TABLE 4.

Key Research Questions in Developing Knowledge to Support Pathway Testing

Toxicity-pathway identification—What are the key pathways whose perturbations result in toxicity? Multiple pathways—What alteration in response can be expected from simultaneous perturbations of multiple toxicity pathways?

Adversity—What adverse effects are linked to specific toxicity-pathway perturbations? What patterns and magnitudes of perturbations are predictive of adverse health outcomes?

Life stages—How can the perturbations of toxicity pathways associated with developmental timing or aging be best captured to enable the advancement of high-throughput assays?

Effects of exposure duration—How are biologic responses affected by exposures of different duration?

Low-dose response—What is the effect on a toxicity pathway of adding small amounts of toxicants in light of preexisting endogenous and exogenous human exposures?

Human variability—How do people differ in their expression of toxicity-pathway constituents and in their predisposition to disease and impairment?