Evaluation of mode of action plays a critical role in both the hazard characterization and dose-response portions of assessments. Some chemicals may be data-rich, but still lack the data addressing key issues related to MOA. Other chemicals may have data supporting the involvement of multiple MOAs (either simultaneously or dominating different portions of the dose-response curve). TERA can work with interested parties to design and conduct (either in-house, or in the laboratories of our collaborators) studies targeted to address key MOA questions. We have active research projects aimed at developing approaches to quantitatively describing the dose-response for chemicals with multiple MOAs. We are also researching approaches to quantitatively incorporate biomarker data into quantitative assessments. These approaches allow one to use the biomarker data to inform the dose-response curve and decrease the amount of extrapolation needed, rather than simply using biomarker data to drive down the point of departure.
How much data is enough to meet EPA’s criteria for identifying a mode of action (MOA)? What studies are needed to address EPA’s framework?
How can data be used to move away from default approaches, and what are the implications for risk assessment?
How can biomarker data be appropriately incorporated quantitatively into assessments?
How should assessors address new categories of materials, such as those resulting from nanotechnology?
How can assessments address human variability, including genetic polymorphisms and other sources of human variability?
TERA scientists have extensive experience with these and related issues. Example projects include [add links to publications page, etc., as noted below]: