双酚A（BPA）广泛应用于塑料制品、食品容器和收据墨水生产中，但研究发现其为内分泌干扰物质，影响生物体的激素平衡。作为替代物之一，双酚S（BPS）得到了开发，但其对人体健康的影响和潜在机制仍不明确。具体而言，关于口服暴露于双酚对肺部的影响的研究还不足。我们检测了体外和体内肺细胞中这些化合物毒性差异的潜力。我们对BPA或BPS暴露的MRC5和A549细胞进行的毒性机制研究发现，BPA诱导了肌动蛋白丝的异常和上皮间质转化（EMT）的激活。这一发现表明肺纤维化和肺癌转移的潜力增加。然而，考虑到在特定的实验条件下，治疗剂量下没有检测到BPS，这些情况发生的可能性被认为是很小的。此外，动物实验证实口服暴露于BPA可以激活肺部的EMT。我们的研究提供了证据，表明长期口服暴露于BPA可以导致肺组织中的EMT激活，类似于细胞实验中观察到的情况，这表明可能诱导肺纤维化。这项研究强调了规范BPA的使用以减轻其相关肺毒性的重要性。此外，在我们的实验条件下，BPS没有表现出BPA中明显的毒理通路是非常重要的。版权所有©2023年作者。由Elsevier Inc.发表。保留所有权利。

Bisphenol A (BPA) is widely used in the production of plastics, food containers, and receipt ink globally. However, research has identified it as an endocrine disruptor, affecting the hormonal balance in living organisms. Bisphenol S (BPS), one of the alternative substances, was developed, but its effects on human health and the underlying mechanisms remain unclarified. Specifically, research on the effects of oral exposure to bisphenol on the lungs is lacking. We examined the potential differences in toxicity between these compounds in lung cells in vitro and in vivo. Our toxicity mechanism studies on MRC5 and A549 cells exposed to BPA or BPS revealed that BPA induced actin filament abnormalities and activated epithelial-mesenchymal transition (EMT). This finding suggests an increased potential for lung fibrosis and metastasis in lung cancer. However, given that BPS was not detected at the administered dose and under the specific experimental conditions, the probability of these occurrences is considered minimal. Additionally, animal experiments confirmed that oral exposure to BPA activates EMT in the lungs. Our study provides evidence that prolonged oral exposure to BPA can lead to EMT activation in lung tissue, similar to that observed in cell experiments, suggesting the potential to induce lung fibrosis. This research emphasizes the importance of regulating the use of BPA to mitigate its associated pulmonary toxicity. Furthermore, it is significant that within the parameters of our experimental conditions, BPS did not exhibit the toxicological pathways clearly evident in BPA.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.