Moving Upstream: A Workshop on Evaluating Adverse Upstream Endpoints for Improved Decision Making and Risk Assessment

An initial step in hazard and risk assessment for an environmental contaminant is to identify the adverse effects resulting from exposure to a contaminant. What constitutes an adverse effect is not defined in environmental health legislation but is broadly defined in Federal risk assessment guidelines. For example, the EPA Integrated Risk Information System defines an adverse effect as “a biochemical change, functional impairment, or pathologic lesion that affects the performance of the whole organism, or reduces an organism's ability to respond to an additional environmental challenge”[1]. This lack of specification reflects recognition that the definition of an adverse effect will change as science and our understanding of the toxic mechanisms of environmental hazards advances. It also recognizes the connection between perturbations in the system, which can in themselves lead to more overt effects or create sensitivities to further environmental exposures, and more downstream overt effects. Continuing to focus on events that are farther upstream enhances the ability of the risk assessment and decision-making processes to better prevent more downstream events.