Chilcott Robert P, Dalton Christopher H, Hill Ira, Davison Corey M, Blohm Kendal L, Clarkson Edward D, Hamilton Murray G
Chemical Hazards and Poisons Division, Health Protection Agency, Chilton, Didcot, Oxfordshire, OX11 0RQ, UK.
Basic Clin Pharmacol Toxicol. 2005 Jul;97(1):35-8. doi: 10.1111/j.1742-7843.2005.pto_97106.x.
The purpose of this study was to evaluate the efficacy of a novel barrier cream formulation at reducing the percutaneous toxicity of a 2xLD(50) liquid challenge of nerve agent (VX). The study was conducted in vitro and in vivo using the domestic pig. Pretreatment of the (inner ear skin) exposure site with barrier cream eliminated mortality, reduced cholinesterase inhibition and prevented any physiological or biochemical signs of intoxication. In contrast, untreated animals exposed to VX exhibited severe signs of intoxication, near total AChE inhibition and generally died within the (3 hr) exposure period (5/6 animals). Application of the barrier cream caused a significant decrease in the area of skin contaminated by VX. It was tentatively concluded that spreading was predominantly a surface phenomena (possibly mediated by capillary movement of the agent through the microrelief or between hair follicles) with little or no contribution from lateral diffusion within the stratum corneum. There was a disparity between the in vitro and in vivo skin absorption measurements that was ascribed to the absence of systemic clearance in vitro. However, both models indicated a substantial reservoir of VX within the skin, providing a potential strategy for future investigations into "catch-up therapies". In summary, the novel barrier cream formulation was effective against a 2xLD(50) (liquid, percutaneous) dose of VX applied for 3 hr. Further work should be conducted to investigate more pragmatic issues such as optimal reapplication frequency and environmental effects such as temperature and humidity.
本研究的目的是评估一种新型防护霜配方在降低神经毒剂（VX）2倍半数致死剂量（LD50）液体攻击所致经皮毒性方面的效果。该研究使用家猪进行了体外和体内实验。用防护霜预处理（内耳皮肤）暴露部位可消除死亡情况，减少胆碱酯酶抑制，并防止出现任何中毒的生理或生化迹象。相比之下，暴露于VX的未处理动物表现出严重的中毒迹象，乙酰胆碱酯酶（AChE）几乎完全被抑制，并且通常在（3小时）暴露期内死亡（6只动物中有5只）。涂抹防护霜使VX污染的皮肤面积显著减少。初步得出的结论是，扩散主要是一种表面现象（可能是由毒剂通过微起伏或毛囊之间的毛细管运动介导的），角质层内横向扩散的作用很小或没有作用。体外和体内皮肤吸收测量结果存在差异，这归因于体外缺乏全身清除。然而，两种模型均表明皮肤内存在大量VX蓄积，为未来“追赶疗法”的研究提供了一种潜在策略。总之，这种新型防护霜配方对3小时内涂抹的2倍LD50（液体，经皮）剂量的VX有效。应进一步开展工作，研究更实际的问题，如最佳再涂抹频率以及温度和湿度等环境影响。
