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Suggested Citation:"ED50 for Severe 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 39

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GD (SOMAN) 39 man, or 5 mg/kg. The existing LD50 estimate for GD following percutaneous liquid exposure is the same (CDEPAT 1994). The available animal-toxicity data are insufficient for estimating the human LD50 for percutaneous exposure to GD liquid with any degree of confidence. The most often quoted estimate is 350 mg for a 70-kg man, an estimate based on a study by Cullumbine et al. (1954) investigating the effect of percutaneous exposure of rabbits to GD liquid. The rabbit is more sensitive to GD liquid than any other nonhuman species (Henry 1989). The reported LD50s in animals range from < 1 to 14 mg/kg (< 70 to 980 mg for a 70-kg man). Given this wide range in LD50 values, the subcommittee's degree of confidence in CDEPAT's proposed estimate of 350 mg for a 70-kg man is moderately low. The subcommittee recommends that CDEPAT's proposed estimate serve as an interim value until further research is conducted to establish this estimate with a greater degree of confidence. ED50 for Severe Effects CDEPAT's proposed estimate for the ED50 for severe effects following percutaneous exposure to GD liquid on bare skin is 200 mg for a 70-kg man or approximately 3 mg/kg. There is no existing ED50 estimate for GD (CDEPAT 1994). The available data are insufficient for estimating the human ED50 for severe effects (incapacitation, prostration, collapse, and convulsion) after percutaneous exposure to GD liquid. Data on exposure of pigs indicate that the slopes for lethality and severe effects are parallel and that the ID50-to-LD50 ratio is about 0.8 (Manthei et al. 1988; CDEPAT 1994). Other data suggest that the ratio is approximately 0.6 (Reutter et al. 1992). On the basis of the more conservative ratio of 0.6, CDEPAT derived the human-toxicity estimate of 3 mg/kg (5 mg/kg (LD50) × 0.6 = 3 mg/kg). In the absence of adequate human data or animal data on GD for this effect, the subcommittee accepts CDEPAT's approach of using the ID50-to-LD50 ratio of 0.6 to derive the ED50 estimate. The subcommittee's degree of confidence in CDEPAT's proposed estimate is low to moderate because of the insufficient data. The subcommittee recommends that the proposed estimate serve as an interim value until further research is conducted to establish this 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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