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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Toxicology and Appli...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Toxicology and Applied Pharmacology
Article . 1998 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Inhalation Toxicokinetics of Soman Stereoisomers in the Atropinized Guinea Pig with Nose-Only Exposure to Soman Vapor

Authors: Langenberg, J.P.; Spruit, W.E.T.; Wiel, H.J. van der; Trap, H.C.; Helmich, R.B.; Bergers, W.W.A.; Helden, H.P.M. van; +1 Authors

Inhalation Toxicokinetics of Soman Stereoisomers in the Atropinized Guinea Pig with Nose-Only Exposure to Soman Vapor

Abstract

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.

Country
Netherlands
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Keywords

Male, Atmosphere Exposure Chambers, Injections, Subcutaneous, Sus scrofa, Guinea Pigs, Soman, Absorption, Lethal Dose 50, Cavia porcellus, Administration, Inhalation, Animalia, Animals, Chemical Warfare Agents, Administration, Intranasal, Dose-Response Relationship, Drug, Respiration, Stereoisomerism, Cavia, Injections, Intravenous, Acetylcholinesterase, Regression Analysis, Cholinesterase Inhibitors, Mathematics, Half-Life

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
33
Average
Top 10%
Average
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