Toxic Effects of a Whole-body Inhalation Sarin (GB) Vapor Exposure in the Gottingen Minipig

Abstract : Exposure to nerve agent vapors may result in a diverse array of clinical responses including threshold effects to lethality over a relatively small range of dosages. In order to assess the toxic hazards of such exposures and define chemical defense materiel requirements, it is essential to fill gaps in toxicological databases that define the physiological progression; from the first noticeable effect (miosis) to potentially fatal effects of inhalation exposure. Although there are numerous published works investigating the progression of toxic signs elicited by sarin (GB) exposures, both by accidental exposures and in research applications, never has there been a systematic whole-body inhalation study investigating the effects on multiple systems in real-time. While information gleamed from accidental inhalation exposures provides valuable insights on the short and long term sequalae of the exposure, by their nature they do not provide this information until after the subject has been removed from imminent danger, detoxified, and stabilized. In the past, the logistical problems encountered when performing whole-body inhalation experiments with nerve agents have severely limited the ability to collect data in real-time during the exposure. Therefore, the majority of work encompassing nerve agent studies and real-time data collection involves subcutaneous or intravenous injections as the delivery route. While the data collected from these studies is invaluable for assessing medical treatments and short and long-term effects from the agents, the time course of effects (from first evidence of agent in the systemic circulation, to onset of signs, to progression from mild to moderate to severe signs, to death) and compartmental distribution is vastly different. Additionally, and most importantly, they do not address the most likely route of exposure on the battlefield, i.e., inhalation.