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REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR VX 56 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 ECt 50 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 Human-Toxicity Estimates for VX 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 VX LCt50 a Percutaneous, None 150 mg-min/ Proposed estimate should Degree of confidence in data is low to moderate; further vapor m3 be considered an interim research recommended value Inhalation, 30 mg-min/ 15 mg-min/ Proposed estimate should Degree of confidence in data is low to moderate; further vapor m3 m3 be lowered research recommended ECt50 b Threshold Percutaneous, None 10 mg-min/ Proposed estimate should Degree of confidence in data is low; a no-observed- effects vapor m3 be considered an interim adverse-effect level (NOAEL) was not defined; further value research recommended Severe Percutaneous, None 25 mg-min/ Proposed estimate should Degree of confidence low to moderate; further research effects vapor m3 be considered an interim recommended value REVIEW OF ACUTE HUMAN-TOXICITY ESTIMATES FOR VX Inhalation, 25 mg-min/ 10 mg-min/ Proposed estimate should Insufficient data; further research recommended vapor m3 m3 be considered an interim value Mild effects Inhalation, 0.09 mg- 0.09 mg- Proposed estimate is Available human data support the proposed estimate vapor min/m3 min/m3 scientifically valid LD50 c Percutaneous, 10 mg/70- 5 mg/70-kg Proposed estimate should Animal data indicate that the proposed estimate is too liquid kg man man be lowered high; furthermore, no uncertainty factor used in lieu of variability associated with dermal penetration of various regions of body; further research recommended 57
Human-Toxicity Estimates for VX 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 VX ED50 d Severe Percutaneous, 5 mg/70-kg 2.5 mg/70-kg Proposed estimate should The ED50 is based on the ID50 e/LD50 ratio; the effects liquid man man be lowered subcommittee recommends that the LD50 be lowered, therefore, the ED50 should be lowered correspondingly; 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 VX 58