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Clinical manifestations of VX poisoning following percutaneous exposure in the domestic white pig

Dstl Biomedical Sciences, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK rchilcott{at}mail.dstl.gov.uk

C H Dalton

Dstl Biomedical Sciences, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK

I Hill

C M Davidson

K L Blohm

Kinchyle Enterprises Inc., PO Box 4000, Station Main, Medicine Hat, Alberta, Canada T1A 8K6

M G Hamilton

Medical Therapy Group, Defence Research Establishment Suffi eld, PO Box 4000, Station Main, Medicine Hat, Alberta, Canada T1A 8K6

Nerve agents are a class of organophosphorus chemicals that inhibit certain cholinesterase enzymes (ChE). If untreated, percutaneous exposure to nerve agents, such as VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) can cause paralysis, apnoea and death. Much of the information concerning the percutaneous absorption and subsequent toxicity of nerve agents has been obtained using various rodent models. However, the most relevant ‘skin model’ is arguably the pig. Therefore, the purpose of this study was to examine the clinical manifestations of VX intoxication in the domestic white pig following a 2 LD₅₀ (120 mg/kg) percutaneous challenge. There was a consistent onset of signs (where present) in each animal: mastication was followed by miosis, salivation, fasciculations and apnoea. Whilst ChE activity did not correlate with the onset of signs, there was a qualitative relationship in that mastication preceded substantial ChE inhibition, miosis lagged behind the linear decrease in acetylcholinesterase (AChE) activity and fasciculations and apnoea occurred after maximum ChE inhibition had been attained (5 ^/ 10% of normal). These observations may be of use for the triage of patients exposed to VX. In comparison with similar studies with GD, VX did not affect glucose utilization. However, VX was similar to GD in that it caused a mild hyperkalaemia and hyperphosphataemia, although the significance of this observation was not clear. There was substantial lateral diffusion of the initial droplet of VX over the application site, indicating that, when decontaminating exposed skin, attention should also be directed to areas peripheral to the original site of exposure.

Key Words: cholinesterase • clinical reference values • nerve agent • pig • skin absorption • toxicity

Human & Experimental Toxicology, Vol. 22, No. 5, 255-261 (2003)
DOI: 10.1191/0960327103ht359oa


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