VX penetration following percutaneous poisoning: a dermal microdialysis study in the guinea pig
VX penetration following percutaneous poisoning: a dermal microdialysis study in the guinea pig
VX, a potent organophosphorus compound, acts primarily by irreversibly inhibiting acetylcholinesterase resulting in an accumulation of acetylcholine, which produces the characteristic signs of nerve agent poisoning. VX is a low-volatility agent, and therefore the most likely route of absorption into the body is via the skin. This study demonstrates for the first time that it is possible to follow the time course of percutaneous VX penetration using the technique of dermal microdialysis and that VX is absorbed through the skin of the anesthetized guinea pig in a concentration-dependent manner. A linear microdialysis probe (5-kDa cut-off) was implanted in the dermis of the back of the guinea pig and perfused (5 mu L/min) with physiological Ringer's solution. VX (296 or 592 mu g/kg) was applied (33 mu L/kg) over the site of the microdialysis probe and dialysate samples collected for up to 6 h. The VX dialysate concentration was measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Quantitation was performed over the range 0.1 to 100 ng/mL and the calibration was linear. VX was detected within 15 min, reaching a peak at 30 min following both VX doses. After this time the VX concentration decreased. There was a clear dose-dependent recovery of VX in the dialysate and the total amount recovered was statistically significant between the two doses. This study has clearly shown that microdialysis can be used to follow the time course of the percutaneous absorption of VX in the anesthetized guinea pig and will be used in future studies to develop improved medical countermeasures.
agent, acetylcholine, microdialysis, mass, skin
313-321
Wetherell, Janet R.
5e5d80de-ffd5-42e4-b499-620dc7b4ca30
Armstrong, Stuart J.
c9e031d4-087d-4394-bc85-aee231f7740e
Read, Robert W.
d08cc3a9-7721-4173-b29b-e995138dd2a3
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
2008
Wetherell, Janet R.
5e5d80de-ffd5-42e4-b499-620dc7b4ca30
Armstrong, Stuart J.
c9e031d4-087d-4394-bc85-aee231f7740e
Read, Robert W.
d08cc3a9-7721-4173-b29b-e995138dd2a3
Clough, Geraldine F.
9f19639e-a929-4976-ac35-259f9011c494
Wetherell, Janet R., Armstrong, Stuart J., Read, Robert W. and Clough, Geraldine F.
(2008)
VX penetration following percutaneous poisoning: a dermal microdialysis study in the guinea pig.
Toxicology Mechanisms and Methods, 18 (4), .
(doi:10.1080/15376510701884944).
Abstract
VX, a potent organophosphorus compound, acts primarily by irreversibly inhibiting acetylcholinesterase resulting in an accumulation of acetylcholine, which produces the characteristic signs of nerve agent poisoning. VX is a low-volatility agent, and therefore the most likely route of absorption into the body is via the skin. This study demonstrates for the first time that it is possible to follow the time course of percutaneous VX penetration using the technique of dermal microdialysis and that VX is absorbed through the skin of the anesthetized guinea pig in a concentration-dependent manner. A linear microdialysis probe (5-kDa cut-off) was implanted in the dermis of the back of the guinea pig and perfused (5 mu L/min) with physiological Ringer's solution. VX (296 or 592 mu g/kg) was applied (33 mu L/kg) over the site of the microdialysis probe and dialysate samples collected for up to 6 h. The VX dialysate concentration was measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Quantitation was performed over the range 0.1 to 100 ng/mL and the calibration was linear. VX was detected within 15 min, reaching a peak at 30 min following both VX doses. After this time the VX concentration decreased. There was a clear dose-dependent recovery of VX in the dialysate and the total amount recovered was statistically significant between the two doses. This study has clearly shown that microdialysis can be used to follow the time course of the percutaneous absorption of VX in the anesthetized guinea pig and will be used in future studies to develop improved medical countermeasures.
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Published date: 2008
Keywords:
agent, acetylcholine, microdialysis, mass, skin
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Local EPrints ID: 70574
URI: http://eprints.soton.ac.uk/id/eprint/70574
ISSN: 1537-6524
PURE UUID: 9d94344c-cd2e-4ccb-acef-521d63153af7
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Date deposited: 16 Feb 2010
Last modified: 14 Mar 2024 02:40
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Author:
Janet R. Wetherell
Author:
Stuart J. Armstrong
Author:
Robert W. Read
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