Can we conclude on mutagenicity classification based in in vitro data only?
The increasing number of new chemical substances covering various industry sectors has raised concerns about their potential to harm human health and the environment. Criteria for hazard classification of chemicals are implemented by the UN Globally Harmonised System for Classification and Labelling (GHS) to facilitate chemical risk management and transport. Currently, the GHS criteria for germ cell mutagenicity are being revised to clarify issues that have brought to difficulties in their interpretation, consider current state of science and facilitate hazard classification using non-animal methods. To support these discussions we explored whether there are situations where the standard in vitro tests alone can be sufficient to classify substances as mutagenic. Currently, the genotoxicity testing strategy involves a step-wise approach, starting with in vitro tests that cover gene mutations, clastogenicity and aneugenicity. If in vitro tests yield positive results, follow-up confirmatory in vivo tests are required. In our study, we analysed the EURL-ECVAM genotoxicity database which includes over 700 chemicals, exploring six combinations of in vitro tests that cover all the three key endpoints. We then compared the in vitro results with overall in vivo assay outcome. We observed that most combinations of in vitro results that were positive for all endpoints (gene mutation, clastogenicity and aneugenicity) were confirmed in vivo, with at least one positive study. Additionally, the number of substances that were negative for genotoxicity in vivo was very low (>3%). Interestingly, for the most part of these outliers there is a clear insight of why they are misleading positives. These findings indicate that it may, in some cases, be possible to classify a chemical as a somatic cell mutagen using in vitro assays alone. Novel in vitro assays that address specific biological mechanisms providing supporting information in a weight of evidence may help increasing confidence in the results.
CAPELOA Tania;
CORVI Raffaella;
2026-03-11
Publications Office of the European Union
JRC145137
978-92-68-37660-7 (online),
1831-9424 (online),
EUR 40643,
OP KJ-01-26-070-EN-N (online),
https://publications.jrc.ec.europa.eu/repository/handle/JRC145137,
10.2760/0202127 (online),
Additional supporting files
| File name | Description | File type | |
|---|
