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. We conducted microarray analysis with rat primary hepatocytes exposed by DDMB, DDEB, CDMB, CDEB. After 24 h pre-culture, the cells were exposed to each compound at 300 µM for 24 h. Three independent experiments were performed at each condition. In this study, the normalization was divided into two group; (DDMB,CDMB,CDEB vs VC_1), (DDEB vs VC_2) because of lot differences on microarray chips.