Rapid, Physiologically Based Method for Evaluating Candidate Chemical Warfare Agent Uptake Simulants

摘要

Potential chemical warfare agent uptake simulants were selected and evaluated using a physiologically based method. Measurements of the partitioning of a chemical in body tissues and its physical properties, together with animal exposures in a closed chamber system interpreted by kinetic modeling, provided a rapid means of assessing the conformance of a particular chemical to criteria established for a useful simulant. A potential chemical warfare agent uptake simulant should as a minimum 1) have physical properties that allow for generation of realistic exposure conditions for the agent being simulated, 2) have good detectability, 3) be very poorly metabolized (biologically inert), and 4) be safe to humans in the concentrations to be encountered. Perfluorochemicals representing both aliphatic and aromatic compounds were used as initial candidates since they afford excellent detectability and relative biological inertness. Analogs of the initial compounds were subsequently tried until satisfaction of the established criteria was obtained. The required changes in chemical structure were driven by predictions from a physiologically based computer model. The main thrust of this report is to outline the application of physiological modeling to the important task of chemical warfare agent uptake simulant selection (design). Chloropentafluorobenzene was identified as a potential uptake simulant for non-persistent chemical warfare agents. (Author)