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In vivo skin absorption and distribution of the nerve agent VX (O–ethyl–S–[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic white pig

Chemical Hazards and Poisons Division, Health Protection Agency, Chilton, Didcot, Oxfordshire, OXfordshire, UK; rob.chilcott{at}hpa.org.uk

C H Dalton

Dstl Biomedical Sciences, Porton Down, Salisbury, Wiltshire, UK

I Hill

C M Davison

K L Blohm

Kinchyle Enterprises Inc., PO Box 4000, Station Main, Medicine Hat, Alberta, Canada

E D Clarkson

Drug Assessment Division, US Institute for Chemical Defense, Aberdeen Proving Ground, Maryland, USA

M G Hamilton

Medical Therapy Group, Defence Research and Development Canada, Station Main, Medicine Hat, Alberta, Canada

The purpose of this study was to characterize the skin absorption and distribution of VX (Oethyl–S–[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic pig in order to evaluate the animal as a potential model for assessing pretreatments against toxic anti–cholinesterase compounds. A liquid droplet (equivalent to a 2 LD₅₀ dose) of radiolabelled VX was applied to the inner ear–skin of each anaesthetized animal. Blood and tissue samples (liver, lung, kidney, heart and skin exposure sites) were obtained post–mortem. The amount of radioactivity in each sample was measured by liquid scintillation counting, from which the skin absorption rate and dose distribution of VX were calculated. A substantial proportion (229±3%) of the applied dose remained within the skin at the site of application. It is conceivable that strategies to minimize or remove this reservoir may be of benefit in the early treatment of VX–exposed casualties. Image analysis of autoradiographs of exposed skin sites indicated that each milligram of radioactive VX covered an area of 1.29±0.5 cm². The average skin absorption rate of ¹⁴C-VX was 6619±126 mg/cm² per hour. Comparison of these data with previous studies suggests that human skin is less permeable to VX than pig skin, but VX spreads over a greater surface area when applied to human skin. Thus, paradoxically, while pig-ear skin is more permeable than human skin, the difference in skin surface spreading may lead to the absorption of an equivalent systemic dose.

Key Words: anti–cholinesterase • in vivo • pig

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