Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents (1997)
Chapter: ED50 for Severe Effects
Percutaneous Liquid Exposure
Lethal Effects (LD50)
CDEPAT's proposed LD50 estimate for percutaneous exposure to VX liquid on bare skin is 5 mg for a 70-kg man. The existing estimate is 10 mg for a 70-kg man (CDEPAT 1994).
No human studies have been conducted for this effect and route of exposure. Most of the animal studies do not take into account the sensitivity of various areas of the human body to dermal penetration by toxicants.
Animal data indicate that CDEPAT's proposed estimate of 5 mg for a 70-kg man is too high because it underestimates the potency of VX liquid on bare skin. Studies have shown the LD50s in clipped rabbits, pigs, and guinea pigs to be 0.02 mg/kg (1.4 mg for a 70-kg man), 0.12 mg/kg (8.4 mg for a 70-kg man), and 0.077 mg/kg (5.4 mg for a 70-kg man), respectively (Wiles and Shaw 1960).
No uncertainty factors were applied when extrapolating from animal data to compensate for the variability associated with dermal penetration of various areas of the human body. Thus, the subcommittee concludes that CDEPAT's proposed estimate of 5 mg for a 70-kg man (0.07 mg/kg) for percutaneous exposure to VX liquid is too high. The subcommittee also recommends that the proposed estimate be lowered. The subcommittee recommends that further research be conducted to establish the LD 50 estimate with a greater degree of confidence.
ED50 for Severe Effects
CDEPAT's proposed ED50 estimate for severe effects from percutaneous exposure to VX liquid is 2.5 mg for a 70-kg man. The existing estimate is 5 mg/70-kg man (CDEPAT 1994).
There are no human data and few animal data for this end point by this route of exposure. A study in rabbits showed that the ratio of Ict50 to LD50 for VX is O.5 (Manthei and Callahan 1991). Therefore, in the absence of adequate human or animal data for severe effects via percutaneous exposure to VX liquid, the ratio was used to derive the ED50 for severe effects. The subcommittee agrees with this approach.
The subcommittee recommends that CDEPAT's ED50 estimate of 2.5
