title: Inhalation toxicity of Cyclosarin (GF) vapor in rats as a function of exposure concentration and duration: potency comparison to sarin (GB).
abstract: 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) generate GF vapor in a dynamic inhalation chamber system, starting in the lethal to near-lethal concentration range, (2) examine dose-response effects of inhaled GF vapor and 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). Using a syringe pump, GF vapor concentrations were generated for exposure times of 10, 60, and 240 min. Dose-response curves with associated slopes were determined for each exposure duration by the Bliss probit method. GF vapor exposures were associated with sublethal clinical signs such as tremors, convulsions, salivation, and miosis. Concentration-exposure time values for lethality in 50% of the exposed population (LCT(50)) were calculated for 24-h and 14-day postexposure periods for 10-, 60-, and 240-min exposures. In general, LCT(50) values were lower in female rats than males and increased with exposure duration; that is, CT was not constant over time. The GF LCT(50) values for female rats were 253 mg min/m(3) at 10 min, 334 mg min/m(3) at 60 min, and 533 mg min/m(3) at 240 min, while the values for males were 371, 396, and 585 mg min/m(3), respectively. The GB LCT(50) values for female rats were 235 mg min/m(3) at 10 min, 355 mg min/m(3) at 60 min, and 840 mg min/m(3) at 240 min, while the values for males were 316, 433, and 1296 mg min/m(3), respectively. At longer exposure durations, the LCT(50) for GF was less than that found for GB but at shorter exposure durations, the LCT(50) for GF was more than that found for GB. Empirical models, consisting of the toxic load model plus higher order terms, were developed and successfully fit to the data.
authors.affiliation: U.S. Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Maryland, USA. j.steven.anthony@us.army.mil
authors.forename: J Steven
authors.initials: JS
authors.lastname: Anthony
authors.forename: M
authors.initials: M
authors.lastname: Haley
authors.forename: J
authors.initials: J
authors.lastname: Manthei
authors.forename: R
authors.initials: R
authors.lastname: Way
authors.forename: D
authors.initials: D
authors.lastname: Burnett
authors.forename: B
authors.initials: B
authors.lastname: Gaviola
authors.forename: D
authors.initials: D
authors.lastname: Sommerville
authors.forename: R
authors.initials: R
authors.lastname: Crosier
authors.forename: R
authors.initials: R
authors.lastname: Mioduszewski
authors.forename: S
authors.initials: S
authors.lastname: Thomson
authors.forename: C
authors.initials: C
authors.lastname: Crouse
authors.forename: K
authors.initials: K
authors.lastname: Matson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D019570:Inhalation Exposure; D007928:Lethal Dose 50; D008136:Longevity / Q000187:drug effects; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012524:Sarin / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D014835:Volatilization
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012524:Sarin; C053914:cyclohexyl methylphosphonofluoridate