Comparison of the modes of action of p-dialkoxy chlorobenzenes in rat primary hepatocytes

It is considered that read-across based on only structure similarity has a risk of error on risk assessment. Under this circumstances, considering biological similarity based on adverse outcome pathways (AOPs) using in vitro omics technologies is expected to enhance the accuracy and robustness of conclusions in read-across. However, because of a lack of practical case studies, it is not well discussed key considerations and how to use these technologies for data gap filling. In the present case study, we elucidated and compared the mode of action for structural analogs ; p-dialkoxy chlorobenzenes including 1,4-dichloro-2,5-dimethoxybenzene (DDMB), 2,5-dichloro-1,4-diethoxybenzene (DDEB), 2-chloro-1,4-dimethoxybenzene (CDMB), and 1-chloro-2,5-diethoxybenzene (CDEB) using in vitro omics technologies. To reveal the modes of action, we conducted microarray analysis with rat primary hepatocytes.学界普遍认为，仅基于结构相似性开展的交叉参照（read-across）法在风险评估中存在引入误差的风险。在此背景下，基于不良结局途径（AOPs）、结合体外组学技术考量生物相似性，有望提升交叉参照法结论的准确性与稳健性。然而，由于缺乏实际案例研究，目前针对交叉参照法的关键考量要点，以及如何利用此类技术填补数据缺口的相关探讨仍较为匮乏。本案例研究中，我们借助体外组学技术，对结构类似物——包括1,4-二氯-2,5-二甲氧基苯（DDMB）、2,5-二氯-1,4-二乙氧基苯（DDEB）、2-氯-1,4-二甲氧基苯（CDMB）以及1-氯-2,5-二乙氧基苯（CDEB）在内的对二烷氧基氯苯类化合物的作用模式进行了阐明与比较。为明确此类化合物的作用模式，我们采用大鼠原代肝细胞开展了微阵列分析。