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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GB (SARIN) 32 subcommittee concludes that the degree of confidence in CDEPAT's estimate is low. The subcommittee recommends that the proposed LD 50 estimate of 1,700 mg for a 70-kg man be considered an interim value until further research is done. The subcommittee also recommends that further research be conducted to establish the LD50 estimate with a greater degree of confidence. ED50 for Severe Effects CDEPAT's proposed ED50 for severe effects after percutaneous exposure to GB liquid on bare skin is 1,000 mg for a 70-kg man. There is no existing toxicity estimate for GB via this route (CDEPAT 1994). Data are not sufficient to estimate the human ED50 for severe effects after percutaneous exposure to liquid GB, and there are few estimates. The proposed estimate of 1,000 mg per a 70-kg man is based on data assuming that the ID50- to-LD50 ratio of 0.6 is valid. The data were extrapolated from relative similarities in ChE inhibition in pigs and humans; the human LD50 was estimated to be 2,500 mg for a 70-kg man, and the ID50 was estimated to be 1,500 mg for a 70-kg man (Silver 1953). Thus, the ratio of 0.6 (1,500 mg for a 70-kg man to 2,500 mg for a 70-kg man = 0.6) was used to estimate the ED50 for severe effects from percutaneous liquid exposure to GB (Reutter et al. 1992). The subcommittee supports CDEPAT's proposed ED50 estimate of 1,000 mg for a 70-kg man (0.6 Ã 1,700 1,000) as an interim value. The subcommittee recommends that further research be conducted to establish the ED50 estimate for severe effects with a greater degree of confidence. CONCLUSIONS AND RECOMMENDATIONS The subcommittee's conclusions concerning CDEPAT's proposed estimates for GB are summarized in Table 3-1. Of the seven human-toxicity estimates for GB proposed by CDEPAT, the subcommittee agrees that two estimates are scientifically valid for protecting soldiers. The subcommittee recommends that two serve as interim estimates, two be lowered, and one raised. The subcommittee recommends further research for most of the adverse health effects to establish the estimates with a greater degree of confidence.
TABLE 3-1 Evaluation of Human-Toxicity Estimates for GB Human-Toxicity Estimates for GB 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 GB LCt50 a Percutaneous, 15,000 mg- 10,000 mg- Proposed estimate is Proposed estimate supported by studies in monkeys and vapor min/m3 min/m3 scientifically valid humans Inhalation, 70 mg-min/ 35 mg-min/ Proposed estimate should Estimate too high because human studies show 100% vapor m3 m3 be lowered lethality at 40 mg-min/m3 ECt50 b Threshold Percutaneous, None 1,200 mg- Proposed estimate is Estimate supported by studies of ChE inhibition in effects vapor min/m3 scientifically valid humans; further research recommended Severe Inhalation, 35 mg-min/ 25 mg-min/ Proposed estimate should ECt50 /LCt50 ratio of 0.7 used to develop estimate; LCt50 effects vapor m3 m3 be lowered for this route of exposure was lowered; therefore, ECt50 should be lowered correspondingly; further research recommended Mild effects Inhalation, 2 mg-min/ 0.5 mg-min/ Proposed estimate should No effects in humans at 0.5 mg-min/m3; effects begin to vapor m3 m3 be raised appear at 2 mg-min/m3; further research recommended LD50 c Percutaneous, 1,700 mg 1,700 mg for Low confidence in Estimate based on a ratio of ChE inhibition in rabbits REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GB (SARIN) liquid for 70-kg 70-kg man proposed estimate; and humans; however, human data concerning the man proposed estimate should relation between ChE inhibition and adverse effects are serve as interim value inconsistent; further research recommended 33
Human-Toxicity Estimates for GB 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 GB ED50 d Severe Percutaneous, None 1,000 mg for Proposed estimate should In the absence of adequate data on GB for this effect, effects liquid 70-kg man serve as interim value CDEPAT assumed that the ratio of ID50 e/LD50 is 0.6 and used that to estimate the ED50 values; 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 ID : Liquid dose causing incapacitation in 50% of the exposed population. 50 REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR GB (SARIN) 34