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

Abstract

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Approved for public release; distribution is unlimited. ABSTRACT (Maximum 200 words)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. Doseresponse curves with associated slopes were determined by the Bliss probit method. Concentration-exposure time values for lethality in 50% of the exposed population (LCt 5 o) were calculated for 24-hr and 14-day post exposure periods for 10-, 60-, and 240-min exposures. At longer exposure durations, the LCt 50 for GF was less than for GB, but at shorter exposure durations, the LCt 50 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.

Effects of Whole-Body VX Vapor Exposure on Lethality in Rats

“…It is extremely toxic with an equivalent dose of VX being substantially more toxic than related nerve agents such as sarin (GB), cyclosarin (GF), tabun (GA) and soman (GD). Most of what is known of the effects of VX on whole animals is derived from studies administering VX subcutaneously, percutaneously, intravenously or as an inhaled aerosol (Bide and Risk, 2000;Craig, et al, 1977;Gupta, et al, 1991;Rickett, et al, 1986). However, few studies exist in which reliable toxicity estimates in animals have been established for VX administered as a vapor (Hartman, 2002).…”

Low-Level Effects of VX Vapor Exposure on Pupil Size and Cholinesterase Levels in Rats

“…There are several studies, which dealt with either aerosolized VX (Bide and Risk, 2000), or VX mixed with other compounds (Weimer and Ballard, 1960;Dimmick et al, 1979). One recent study examined the toxicity of VX vapor inhalation in rats using a "nose-only" exposure design (Bide et al, 1996), but did not address the issue of "first noticeable effect" (FNE) associated with very low concentrations of VX vapor.…”

“…This approach has been used successfully in several previous mammalian CW agent toxicity studies (Anthony et al, 2004;* Mioduszewski et al, 2002a* Mioduszewski et al, , 2002b** Whalley et al, 2004). The model used follows:…”

Evaluating Performance Effects of Low-Level Inhalation Exposure to Nerve Agents in Rats

“…Rats were exposed to vapor generated by two methods, depending upon the concentration required. For higher concentrations, the vapor generation system consisted of a gas-tight syringe (Hamilton, Reno, NV), variable-rate syringe drive (Model 22, Harvard Apparatus Inc., South Natick, MA), and other vaporization equipment (see Anthony, et al, 2004;Mioduszewski, et al, 2002). For lower concentrations, saturated vapor streams were generated by directing nitrogen carrier gas through the inlet of a glass vessel containing liquid agent.…”

“…The first method was a quantitative technique using solid sorbent tubes (Tenax/Haysep) to trap GB or GF vapor, followed by thermal desorption and gas chromatographic (GC) analysis (HP Model 6890, Agilent Technology, Baltimore, MD). The second method was a continuous monitoring technique using a phosphorus monitor (HYFED, Model PH262, Columbia Scientific, Austin, TX) (see Anthony, et al, 2004;.…”