Benchmark Dose Modeling of In Vitro Genotoxicity Data: a Reanalysis
Toxicol. Res. 2018;34:303−310
Published online October 15, 2018;  https://doi.org/10.5487/TR.2018.34.4.303
© 2018 Korean Society of Toxicology.

Xiaoqing Guo and Nan Mei

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR, USA
Xiaoqing Guo, 3900 NCTR Road, Jefferson, AR 72079, USA
E-mail: xiaoqing.guo@fda.hhs.gov
Nan Mei, 3900 NCTR Road, Jefferson, AR 72079, USA
E-mail: nan.mei@fda.hhs.gov
Received: August 10, 2018; Revised: August 16, 2018; Accepted: August 30, 2018
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA’s BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA’s BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.
Keywords : Benchmark dose, Quantitative analysis, In vitro genotoxicity, Mouse lymphoma assay


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