Low level nose-only exposure to the nerve agent soman: Toxicokinetics of soman stereoisomers and cholinesterase inhibition in atropinized guinea pigs

In order to initiate a quantitative basis for the toxicology of low level e xposure to nerve agents, the toxicokinetics of soman stereoisomers during n ose-only exposure for 5 h to 20 ppb (160 mu g/m(3)) of C(+/-)P(+/-)-soman i n air were studied in restrained, anesthetized, and atropinized guinea pigs . The concentrations of the toxic C(+/-)P(-)-soman stereoisomers in blood i ncreased according to a biexponential function, after an initial lag time o f ca. 30 min for C(+)P(-)-soman, with final concentrations less than or equ al to 36 pg/ml. It is hypothesized that the lag time is due to binding to c arboxylesterases (CaE), partly in the airways prior to systemic uptake. The gradual inhibition of acetylcholinesterase (AChE) in erythrocytes during t he exposure appeared to be in satisfactory accordance with the observed lev els of the C(+/-)P(-)-soman stereoisomers in blood. Inhibition of AChE in b rain and diaphragm is insignificant at the end of the exposure period. This result suggests that neuropsychological disorders are unlikely to develop in this exposure scenario. However, incapacitating miosis due to direct pen etration of nerve agent into the eye would probably occur. Our experiments should be reconsidered for exposure of primates, which lack scavenging CaE in their blood. It is argued that the same challenge level in primates migh t give rise to higher blood levels of C(+)P(-)-soman stereoisomers and conc omitantly higher inhibition levels of AChE. Therefore, the critical Ct (mg . min/m(3)) values for nonsystemic effects on eyes and airways and systemic effects might be less divergent than in guinea pigs. (C) 1998 Academic Pre ss.