Covestro Deutschland AG, Global Phosgene Steering Group, 51365, Leverkusen, Germany.
Regul Toxicol Pharmacol. 2023 Sep;143:105441. doi: 10.1016/j.yrtph.2023.105441. Epub 2023 Jul 9.
In contrast to water-soluble respiratory tract irritants in their gas phase, the physicochemical properties of 'hydrophilicity' vs. 'lipophilicity' are the preponderant factors that dictate the site of major retention of the gas at the portal of entry. The lipophilic physical properties of phosgene gas facilitate retention in the alveolar region lined with amphipathic pulmonary surfactant (PS). The relationship between exposure and adverse health outcomes is complex, may vary over time, and is dependent on the biokinetics, biophysics, and pool size of PS relative to the inhaled dose of phosgene. Kinetic PS depletion is hypothesized to occur as inhalation followed by inhaled dose-dependent PS depletion. A kinetic model was developed to better understand the variables characterizing the inhaled dose rates of phosgene vs. PS pool size reconstitution. Modeling and empirical data from published evidence revealed that phosgene gas unequivocally follows a concentration x exposure (C × t) metric, independent of the frequency of exposure. The modeled and empirical data support the hypothesis that the exposure standards of phosgene are described best by a C × t time-averaged metric. Modeled data favorably duplicate expert panel-derived standards. Peak exposures within a reasonable range are of no concern.
与气相中的水溶性呼吸道刺激物相反，“亲水性”与“疏水性”的物理化学特性是决定主要进入部位（呼吸道门户）气体主要滞留位置的主导因素。光气气体的亲脂物理特性有助于其在具有两亲性肺表面活性剂（PS）的肺泡区域内保留。暴露与不良健康结果之间的关系很复杂，可能随时间而变化，并且取决于 PS 的生物动力学、生物物理学和池大小与吸入光气剂量的关系。据推测，吸入后会发生 PS 动力学消耗，并且会出现与吸入剂量相关的 PS 消耗。建立了一个动力学模型，以更好地了解吸入光气剂量率与 PS 池大小再构成的变量。建模和来自已发表证据的经验数据表明，光气气体无疑遵循浓度 x 暴露（C×t）度量标准，而与暴露频率无关。建模和经验数据支持这样的假设，即光气的暴露标准最好由 C×t 时间平均度量来描述。模型数据很好地复制了专家小组制定的标准。在合理范围内的峰值暴露没有关系。
