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EPA ExpoBox

Exposure Assessment Tools by Tiers and Types - Aggregate and Cumulative

Overview

Aggregate and Cumulative

Humans and ecological receptors are exposed to multiple stressors via multiple pathways. Considerable attention has been dedicated to assessing how different stressors interact and how overall exposure is influenced by uptake via different routes and pathways.

Assessments that examine exposure to more than one stressor and/or route and pathway are considered “combined” exposure assessments. Cumulative and aggregate assessments represent the two major categories of combined exposure assessments currently in use.

Aggregate

Aggregate exposureHelpAggregate exposureThe combined exposure of an individual (or defined population) to a specific agent or stressor via relevant routes, pathways, and sources. Total exposure can include exposure through multiple routes (e.g., dermal, inhalation, and ingestion). assessment considers combined exposures to a single stressor across multiple routes and multiple pathways (U.S. EPA, 2003).

 

Cumulative

Cumulative exposureHelpCumulative exposureExposure via mixtures of contaminants both indoors and outdoors. Exposure may also occur through more than one pathway. New directions in risk assessments in U.S. EPA put more emphasis on total exposures via multiple pathways. assessment generally evaluates combined exposure to multiple stressors via multiple exposure pathways (U.S. EPA, 2003) that affect a single biological target. In addition to chemical stressors, cumulative exposure assessments might also take into account non-chemical stressors. Non-chemical stressors may include physical or biological stressors.

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Description

Cumulative and aggregate exposure assessments are referred to as “combined exposure assessments” because cumulative assessments estimate exposure to multiple stressors by multiple routes. Aggregate assessments estimate exposures to a single stressor from multiple sources and by multiple routes.

Cumulative assessments more realistically depict real-world exposure, but also introduce a layer of complexity not found in traditional exposure assessments, which evaluate stressors individually.

Although exposure assessments conducted by EPA are usually focused on exposures to chemical, non-chemical stressors can be considered in a cumulative assessment – and can sometimes be very important. Biological threats (such as mold or other microorganisms), physical threats (e.g., noise, temperature), can cause direct effects on those exposed (such as hearing loss). They can modify the exposures or level of effects.

(U.S. EPA, 1992) Guidelines for Exposure Assessment

Whether a cumulative or aggregate approach (or some combination of the two) is used will vary according to the scope and objective of the assessment. The aggregate exposure assessment approach is commonly used when receptors can be exposed to a single contaminant in various ways.

For example, residues of the same pesticide could be found on multiple foods, in water, and/or in products used in and around the home. A receptor might have the opportunity to take up the contaminant via dermal contact, inhalation, ingestion, and other routes. 

On the other hand, cumulative exposure assessments are conducted for contaminants that produce toxic responses by the same mode of action. For example, cumulative exposure could occur for a population in a specific location that is exposed to a variety of stressors

Cumulative exposure assessments can be conducted for chemical stressors and also for non-chemical stressors, including:

“current physical and mental health status and past exposure histories…and social factors such as community property values, sources of income, level of income, and standard of living” (U.S. EPA, 2003).

Examples of non-chemical stressors could include biological threats (e.g., mold or other microorganisms) and physical threats (e.g., noise, odor, and temperature). Non-chemical stressors might increase the vulnerability of a population to exposure or the effects of exposure to chemical stressors.

Cumulative exposures are of particular interest when conducting community-based assessments. Community-based assessment are intended to encompass exposure to both chemical and non-chemical stressors potentially affecting a community. A community can be defined as “a group of individuals in the same geographical area and/or with the same demographic attributes considered to be key factors in assessing human exposure” (Zartarian and Schultz, 2010).

EPA has developed a range of tools, guidelines, and other resources (including grant programs) intended for use by community groups or other organizations interested in evaluating cumulative exposure and risk for a community.

Cumulative, community-based assessments are a cornerstone of assessments of environmental justice issues because they can characterize exposures or risks that disproportionately and unfairly affect certain communities. (See EPA’s Environmental Justice website for more information.)

Listed below are characteristics typical of aggregate and cumulative assessments, but these are not necessarily components of all aggregate or cumulative assessments.

  Aggregate Cumulative
Inputs
  • Single stressor (chemical only)
  • Individual action of stressor
  • Different modes of action
  • Summation of exposures across all pathways
  • Multiple stressors (chemicals and non-chemicals)
  • Consider interactions among stressors
  • Consider exposure to mixtures
  • Often similar mode of action
  • Additivity of exposure not assumed as a default approach
Aggregate exposure assessments often include a summation of all potential exposure pathways for a single stressor. This is a conservative, health-protective approach. It  assumes that a single receptor will be exposed to one stressor through all possible exposure pathways.

Cumulative exposures to multiple stressors, on the other hand, generally are not additiveHelpadditiveCombined exposure or risk summed, assuming each component acts as if the other were not present (U.S. EPA, 2003). unless they act via the same mode of action. Cumulative exposure assessments might also take into account non-chemical stressorsHelpnon-chemical stressorsBiological, radiological, and other physical stressors; socioeconomic stressors; and lifestyle conditions that might contribute to differences in exposure and adverse health outcomes..  It may also be necessary to determine how the various stressors interact to amplify or attenuate a response (i.e., synergisticHelpsynergisticExposure to multiple stressors leads to an increased response that exceeds what would be estimated for exposure to each chemical independently., antagonisticHelpantagonisticExposure to multiple stressors leads to an decreased response that is less than what would be estimated for exposure to each chemical independently., or additive).
Tools
  • Multipathway models
  • Models that consider a single chemical
  • Multimedia models
  • Models that consider exposure to mixtures

Both aggregate and cumulative assessments can use either a deterministic or a probabilistic approach.

Higher-tier or more refined exposure assessments for combined exposures are more common for aggregate exposure scenarios than for cumulative scenarios. This is due to the complexities of determining exposure that encompasses information about multiple stressors and multiple pathways.

Aggregate and cumulative exposure assessments can include both deterministic and probabilistic components. See the Deterministic and Probabilistic Module in this tool set for more information and resources. Screening-level assessments for combined exposures are typically more resource-intensive and complex, than screening-level assessments for single stressors.

Aggregate exposure can be assessed using tools available for exposure to agricultural and residential pesticides (e.g., CALENDEX, CARES, LifeLine), or exposure to chemicals in the environment (e.g., SHEDS, TRIM).

Cumulative exposures can be assessed using similar tools (e.g., APEX, CALENDEX). Fewer tools are available for non-chemical stressors, although some guidelines and resources have been developed by EPA and other groups.

Results
  • Effect of single stressor
  • Useful to inform cumulative assessments
  • Generally quantitative
  • Combined effects of stressors
  • Greater ability to assess population vulnerability
  • Quantitative and/or qualitative

An aggregate approach produces a summation of all potential exposure pathways for a single chemical stressor. This approach does not consider stressors beyond the single chemical of interest.

For example, this is commonly used in the regulation of pesticides. EPA conducts risk assessments for active ingredients in pesticides by evaluating all of the potential pathways of exposure for pesticide residues to determine the potential risk from aggregate exposure.

Cumulative assessments address the overall impact on human health of multiple stressors (chemical and non-chemical) that often act by the same mechanism of toxicity. The presence of multiple stressors, however, does not necessarily mean that all of the stressors will cause or contribute to an adverse effect.

Cumulative exposure assessment is not always the simple sum of multiple, aggregate exposure assessments. Incorporating the effects of exposure to non-chemical stressors often results in a qualitative description of exposure or risk because numeric values for these factors are often not available.

Identification and characterization of VULNERABILITYHelpVULNERABILITYDifferences in risk resulting from the combination of both intrinsic differences in susceptibility and extrinsic social stress factors such as low socioeconomic status, crime and violence, lack of community resources, crowding, access to health care, education, poverty, segregation, geography, etc. in terms of SUSCEPTIBILITYHelpSUSCEPTIBILITYDifferences in risk resulting from variation in both toxicity response (sensitivity) and exposure (as a result of gender, lifestage, and behavior)./sensitivity in populations is limited when using aggregate approaches. However, it may be possible with cumulative approaches, provided a relationship exists between these factors and changes in risk U.S. EPA, 2003). Research to improve the ability of cumulative exposure assessments to identify areas of high exposure and high vulnerability is underway.

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Guidance Tools

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

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Methods

Thoughtful planning, scoping, and problem formulation is important. It can help to determine the stressor(s) of interest, the potential effects of the stressor(s), and possible interactions between stressors.

This process can consider 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.)

Topics that might require 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.  However, 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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Input Data

Data availability ranges from relatively abundant for many chemical stressors to somewhat sparse for many biological and radiological stressors. Almost no information is available for the many other types of stressors (U.S. EPA, 2003).

In many cases, data may need to be collected specifically to support a combined risk assessment. For example, data used for a cumulative assessment should ideally “conserve the covariance and dependency structures associated with the [stressors] of concern” [ILSI (1999) as cited in EPA (2003)]. Moreover, because the exposure and dose-response analyses cannot easily be separated in a combined assessment, extremely detailed exposure estimates are only useful when the dose-response data are equally detailed.

Descriptions of the input data for aggregate and cumulative assessments can be found in multiple Tool Sets on the home page. In fact, the Indirect Estimation (Scenario Evaluation) module of the Approaches Tool Set includes the following categories for input data:

  • Sources and Releases
  • Fate and Transport
  • Concentrations
  • Characterizing Populations
  • Exposure Factors

Tools related to input data for fate and transport, concentrations, and exposure factors are also described in the Media and Routes Tool Sets.

Quantitative input data to characterize the effects of non-chemical stressors are often lacking, but recent journal articles and symposia have proposed strategies for incorporating these effects. Refer to:

  • Lewis, AS; Sax, SN; Wason, SC; Campleman, SL. (2011). Non-chemical stressors and cumulative risk assessment: An overview of current initiatives and potential air pollutant interactions. International Journal of Environmental Research and Public Health 8:2020-2073.
  • Rider, CV; Dourson, ML; Hertzberg, RC; Mumtaz, MM; Price, PS; Simmons, JE. (2012). Incorporating nonchemical stressors into cumulative risk assessments. Toxicol Sci.: 127(1):10-7.

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Applications

A number of example assessments are available that demonstrate the application of a combined exposure approach.

Programs Using a Combined Approach to Estimate Exposure and Risk

Cumulative assessments of pesticides and residual risks of air toxics by EPA are examples of a how a combined approach has been used. These example illustrate how these approaches can be used to better understand the complicated relationships that exist when analyzing multiple chemicals, routes of exposure, and pathways.

  • Pyrethroids and Pyrethrins
    EPA’s Office of Pesticide Programs conducted a cumulative exposure assessment for the pyrethroid pesticides. Pyrethroids are a family of chemicals with similar neurotoxic modes of action. EPA considered acute and chronic exposure to residues of pyrethroids in food, water, and other potential residential exposures; oral, dermal, and inhalation exposures were considered.
     
  • Revised Organophosphate Cumulative Risk Assessment (OPCRA)
    EPA conducted a cumulative exposure assessment for organophosphate pesticides. The preliminary assessment was designed to test and improve method for conducting cumulative risk assessments in the future. The revised assessment evaluated more than 1,000 organophosphate pesticides in food, water, and other potential residential exposures.
     
  • OAQPS National Air Toxics Assessments (NATA)
    EPA’s National-Scale Air Toxics Assessment (NATA) is a screening tool to prioritize pollutants, emission sources, and locations of interest for further study. NATA estimates exposures at census blocks and then estimates risk at the population level, and the number of people estimated to be above certain cancer risk levels. Since 1996, four NATA assessments have been completed to characterize the chronic cancer risk estimates and noncancer hazards from inhaling air toxics

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References

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