An anesthetized domestic swine model was used to compare the efficacy and cross-contamination potential of selected skin decontaminant products and regimens against the chemical warfare agent, VX. Animals topically exposed to 2×, 3× or 5× LD50 VX showed typical signs of organophosphate nerve agent poisoning, including miosis, salivation, mastication, dysrhythmias, and respiratory distress prior to death. Animals were exposed to 5× LD50 VX and then decontaminated 45 min later with the reactive skin decontamination lotion (RSDL®), Fuller’s earth (FE), 0.5% hypochlorite, or soapy water. Survival was 100% when the reactive skin decontamination lotion or FE was utilized, although 50% of Fuller’s earth-decontaminated animals exhibited serious signs of VX poisoning. Decontamination of VX-treated animals with 0.5% hypochlorite was less effective but also increased survival. Soapy water was ineffective in preventing lethality. Blood cholinesterase levels were not predictive of clinical outcome in decontaminated animals. The potential of “decontaminated” VX in open wounds to cause poisoning was assessed by vigorously mixing 5× LD50 VX with the test decontaminants for 5 min and then placing the mixture onto a full-thickness skin wound. Soapy water was ineffective in preventing lethality. Although treatment with dry Fuller’s earth prevented death and all signs of organophosphate poisoning, a significant proportion of treated animals decontaminated with Fuller’s earth in aqueous suspension exhibited serious signs of organophosphate poisoning, suggesting that live agent may be desorbed from Fuller’s earth when it is exposed to a liquid environment. Animals treated with reactive skin decontamination lotion or 0.5% hypochlorite-VX mixtures showed no signs of organophosphate poisoning during the 6- h test period.

Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus CompoundsInhibition of acetylcholinesterase (AChE) is regarded as the primary toxic mechanism of organophosphorus compounds (OP). Therapeutic strategies are directed to antagonise overstimulation of muscarinic receptors with atropine and to reactivate inhibited AChE with oximes. Reactivation is crucial within the neuromuscular synapse, where atropine is ineffective, since peripheral neuromuscular block eventually leads to respiratory failure. Patients with OP intoxication have to be identified as early as possible.During an international NBC-defence exercise anesthetised pigs were poisoned with sarin, followed by treatment with atropine and oxime. Blood samples were drawn and red blood cell (RBC)-AChE activity determined with a fielded test system on-site. Within a few minutes the poisoning was verified. After administration of HI-6, RBC-AChE activity increased rapidly. Blood samples were reanalysed in our laboratory in Munich. Almost identical course of the AChE activities was recorded by both systems.The more comprehensive cholinesterase status was determined in Munich. Oxime administration can be stopped when AChE is aged completely, but has to be continued as long as poison is present in the body and reactivation is possible.To aid the on-site physician in optimising diagnosis and treatment, a fielded test system should be available to allow rapid determination of the complete cholinesterase status.

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The percutaneous penetration and metabolic disposition of 14C-3-4,4'-trichlorocarbanilide (triclocarban, TCC) after body showering has been determined in man. Single intravenous doses of trace amounts 14C-triclocarban were given to subjects to determine the pharmacologic disposition of the compound before conducting the shower study. Radioactivity was rapidly cleared from blood after intravenous administrations of 14C-triclocarban in propylene glycol with a blood clearance half-life of 8.6 hours. About 54% of the dose was excreted in the feces and 21% of the dose in the urine with a urinary elimination half-life of ten hours. No radioactivity was detected in the saliva. Subjects took a single shower employing a whole body lather with approximately 7 gm of soap containing 2% 14C-triclocarban on a soap basis. Special blood withdrawal and urinary/fecal collection techniques were utilized that minimized contamination of samples by extraneous 14C-triclocarban. About 0.23% of the applied radioactive dose was recovered in the feces after six days and 0.16% of the dose in the urine after two days. At all sampling times blood levels of radioactivity were below the detection limit of the method (10 part per billion).

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.