Development of an acute, short-term exposure model for phosgene.
Development of an acute, short-term exposure model for phosgene.
复制标题
开发光气急性、短期暴露模型。
DOI：
10.1080/15376516.2019.1636170
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发表时间：
2019
影响因子：
3.2
通讯作者：
Parseghian,MissagH
中科院分区：
文献类型：
--
作者：
Hobson,StephenT;Casillas,RobertP;Richieri,RichardA;Nishimura,RobertN;Weisbart,RichardH;Tuttle,Rick;Reynolds,GlennT;Parseghian,MissagH
光气被归类为化学战剂，但关于其在仅经鼻接触的大鼠模型中的短期高浓度毒性的数据稀少且不一致。因此，开发了一种用于短期/高浓度曝光的曝光系统并进行了表征。在此，我们报告的半数致死浓度（LC 50）为10分钟的鼻暴露的光气在24小时的大鼠生存模型。在暴露当天体重为180-210 g的雄性Wistar大鼠（Envigo）通过仅鼻吸入暴露于光气气体，使用专门设计的允许同时暴露和定量光气的系统。24小时后，对存活大鼠实施安乐死，测定肺/体重比，并分析肺组织的组织病理学。主要位于肺泡的肺部终末气道水肿增加（导致肺/体重比增加）与观察到的死亡率一致。经测定，暴露10 min的LC 50值为129.2 mg/m3。此外，与其他高毒性化合物一致，本研究揭示了支持非线性毒性负荷模型的LC 50浓度值，其中毒性负荷指数>1（ne= 1.17）。因此，与其他化学战剂一样，预计短时间、高浓度接触光气的毒性比长时间、低浓度接触更严重。该模型预计将得到完善和发展，以筛选新的治疗方法，对相关的短期高浓度光气暴露预期从恐怖袭击，战场部署，或工业事故。
Phosgene is classified as a chemical warfare agent, yet data on its short-duration high concentration toxicity in a nose-only exposure rat model is sparse and inconsistent. Hence, an exposure system for short-term/high concentration exposure was developed and characterized. Herein, we report the median lethal concentration (LC50) for a 10-min nasal exposure of phosgene in a 24-h rat survival model. Male Wistar rats (Envigo) weighing 180–210 g on the day of exposure, were exposed to phosgene gas via nose-only inhalation using a system specifically designed to allow the simultaneous exposure and quantification of phosgene. After 24 h, the surviving rats were euthanized, the lung/body mass ratio determined, and lung tissues analyzed for histopathology. Increased terminal airway edema in the lungs located primarily at the alveoli (resulting in an increased lung/body mass ratio) coincided with the observed mortality. An LC50value of 129.2 mg/m3for a 10-min exposure was determined. Furthermore, in agreement with other highly toxic compounds, this study reveals a LC50concentration value supportive of a nonlinear toxic load model, where the toxic load exponent is >1 (ne= 1.17). Thus, in line with other chemical warfare agents, phosgene toxicity is predicted to be more severe with short-duration, high-concentration exposures than long-duration, low-concentration exposures. This model is anticipated to be refined and developed to screen novel therapeutics against relevant short-term high concentration phosgene exposures expected from a terrorist attack, battlefield deployment, or industrial accident.