High information content assays for genetic toxicology testing: A report of the International Workshops on Genotoxicity Testing (IWGT)
- DOI
- Language of the publication
- English
- Date
- 2019-02-21
- Type
- Article
- Author(s)
- Dertinger, Stephen D.
- Totsuka, Yukari
- Bielas, Jason H.
- Doherty, Ann T.
- Kleinjans, Jos
- Honma, Masamitsu
- Marchetti, Francesco
- Schuler, Maik J.
- Thybaud, Veronique
- White, Paul
- Yauk, Carole L.
- Publisher
- Elsevier
Abstract
We live in an era of ‘big data’, where the volume, velocity, and variety of the data being generated is increasingly influencing the way toxicological sciences are practiced. With this in mind, a workgroup was formed for the 2017 International Workshops on Genotoxicity Testing (IWGT) to consider the use of high information content data in genetic toxicology assessments. Presentations were given on adductomics, global transcriptional profiling, error-reduced single-molecule sequencing, and cellular phenotype-based assays, which were identified as methodologies that are relevant to present-day genetic toxicology assessments. Presenters and workgroup members discussed the state of the science for these methodologies, their potential use in genetic toxicology, current limitations, and the future work necessary to advance their utility and application. The session culminated with audience-assisted SWOT (strength, weakness, opportunities, and threats) analyses. The summary report described herein is structured similarly. A major conclusion of the workgroup is that while conventional regulatory genetic toxicology testing has served the public well over the last several decades, it does not provide the throughput that has become necessary in modern times, and it does not generate the mechanistic information that risk assessments ideally take into consideration. The high information content assay platforms that were discussed in this session, as well as others under development, have the potential to address aspect(s) of these issues and to meet new expectations in the field of genetic toxicology.
Plain language summary
Health Canada (HC) is responsible for assessing whether chemicals in the Canadian environment may adversely impact health. Within this mandate, HC works with international regulatory partners to evaluate the utility of new methodologies that can be used to improve toxicity testing. We currently live in an era of ‘big data’, which is increasingly influencing the way toxicological sciences are practiced. With this in mind, a workgroup (chaired by HC) was formed for the 2017 International Workshops on Genotoxicity Testing to consider the use of high-information content data in genetic toxicology assessments. Presentations were given on the following methodologies identified as relevant and promising to present-day genetic toxicology assessments: adductomics (measuring chemical groups that bind to DNA), global transcriptional profiling (measuring levels of gene products), error-reduced single-molecule sequencing (high accuracy DNA sequencing), and cellular phenotype-based tests (rapidly exploring protein changes and other indicators of genetic effects). Workgroup members discussed the state-of-the-science for these methodologies, their potential use in genetic toxicology, current limitations, and future work necessary to advance their utility and application. The session culminated with audience-assisted SWOT (strength, weakness, opportunities, and threats) analyses. A major conclusion is that while conventional regulatory genetic toxicology testing has served the public well over the last several decades, it does not provide the throughput that has become necessary in modern times, and it does not generate the mechanistic information that risk assessments ideally take into consideration. The high information content assay platforms that were discussed in this session, as well as others under development, have the potential to address aspects of these issues to meet new expectations in the field of genetic toxicology. The outcomes of this workshop will help to identify and prioritize which methods are ready for use in risk assessment and direct future work at HC.
Subject
- Health,
- Health and safety