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Suggested Citation:"CONCLUSIONS AND RECOMMENDATIONS." 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 25
Suggested Citation:"CONCLUSIONS AND RECOMMENDATIONS." 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 26
Suggested Citation:"CONCLUSIONS AND RECOMMENDATIONS." 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 27

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GA (TABUN) 25 incapacitation in 50% of animals, or ID 50) following acute percutaneous exposure to GA liquid on bare skin is 880 mg for a 70-kg man. There is no existing ED50 estimate (CDEPAT 1994). Because of the lack of human or animal data on GA for severe effects, the ED50 was derived by assuming that the ratio of ID50 to LD50 is 0.6 (CDEPAT 1994). The assumption that the ratio is 0.6 is based on a study using weanling pigs in which the ratio of ID50 to LD50 for GB was 0.6 (Silver 1953). CDEPAT assumed the same ratio for GA because GA and GB belong to the same class of compounds. The subcommittee believes that the CDEPAT approach is reasonable. The subcommittee recommends that CDEPAT's estimate of 880 mg for a 70-kg man, based on the ID 50-to-LD50 ratio of 0.6, be lowered to correspond to the lowered estimate for LD50 until further research is done to establish the ED50 estimate with a greater degree of confidence. CONCLUSIONS AND RECOMMENDATIONS The subcommittee's conclusions concerning CDEPAT's proposed human- toxicity estimates for GA are summarized in Table 2-1. Of the seven human-toxicity estimates for GA proposed by CDEPAT, the subcommittee agrees that two estimates are scientifically valid for protecting the soldier and recommends that four be lowered and one raised. The subcommittee also recommends the need for additional research to establish human-toxicity estimates with a greater degree of confidence.

TABLE 2-1 Evaluation of Human-Toxicity Estimates for GA Human-Toxicity Estimates for GA Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LCt50 a Percutaneous, 20,000 mg- 15,000 mg- Proposed estimate is Proposed estimate supported by human data vapor min/m3 min/m3 scientifically valid Inhalation, 135 mg- 70 mg-min/ Proposed estimate should Because of inadequate data on GA for this route, vapor min/m3 m3 be lowered CDEPAT derived the estimate by assuming that GA is 0.5 times as toxic as GB; approach reasonable but estimate should be lowered because of recommended lowering of LCt50 for GB for this route; further research recommended ECt50 b Threshold Percutaneous, None 2,000 mg- Proposed estimate is ChE inhibition data used for proposing new effects vapor min/m3 scientifically valid recommendation Severe Inhalation, None 50 mg-min/ Proposed estimate should CDEPAT's proposed estimate based on a study that effects vapor m3 be lowered indicated the ratio of ICt50e/LCt50 is 0.75; that assumption used to establish ECt50 for severe effects; the subcommittee recommends that the ECt50 estimate be lowered to correspond to the lowered estimate for LCt50 ; REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GA (TABUN) further research recommended Mild effects Inhalation, 0.9 mg- 0.5 mg-min/ Proposed estimate should Human data show that humans can tolerate higher vapor min/m3 m3 be raised exposures; further research recommended 26

Human-Toxicity Estimates for GA Toxicity Route and Form Existing CDEPAT's Subcommittee's Rationale for Subcommittee's Evaluation Type of Exposure Estimates Proposed Evaluation of Proposed Estimates Estimates for GA LD50 c Percutaneous, 1,500 mg 1,500 mg for Proposed estimate should No uncertainty factors used in lieu of limited animal data liquid for 70-kg 70-kg man be lowered for proposed estimate; further research recommended man ED50 d Percutaneous, None 880 mg for Proposed estimate should In the absence of adequate human or animal data for this liquid 70-kg man be lowered effect, CDEPAT established the estimate by assuming ID50 f/LD50 ratio of 0.6 to estimate ED50; the subcommittee recommends that the ED50 estimate be lowered to correspond to the lowered estimate for LD50; further research recommended a LCt : Vapor exposure that produces lethality in 50% of the exposed animals. Ct refers to the product of concentration (c) and exposure time (t). Note that Ct is not 50 necessarily a constant. b ECt : Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). 50 c LD : Liquid dose causing lethality in 50% of the exposed animals. 50 d ED : Liquid dose causing a defined effect in 50% of the exposed animals. 50 e ICt : Vapor exposure that produces incapacitation in 50% of the exposed population. 50 f ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GA (TABUN) 27

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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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