When the current risk assessment�risk management paradigm as applied to humans was first elucidated in 1983, it did not explicitly include a problem formulation phase. The concept of problem formulation was first introduced in the context of ecotoxicological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs to the key questions. Subsequently, problem formulation has been introduced into human health risk assessment and is particularly pertinent in the context of cumulative risk assessment (CRA). In its broadest sense, CRA encompasses the combined risks from exposure via all relevant routes to all stressors, including biological, chemical, physical, and psychosocial. As part of the RISK21 program at HESI, we have proposed a framework for CRA that includes a problem formulation step. This framework is based on the tiered framework recommended for cumulative risk assessment of chemicals by WHO. Relative timing of exposures to multiple stressors is a major determinant of risks of adverse responses to cumulative exposures. In addition to contemporaneous, consecutive, or separate, exposures might also be important, depending on the kinetics of the chemicals, the duration of the response, any latency, and rate of recovery. Conceptual models for exposures in CRA need to include consideration and eventual quantification of non-chemical stressors such as physical environment, state of health and nutrition, and psychosocial status. At the highest tier, conceptual models for responses need to include measures of the interactions between stressors and the toxicodynamics and toxicokinetics that determine the cumulative response. This presentation will illustrate how conceptual models for exposures and responses can be developed, how data from new approaches to assessing responses can be used, and how testable risk hypotheses can be elaborated.

Cumulative risk assessment for human health: Asking the right questions

246th National Meeting (2013)

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