Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents (1997)
Chapter: CONCLUSIONS AND RECOMMENDATIONS
(Cullumbine et al. 1954). The subcommittee believes that, in the absence of adequate data, the use of this assumption is a reasonable approach. The subcommittee recommends that CDEPAT's estimate of 350 mg for a 70-kg man be considered an interim estimate until further research on GF is conducted to establish this estimate with a greater degree of confidence.
ED50 for Severe Effects
CDEPAT's proposed ED50 estimate for severe effects from percutaneous liquid exposure to GF is 200 mg for a 70-kg man, assuming exposure durations of 2 to 10 min and moderate temperatures. There is no existing ED50 estimate (CDEPAT 1994).
In the absence of adequate human and animal data on the severe effects following percutaneous exposure to GF liquid, CDEPAT (1994) assumed that GD and GF are equipotent. The subcommittee concludes that the approach used by CDEPAT (1994) to derive the ED50 is reasonable and recommends that the proposed estimate be considered an interim value until further research on GF is conducted to establish this estimate with a greater degree of confidence.
Conclusions and Recommendations
The subcommittee's conclusions concerning CDEPAT's proposed estimates for GF are summarized in Table 5-1.
Of the seven acute human-toxicity estimates for GF proposed by CDEPAT (1994), the subcommittee agrees that the estimates are not scientifically valid or appropriate for protecting soldiers. Four estimates are recommended to serve as interim values until further research is conducted, one estimate should be raised, and two estimates should be lowered. The subcommittee recommends that further research be conducted to establish estimates with a greater degree of confidence.
TABLE 5-1 Evaluation of Human-Toxicity Estimates for GF
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Human-Toxicity Estimates for GF |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for GF |
Rationale for Subcommittee's Evaluation |
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LCt50a |
Percutaneous, vapor |
15,000 mg-min/m3 |
2,500 mg-min/m3 |
Proposed estimate should serve as an interim value |
Rationale for the CDEPAT estimate not supported by data; further research recommended |
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Inhalation, vapor |
None |
35 mg-min/m3 |
Proposed estimate should be lowered |
In the absence of adequate data, proposed estimate based on assumption that GF, GD, and GB are equipotent; approach is reasonable; because LCt50 for GB was recommended to be lowered, proposed value for GF should be lowered correspondingly; further research recommended |
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ECt50b |
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Threshold effects |
Percutaneous, vapor |
None |
300 mg-min/m3 |
Proposed estimate should serve as an interim value |
Proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; further research recommended |
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Severe effects |
Inhalation, vapor |
None |
25 mg-min/m3 |
Proposed estimate should be lowered |
In the absence of adequate data, proposed estimate based on assumption that GF, GD, and GB are equipotent; approach is reasonable, because ECt50s for severe effects for GB and GD were recommended to be lowered, proposed value for GF should be lowered correspondingly; further research recommended |
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Human-Toxicity Estimates for GF |
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Toxicity Type |
Route and Form of Exposure |
Existing Estimates |
CDEPAT's Proposed Estimates |
Subcommittee's Evaluation of Proposed Estimates for GF |
Rationale for Subcommittee's Evaluation |
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Mild effects |
Inhalation, vapor |
None |
0.2 mg-min/m3 |
Proposed estimate should be raised |
In the absence of adequate human or animal data, the proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; because ECt50 for mild effects for GD was recommended to be raised, proposed value for GF should be raised correspondingly; further research recommended |
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LD50c |
Percutaneous, liquid |
None |
350 mg for 70-kg man |
Proposed estimate should serve as an interim value |
In the absence of adequate human or animal data, proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; further research recommended |
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ED50d |
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Severe effects |
Percutaneous, liquid |
None |
200 mg for 70-kg man |
Proposed value should serve as an interim value |
In the absence of adequate human or animal data, the proposed estimate based on assumption that GF and GD are equipotent; approach is reasonable; 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. |
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