Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents (1997)
Chapter: CONCLUSIONS AND RECOMMENDATIONS
incapacitation in 50% of animals, or ID50) 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 ID50-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
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Human-Toxicity Estimates for GA |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for GA |
Rationale for Subcommittee's Evaluation |
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LCt50a |
Percutaneous, vapor |
20,000 mg-min/m3 |
15,000 mg-min/m3 |
Proposed estimate is scientifically valid |
Proposed estimate supported by human data |
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Inhalation, vapor |
135 mg-min/m3 |
70 mg-min/m3 |
Proposed estimate should be lowered |
Because of inadequate data on GA for this route, 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 |
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ECt50b |
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Threshold effects |
Percutaneous, vapor |
None |
2,000 mg-min/m3 |
Proposed estimate is scientifically valid |
ChE inhibition data used for proposing new recommendation |
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Severe effects |
Inhalation, vapor |
None |
50 mg-min/m3 |
Proposed estimate should be lowered |
CDEPAT's proposed estimate based on a study that 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; further research recommended |
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Mild effects |
Inhalation, vapor |
0.9 mg-min/m3 |
0.5 mg-min/m3 |
Proposed estimate should be raised |
Human data show that humans can tolerate higher exposures; further research recommended |
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Human-Toxicity Estimates for GA |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for GA |
Rationale for Subcommittee's Evaluation |
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LD50c |
Percutaneous, liquid |
1,500 mg for 70-kg man |
1,500 mg for 70-kg man |
Proposed estimate should be lowered |
No uncertainty factors used in lieu of limited animal data for proposed estimate; further research recommended |
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ED50d |
Percutaneous, liquid |
None |
880 mg for 70-kg man |
Proposed estimate should be lowered |
In the absence of adequate human or animal data for this effect, CDEPAT established the estimate by assuming ID50f/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 |
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a LCt50: 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 necessarily a constant. b ECt50: Percutaneous vapor exposure or inhalation vapor exposure causing a defined effect (e.g., incapacitation, severe effects, mild effects, threshold effects). c LD50: Liquid dose causing lethality in 50% of the exposed animals. d ED50: Liquid dose causing a defined effect in 50% of the exposed animals. e ICt50: Vapor exposure that produces incapacitation in 50% of the exposed population. f ID50: Liquid dose causing incapacitation in 50% of the exposed population. |
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