ABSTRACT
The in vivo test was performed by applying a 0 .1-mm-thick layer of TSP on the shaved dorsa of New Zealand White rabbits followed by application of either GD (1.35 mg/kg), TGD (3.35 mg/kg), VX (0.5 mg/kg), or HD (1.0 jxl doses at multiple test sites per rabbit). The endpoint
for in vivo screening with nerve agent challenges was the timed measurement (30, 60, and 120 min of erythrocyte acetylcholinesterase (AChE) activity expressed as a percentage of preexposure baseline values. Nerve agent doses were selected to produce between 10 and 30% AChE relative activity (RA) in the 120-min blood samples from rabbits protected by polyethylene glycol with a mean molecular mass of 540 daltons (PEG 540). TSP efficacy was expressed as an “RA score” value, the average of AChE RA levels across sample times for each animal. The measure in all screens with HD challenges was the dermal lesion area ratio (LAR), the lesion area at a TSPpretreated site divided by the lesion area at an unprotected, challenged site on the same rabbit. A composite endpoint variable, “LAR score,” was calculated as the mean LAR for the 1-, 2-, and 4-h exposures for each rabbit. Thus, high TSP efficacy against nerve agents was indicated by a high mean RA score, but against HD by a low mean LAR score.
