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Suggested Citation:"ECt50 for Threshold Effects." 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 52

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR VX 52 exposure to VX vapor is 25 mg-min/m3, assuming exposure durations of 30 to 50 min and moderate temperatures. There are no existing ECt50 estimates (CDEPAT 1994). In one study in humans, a spirometer mouthpiece was used for breathing; a clip was placed over the nose, and the eyes were kept closed (Bramwell et al. 1963). Percutaneous exposure of the head and neck to VX vapor at a rate of 1 mg-min and a temperature of 32°C resulted in miosis in almost all subjects even though the eyes were closed (Bramwell et al. 1963). The ECt50s were 0.7 to 25.6 mg-min/m3; exposure durations were 15 to 24 min and concentrations ranged from 0.23 to 5 mg/m3. In one or more trials, five of eight individuals experienced local flushing (transient redness) over the face and neck. After 24 hr of exposure, the ChE activity ranged from 37% to 108% of baseline. Nausea, vomiting, cold sweats, and pallor were also observed. The effective dose for 50% inhibition of ChE activity was 27 mg-min/m 3 (Bramwell et al. 1963). This study did not identify a no-observed-adverse-effect level (NOAEL). Because the subcommittee's degree of confidence in the proposed ECt 50 estimate is low to moderate, the subcommittee recommends that the estimate of 25 mg-min/m3 for severe effects serve as an interim value until further research on VX is conducted to establish the ECt50 estimate with a greater degree of confidence. ECt50 for Threshold Effects CDEPAT's proposed ECt50 estimate for threshold (minimal) effects from percutaneous exposure to VX vapor is 10 mg-min/m3, assuming exposure durations of 30 to 50 min and moderate temperatures. There is no existing ECt50 estimate for threshold effects (CDEPAT 1994). In one human study, exposures investigated for severe effects produced adverse effects at the highest exposure level, which was 25.6 mg-min/m 3 (Bramwell et al. 1963). At this exposure level, approximately 50% ChE inhibition occurred. This study did not identify a NOAEL. The subcommittee's degree of confidence in the proposed estimate is low because a true NOAEL was not established. The subcommittee recommends that the proposed estimate be considered an interim value until further research on VX is conducted to establish the NOAEL.

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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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