Wright Linnzi K M, Lee Robyn B, Clarkson Edward D, Lumley Lucille A
US Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010, USA.
Edgewood Chemical Biological Center, 5183 Blackhawk Rd, Aberdeen Proving Ground, MD 21010, USA.
Toxicol Rep. 2015 Dec 17;3:895-899. doi: 10.1016/j.toxrep.2015.12.003. eCollection 2016.
Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to more easily penetrate through the skin. However, age-related differences in the lethal potency of VX have yet to be evaluated using the percutaneous (pc) route of exposure. Thus, we estimated the 24 and 48 h median lethal dose for pc exposure to VX in male and female rats during puberty and early adulthood. Pubescent, female rats were less susceptible than both their male and adult counterparts to the lethal effects associated with pc exposure to VX possibly because of hormonal changes during that stage of development. This study emphasizes the need to control for both age and sex when evaluating the toxicological effects associated with nerve agent exposure in the rat model.
诸如VX这类低挥发性神经毒剂在战斗或恐怖袭击释放时主要通过皮肤吸收。角质层的屏障功能在发育的某些阶段可能会受损,使得VX更容易穿透皮肤。然而,尚未通过经皮(pc)暴露途径评估VX致死效力的年龄相关差异。因此,我们估算了青春期和成年早期雄性和雌性大鼠经皮暴露于VX后的24小时和48小时半数致死剂量。青春期雌性大鼠比雄性和成年雌性大鼠对经皮暴露于VX所产生的致死效应更不敏感,这可能是由于该发育阶段的激素变化所致。本研究强调在大鼠模型中评估与神经毒剂暴露相关的毒理学效应时需要同时考虑年龄和性别因素。