Toxicologic Pathology Associates, Jefferson, Arkansas 72079, United States of America.
Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States of America.
Chem Res Toxicol. 2021 Mar 15;34(3):754-766. doi: 10.1021/acs.chemrestox.0c00379. Epub 2021 Feb 8.
Ortho-phthalaldehyde (OPA) is a chemical disinfectant used for the high-level sterilization of heat-sensitive medical instruments. Although OPA is considered a safer alternative to glutaraldehyde, no exposure limits have been established for respiratory exposures to ensure the safety of OPA sterilization and the safe use of OPA-treated medical instruments. In order to address data gaps in the toxicological profile of OPA, we treated human air-liquid-interface (ALI) airway cultures at the air interface with various concentrations of OPA aerosols for 10 consecutive days. Temporal tissue responses were evaluated at multiple time points during the treatment phase as well as 10 days following the last exposure. The disturbance of glutathione (GSH) homeostasis occurred as early as 20 min following the first exposure, while oxidative stress persisted throughout the treatment phase, as indicated by the sustained induction of heme oxygenase-1 (HMOX-1) expression. Repeated exposures to OPA aerosols resulted in both functional and structural changes, including the inhibition of ciliary beating frequency, aberrant mucin production, decreases in airway secretory cells, and tissue morphological changes. While OPA-induced oxidative stress recovered to control levels after a 10 day recovery period, functional and structural alterations caused by the high concentration of OPA aerosols failed to fully recover over the observation period. These findings indicate that aerosolized OPA induces both transient and relatively persistent functional and structural abnormalities in ALI cultures under the conditions of the current study.
邻苯二甲醛（OPA）是一种化学消毒剂，用于对热敏感医疗器械进行高水平消毒。虽然 OPA 被认为是戊二醛的更安全替代品，但尚未为呼吸道暴露制定呼吸暴露限值，以确保 OPA 消毒的安全性和 OPA 处理的医疗器械的安全使用。为了解决 OPA 毒理学特征中的数据空白，我们用不同浓度的 OPA 气溶胶在气道界面处理人肺泡液-气界面（ALI）气道培养物，连续 10 天。在治疗阶段以及最后一次暴露后 10 天的多个时间点评估了组织的时间反应。暴露后 20 分钟，谷胱甘肽（GSH）稳态就发生了紊乱，氧化应激一直持续到治疗阶段，这表现为血红素加氧酶-1（HMOX-1）表达的持续诱导。反复暴露于 OPA 气溶胶会导致功能和结构改变，包括纤毛摆动频率抑制、粘蛋白产生异常、气道分泌细胞减少以及组织形态学改变。虽然 OPA 诱导的氧化应激在 10 天恢复期后恢复到对照水平，但在观察期间，高浓度 OPA 气溶胶引起的功能和结构改变未能完全恢复。这些发现表明，在本研究条件下，气溶胶化的 OPA 会在 ALI 培养物中引起短暂和相对持久的功能和结构异常。
