Vallet V, Cruz C, Josse D, Bazire A, Lallement G, Boudry I
Department of Toxicology, Centre de Recherche du Service de Santé des Armées, 24 avenue des maquis du Grésivaudan, 38702 La Tronche cedex, France.
Toxicol In Vitro. 2007 Sep;21(6):1182-90. doi: 10.1016/j.tiv.2007.03.007. Epub 2007 Mar 24.
Organophosphorus compounds (OPs), such as pesticides and chemical warfare agents like sarin (GB), soman (GD) and VX, are highly toxic compounds. The OP vapours and their liquid forms are readily absorbed through the skin, therefore, protecting the skin of people who are potentially exposed to these agents is crucial. The development of effective countermeasures relies on a better knowledge of the percutaneous penetration of such molecules. The purpose of this present study is to determine the in vitro percutaneous penetration parameters of two pesticides DSM and DFP, as potential simulants of V and G agents, respectively, using four in vitro systems: full-thickness and split-thickness human abdominal and pig-ear skin membranes mounted on static diffusion cells. Based on the toxicokinetic parameters of the percutaneous penetration of DSM and DFP, we demonstrated that (a) pig-ear skin is a relevant model to predict the in vitro human skin permeability taking into account a 2-fold difference between these two species (b) both full and split-thickness skin membranes could be used indiscriminately, (c) DSM and DFP would be appropriate surrogates for V and G agents to perform skin permeation studies.
有机磷化合物（OPs），如农药以及沙林（GB）、梭曼（GD）和VX等化学战剂，都是剧毒化合物。OP蒸汽及其液体形式很容易通过皮肤吸收，因此，保护可能接触这些制剂的人的皮肤至关重要。有效对策的开发依赖于对这类分子经皮渗透的更好了解。本研究的目的是分别使用四种体外系统：安装在静态扩散池上的全层和分层人腹部及猪耳皮肤膜，来确定两种农药二甲基辛酯（DSM）和二异丙基氟磷酸酯（DFP）的体外经皮渗透参数，它们分别作为V类和G类制剂的潜在模拟物。基于DSM和DFP经皮渗透的毒代动力学参数，我们证明：（a）考虑到这两个物种之间2倍的差异，猪耳皮肤是预测体外人体皮肤渗透性的相关模型；（b）全层和分层皮肤膜均可随意使用；（c）DSM和DFP将是用于进行皮肤渗透研究的V类和G类制剂的合适替代物。
