Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents (1997)

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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GB (SARIN) 30 durations of 2 to 10 min. The existing LCt50 estimate is 70 mg-min/m 3 (CDEPAT 1994). The LCt50 data for inhalation exposure for several animal species (mouse, rat, primate, dog, rabbit, cat, and pig) provide an LCt50 estimate for humans of 60 mg-min/m3 for 10-min exposures. The average ratio (of LCt50 for GA, GB, and GF) for 10-min and 2-min exposures was calculated to be 0.6 (CDEPAT 1994) and that ratio was also supported by a classified study. Using a factor of 0.6 to estimate the 2-min LCt50 from the 10-min LCt 50, CDEPAT obtained a value of 35 mg-min/m 3 (60 × 0.5 35). Human data from the Adamek Report (as cited in Wills and DeArmon 1954) showed deaths in four of four subjects exposed at 4 mg/m3 for 10 min (a Ct (concentration × time) of 40 mg-min/m3). Data were available for 48 other subjects, all of whom received some type of post-exposure therapy. Using data from exposed and unexposed individuals, the authors calculated an LCt50 of 24 mg-min/m3 (Wills and DeArmon 1954). However, on the basis of the 100% lethality observed in humans exposed at 40 mg-min/m3, the subcommittee recommends that the CDEPAT's proposed LCt50 estimate of 35 mg-min/m3 be lowered. The subcommittee also recommends that further research be conducted to establish the LCt 50 estimate for inhalation with a greater degree of confidence. ECt50 for Severe Effects CDEPAT's proposed ECt50 estimate for severe effects following inhalation exposure to GB vapor is 25 mg-min/m3, assuming minute volumes of 15 liters and exposure durations of 2 to 10 min. The existing ECt 50 estimate is 35 mg- min/m3 (CDEPAT 1994). In the absence of adequate data on GB for this effect, CDEPAT's proposed estimate is based on the assumption that the ratio of ICt50 (incapacitation dose for 50% of a given population) and LCt50 is about 0.7. The ratio is supported by a study conducted in monkeys (Cresthull et al. 1957). The proposed ECt50 estimate of 25 mg-min/m3 was calculated by multiplying the LCt50 of 35 mg-min/m3 by 0.7, which equals 25 mg-min/m3. The subcommittee believes this approach is reasonable. However, the subcommittee recommended that the LCt 50 for inhalation exposure be lowered; therefore, the ECt50 should be lowered correspondingly. The subcommittee recommends that further research be conducted to establish the ECt50 for severe effects with a greater degree of confidence.