Clinical Aspects of Percutaneous Poisoning by the Chemical Warfare Agent VX: Effects of Application Site and Decontamination

Abstract

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

Percutaneous Exposure to VX: Clinical Signs, Effects on Brain Acetylcholine Levels and EEG

“…The toxicokinetics of VX following skin application in the guinea pig have shown a delayed penetration through the skin [10], resulting in a delayed appearance of cholinergic signs [12,19]. It is obvious that this delayed penetration of VX through the skin contributes to the variation with regard to onset times of clinical signs in the present study.…”

“…In spite of the use of anaesthetized animals, the variability in toxicokinetics was considerable. The latter variable and delayed absorption of VX from the skin may have important implications for military or civilian first responders with respect to triage, decontamination and therapeutic drug regimens [11,12]. The present study was designed to investigate the central and peripheral effects of exposure to percutaneous VX in hairless guinea pigs, in order to broaden the scope for possible treatment.…”

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo

“…For in vivo studies, experimental animal models, such as rodents (rat, mouse, guinea pig) or rabbits have been used first (Ballantyne and Marrs, 1992;Liu et al, 1999). More recently, in vivo approaches using the domestic pig have demonstrated a real interest of this model for CWA skin absorption studies (Dorandeu et al, 2007;Hawkins and Reifenrath, 1984;Simon and Maibach, 2000;Amitai et al, 2003;Chilcott et al, 2003Chilcott et al, , 2005bHamilton et al, 2004;Duncan et al, 2002;Van der Schans et al, 2003;Kadar et al, 2003). Nevertheless, the in vivo swine model showed many disadvantages, such as the supply and stabling of a large number of pigs or the handling of these animals.…”

Percutaneous Toxicity and Decontamination of Soman, Vx, and Paraoxon in Rats Using Detergents

“…In some studies, dilution was found to elevate skin permeation in vitro (13,14), which could possibly lead to an earlier manifestation of cholinergic signs and higher VX toxicity in vivo. On the other hand, Hamilton et al (15) found little or no effect of dilution on VX absorption. The extreme toxicity of agent VX is caused by a preferential reaction with AChE, contrary to G-agents which are more willing to be hydrolyzed by other ChE (2).…”

“…The response time is an important factor which infl uences the effectiveness of the decontamination (15,17,25,26). In this study, decontamination was performed 2 min after exposure and the effectiveness would have certainly been decreased had the treatment been delayed.…”