RNA-seq analysis of concentration-response transcriptomic changes induced by cannabinol (CBN) in hepatocytes derived from human induced pluripotent stem cells (iPSCs)

Currently little is known about the safety of nonintoxicating cannabinoids such as cannabinol (CBN). New approach methodologies (NAMs) based on bioinformatic analysis of high-throughput transcriptomic data are gaining increasing importance in risk assessment and regulatory decision-making of data-poor chemicals. In this study, we conducted a concentration response transcriptomic analysis of CBN in hepatocytes derived from human induced pluripotent stem cells (iPSCs). Biological functions and pathways impacted by CBN exposure were identified, including liver metabolism and cellular oxidative stress. In addition, a transcriptomic point-of-departure (tPoD) value was determined for CBN through benchmark concentration (BMC) analysis of the transcriptomic data. The present study demonstrates the potential utility of transcriptomic BMC analysis as a NAM for hazard assessment of data-poor chemicals, improves our understanding of the possible health effects of CBN, and provides important tPoD data that could contribute to inform human safety assessment of cannabinoid compounds. Cells were exposed to increasing concentrations of CBN (0.1-20 μM) for 24 h. Transcriptomic gene expression was characterizecd using RNA-seq. Three replicates were included for each concentration group including the control (0.0 μM).