Pharmaceutical Sciences Department, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
Ann N Y Acad Sci. 2020 Nov;1479(1):168-179. doi: 10.1111/nyas.14343. Epub 2020 Apr 3.
Exposure to phosphine (PH ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH poisoning is thought to target oxidative respiration, the exact mechanism of action remains largely unknown, resulting in limited treatment options. In our study, the effects of PH on female rats were assessed to elucidate potential sex-specific differences and obtain a more comprehensive understanding of PH toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH (13,200-26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration-time (LCt ) and time of death (t ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH were also of comparable magnitude, although temporally, respiratory responses occurred earlier and cardiovascular variations manifested later in female rats. Behavioral observations corroborated physiological findings and indicated a response to hypoxic conditions and low cardiac output. Together, these results provided insights on the toxic mechanisms of PH , in particular, its potential interference with oxygen transport and circulation.
磷化氢（PH ）是一种常见的谷物熏蒸剂，其暴露特征为多种非特异性症状和高死亡率。虽然 PH 中毒被认为靶向氧化呼吸，但确切的作用机制仍知之甚少，导致治疗选择有限。在我们的研究中，评估了 PH 对雌性大鼠的影响，以阐明潜在的性别特异性差异，并更全面地了解 PH 毒性。评估了暴露于气态 PH（13200-26400ppm×min）的雌性大鼠的致死率、生理学和行为，将结果与雄性大鼠的相应发现进行了比较。性别之间的半数致死浓度-时间（LCt ）和死亡时间（t ）中位数没有显著差异。PH 引起的心肺变化也具有相当的幅度，尽管在时间上，雌性大鼠的呼吸反应更早发生，心血管变化更晚发生。行为观察结果与生理学发现一致，并表明对低氧条件和低心输出量的反应。这些结果共同提供了 PH 毒性机制的见解，特别是其对氧运输和循环的潜在干扰。
