1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (EDPrB) is a typical fluorinated liquid-crystal monomer (LCM). LCMs contaminants are becoming increasingly concerning due to their potential persistence, bioaccumulation, toxicity, and broad prevalence in environmental and human samples. However, LCM metabolism is poorly understood. Herein, by introducing selected EDPrB into the appropriate liver microsomes in vitro, we examined the metabolic pathways of LCM in humans, rats, pigs, Cyprinus carpio, crucian carp, and Channa argus. A total of 20 species-dependent metabolites were identified and structurally elucidated by gas and liquid chromatography-high resolution mass spectrometry for the first time. Dealkylation, H-abstraction, and hydroxylation reactions are the primary metabolic pathways. Half of these in vitro metabolites were found in the urine, serum, and fecal samples of Sprague–Dawley rats exposed to EDPrB. Toxicity predictions indicate that 17 metabolites can be classified as toxic. According to the Ecological Structure Activity Relationships (ECOSAR), a number of metabolites exhibit equivalent or greater aquatic toxicity to that of EDPrB. Toxicity Estimation Software Tool (T.E.S.T.) predicts that some metabolites exhibit developmental toxicity and mutagenicity in rats. These findings suggest that biotransformation should be particularly emphasized, and more toxicological and monitoring studies should be performed to assess the ecological and human safety of LCMs.

1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)benzene (EDPrB) 是一种典型的氟化液晶单体 (LCM)。LCMs 污染物由于其潜在的持久性、生物蓄积性、毒性以及在环境和人类样本中的广泛流行而越来越受到关注。然而，人们对 LCM 代谢知之甚少。在此，通过在体外将选定的 EDPrB 引入适当的肝微粒体，我们检查了 LCM 在人类、大鼠、猪、鲤鱼、鲫鱼和黑鳢中的代谢途径. 首次通过气相色谱和液相色谱-高分辨率质谱法鉴定并阐明了总共 20 种依赖于物种的代谢物。脱烷基化、H-提取和羟基化反应是主要的代谢途径。其中一半在体外在暴露于 EDPrB 的 Sprague-Dawley 大鼠的尿液、血清和粪便样本中发现了代谢物。毒性预测表明 17 种代谢物可归类为有毒物质。根据生态结构活动关系 (ECOSAR)，许多代谢物表现出与 EDPrB 相当或更大的水生毒性。毒性估计软件工具 (TEST) 预测某些代谢物在大鼠中表现出发育毒性和致突变性。这些发现表明，应特别强调生物转化，并应进行更多的毒理学和监测研究，以评估 LCM 的生态和人类安全性。