The use of benchmark dose uncertainty measurements for robust comparative potency analyses

The Benchmark Dose (BMD) method is the favored approach for quantitative dose–response analysis where uncertainty measurements are delineated between upper (BMDU) and lower (BMDL) confidence bounds, or intervals (CIs). Little has been published on accurate interpretation of potency comparative analyses different test conditions. We highlight this by revisiting a previously in vitro genotoxicity dataset human lymphoblastoid TK6 cells that were exposed to each 10 clastogens presence absence (+/−) low concentration (0.25%) S9, scored p53, γH2AX Relative Nuclei Count (RNC) responses at two timepoints (Tian et al., 2020). researchers utilized BMD point estimates S9 treatment Here we shortcoming use can mischaracterize differences systems. reanalyzed dose modeling using PROAST v69.1. used resulting BMDL BMDU metrics calculate “S9 ratio intervals” compare relative compounds +/− as more statistically robust compared estimate ratios. performed unsupervised hierarchical clustering identified four S9-dependent groupings: high low-level potentiation, no effect, diminution. This work demonstrates importance Irrespective source data, propose stepwise when performing