FDA’s Center for Tobacco Products

This page hosts your interactive ENDS genotoxicity/carcinogenicity tiering flowchart.

Interactive Genotoxicity Tiering Flowchart for ENDS Constituents

Based on FDA’s Weight of Evidence (WOE) approach. Click any box to see a simple explanation.

Tier 1–3
Tier 4 (Potential Hazard)
Tier 5 (Unlikely Hazard)
Include in Cancer Risk Calc.
Exclude from Cancer Risk Calc.
  • Start: Identify a constituent in an ENDS product
    • Has the constituent been evaluated for carcinogenicity by IARC or EPA?
      • YES
        Tier 1, 2, or 3
        Based on IARC/EPA classification
        • Include in ELCR Calculation
      • NO
        Is there a positive result from an in vivo (live animal) genotoxicity or carcinogenicity study?
        • YES
          Tier 4A: Positive in vivo evidence
          • Include in ELCR Calculation
        • NO
          Positive Ames test (in vitro or in silico) for mutagenicity?
          • YES
            Tier 4B: Mutagenicity concern
            • Potentially in ELCR (Follow-up needed)
          • NO
            Positive result from other in vitro genotoxicity tests?
            • YES
              Tier 4C: Other in vitro genotoxicity
              • Potentially in ELCR (Follow-up needed)
            • NO
              Positive non-Ames computational predictions for toxicity?
              • YES
                Tier 4D: Computational toxicity alert
                • Potentially in ELCR (Follow-up needed)
              • NO
                Is there sufficient negative evidence for a Tier 5 classification?
                • YES
                  Tier 5: Unlikely to contribute to carcinogenic risk
                  • Not in ELCR Calculation
                • NO
                  Tier 4E: Insufficient data for Tier 5
                  • Potentially in ELCR (Follow-up needed)