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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.
Page 46

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GF 46 as GD and GB (CDEPAT 1994) in monkeys and other species by the inhalation route. That assumption is supported by animal studies that show that GF, GB, and GD are equipotent for this effect via inhalation vapor exposures (Cresthull et al. 1957; CDEPAT 1994). In the absence of adequate data on GF for severe effects, the subcommittee recommends that CDEPAT's proposed ECt50 estimate be lowered to correspond to lowered estimates for GB and GD until further research on GF is conducted to establish the estimate with a greater degree of confidence. ECt50 for Mild Effects CDEPAT's proposed ECt50 estimate for ocular effects from exposure to GF is 0.2 mg-min/m3, assuming exposure durations of 2 to 10 min and moderate temperatures. There is no existing ECt50 estimate (CDEPAT 1994). No data are available on the ocular toxicity of GF in humans or experimental animals. The proposed estimate is based on the assumption that GF and GD are equipotent (Cullumbine et al. 1954). The subcommittee agrees with CDEPAT's approach. The subcommittee recommends that CDEPAT's ECt50 estimate for ocular effects be raised to correspond to the recommended raised estimate for GD until further research is conducted on GF to establish this estimate with a greater degree of confidence. PERCUTANEOUS LIQUID EXPOSURE Lethal Effects (LD50) CDEPAT's proposed LD50 estimate for percutaneous exposure to GF vapor is 350 mg for a 70-kg man, assuming exposure at moderate temperatures. There is no existing LD50 estimate (CDEPAT 1994). Limited human data are available, and the data that are available suggests a fourfold variation in ChE inhibition. Studies have been conducted in rabbits and pigs to determine the LCt50 of GF liquid after percutaneous exposure. In one study (Marzulli et al. 1952), rabbits were exposed at four levels. A similar protocol was used for pigs. The LD50 in rabbits was 1.3 mg/kg (91 mg for a 70-kg man); the LD50 in pigs was 16.5 mg/kg (1,155 mg for a 70-kg man). On the basis of the rabbit data, CDEPAT concluded that liquid GF poses a serious threat to soldiers in a moderate climate. The proposed LD50 estimate assumes that GF and GD are equipotent

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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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