Mode of action (MOA) information describes key events and processes that would, in general, explain the overall process of development of a toxic effect. MOA is also relevant in considering susceptibility factors within populations, and in considering the cumulative effects of exposure to more than a single agent.
MOA is part of the movement away from the default assumptions of the mid-twentieth century to more modern science-based decisions. In practice, however, in some governmental programs, recognition of this movement has been slow to develop. Promoting the thoughtful application of MOA in risk assessment is a core activity of ACC’s Center for Advancing Risk Assessment Science and Policy (ARASP).
Examples of Scientific Knowledge for Chemical Risk Assessments
Substantial investments in research by both the public and private sectors over the last 30 years to improve the scientific understanding of the ways that chemicals interact with biological systems have yielded rigorous scientific frameworks for evaluating toxicity datasets to determine biologically plausible modes of action and determine relevance to humans.
There is a need to move away from defaults and adopt modern knowledge on MOA to improve risk assessments. There are many examples of methods for conducting MOA analysis and the use of MOA in risk assessments. In fact, a search of PubMed database revealed more than 20,000 records with “mode of action” as a key phrase.
Decision logic for evaluating the biological events leading to an animal tumor response, and consideration of how these events relate to human risk is possible as a routine matter in cancer risk assessment, are reflected in examples of evaluating relevance of different MOA to humans.
Studies focused on MOA of specific chemicals help to provide the most up-to-date and accurate assessment of potential risks of chemicals to human health. ARASP, however, does not advocate for any specific chemical.