Mode of Action (MoA)

Although the default assumption that the toxicity or carcinogenicity seen in a laboratory animal species will also potentially occur in an exposed human population still dominates the life of the risk assessor, there are increasing opportunities to introduce something more nuanced to the evaluative process. The identification of Modes of Action (or Adverse Outcome Pathways) with their associated Key Events is the improved way forward, ensuring a more transparent and data-driven bottom line on risk, and just as importantly, a more focused, and cost-effective, investment in additional research.

Over the past 15-or-so years, distinguished scientists working under the auspices of the International Programme on Chemical Safety (IPCS) and the International Life Sciences Institute (ILSI) have gradually developed a scheme (the Human Relevance Framework) for assessing a chemical’s cancer or non‑cancer mode of action and for determining its relevance to humans.

Our scientists have developed a good understanding of MoA precepts, and have proposed and discussed possible sequences of key events leading to chemical toxicities, including cancer, in the context of Bradford-Hill criteria for causality. We have a number of years of experience of applying the Human Relevance Framework to better understand whether individual chemical carcinogens/suspected carcinogens or toxins are likely to pose a real threat to human health. Of particular note, we have applied the MoA approach to mixtures, in a bid to determine which components might be making the most important contributions to the overall mixture’s toxicity and carcinogenicity.

Recent work in this field

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