Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents (1997)
Chapter: CONCLUSIONS AND RECOMMENDATIONS
mg for a 70-kg man be lowered because of the subcommittee's recommendation for lowering the LD50 estimate. The subcommittee also recommends that further research on VX be conducted to establish an ECt50 estimate with a greater degree of confidence.
Conclusions and Recommendations
The subcommittee's conclusions concerning the scientific validity of CDEPAT's proposed human-toxicity estimates for VX are summarized Table 6-1.
Eight human-toxicity estimates, instead of the seven proposed for the other organophosphate agents, were calculated for VX; an ECt50 for severe effects from percutaneous vapor exposure was also calculated. Of the eight human-toxicity estimates for VX proposed by CDEPAT, the subcommittee concludes that only one estimate is appropriate for protecting soldiers and is scientifically valid. The subcommittee recommends that four estimates serve as interim values until further research is conducted, and three estimates are to be lowered. The subcommittee recommends that further research be conducted on VX to establish the human-toxicity estimates with a greater degree of confidence.
TABLE 6-1 Evaluation of Human-Toxicity Estimates for VX
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Human-Toxicity Estimates for VX |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for VX |
Rationale for Subcommittee's Evaluation |
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LCt50a |
Percutaneous, vapor |
None |
150 mg-min/m3 |
Proposed estimate should be considered an interim value |
Degree of confidence in data is low to moderate; further research recommended |
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Inhalation, vapor |
30 mg-min/m3 |
15 mg-min/m3 |
Proposed estimate should be lowered |
Degree of confidence in data is low to moderate; further research recommended |
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ECt50b |
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Threshold effects |
Percutaneous, vapor |
None |
10 mg-min/m3 |
Proposed estimate should be considered an interim value |
Degree of confidence in data is low; a no-observed-adverse-effect level (NOAEL) was not defined; further research recommended |
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Severe effects |
Percutaneous, vapor |
None |
25 mg-min/m3 |
Proposed estimate should be considered an interim value |
Degree of confidence low to moderate; further research recommended |
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Inhalation, vapor |
25 mg-min/m3 |
10 mg-min/m3 |
Proposed estimate should be considered an interim value |
Insufficient data; further research recommended |
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Mild effects |
Inhalation, vapor |
0.09 mg-min/m3 |
0.09 mg-min/m3 |
Proposed estimate is scientifically valid |
Available human data support the proposed estimate |
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LD50c |
Percutaneous, liquid |
10 mg/70-kg man |
5 mg/70-kg man |
Proposed estimate should be lowered |
Animal data indicate that the proposed estimate is too high; furthermore, no uncertainty factor used in lieu of variability associated with dermal penetration of various regions of body; further research recommended |
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Human-Toxicity Estimates for VX |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for VX |
Rationale for Subcommittee's Evaluation |
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ED50d |
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Severe effects |
Percutaneous, liquid |
5 mg/70-kg man |
2.5 mg/70-kg man |
Proposed estimate should be lowered |
The ED50 is based on the ID50e/LD50 ratio; the subcommittee recommends that the LD50 be lowered, therefore, the ED50 should be lowered correspondingly; 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 ID50: Liquid dose causing incapacitation in 50% of the exposed population. |
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