was 13.6 mg-min/m3. The LCt50 value reported for goats was 9.2 mg- min/m3 (Koon et al. 1960). In deriving the human-toxicity estimates for inhalation, CDEPAT assumed that the dose delivered to the target tissue is greater for inhalation than for percutaneous vapor exposure. Although humans tolerated (26% ChE inhibition) 3.6 mg-min/m3 via inhalation for 1.5 min, higher exposures were not used. The subcommittee agrees with CDEPAT's evaluation that degree of confidence in the proposed estimate of 15 mg-min/m 3 is low to moderate. The subcommittee recommends that CDEPAT's proposed estimate of 15 mg-min/m3 be lowered. The subcommittee also recommends that research on VX be done to establish the LCt50 estimate with a greater degree of confidence.

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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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