Overall goal/objectives:
The overall goal of the project is to critically evaluate genetic toxicology NAMs and determine how in vitro to in vivo extrapolation (IVIVE) could be applied to these data to support human health risk assessment. Recently, genetic toxicology data from various endpoints (mutagenicity, aneugenicity, clastogenicity, DNA damage response elements) has been provided by members of the Genetic Toxicology Technical Committee and IVIVE is being applied to genetox benchmark concentrations to derive administered equivalent doses (AEDs). These AEDs were compared to points-of-departure from traditional in vivio genotoxicity data to build confidence in the approach.
Case Study Leader:
Health Canada (Marc Beal)
Collaborators:
Health Canada, US EPA, AICIS
Status: Completed
There are opportunities for collaboration for APCRA members that have IVIVE expertise or experience in genotoxicity hazard assessment to support the project.
Presentations or publications that have been publicly released:
- Beal MA, Audebert M, Barton-Maclaren T, Battaion H, Bemis JC, Cao X, Chen C, Dertinger SD, Froetschl R, Guo X, Johnson G, Hendriks G, Khoury L, Long AS, Pfuhler S, Settivari RS, Wickramasuriya S, White P. Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose. Environ Mol Mutagen. 2023 Feb;64(2):105-122. doi: 10.1002/em.22521. Epub 2022 Dec 22. PMID: 36495195. https://pubmed.ncbi.nlm.nih.gov/36495195/
- Beal MA. 2021. Application of in vitro to in vivo extrapolation to ToxTracker Data for Point of Departure Derivation. 11th World Congress on Alternatives and Animal Use in the Life Sciences. Virtual Meeting.
- Paul-Friedman K, Beal MA. 2021. In Vitro to In Vivo Extrapolation Incorporating Toxicokinetics. 52nd Annual Meeting of the Environmental Mutagenesis Society. Virtual Meeting.