Comparing BMD ‐derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay

This study therefore employed the BMD approach to examine the ability of different TGR variants to yield comparable genotoxic potency estimates. Review of over 2000 dose‐response datasets identified suitably‐matched dose‐response data for three compounds (ethyl methanesulfonate or EMS, N‐ethyl‐N‐nitrosourea or ENU, and dimethylnitrosamine or DMN) across four commonly‐used murine TGR variants (Muta™Mouse lacZ, Muta™Mouse cII, gpt delta and BigBlue® lacI). Dose‐response analyses provided no conclusive evidence that TGR variant choice significantly influences the derived genotoxic potency estimate. This conclusion was reliant upon taking into account the importance of comparing BMD confidence intervals as opposed to directly comparing PoD values (e.g., comparing BMDLs). Comparisons with earlier works suggested that with respect to potency determination, tissue choice is potentially more important than choice of TGR assay variant. Scoring multiple tissues selected on the basis of supporting toxicokinetic information is therefore recommended. Finally, we used typical within‐group variances to estimate preliminary endpoint‐specific benchmark response (BMR) values across several TGR variants/tissues. We discuss why such values are required for routine use of genetic toxicity PoDs for HHRA. Environ. Mol. Mutagen., 2017. © 2017 Wiley Periodicals, Inc.

Source: Environmental and Molecular Mutagenesis - September 25, 2017 Category: Molecular Biology Authors: John W. Wills, George E. Johnson, Hannah L. Battaion, Wout Slob, Paul A. White Tags: Research Article Source Type: research