Document Detail


Inhalation toxicokinetics of soman stereoisomers in the atropinized guinea pig with nose-only exposure to soman vapor.
MedLine Citation:
PMID:  9705889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman were studied in anesthetized, atropinized guinea pigs for nose-only exposure to soman vapor. During exposure the respiratory minute volume (RMV) and respiratory frequency (RF) were monitored. Blood samples were taken for chiral gas chromatographic analysis of the concentrations of nerve agent stereoisomers and for measurement of the progressive inhibition of acetylcholinesterase (AChE). The animals were exposed for 4-8 min to 0.4-0.8 LCt50 of C(+/-)P(+/-)-soman. Concentrations of the P(-)-isomers increased rapidly during exposure, up to several nanograms per milliliter of blood. Mathematical equations describing the concentration-time courses of the P(-)-isomers were obtained by nonlinear regression. The kinetics were mathematically described as a discontinuous process, with a monoexponential equation for the exposure period and a two-exponential equation for the postexposure period. The absorption phase of C(+)P(-)-soman lagged behind that of the C(-)P(-)-isomer, presumably due to preferential covalent binding at as yet unidentified binding sites. The terminal half-life observed after nose-only exposure is longer than that observed after an equitoxic iv bolus administration, which suggests the presence of a depot in the upper respiratory tract from which absorption continues after termination of the exposure. Two types of nonlinearity of the toxicokinetics were observed, i.e., with dose and with exposure time. The AChE activity was rapidly inhibited during exposure to the nerve agent vapor. There were no soman-related effects on RMV and RF. The toxicokinetics of the soman stereoisomers observed for nose-only exposure are compared with those determined for iv bolus and sc administration.
Authors:
J P Langenberg; H E Spruit; H J van der Wiel; H C Trap; R B Helmich; W W Bergers; H P van Helden; H P Benschop
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  151     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-09-11     Completed Date:  1998-09-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  79-87     Citation Subset:  IM    
Copyright Information:
Copyright 1998 Academic Press.
Affiliation:
TNO Prins Maurits Laboratory, Rijswijk, 2280 AA, The Netherlands. langenberg@pml.tno.nl
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MeSH Terms
Descriptor/Qualifier:
Absorption
Acetylcholinesterase / blood
Administration, Inhalation
Administration, Intranasal
Animals
Atmosphere Exposure Chambers
Chemical Warfare Agents / pharmacokinetics*,  toxicity
Cholinesterase Inhibitors / administration & dosage,  pharmacokinetics*,  toxicity
Dose-Response Relationship, Drug
Guinea Pigs
Half-Life
Injections, Intravenous
Injections, Subcutaneous
Lethal Dose 50
Male
Mathematics
Regression Analysis
Respiration / drug effects*
Soman / administration & dosage,  pharmacokinetics*,  toxicity*
Stereoisomerism
Chemical
Reg. No./Substance:
0/Chemical Warfare Agents; 0/Cholinesterase Inhibitors; 96-64-0/Soman; EC 3.1.1.7/Acetylcholinesterase

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