Towards quantitative genotoxicity assessment: ToxTracker reporting will include BMD Analysis
For hazard identification, a qualitative answer whether a substance is genotoxic or not is often sufficient. To use ToxTracker data for risk assessment, quantification of the dose response of a test substance will be required. Therefore, Toxys has incorporated benchmark dose (BMD) response modeling into the standard ToxTracker assay data analysis pipeline. This addition will expand the applicability domain of ToxTracker.
Application of BMD analysis in ToxTracker
The benchmark dose is the concentration of a compound that elicits a pre-defined increase in response when compared to concurrent vehicle controls. Addition of quantitative dose response modeling will determine the benchmark concentration that induces biologically meaningful increases in each of the ToxTracker reporters1. The BMD will be calculated using PROAST software, which provides quantitative information about genotoxic mode of action and facilitates quantitative in vitro to in vivo (qIVIVE) extrapolation2.
A) Typical dose response for the clastogenic chemotherapeutic cisplatin across all ToxTracker reporters. The highest induction is noted in Rtkn-GFP, the marker for DNA double strand breaks. B) Bootstrapping dose response models provide lower and upper estimates of the BMD using a benchmark response of 100 (100% increase over background, 2-fold). C) Lower and upper BMD bounds of the 90% confidence interval (CI) across the positive ToxTracker reporters for cisplatin.
Typical applications of BMD modeling include:
- Potency comparison of related substances (i.e. read-across or weight of evidence (WoE) approach)
- Determining safe exposure levels such as the acceptable daily intake (ADI)
- Protective estimates of in vivo dose using qIVIVE
If you would like to learn more about BMD and how it can help your study, please feel free to reach out via enquiries@toxys.com
References
- Boisvert L, Derr R, Osterlund T, Hendriks G, Brandsma I. Quantitative interpretation of ToxTracker dose-response data for potency comparisons and mode-of-action determination. Environ Mol Mutagen. 2023;64(2):132-143. doi:10.1002/em.22525
- Beal MA, Audebert M, Barton-Maclaren T, et al. Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose. Environ Mol Mutagen. 2023;64(2):105-122. doi:10.1002/em.22521
Sampath Kumar Rompicherla
June 3, 2025 at 3:30 pmThanks for sharing, Toxys Team. Very insightful.
Regards,
Sampath