Table 4.

Important Differences between Stressor-Based (Bottom-up) and Effects-Based (Top-Down) Approaches to Cumulative Risk Assessment.

Attribute	Stressor-Based Approach	Effects-Based Approach
Analytical Strategy	Prospective, bottom-up analysis (evaluate constituent interactions)	Retrospective, top-down analysis (deconstruct and elucidate outcomes)
Central Question	What health effects are associated with a defined set of stressors?	Which stressors explain observed or hypothesized health outcomes?
Starting Point	Identification of key stressors and recognition of the populations and health end points influenced by them	Development of a conceptual model incorporating the stressors plausibly associated with critical health outcomes
Primary Emphasis	Analysis of stressor interactions to predict likelihood and severity of future adverse health outcomes	Determination of stressor contributions to observed or hypothesized health outcomes, including consideration of co-exposures and background processes
Typical Applications	Chemical mixtures	Combinations of chemical and nonchemical stressors
Driving Force(s)	Regulatory decisions about protection of human health from exposure to multiple chemicals [8,9,10,18,36,37,38,39,44,45,46]	Demands for “environmental justice”, concerns about health disparities, and calls for community-based risk assessments [3,4,11,12,13,14,15,16,28,64,65,66,77,78,79]