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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 63

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR HD 63 PERCUTANEOUS LIQUID EXPOSURE Lethal Effects (LD50) CDEPAT's LD50 estimate for percutaneous exposure to HD liquid is 1,400 mg for a 70-kg man. The existing estimate is 7,000 mg for a 70-kg man (CDEPAT 1994). As for most LD50 estimates for humans, animal data must be relied on primarily. In this case, there is even a paucity of animal data. The Army's existing estimate was based on early data that indicated an LD50 of approximately 100 mg/kg for the rabbit; extrapolation to a 70-kg man yielded an estimated LD50 of 7,000 mg for a 70-kg man. CDEPAT (1994) chose to base its LD50 estimate on the LD50 of 20 mg/kg (1,400 mg for a 70-kg man) for the dog and guinea pig rather than the LD50 for the rabbit. Based on the data of Henry (1991), that choice is reasonable. The data indicate that rabbits are 10 times less sensitive to percutaneous HD than are humans. The subcommittee agrees with the proposed estimate of 1,400 mg for a 70-kg man. ED50 for Severe Effects The proposed ED50 for severe effects from percutaneous exposure to HD was estimated by CDEPAT to be 610 mg for a 70-kg man. There is no existing estimate (CDEPAT 1994). HD has a very low vapor pressure and stays on the ground for a long time. This persistence of HD on the ground can cause toxicity to people or animals over a long time. However, decontamination procedures can be followed to remove HD from the ground. CDEPAT's proposed estimate is based on the observation of vesication of the human forearm (an area of moderate sensitivity to HD) following application of HD at a dose of 34 µg/cm2 (Landhal 1945). Landhal (1945) collected data on hundreds of human exposures at the University of Chicago Toxicology Laboratory and concluded that 34 µg/cm2 was the threshold blister dose on the volar forearm. Extrapolation of that dose to the estimated 1.8 m2 surface area of the average male yielded CDEPAT's proposed ED50 estimate of 610 mg for severe effects for a 70-kg man. Therefore, the subcommittee finds CDEPAT's proposed estimate to be scientifically valid. However, the proposed value of 610 mg should be rounded to 600 mg for a 70-kg man to avoid the appearance of precision that is not there.

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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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