PROPHYLAXIS AGAINST SOMAN INHALATION TOXICITY IN GUINEA-PIGS BY PRETREATMENT ALONE WITH HUMAN SERUM BUTYRYLCHOLINESTERASE

Human butyrylcholinesterase (HuBChE) has previously been shown to prot ect mice, rats, and monkeys against multiple lethal toxic doses of org anophosphorus (OP) anticholinesterases that were challenged by iv bolu s injections. This study examines the concept of using a cholinesteras e scavenger as a prophylactic measure against inhalation toxicity, whi ch is the more realistic simulation of exposure to volatile OPs. HuBCh E-treated awake guinea pigs were exposed to controlled concentration o f soman vapors ranging from 417 to 430 mu g/liter, for 45 to 70 s. The correlation between the inhibition of circulating HuBChE and the dose of soman administered by sequential iv injections and by respiratory exposure indicated that the fraction of the inhaled dose of soman that reached the blood was 0.29. HuBChE to soman molar ratio of 0.11 was s ufficient to prevent the manifestation of toxic signs in guinea pigs f ollowing exposure to 2.17x the inhaled LD50 dose of soman (LLD50, 101 mu g/kg). A slight increase in HuBChE:soman ratio (0.15) produced sign -free animals after two sequential respiratory exposures with a cumula tive dose of 4.5 x ILD50. Protection was exceptionally high and far su perior to the currently used traditional approach that consisted of pr etreatment with pyridostigmine and postexposure combined administratio n of atropine, benactyzine, and an oxime reactivator. Quantitative ana lysis of the results suggests that in vivo sequestration of soman, and presumably other OPs, by exogenously administered HuBChE, is independ ent of the species used or the route of challenge entry. This assuring conclusion significantly expands the database of the bioscavenger str ategy that now offers a dependable extrapolation from animals to human .