Strategies in genotoxicology: Acceptance of innovative scientific methods in a regulatory context and from an industrial perspective

https://doi.org/10.1016/j.mrgentox.2020.503171Get rights and content

Highlights

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    New Strategy in genotoxicology has been proposed (Adverse Outcome Pathway (AOP)).

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    Germ cells classification use in genotoxicology under Global Harmonized System (GHS) should re-discussed.

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    Quantitative genotoxicity, a new approach to assess risk assessment.

Abstract

The tests used and the general principles behind test strategies are now often over 30 years old. It may be time by now, given that our knowledge of genetic toxicology has improved and that we also technically are better able to investigate DNA damage making use of modern molecular biological techniques, to start thinking on a new test strategy. In the present paper, it is discussed that the time is there to consider a new approach for genotoxicity assessment of substances. A fit for all test strategy was discussed making use of the most recent technological methods and techniques.

It was also indicated that in silico tools should be more accepted by regulatory institutes/bodies as supporting information to better conclude which tests should be required for each separate substance to demonstrate its genotoxic potency. Next to that there should be a good rationale for performing in vivo studies. Finally, the need for germ cell genotoxicity testing, essential when classification and labeling of substances is mandatory, was discussed. It was suggested to change the GHS for genotoxicity classification and labelling from in vivo tests in germ cells into in vivo tests in somatic cells.

Quantitative genotoxicology was also discussed. It appeared that we are currently at a transition, where the science developing to justify carrying out human health risk assessments based on genetic toxicology data sets supported by mechanistic data and exposure data. However, implementation will take time, and acceptance will be supported through the development of numerous case studies. Major remaining questions are: is genetic damage a relevant endpoint in itself, or should the risk assessment be carried out on the apical endpoint of cancer and which genotoxic endpoint should be used to derive the point of departure (PoD) for the human exposure limit?

Section snippets

Summary and perspectives

The field of genetic toxicity testing is strongly in motion. There are many new developments and approaches, including the development of high throughput and screening tests. In silico approaches like QSAR and read across are generally accepted. The idea for quantitative genotoxicity, in which genotoxicity is a toxicological endpoint, gains more and more ground. Taking into account the quality of the current classical tests as compared to the new developments, it may be clear that genotoxicity

Declaration of Competing Interest

None.

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