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Synthesizing Genotoxicity Results in the MultiFlow® Assay with Point-of-Departure Analysis and ToxPi Visualization Techniques
  • Yusuf Hussien,
  • Stephen Dertinger,
  • George Johnson
Yusuf Hussien
Swansea University Medical School

Corresponding Author:957196@swansea.ac.uk

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Stephen Dertinger
Litron Laboratories
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George Johnson
Swansea University
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Abstract

In vitro genotoxicity has historically served a hazard identification role, with simple binary outcomes provided for each of several single endpoint assays. This will need to change, given: i) efforts to curtail animal testing, ii) the increased use of multiplexed in vitro assays and the ongoing development of NAMS, and iii) the desire to holistically consider quantitative results from multiple biomarkers/endpoints that take potency into consideration. To help facilitate more quantitative analyses of multiple biomarkers and/or assay streams, we explored the combined use of PROAST and Toxicological Prioritization Index (ToxPi) software. As a proof-of-concept, this investigation employed the MultiFlow® DNA damage assay, focusing on γH2AX and p53 biomarkers at two time points, whereby 10 genotoxicants were evaluated in the presence and absence of rat liver S9 metabolic activation. Whereas PROAST was used to calculate BMD point estimates and confidence intervals (CI), ToxPi synthesized the BMD results into visual, quantitative summaries conveying genotoxic potency and metabolic properties. Our analyses suggest that ToxPi’s data synthesis and visualization modules provide useful insights into compound potency, chemical grouping, and genotoxic mechanisms. By integrating multiple data sources, we find that ToxPi offers a powerful complementary approach to traditional BMD CI potency graphs, particularly for the simultaneous analysis of multiple biomarkers enhancing chemical potency analysis of complex datasets.
13 Dec 2024Submitted to Environmental and Molecular Mutagenesis
16 Dec 2024Submission Checks Completed
16 Dec 2024Assigned to Editor
16 Dec 2024Review(s) Completed, Editorial Evaluation Pending
16 Dec 2024Reviewer(s) Assigned