The validation case study of read-across based on IATA for hepatotoxicity of Naphthalene and its structurally similar analogs

Comparing biological similarity with in vitro test is expected to improve the reliability of read-across for systemic toxicity without animal test. However, because of few case studies, it was hindered to use of this concept for regulatory context. Thus, we compared biological similarity with in vitro test for structurally similar chemicals to demonstrate its validity for grouping chemicals and extract key considerations in read-across. In this study, we selected the hepatotoxicity of Naphthalene and its structurally similar analogs which have 90-day repeated dose toxicity data including 2,7-Naphthalenediol, 1,5-Naphthalenediol, and 1-Naphthol. To elucidate the potential mechanisms and compared them, we conducted in vitro microarray analysis with rat primary hepatocytes We conducted microarray analysis with Wister rat primary hepatocytes exposed by 2,7-Naphthalenediol, 1,5-Naphthalenediol, 1-Naphthol, and Naphthalene. After 24 h pre-culture, the cells were exposed to each chemical at 30 µM for 24 h. Three independent experiments were performed at each condition.