Toxicokinetic studies of nerve agents deal with the in vivo absorption, distribution, and elimination of these agents as a function of animal species, route of administration, dose and time after administration. Such studies provide a quantitative basis for toxicodynamic studies of nerve agents, which should result in causal treatment of intoxications with these agents. While toxicodynamic studies of nerve agents have been intensively pursued since WW II, toxicokinetic studies were only initiated in the last two decennia of the twentieth century. The late start of the latter type of research was caused by the long held but uncorrect assumption that nerve agents were so-called “hit-and-run” poisons, with extremely short in vivo persistence. 0n the other hand, such in vivo analyses had to wait for the development, in that period of time, of trace analytical methods which were needed to determine the extremely low (ng to low pg range/ml plasma) but toxicologically significant in vivo levels of the various stereoisomers of nerve agents.
This review will deal first with the development of analytical procedures for chiral trace analysis of the stereoisomers of nerve agents, as well as with the toxicology and routes of in vivo elimination of the stereoisomers. Next, results of toxicokinetic studies will be given, mainly dealing with soman but some results for other nerve agents will also be given. The effect of dose, route of adminstration (iv, inhalation, pc) and animal species will be dealt with, emphasizing the toxicokinetics after low level respiratory exposure. Finally, consequences for prophylactic and therapeutic approaches as well as future directions of research are discussed.

Keywords: Nerve agents; toxicology