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

Wheeldon, Ryan P.; Dertinger, Stephen D.; Bryce, Steven M.; Bemis, Jeffrey C.; Johnson, George E.

doi:10.1002/em.22422

[해외논문] The use of benchmark dose uncertainty measurements for robust comparative potency analyses 원문보기

Environmental and molecular mutagenesis, v.62 no.3, 2021년, pp.203 - 215

Wheeldon, Ryan P. (Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, UK) , Dertinger, Stephen D. (Litron Laboratories, Rochester, New York,) , Bryce, Steven M. (Litron Laboratories, Rochester, New York,) , Bemis, Jeffrey C. (Litron Laboratories, Rochester, New York,) , Johnson, George E. (Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, UK)

Abstract ▼ AI-Helper

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

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참고문헌 (23)

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[해외논문] The use of benchmark dose uncertainty measurements for robust comparative potency analyses 원문보기

Abstract ▼ AI-Helper

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