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EPA-Expo-Box (A Toolbox for Exposure Assessors)

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Aggregate and Cumulative


In advance of undertaking a combined exposure assessment, the assessor adequately defines the problem. Thoughtful planning, scoping, and problem formulation at the beginning of the project is necessary to determine the stressor(s) of interest, the potential effects of the stressor(s), and in the case of cumulative exposures, possible interactions between stressors. This process considers cross-disciplinary issues, including critical windows of susceptibility based on lifestages and toxicological endpoints. Effectively articulating these issues allows for the exposure assessor to outline data needs, select the proper approach, and anticipate assessment results. (See discussion of Problem Formulation in the Approaches Tool Set.)

When conducting an aggregate or cumulative assessment, the exposed population must be clearly defined. One or more stressors is then assessed with regard to impact on that population, although not every individual will see the same (or all) effects. This does not mean, however, that all combined assessments must start with a population and work “backwards” toward the source.

Other complexities that can usually be addressed in single stressor, single pathway assessments through the use of "simplifying assumptions" cannot always be addressed in the same fashion when assessing multiple stressors or multiple exposures (U.S. EPA, 2003). For example, risk assessments that analyze combined exposures, such as cumulative and aggregate exposures, generally follow the paradigm that the National Research Council recommends for all risk assessments, except that the approximation that allows for the “simplifying assumptions” that dose-response and exposure analyses can be analyzed separately cannot always be invoked for combined assessments. In a combined assessment for multiple stressors or a single stressor, the exposure and dose-response components of the paradigm generally need to be evaluated as a single component (U.S. EPA, 2003).

Other topics that might require additional consideration when conducting a combined exposure assessments include the following.

  • Combined Effects of Multiple Stressors—Potential synergistic and antagonistic interactions related to exposure to multiple stressors can increase or decrease the expected effects of the stressors.
  • Time—Exposure during susceptible lifestages might lead to increased effects; these are often described as “critical windows of exposure.” In addition, the sequence of exposure should be considered especially for stressors known to have synergistic or antagonistic effects.
  • Background Sources of Exposure—When examining combined exposures, background sources are typically considered to be important sources of exposure.
  • Assessing Exposure to Mixtures—Mixtures can be assessed as whole mixtures or as multi-component mixtures, but for either approach, describing the assumptions made (e.g., additive effects, toxicologic similarity) and the potential uncertainty in the assessment is critical.
  • Assessing Effect of Exposure to Non-Chemical Stressors—Non-chemical stressors include biological, radiological, and other physical stressors as well as socioeconomic stressors and lifestyle conditions. Combining the effects of exposure to chemical and non-chemical stressors is an area of continued research. For example, epigenetic studies examine how chemical and non-chemical stressors lead to changes in gene expression.
  • Quantification of Risks—Combining exposure and effects of chemical and non-chemical stressors with numeric exposure or risk estimates is difficult and sometimes qualitative descriptions (e.g., high, medium, low, weight of evidence descriptors) are necessary to summarize the expected exposure or risk.

Organizations in the United States and in other countries have begun to develop frameworks and guidance for combined exposure and risk assessments, but this branch of exposure assessment science is continuing to develop as more combined exposure assessments are conducted and more of the complexities resolved.

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Tools for Conducting Aggregate and Cumulative Assessments

The following resources provide information for conducting aggregate and cumulative exposure assessments.

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