Table 1.

Key characteristics of carcinogens identified by IARC expert review of all Group 1 agents (Smith et al., 2016).

Characteristic	Examples of relevant evidence
1. Is electrophilic or can be metabolically activated	Parent compound or metabolite with an electrophilic structure (e.g., epoxide, quinone, etc), formation of DNA and protein adducts.
2. Is genotoxic	DNA damage (DNA strand breaks, DNA- protein cross-links, unscheduled DNA synthesis), intercalation, gene mutations, cytogenetic changes (e.g., chromosome aberrations, micronuclei).
3. Alters DNA repair or causes genomic instability	Alterations of DNA replication or repair (e.g., topoisomerase II, base-excision or double-strand break repair)
4. Induces Epigenetic Alterations	DNA methylation, histone modification, microRNA expression
5. Induces oxidative stress	Oxygen radicals, oxidative stress, oxidative damage to macromolecules (e.g., DNA, lipids)
6. Induces chronic inflammation	Elevated white blood cells, myeloperoxidase activity, altered cytokine and/or chemokine production
7. Is immunosuppressive	Decreased immunosurveillance, immune system dysfunction
8. Modulates receptor-mediated effects	Receptor in/activation (e.g., ER, PPAR, AhR) or modulation of endogenous ligands (including hormones)
9. Causes immortalization	Inhibition of senescence, cell transformation
10. Alters cell proliferation, cell death or nutrient supply	Increased proliferation, decreased apoptosis, changes in growth factors, energetics and signaling pathways related to cellular replication or cell cycle control, angiogenesis