title: Biomarkers of low-level exposure to soman vapor: comparison of fluoride regeneration to acetylcholinesterase inhibition.
abstract: The nerve agent O-pinacolyl methylphosphonofluoridate, also known as soman or by its military designation GD, is a highly toxic organophosphorous compound that exerts its effects through inhibition of the enzyme acetylcholinesterase (AChE). In the present study, a fluoride ion based regeneration assay was developed to quantify the level of soman present in the blood of rats following a low-level whole-body inhalation exposure. It was hypothesized that the amount of regenerated nerve agent in the blood would be dose dependent in rats subjected to a whole-body inhalation exposure to a low-level dose of soman vapor, and that the fluoride ion-based regeneration method would be more sensitive for the detection of a low-level exposure to soman vapor than the measurement of whole blood AChE activity. Regenerated soman was dose-dependently detected in both the red blood cells (RBCs) and plasma of exposed rats at all concentrations tested (0.033-0.280 mg/m(3) for a 240-min exposure). Significant inhibition of whole blood AChE activity did not occur below a concentration of 0.101 mg/m(3), and was only depressed by approximately 10-25% at concentrations ranging from 0.101 mg/m(3) to 0.280 mg/m(3). This study is the first to utilize a fluoride ion-based regeneration assay to demonstrate the dose-dependent increases in soman in the blood following whole-body inhalation exposure to low levels of vapor. Additionally, the results of the present study demonstrate that the fluoride ion based regeneration assay was approximately threefold more sensitive than the measurement of AChE activity in the blood for the detection of exposure to soman, and also that miosis is a more sensitive marker of soman exposure than inhibition of AChE activity.
authors.affiliation: Operational Toxicology, U.S. Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, Maryland 21010-5454, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Dabisch
authors.forename: E A
authors.initials: EA
authors.lastname: Davis
authors.forename: J A
authors.initials: JA
authors.lastname: Renner
authors.forename: E M
authors.initials: EM
authors.lastname: Jakubowski
authors.forename: R J
authors.initials: RJ
authors.lastname: Mioduszewski
authors.forename: S A
authors.initials: SA
authors.lastname: Thomson
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002091:Butyrylcholinesterase / Q000097:blood; D002619:Chemical Warfare Agents / Q000378:metabolism* / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004793:Enzyme Reactivators / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D019570:Inhalation Exposure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012969:Sodium Fluoride / Q000494:pharmacology*; D012999:Soman / Q000097:blood* / Q000633:toxicity; D014835:Volatilization
chemical_list: D015415:Biomarkers; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D004793:Enzyme Reactivators; D012969:Sodium Fluoride; D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase