The next SOT FDA colloquium focuses on mode of action in dose-response assessment. The event is January 25 from 8:30 am–1:00 pm ET at the Wiley Auditorium, US FDA, College Park, Maryland. Participants can attend on-site or via webcast.
Registration for onsite
Among the primary goals of a risk assessment are determination of the presence or absence of a cause-effect relationship and quantifying the risk through dose-response analysis. Dose-response data may be derived from in vivo studies in animals or humans, which usually provide the basis for risk characterization, and in vitro studies, which are often related to investigations of mode of action (MOA). The MOA information describes key events and processes that would explain the overall process of development of a toxic effect. MOA can also be relevant in considering susceptibility factors within populations and in considering the cumulative effects of exposure to more than a single agent.
Over the last several years, advances in our understanding of the ways that chemicals interact with biological systems have yielded several frameworks for evaluating toxicity datasets to determine biologically plausible modes of action and relevance to humans. These frameworks can be used to consider the weight of evidence of hypothesized modes of action in animals and their potential human relevance for both cancer and non-cancer effects. This could result in a move away from defaults to adopt modern knowledge on MOA to improve risk assessments, including the choices for dose-response assessment.
Suzanne Fitzpatrick, FDA, is chair and Ji-Eun Lee, Kellogg, is co-chair. Elaine Faustman, University of Washington, will moderate the roundtable discussion that concludes the session.
Topics and speakers include:
- The Role of Mode of Action in Dose-Response Assessments: Recommendations from the 2009 NRC Report “Science and Decisions,” Lauren Zeise, NRC Committee Member, Berkeley, California
- Mode of Action, Distinguishing between Mode and Mechanism of Action, and Some Key Events for MOA, Michael Dourson, TERA, Cincinnati, Ohio
- The Mutagenic Mode of Action and the Choices for the Dose-Response Analysis, Rita Schoeny, US EPA (retired), Washington, DC
- Risk21 Quantitative Key Events Dose-Response Framework, J. Craig Rowlands, Dow Chemical Company, Midlands, Michigan
SOT and CFSAN have partnered to provide a colloquia series that presents scientific information that is high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of FDA employees. These events are not a public forum for discussion of toxicology regulatory issues. More information and the colloquia recordings and slides are available at the Colloquia website.