Inhalation Toxicity of GF Vapor in Rats as a Function of Exposure Concentration and Duration and Its Potency Comparison to GB

摘要

The inhalation toxicity of cyclohexyl methylphosphonofluoridate (GF) was examined in male and female Sprague-Dawley rats exposed by whole-body in a dynamic 750-L chamber. The objectives of this study were to (1) validate vapor detection methods for GF, starting in the lethal to near-lethal concentration range; (2) examine dose-response effects of inhaled GF vapor, analyze the relationship between concentration (C) and exposure duration (t) in determining probability of lethality; and (3) establish a lethal potency ratio between GF and the more volatile agent sarin (GB). The GF vapor concentrations were generated for exposure times of 10, 60, and 240 min. Dose- response curves with associated slopes were determined by the Bliss probit method. Concentration-exposure time values for lethality in 50% of the exposed population (LCt50) were calculated for 24-hr and 14-day post exposure periods for 10-, 60-, and 240-min exposures. At longer exposure durations, the LCt50 for GF was less than for GB, but at shorter exposure durations, the LCt50 for GF was more than for GB. Empirical models, consisting of the toxic load model plus higher order terms, were fit to the data to test the adequacy of the model and to identify statistically significant patterns.