(Adapted from Smith et al. 2016, 2020)
Characteristic | Examples of relevant evidence |
1. Is Electrophilic or Can Be Metabolically Activated 是亲电子的或可以被代谢激活 Est électrophile ou peut être activé métaboliquement | Parent compound or metabolite with an electrophilic structure (e.g., epoxide, quinone, etc), formation of DNA and protein adducts. |
2. Is Genotoxic 有遗传毒性 Est génotoxique | DNA damage (DNA strand breaks, DNA-protein cross-links, unscheduled DNA synthesis), intercalation, mutations/single nucleotide variants, structural and numerical chromosome alterations (clastogenicity/aneugenicity), cytogenetic changes (e.g., chromosome aberrations, micronuclei). |
| 3. Alters DNA repair or causes genomic instability | Alterations of DNA replication and repair capacity (e.g., topoisomerase II, base-excision or double-strand break repair); Copy number variations (duplications, deletions, amplifications, insertions), Inter-/intra-chromosomal translocations, Microsatellite instability, Increased expression of activation-induced cytidine deaminase (AICD). |
| 4. Induces Epigenetic Alterations | Global and locus-specific DNA methylation, histone modifications, Chromatin remodeling, Changes in non-coding RNAs |
| 5. Induces Oxidative Stress | Reactive oxygen species (ROS) formation, oxidative damage to macromolecules (e.g., DNA, lipids), Glutathione depletion, NFE2L2-ARE-dependent gene expression response, Lipid peroxidation. |
| 6. Induces chronic inflammation | Tissue inflammation, Inflammatory signaling. |
| 7. Is Immunosuppressive | Decreased immunosurveillance, immune system dysfunction, T cell activation and proliferation, Cytotoxic T-lymphocyte (CTL) activity, Natural killer cell activity. |
| 8. Modulates receptor-mediated effects | Interacts with receptors, receptor activation, modulation of endogenous ligands (including hormones) |
| 9. Causes Immortalization | Altered cellular senescence markers, Modified in vitro cell transformation activity, Increases in telomere length and telomerase activity, Alterations in stem cell genes. |
| 10. Alters cell proliferation, cell death or nutrient supply | Increased proliferation, decreased apoptosis, changes in growth factors, alterations in signaling pathways related to cellular replication or cell cycle control, changes to energetics reflected as a glycolytic (Warburg) shift, angiogenesis. |